{
    "info": {
        "nct_id": "NCT04648020",
        "official_title": "A Phase 2b/3, Multicenter, Randomized, Double-blind, Placebo-controlled Study Comparing the Efficacy and Safety of Clonidine Mucoadhesive Buccal Tablet to Placebo to Prevent Chemoradiotherapy-induced Severe Oral Mucositis in Patients With Oropharyngeal Cancer",
        "inclusion_criteria": "1. Male/Female patients of ≥ 18 years of age. Patients with histologically or pathologically confirmed squamous cell carcinoma of the oropharynx (including tonsils or the base of tongue) at one or several sites.\n2. Patients treated with surgical resection of their primary tumor for localized or locally advanced disease T ≥ T0 and/or N ≥ N1 without distant metastasis (M0) (American Joint Committee on Cancer - AJCC 8th edition) and initiating adjuvant concurrent CRT within 8 weeks post-operatively. Unknown primary with node-positive disease confirmed to be Squamous Cell Carcinoma would be allowed or Patients who will be treated with definitive concurrent CRT for locally advanced disease T ≥ T0 and/or N ≥ N1 M0 (American Joint Committee on Cancer - AJCC 8th edition).\n3. Patients eligible to receive a continuous course of external fractionated irradiation [conventional or intensity modulated radiation therapy (IMRT)] based on a daily dosing of 1.8 to 2.2 Gy/day 5 days/week in combination with cisplatin monotherapy either every 3 weeks (100 mg/m2) or weekly cisplatin (40 mg/m2). Alternative treatment regimens are allowed only if cisplatin is contraindicated. The decision on which cisplatin regimen to use in combination with IMRT and study drug/placebo will be at the discretion of the investigator.\n4. Radiation plan must include delivery of a cumulative dose of 60-72 Gy. The oropharynx should receive at least 50 Gy.\n5. Patients with adequate laboratory values defined as:\n\n   1. Absolute neutrophil count ≥ 1.5 × 10^9/L\n   2. Platelet count ≥ 75 × 10^9/L\n   3. Hemoglobin ≥ 9 g/dL\n   4. Creatinine blood level ≤ 1.5 × upper limit of the normal range (ULN)\n   5. Total bilirubin ≤ 1.5 × ULN; patients with Gilbert's Syndrome can be included if hyperbilirubinemia ≤ 3 × ULN\n   6. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × ULN\n6. Patients with Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. A performance status of 2 is allowed only if due to a patient's malignancy.\n7. Patients must provide written informed consent.\n8. Human Papillomavirus (HPV) status documented by immunohistochemical detection of p16 expression in the tumor.\n9. Negative serum pregnancy test for females of child-bearing potential at screening. A female is eligible to enter and participate in the study if the female is of non-child-bearing potential (i.e., physiologically incapable of becoming pregnant), including any female who has had a hysterectomy, a bilateral oophorectomy (ovariectomy), a bilateral tubal ligation, or is post-menopausal with a minimum of 1 year without menses.\n10. Males with female partners of child-bearing potential and females of child-bearing potential must agree to use effective contraception starting prior to the first day of study drug treatment and continuing for 3 months after the last dose of study drug MBT.\n11. Patients must be willing to complete questionnaires on a tablet, home computer, or paper form.\nHealthy volunteers allowed\nMust have minimum age of 18 Years",
        "exclusion_criteria": "1. Patients with no tumor or lesion in the oropharynx.\n2. Prior induction chemotherapy for treatment of current malignancy.\n3. Patients with planned accelerated IMRT.\n4. Evidence of a concomitant other malignancy and/or any prior malignancy without complete remission in the last 2 years, except adequately treated basal or squamous cell carcinoma of the skin or in situ cervical cancer.\n5. Patients with OM at baseline, any other oral ulceration or active oral infection (e.g., aphthous ulcers, orofacial herpes). Patients with post-operative pain of the mouth or throat are eligible.\n6. Patients with known human immunodeficiency virus (HIV) seropositivity, known active Hepatitis B or C or known active tuberculosis.\n7. Patients with systolic blood pressure (BP) < 100 mmHg and/or diastolic BP < 50 mmHg.\n8. Patients with symptomatic cardiac dysrhythmia.\n9. Patients with recent (less than 6 months) acute cardiovascular diseases (i.e., stroke, myocardial infarction).\n10. Patients with any clinical condition, psychiatric condition, or prior therapy that, in the opinion of the investigator, would make the patient unsuitable for the study or unable to comply with study requirements and follow-up visits.\n11. Patients currently being treated with sultopride, clonidine hydrochloride (eg, Catapres®), pentoxifylline or pilocarpine.\n12. Patients intended to be treated specifically to prevent OM with any of the following:\n\n    a. Bioadherent agents and mouthwashes: i. GelClair (consists of polyvinylpyrrolidone, hyaluronic acid, and glycyrrhetinic acid) ii. Sucralfate iii. Episil mouth spray iv. MuGard oral mucoadhesive v. Saforis (L-glutamine (topical)) b. Drug therapies and biologics: i. Amifostine (and similar free radical scavenger/antioxidant medications) ii. Palifermin (recombinant human keratinocyte growth factor-(KGF-1)) iii. Glutamine b. Interventional therapies i. Low level laser therapy (LLLT)\n13. Patients who are unable to tolerate oral diet and/or are feeding tube dependent at baseline.\n14. Patients receiving an approved or an investigational anti-cancer agent other than those specified in this study.\n15. Patients with a known hypersensitivity to clonidine or any of the MBT excipients.\n16. Women who are pregnant or breast-feeding.\n17. Patients whose medical, psychological or surgical conditions are unstable and may affect the study completion and/or compliance and/or the ability to give informed consent.\n18. Men and women of child-bearing age and their respective partners unwilling to use a highly effective contraception method during the study and for 3 months after the last administration of study drug.\n19. Patient who has participated in another clinical trial with an investigational drug in the last 30 days prior to randomization in the present clinical study.\n20. Subjects with orthostatic hypotension, defined by a decrease of systolic BP and/or diastolic BP above 20 mmHg when the patient stands up.\n21. Conditions including but not limited to COVID-19 which would confound the assessment of the effects and/or safety of study medication in the opinion of the investigator.",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "1. Male/Female patients of ≥ 18 years of age. Patients with histologically or pathologically confirmed squamous cell carcinoma of the oropharynx (including tonsils or the base of tongue) at one or several sites.",
            "criterions": [
                {
                    "exact_snippets": "Male/Female patients",
                    "criterion": "gender",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": [
                                "male",
                                "female"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "≥ 18 years of age",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "minimum",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "years"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "histologically or pathologically confirmed squamous cell carcinoma",
                    "criterion": "squamous cell carcinoma",
                    "requirements": [
                        {
                            "requirement_type": "confirmation",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "squamous cell carcinoma of the oropharynx (including tonsils or the base of tongue)",
                    "criterion": "location of squamous cell carcinoma",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": [
                                "oropharynx",
                                "tonsils",
                                "base of tongue"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Patients treated with surgical resection of their primary tumor for localized or locally advanced disease T ≥ T0 and/or N ≥ N1 without distant metastasis (M0) (American Joint Committee on Cancer - AJCC 8th edition) and initiating adjuvant concurrent CRT within 8 weeks post-operatively. Unknown primary with node-positive disease confirmed to be Squamous Cell Carcinoma would be allowed or Patients who will be treated with definitive concurrent CRT for locally advanced disease T ≥ T0 and/or N ≥ N1 M0 (American Joint Committee on Cancer - AJCC 8th edition).",
            "criterions": [
                {
                    "exact_snippets": "surgical resection of their primary tumor",
                    "criterion": "surgical resection",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "localized or locally advanced disease T ≥ T0 and/or N ≥ N1",
                    "criterion": "disease stage",
                    "requirements": [
                        {
                            "requirement_type": "stage",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 0,
                                        "unit": "T"
                                    },
                                    {
                                        "operator": ">=",
                                        "value": 1,
                                        "unit": "N"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "without distant metastasis (M0)",
                    "criterion": "distant metastasis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "initiating adjuvant concurrent CRT within 8 weeks post-operatively",
                    "criterion": "adjuvant concurrent CRT initiation",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": "within 8 weeks post-operatively"
                        }
                    ]
                },
                {
                    "exact_snippets": "Unknown primary with node-positive disease confirmed to be Squamous Cell Carcinoma",
                    "criterion": "unknown primary with node-positive disease",
                    "requirements": [
                        {
                            "requirement_type": "confirmation",
                            "expected_value": "Squamous Cell Carcinoma"
                        }
                    ]
                },
                {
                    "exact_snippets": "definitive concurrent CRT for locally advanced disease T ≥ T0 and/or N ≥ N1 M0",
                    "criterion": "definitive concurrent CRT",
                    "requirements": [
                        {
                            "requirement_type": "stage",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 0,
                                        "unit": "T"
                                    },
                                    {
                                        "operator": ">=",
                                        "value": 1,
                                        "unit": "N"
                                    }
                                ]
                            }
                        },
                        {
                            "requirement_type": "distant metastasis",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Patients eligible to receive a continuous course of external fractionated irradiation [conventional or intensity modulated radiation therapy (IMRT)] based on a daily dosing of 1.8 to 2.2 Gy/day 5 days/week in combination with cisplatin monotherapy either every 3 weeks (100 mg/m2) or weekly cisplatin (40 mg/m2). Alternative treatment regimens are allowed only if cisplatin is contraindicated. The decision on which cisplatin regimen to use in combination with IMRT and study drug/placebo will be at the discretion of the investigator.",
            "criterions": [
                {
                    "exact_snippets": "eligible to receive a continuous course of external fractionated irradiation",
                    "criterion": "eligibility for external fractionated irradiation",
                    "requirements": [
                        {
                            "requirement_type": "eligibility",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "based on a daily dosing of 1.8 to 2.2 Gy/day 5 days/week",
                    "criterion": "irradiation dosing schedule",
                    "requirements": [
                        {
                            "requirement_type": "dosing schedule",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 1.8,
                                        "unit": "Gy/day"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 2.2,
                                        "unit": "Gy/day"
                                    }
                                ]
                            }
                        },
                        {
                            "requirement_type": "frequency",
                            "expected_value": "5 days/week"
                        }
                    ]
                },
                {
                    "exact_snippets": "in combination with cisplatin monotherapy",
                    "criterion": "cisplatin monotherapy",
                    "requirements": [
                        {
                            "requirement_type": "combination",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "every 3 weeks (100 mg/m2) or weekly cisplatin (40 mg/m2)",
                    "criterion": "cisplatin regimen",
                    "requirements": [
                        {
                            "requirement_type": "regimen options",
                            "expected_value": [
                                "every 3 weeks (100 mg/m2)",
                                "weekly (40 mg/m2)"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "Alternative treatment regimens are allowed only if cisplatin is contraindicated",
                    "criterion": "alternative treatment regimens",
                    "requirements": [
                        {
                            "requirement_type": "condition",
                            "expected_value": "cisplatin contraindicated"
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. Radiation plan must include delivery of a cumulative dose of 60-72 Gy. The oropharynx should receive at least 50 Gy.",
            "criterions": [
                {
                    "exact_snippets": "Radiation plan must include delivery of a cumulative dose of 60-72 Gy.",
                    "criterion": "radiation plan cumulative dose",
                    "requirements": [
                        {
                            "requirement_type": "dose",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 60,
                                        "unit": "Gy"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 72,
                                        "unit": "Gy"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "The oropharynx should receive at least 50 Gy.",
                    "criterion": "oropharynx radiation dose",
                    "requirements": [
                        {
                            "requirement_type": "dose",
                            "expected_value": {
                                "operator": ">=",
                                "value": 50,
                                "unit": "Gy"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. Patients with adequate laboratory values defined as:",
            "criterions": [
                {
                    "exact_snippets": "adequate laboratory values",
                    "criterion": "laboratory values",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "1. Absolute neutrophil count ≥ 1.5 × 10^9/L",
            "criterions": [
                {
                    "exact_snippets": "Absolute neutrophil count ≥ 1.5 × 10^9/L",
                    "criterion": "absolute neutrophil count",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1.5,
                                "unit": "× 10^9/L"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Platelet count ≥ 75 × 10^9/L",
            "criterions": [
                {
                    "exact_snippets": "Platelet count ≥ 75 × 10^9/L",
                    "criterion": "platelet count",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 75,
                                "unit": "× 10^9/L"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Hemoglobin ≥ 9 g/dL",
            "criterions": [
                {
                    "exact_snippets": "Hemoglobin ≥ 9 g/dL",
                    "criterion": "hemoglobin level",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": ">=",
                                "value": 9,
                                "unit": "g/dL"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. Creatinine blood level ≤ 1.5 × upper limit of the normal range (ULN)",
            "criterions": [
                {
                    "exact_snippets": "Creatinine blood level ≤ 1.5 × upper limit of the normal range (ULN)",
                    "criterion": "creatinine blood level",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.5,
                                "unit": "× ULN"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. Total bilirubin ≤ 1.5 × ULN; patients with Gilbert's Syndrome can be included if hyperbilirubinemia ≤ 3 × ULN",
            "criterions": [
                {
                    "exact_snippets": "Total bilirubin ≤ 1.5 × ULN",
                    "criterion": "total bilirubin",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.5,
                                "unit": "× ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "patients with Gilbert's Syndrome ... hyperbilirubinemia ≤ 3 × ULN",
                    "criterion": "hyperbilirubinemia in patients with Gilbert's Syndrome",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 3,
                                "unit": "× ULN"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × ULN",
            "criterions": [
                {
                    "exact_snippets": "Serum aspartate aminotransferase (AST) ... ≤ 3 × ULN",
                    "criterion": "serum aspartate aminotransferase (AST)",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 3,
                                "unit": "× ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "alanine aminotransferase (ALT) ≤ 3 × ULN",
                    "criterion": "alanine aminotransferase (ALT)",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 3,
                                "unit": "× ULN"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Patients with Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. A performance status of 2 is allowed only if due to a patient's malignancy.",
            "criterions": [
                {
                    "exact_snippets": "Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1",
                    "criterion": "ECOG performance status",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": [
                                "0",
                                "1"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "performance status of 2 is allowed only if due to a patient's malignancy",
                    "criterion": "ECOG performance status",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": "2"
                        },
                        {
                            "requirement_type": "condition",
                            "expected_value": "due to a patient's malignancy"
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. Patients must provide written informed consent.",
            "criterions": [
                {
                    "exact_snippets": "Patients must provide written informed consent.",
                    "criterion": "informed consent",
                    "requirements": [
                        {
                            "requirement_type": "provision",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "8. Human Papillomavirus (HPV) status documented by immunohistochemical detection of p16 expression in the tumor.",
            "criterions": [
                {
                    "exact_snippets": "Human Papillomavirus (HPV) status documented by immunohistochemical detection of p16 expression in the tumor.",
                    "criterion": "HPV status",
                    "requirements": [
                        {
                            "requirement_type": "documentation",
                            "expected_value": "immunohistochemical detection of p16 expression in the tumor"
                        }
                    ]
                }
            ]
        },
        {
            "line": "9. Negative serum pregnancy test for females of child-bearing potential at screening. A female is eligible to enter and participate in the study if the female is of non-child-bearing potential (i.e., physiologically incapable of becoming pregnant), including any female who has had a hysterectomy, a bilateral oophorectomy (ovariectomy), a bilateral tubal ligation, or is post-menopausal with a minimum of 1 year without menses.",
            "criterions": [
                {
                    "exact_snippets": "Negative serum pregnancy test for females of child-bearing potential",
                    "criterion": "serum pregnancy test",
                    "requirements": [
                        {
                            "requirement_type": "result",
                            "expected_value": "negative"
                        }
                    ]
                },
                {
                    "exact_snippets": "female is of non-child-bearing potential",
                    "criterion": "child-bearing potential",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "non-child-bearing"
                        }
                    ]
                },
                {
                    "exact_snippets": "female is of non-child-bearing potential ... has had a hysterectomy",
                    "criterion": "hysterectomy",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "female is of non-child-bearing potential ... a bilateral oophorectomy (ovariectomy)",
                    "criterion": "bilateral oophorectomy",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "female is of non-child-bearing potential ... a bilateral tubal ligation",
                    "criterion": "bilateral tubal ligation",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "female is of non-child-bearing potential ... is post-menopausal with a minimum of 1 year without menses",
                    "criterion": "post-menopausal status",
                    "requirements": [
                        {
                            "requirement_type": "duration without menses",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1,
                                "unit": "year"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "10. Males with female partners of child-bearing potential and females of child-bearing potential must agree to use effective contraception starting prior to the first day of study drug treatment and continuing for 3 months after the last dose of study drug MBT.",
            "criterions": [
                {
                    "exact_snippets": "Males with female partners of child-bearing potential ... must agree to use effective contraception",
                    "criterion": "contraception use for males with female partners of child-bearing potential",
                    "requirements": [
                        {
                            "requirement_type": "agreement",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "females of child-bearing potential must agree to use effective contraception",
                    "criterion": "contraception use for females of child-bearing potential",
                    "requirements": [
                        {
                            "requirement_type": "agreement",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "11. Patients must be willing to complete questionnaires on a tablet, home computer, or paper form.",
            "criterions": [
                {
                    "exact_snippets": "Patients must be willing to complete questionnaires",
                    "criterion": "willingness to complete questionnaires",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "on a tablet, home computer, or paper form",
                    "criterion": "method of questionnaire completion",
                    "requirements": [
                        {
                            "requirement_type": "method",
                            "expected_value": [
                                "tablet",
                                "home computer",
                                "paper form"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "Healthy volunteers allowed",
            "criterions": [
                {
                    "exact_snippets": "Healthy volunteers allowed",
                    "criterion": "volunteer health status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "healthy"
                        }
                    ]
                }
            ]
        },
        {
            "line": "Must have minimum age of 18 Years",
            "criterions": [
                {
                    "exact_snippets": "minimum age of 18 Years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "minimum",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "Years"
                            }
                        }
                    ]
                }
            ]
        }
    ],
    "exclusion_lines": [
        {
            "line": "1. Patients with no tumor or lesion in the oropharynx.",
            "criterions": [
                {
                    "exact_snippets": "no tumor ... in the oropharynx",
                    "criterion": "tumor in the oropharynx",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "no ... lesion in the oropharynx",
                    "criterion": "lesion in the oropharynx",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Prior induction chemotherapy for treatment of current malignancy.",
            "criterions": [
                {
                    "exact_snippets": "Prior induction chemotherapy for treatment of current malignancy.",
                    "criterion": "induction chemotherapy",
                    "requirements": [
                        {
                            "requirement_type": "prior treatment",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Patients with planned accelerated IMRT.",
            "criterions": [
                {
                    "exact_snippets": "planned accelerated IMRT",
                    "criterion": "IMRT (Intensity-Modulated Radiation Therapy)",
                    "requirements": [
                        {
                            "requirement_type": "plan",
                            "expected_value": "accelerated"
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. Evidence of a concomitant other malignancy and/or any prior malignancy without complete remission in the last 2 years, except adequately treated basal or squamous cell carcinoma of the skin or in situ cervical cancer.",
            "criterions": [
                {
                    "exact_snippets": "Evidence of a concomitant other malignancy",
                    "criterion": "concomitant other malignancy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "any prior malignancy without complete remission in the last 2 years",
                    "criterion": "prior malignancy",
                    "requirements": [
                        {
                            "requirement_type": "remission status",
                            "expected_value": "without complete remission"
                        },
                        {
                            "requirement_type": "time since remission",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<",
                                        "value": 2,
                                        "unit": "years"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "except adequately treated basal or squamous cell carcinoma of the skin or in situ cervical cancer",
                    "criterion": "adequately treated basal or squamous cell carcinoma of the skin or in situ cervical cancer",
                    "requirements": [
                        {
                            "requirement_type": "exclusion",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. Patients with OM at baseline, any other oral ulceration or active oral infection (e.g., aphthous ulcers, orofacial herpes). Patients with post-operative pain of the mouth or throat are eligible.",
            "criterions": [
                {
                    "exact_snippets": "Patients with OM at baseline",
                    "criterion": "OM at baseline",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "any other oral ulceration",
                    "criterion": "oral ulceration",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "active oral infection",
                    "criterion": "active oral infection",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "post-operative pain of the mouth or throat",
                    "criterion": "post-operative pain of the mouth or throat",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. Patients with systolic blood pressure (BP) < 100 mmHg and/or diastolic BP < 50 mmHg.",
            "criterions": [
                {
                    "exact_snippets": "systolic blood pressure (BP) < 100 mmHg",
                    "criterion": "systolic blood pressure",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": "<",
                                "value": 100,
                                "unit": "mmHg"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "diastolic BP < 50 mmHg",
                    "criterion": "diastolic blood pressure",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": "<",
                                "value": 50,
                                "unit": "mmHg"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "8. Patients with symptomatic cardiac dysrhythmia.",
            "criterions": [
                {
                    "exact_snippets": "symptomatic cardiac dysrhythmia",
                    "criterion": "cardiac dysrhythmia",
                    "requirements": [
                        {
                            "requirement_type": "symptom presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "9. Patients with recent (less than 6 months) acute cardiovascular diseases (i.e., stroke, myocardial infarction).",
            "criterions": [
                {
                    "exact_snippets": "recent (less than 6 months) acute cardiovascular diseases",
                    "criterion": "acute cardiovascular diseases",
                    "requirements": [
                        {
                            "requirement_type": "recency",
                            "expected_value": {
                                "operator": "<",
                                "value": 6,
                                "unit": "months"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "stroke",
                    "criterion": "stroke",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "myocardial infarction",
                    "criterion": "myocardial infarction",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "10. Patients with any clinical condition, psychiatric condition, or prior therapy that, in the opinion of the investigator, would make the patient unsuitable for the study or unable to comply with study requirements and follow-up visits.",
            "criterions": [
                {
                    "exact_snippets": "Patients with any clinical condition ... would make the patient unsuitable for the study",
                    "criterion": "clinical condition",
                    "requirements": [
                        {
                            "requirement_type": "suitability",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Patients with any ... psychiatric condition ... would make the patient unsuitable for the study",
                    "criterion": "psychiatric condition",
                    "requirements": [
                        {
                            "requirement_type": "suitability",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Patients with any ... prior therapy ... would make the patient unsuitable for the study",
                    "criterion": "prior therapy",
                    "requirements": [
                        {
                            "requirement_type": "suitability",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "11. Patients currently being treated with sultopride, clonidine hydrochloride (eg, Catapres®), pentoxifylline or pilocarpine.",
            "criterions": [
                {
                    "exact_snippets": "Patients currently being treated with sultopride",
                    "criterion": "sultopride treatment",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Patients currently being treated with ... clonidine hydrochloride (eg, Catapres®)",
                    "criterion": "clonidine hydrochloride treatment",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Patients currently being treated with ... pentoxifylline",
                    "criterion": "pentoxifylline treatment",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Patients currently being treated with ... pilocarpine",
                    "criterion": "pilocarpine treatment",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "12. Patients intended to be treated specifically to prevent OM with any of the following:",
            "criterions": [
                {
                    "exact_snippets": "Patients intended to be treated specifically to prevent OM",
                    "criterion": "treatment intention",
                    "requirements": [
                        {
                            "requirement_type": "purpose",
                            "expected_value": "prevent OM"
                        }
                    ]
                }
            ]
        },
        {
            "line": "13. Patients who are unable to tolerate oral diet and/or are feeding tube dependent at baseline.",
            "criterions": [
                {
                    "exact_snippets": "unable to tolerate oral diet",
                    "criterion": "oral diet tolerance",
                    "requirements": [
                        {
                            "requirement_type": "tolerance",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "feeding tube dependent",
                    "criterion": "feeding tube dependency",
                    "requirements": [
                        {
                            "requirement_type": "dependency",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "14. Patients receiving an approved or an investigational anti-cancer agent other than those specified in this study.",
            "criterions": [
                {
                    "exact_snippets": "Patients receiving an approved or an investigational anti-cancer agent",
                    "criterion": "anti-cancer agent",
                    "requirements": [
                        {
                            "requirement_type": "type",
                            "expected_value": [
                                "approved",
                                "investigational"
                            ]
                        },
                        {
                            "requirement_type": "exclusion",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "15. Patients with a known hypersensitivity to clonidine or any of the MBT excipients.",
            "criterions": [
                {
                    "exact_snippets": "known hypersensitivity to clonidine",
                    "criterion": "hypersensitivity to clonidine",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "hypersensitivity to ... any of the MBT excipients",
                    "criterion": "hypersensitivity to MBT excipients",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "16. Women who are pregnant or breast-feeding.",
            "criterions": [
                {
                    "exact_snippets": "Women who are pregnant",
                    "criterion": "pregnancy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "breast-feeding",
                    "criterion": "breastfeeding",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "17. Patients whose medical, psychological or surgical conditions are unstable and may affect the study completion and/or compliance and/or the ability to give informed consent.",
            "criterions": [
                {
                    "exact_snippets": "medical, psychological or surgical conditions are unstable",
                    "criterion": "medical, psychological, or surgical conditions",
                    "requirements": [
                        {
                            "requirement_type": "stability",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "ability to give informed consent",
                    "criterion": "ability to give informed consent",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "18. Men and women of child-bearing age and their respective partners unwilling to use a highly effective contraception method during the study and for 3 months after the last administration of study drug.",
            "criterions": [
                {
                    "exact_snippets": "Men and women of child-bearing age",
                    "criterion": "child-bearing age",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "unwilling to use a highly effective contraception method",
                    "criterion": "use of highly effective contraception method",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "during the study and for 3 months after the last administration of study drug",
                    "criterion": "duration of contraception use",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": "during the study and for 3 months after the last administration of study drug"
                        }
                    ]
                }
            ]
        },
        {
            "line": "19. Patient who has participated in another clinical trial with an investigational drug in the last 30 days prior to randomization in the present clinical study.",
            "criterions": [
                {
                    "exact_snippets": "Patient who has participated in another clinical trial with an investigational drug in the last 30 days prior to randomization",
                    "criterion": "participation in another clinical trial with an investigational drug",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 30,
                                        "unit": "days"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "20. Subjects with orthostatic hypotension, defined by a decrease of systolic BP and/or diastolic BP above 20 mmHg when the patient stands up.",
            "criterions": [
                {
                    "exact_snippets": "orthostatic hypotension, defined by a decrease of systolic BP and/or diastolic BP above 20 mmHg when the patient stands up.",
                    "criterion": "orthostatic hypotension",
                    "requirements": [
                        {
                            "requirement_type": "definition",
                            "expected_value": "decrease of systolic BP and/or diastolic BP above 20 mmHg when the patient stands up"
                        }
                    ]
                }
            ]
        },
        {
            "line": "21. Conditions including but not limited to COVID-19 which would confound the assessment of the effects and/or safety of study medication in the opinion of the investigator.",
            "criterions": [
                {
                    "exact_snippets": "Conditions including but not limited to COVID-19",
                    "criterion": "confounding conditions",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [],
    "failed_exclusion": [
        {
            "line": "6. Patients with known human immunodeficiency virus (HIV) seropositivity, known active Hepatitis B or C or known active tuberculosis.",
            "criterions": [
                {
                    "exact_snippets": "known human immunodeficiency virus (HIV) seropositivity",
                    "criterion": "HIV seropositivity",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "known active Hepatitis B",
                    "criterion": "active Hepatitis B",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "known active Hepatitis C",
                    "criterion": "active Hepatitis C",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "known active tuberculosis",
                    "criterion": "active tuberculosis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "a. Bioadherent agents and mouthwashes: i. GelClair (consists of polyvinylpyrrolidone, hyaluronic acid, and glycyrrhetinic acid) ii. Sucralfate iii. Episil mouth spray iv. MuGard oral mucoadhesive v. Saforis (L-glutamine (topical)) b. Drug therapies and biologics: i. Amifostine (and similar free radical scavenger/antioxidant medications) ii. Palifermin (recombinant human keratinocyte growth factor-(KGF-1)) iii. Glutamine b. Interventional therapies i. Low level laser therapy (LLLT)",
            "criterions": [
                {
                    "exact_snippets": "Bioadherent agents and mouthwashes: i. GelClair",
                    "criterion": "use of GelClair",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Bioadherent agents and mouthwashes: ii. Sucralfate",
                    "criterion": "use of Sucralfate",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Bioadherent agents and mouthwashes: iii. Episil mouth spray",
                    "criterion": "use of Episil mouth spray",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Bioadherent agents and mouthwashes: iv. MuGard oral mucoadhesive",
                    "criterion": "use of MuGard oral mucoadhesive",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Bioadherent agents and mouthwashes: v. Saforis (L-glutamine (topical))",
                    "criterion": "use of Saforis (L-glutamine (topical))",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Drug therapies and biologics: i. Amifostine (and similar free radical scavenger/antioxidant medications)",
                    "criterion": "use of Amifostine or similar medications",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Drug therapies and biologics: ii. Palifermin (recombinant human keratinocyte growth factor-(KGF-1))",
                    "criterion": "use of Palifermin",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Drug therapies and biologics: iii. Glutamine",
                    "criterion": "use of Glutamine",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Interventional therapies i. Low level laser therapy (LLLT)",
                    "criterion": "use of Low level laser therapy (LLLT)",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        }
    ],
    "failed_miscellaneous": []
}