{
    "info": {
        "nct_id": "NCT04808531",
        "official_title": "NanaBis™ an Oro-buccal Administered Equimolar d9-THC & CBD Formulation as Monotherapy for Management of Opioid Requiring Bone Pain Due to Metastatic Cancer: Phase 3 Multi Centre Blinded Randomized Withdrawal Active & Placebo Controlled Trial",
        "inclusion_criteria": "At Screening Phase\n\nParticipants must fulfil all of the following criteria:\n\n* Prospective male and female participants that are:\n\n  1. in the age range 18-65 years or\n  2. 65 to 75 years without significant co-morbidities (heart, lung, liver or renal failure, myocardial infarction, cerebral vascular accident, peripheral vascular disease, chronic obstructive pulmonary disease, dementia, connective tissue disease or diabetes mellitus with end-organ damage)\n* Metastatic bone pain from a cancer diagnosis is the only major cause of pain.\n* Documented proof (imaging) confirming the Metastatic Bone Disease at the current site of pain and that there has no been treatment since diagnosis\n* Meet International Classification of Diseases, Tenth Revision (ICD-10) codes for pain management criteria (i.e., bone cancer pain)\n* During the screening period, the participant is on stable opioid pain management and pain severity (NPRS) ≤ 8 with a maximum variation of ± 1\n* Pain Detect score > 18\n* Participant willing and able to provide informed consent and follow study procedures\n\n  1. including agreeing to not drive or operate heavy machinery; and\n  2. females of child-bearing potential agree to use reliable contraception during the duration of the clinical trial\n* Patient deemed tolerable to Oxycodone and NanaBis™ determined by medical history of allergies to cannabinoids or opioids\n* Patient must not be a participant in a clinical trial or study.\nHealthy volunteers allowed\nMust have minimum age of 18 Years\nMust have maximum age of 75 Years",
        "exclusion_criteria": "At Screening Phase\n\nParticipants will be excluded if they meet any of the following criteria that include:\n\n* History of epilepsy or recurrent seizures\n* Moderate to severe medical conditions such as\n\n  1. Severe hepatic, cardiovascular, pulmonary or renal impairment or\n  2. Psychiatric disorders (i.e., unstable schizophrenia, recent drug-induced psychosis, severe mood disorders), that would be assessed at the medical screen\n* If participants have been diagnosed with a current substance abuse disorder\n* Women who are pregnant, lactating or planning to become pregnant\n* Identified concerns by the nursing / medical team relevant to the safe storage of medications (i.e., NanaBis™ or standard medical therapy)\n* Participants who may not be available for follow up (i.e., planned or expected travel or other)\n* Participants plan to undergo any treatment that will substantially reduce the burden of disease (and therefore bone pain) during the screening, titration or maintenance phase of the clinical trial such as radiotherapy or cytotoxic chemotherapy\n* Participants who are unable to withhold all analgesia (apart from which is part of this trial) during the titration and maintenance phase of the study, including bisphosphonates, or are currently exceeding equivalence of 70mg BD Oxycodone CR. Medications such as bisphosphonates may be coordinated so they are given either side of the excluded period that covers the titration and maintenance phases\n* Participants will NOT be excluded if they are being treated with maintenance pharmacotherapy to prevent progression of disease such as steroids and hormone therapy, which may be continued during the trial at a stable dose\n* Participant will be excluded if they are participating in any other clinical trial or study.",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "* Prospective male and female participants that are:",
            "criterions": [
                {
                    "exact_snippets": "male and female",
                    "criterion": "gender",
                    "requirements": [
                        {
                            "requirement_type": "allowed_values",
                            "expected_value": [
                                "male",
                                "female"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "1. in the age range 18-65 years or",
            "criterions": [
                {
                    "exact_snippets": "age range 18-65 years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 18,
                                        "unit": "years"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 65,
                                        "unit": "years"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. 65 to 75 years without significant co-morbidities (heart, lung, liver or renal failure, myocardial infarction, cerebral vascular accident, peripheral vascular disease, chronic obstructive pulmonary disease, dementia, connective tissue disease or diabetes mellitus with end-organ damage)",
            "criterions": [
                {
                    "exact_snippets": "65 to 75 years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 65,
                                        "unit": "years"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 75,
                                        "unit": "years"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "without significant co-morbidities",
                    "criterion": "significant co-morbidities",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "heart ... failure",
                    "criterion": "heart failure",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "lung ... failure",
                    "criterion": "lung failure",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "liver ... failure",
                    "criterion": "liver failure",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "renal failure",
                    "criterion": "renal failure",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "myocardial infarction",
                    "criterion": "myocardial infarction",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "cerebral vascular accident",
                    "criterion": "cerebral vascular accident",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "peripheral vascular disease",
                    "criterion": "peripheral vascular disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "chronic obstructive pulmonary disease",
                    "criterion": "chronic obstructive pulmonary disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "dementia",
                    "criterion": "dementia",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "connective tissue disease",
                    "criterion": "connective tissue disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "diabetes mellitus with end-organ damage",
                    "criterion": "diabetes mellitus with end-organ damage",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Metastatic bone pain from a cancer diagnosis is the only major cause of pain.",
            "criterions": [
                {
                    "exact_snippets": "Metastatic bone pain from a cancer diagnosis is the only major cause of pain.",
                    "criterion": "metastatic bone pain",
                    "requirements": [
                        {
                            "requirement_type": "cause of pain",
                            "expected_value": "only major cause"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Documented proof (imaging) confirming the Metastatic Bone Disease at the current site of pain and that there has no been treatment since diagnosis",
            "criterions": [
                {
                    "exact_snippets": "Documented proof (imaging) confirming the Metastatic Bone Disease",
                    "criterion": "Metastatic Bone Disease",
                    "requirements": [
                        {
                            "requirement_type": "confirmation",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "there has no been treatment since diagnosis",
                    "criterion": "treatment since diagnosis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Meet International Classification of Diseases, Tenth Revision (ICD-10) codes for pain management criteria (i.e., bone cancer pain)",
            "criterions": [
                {
                    "exact_snippets": "Meet International Classification of Diseases, Tenth Revision (ICD-10) codes for pain management criteria",
                    "criterion": "ICD-10 codes for pain management",
                    "requirements": [
                        {
                            "requirement_type": "compliance",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "bone cancer pain",
                    "criterion": "bone cancer pain",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* During the screening period, the participant is on stable opioid pain management and pain severity (NPRS) ≤ 8 with a maximum variation of ± 1",
            "criterions": [
                {
                    "exact_snippets": "During the screening period, the participant is on stable opioid pain management",
                    "criterion": "opioid pain management",
                    "requirements": [
                        {
                            "requirement_type": "stability",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "pain severity (NPRS) ≤ 8",
                    "criterion": "pain severity (NPRS)",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": "<=",
                                "value": 8,
                                "unit": "N/A"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "pain severity (NPRS) ... maximum variation of ± 1",
                    "criterion": "pain severity (NPRS)",
                    "requirements": [
                        {
                            "requirement_type": "variation",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1,
                                "unit": "N/A"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Pain Detect score > 18",
            "criterions": [
                {
                    "exact_snippets": "Pain Detect score > 18",
                    "criterion": "Pain Detect score",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">",
                                "value": 18,
                                "unit": "N/A"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Participant willing and able to provide informed consent and follow study procedures",
            "criterions": [
                {
                    "exact_snippets": "Participant willing and able to provide informed consent",
                    "criterion": "informed consent",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Participant ... able to ... follow study procedures",
                    "criterion": "ability to follow study procedures",
                    "requirements": [
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "1. including agreeing to not drive or operate heavy machinery; and",
            "criterions": [
                {
                    "exact_snippets": "agreeing to not drive",
                    "criterion": "driving",
                    "requirements": [
                        {
                            "requirement_type": "agreement",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "agreeing to not ... operate heavy machinery",
                    "criterion": "operating heavy machinery",
                    "requirements": [
                        {
                            "requirement_type": "agreement",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. females of child-bearing potential agree to use reliable contraception during the duration of the clinical trial",
            "criterions": [
                {
                    "exact_snippets": "females of child-bearing potential",
                    "criterion": "gender and reproductive status",
                    "requirements": [
                        {
                            "requirement_type": "gender",
                            "expected_value": "female"
                        },
                        {
                            "requirement_type": "reproductive status",
                            "expected_value": "child-bearing potential"
                        }
                    ]
                },
                {
                    "exact_snippets": "agree to use reliable contraception during the duration of the clinical trial",
                    "criterion": "contraception use",
                    "requirements": [
                        {
                            "requirement_type": "agreement",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "duration",
                            "expected_value": "during the duration of the clinical trial"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patient deemed tolerable to Oxycodone and NanaBis™ determined by medical history of allergies to cannabinoids or opioids",
            "criterions": [
                {
                    "exact_snippets": "Patient deemed tolerable to Oxycodone",
                    "criterion": "Oxycodone tolerance",
                    "requirements": [
                        {
                            "requirement_type": "tolerance",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "tolerable to ... NanaBis™",
                    "criterion": "NanaBis™ tolerance",
                    "requirements": [
                        {
                            "requirement_type": "tolerance",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "medical history of allergies to cannabinoids",
                    "criterion": "allergies to cannabinoids",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "medical history of allergies to ... opioids",
                    "criterion": "allergies to opioids",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patient must not be a participant in a clinical trial or study.",
            "criterions": [
                {
                    "exact_snippets": "Patient must not be a participant in a clinical trial or study.",
                    "criterion": "participation in a clinical trial or study",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "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"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "Must have maximum age of 75 Years",
            "criterions": [
                {
                    "exact_snippets": "maximum age of 75 Years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "maximum",
                            "expected_value": {
                                "operator": "<=",
                                "value": 75,
                                "unit": "Years"
                            }
                        }
                    ]
                }
            ]
        }
    ],
    "exclusion_lines": [
        {
            "line": "* History of epilepsy or recurrent seizures",
            "criterions": [
                {
                    "exact_snippets": "History of epilepsy",
                    "criterion": "epilepsy",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "recurrent seizures",
                    "criterion": "seizures",
                    "requirements": [
                        {
                            "requirement_type": "recurrence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Moderate to severe medical conditions such as",
            "criterions": [
                {
                    "exact_snippets": "Moderate to severe medical conditions",
                    "criterion": "medical conditions",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": [
                                "moderate",
                                "severe"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "1. Severe hepatic, cardiovascular, pulmonary or renal impairment or",
            "criterions": [
                {
                    "exact_snippets": "Severe hepatic ... impairment",
                    "criterion": "hepatic impairment",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "severe"
                        }
                    ]
                },
                {
                    "exact_snippets": "Severe ... cardiovascular ... impairment",
                    "criterion": "cardiovascular impairment",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "severe"
                        }
                    ]
                },
                {
                    "exact_snippets": "Severe ... pulmonary ... impairment",
                    "criterion": "pulmonary impairment",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "severe"
                        }
                    ]
                },
                {
                    "exact_snippets": "Severe ... renal impairment",
                    "criterion": "renal impairment",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "severe"
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Psychiatric disorders (i.e., unstable schizophrenia, recent drug-induced psychosis, severe mood disorders), that would be assessed at the medical screen",
            "criterions": [
                {
                    "exact_snippets": "Psychiatric disorders (i.e., unstable schizophrenia, recent drug-induced psychosis, severe mood disorders)",
                    "criterion": "psychiatric disorders",
                    "requirements": [
                        {
                            "requirement_type": "types",
                            "expected_value": [
                                "unstable schizophrenia",
                                "recent drug-induced psychosis",
                                "severe mood disorders"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* If participants have been diagnosed with a current substance abuse disorder",
            "criterions": [
                {
                    "exact_snippets": "diagnosed with a current substance abuse disorder",
                    "criterion": "substance abuse disorder",
                    "requirements": [
                        {
                            "requirement_type": "diagnosis",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "current",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Women who are pregnant, lactating or planning to become pregnant",
            "criterions": [
                {
                    "exact_snippets": "Women who are pregnant",
                    "criterion": "pregnancy status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "pregnant"
                        }
                    ]
                },
                {
                    "exact_snippets": "lactating",
                    "criterion": "lactation status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "lactating"
                        }
                    ]
                },
                {
                    "exact_snippets": "planning to become pregnant",
                    "criterion": "pregnancy intention",
                    "requirements": [
                        {
                            "requirement_type": "intention",
                            "expected_value": "planning to become pregnant"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Identified concerns by the nursing / medical team relevant to the safe storage of medications (i.e., NanaBis™ or standard medical therapy)",
            "criterions": [
                {
                    "exact_snippets": "Identified concerns by the nursing / medical team relevant to the safe storage of medications",
                    "criterion": "concerns about safe storage of medications",
                    "requirements": [
                        {
                            "requirement_type": "identification",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Participants who may not be available for follow up (i.e., planned or expected travel or other)",
            "criterions": [
                {
                    "exact_snippets": "Participants who may not be available for follow up",
                    "criterion": "availability for follow up",
                    "requirements": [
                        {
                            "requirement_type": "availability",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Participants plan to undergo any treatment that will substantially reduce the burden of disease (and therefore bone pain) during the screening, titration or maintenance phase of the clinical trial such as radiotherapy or cytotoxic chemotherapy",
            "criterions": [
                {
                    "exact_snippets": "Participants plan to undergo any treatment that will substantially reduce the burden of disease ... such as radiotherapy or cytotoxic chemotherapy",
                    "criterion": "treatment plan",
                    "requirements": [
                        {
                            "requirement_type": "type",
                            "expected_value": [
                                "radiotherapy",
                                "cytotoxic chemotherapy"
                            ]
                        },
                        {
                            "requirement_type": "effect",
                            "expected_value": "substantially reduce the burden of disease"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Participants who are unable to withhold all analgesia (apart from which is part of this trial) during the titration and maintenance phase of the study, including bisphosphonates, or are currently exceeding equivalence of 70mg BD Oxycodone CR. Medications such as bisphosphonates may be coordinated so they are given either side of the excluded period that covers the titration and maintenance phases",
            "criterions": [
                {
                    "exact_snippets": "Participants who are unable to withhold all analgesia ... during the titration and maintenance phase of the study",
                    "criterion": "ability to withhold analgesia",
                    "requirements": [
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "currently exceeding equivalence of 70mg BD Oxycodone CR",
                    "criterion": "Oxycodone CR dosage",
                    "requirements": [
                        {
                            "requirement_type": "dosage",
                            "expected_value": {
                                "operator": "<=",
                                "value": 70,
                                "unit": "mg BD"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Participants will NOT be excluded if they are being treated with maintenance pharmacotherapy to prevent progression of disease such as steroids and hormone therapy, which may be continued during the trial at a stable dose",
            "criterions": [
                {
                    "exact_snippets": "being treated with maintenance pharmacotherapy to prevent progression of disease such as steroids and hormone therapy",
                    "criterion": "maintenance pharmacotherapy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "may be continued during the trial at a stable dose",
                    "criterion": "stable dose",
                    "requirements": [
                        {
                            "requirement_type": "stability",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Participant will be excluded if they are participating in any other clinical trial or study.",
            "criterions": [
                {
                    "exact_snippets": "participating in any other clinical trial or study",
                    "criterion": "participation in other clinical trials or studies",
                    "requirements": [
                        {
                            "requirement_type": "participation",
                            "expected_value": false
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [
        {
            "line": "At Screening Phase",
            "criterions": []
        },
        {
            "line": "Participants must fulfil all of the following criteria:",
            "criterions": []
        }
    ],
    "failed_exclusion": [
        {
            "line": "At Screening Phase",
            "criterions": []
        },
        {
            "line": "Participants will be excluded if they meet any of the following criteria that include:",
            "criterions": []
        }
    ],
    "failed_miscellaneous": []
}