Individuals of non-childbearing potential, or individual of childbearing potential with negative serum pregnancy test =<  days prior to randomization and willing to practice total abstinence or use a highly effective method of contraception, as outlined below:\r\n* Non-childbearing potential (i.e., physiologically incapable of becoming pregnant), including any female individual who has had the following:\r\n** A hysterectomy\r\n** A bilateral oophorectomy (ovariectomy)\r\n** A bilateral tubal ligation\r\n** Is post-menopausal\r\n** NOTE: Subjects not using hormone replacement therapy (HRT) must have experienced total cessation of menses for >=  year and be greater than  years in age, OR, in questionable cases, have a follicle stimulating hormone (FSH) value >  mIU/mL and an estradiol value <  pg/mL (<  pmol/L); subjects using HRT must have experienced total cessation of menses for >=  year and be greater than  years of age OR have had documented evidence of menopause based on FSH and estradiol concentrations prior to initiation of HRT\r\n* Childbearing potential, including any individual who has had a negative serum pregnancy test, =<  days prior to randomization\r\n* Agrees to use adequate contraception; acceptable contraceptive methods, when used consistently and in accordance with both the product label and the instructions of the physician, are as follows:\r\n** Complete abstinence from sexual intercourse for  days before exposure to investigational product, through the dosing period, and for at least  days after the last dose of investigational product\r\n** Oral contraceptive, either combined or progestogen alone\r\n** Intrauterine device (IUD) or intrauterine system (IUS) with a documented failure rate of less than % per year\r\n** Male partner sterilization (vasectomy with documentation of azoospermia) prior to the female subject's entry into the study, and this male is the sole partner for that subject\r\n** Double barrier method: condom and an occlusive cap (diaphragm or cervical/vault caps) with a vaginal spermicidal agent (foam/gel/film/cream/suppository)
Female patients are eligible to enter and participate in the study if they are of: a) Non-childbearing potential (i.e., physiologically incapable of becoming pregnant), including any female who: i. has had a hysterectomy ii. has had a bilateral oophorectomy iii. has had a bilateral salpingectomy iv. is post menopausal (total cessation of menses for ?  year) b) Childbearing potential, has a negative serum pregnancy test at screening (within  days of the first investigational product administration), is not breast feeding, and uses highly effective contraception before study entry and throughout the study until  days after the last investigational product administration. Adequate contraception as recommended by the Clinical Trial Facilitation Group (CTFG)
Female: A female is eligible to enter and participate in the study if she is of: a. non-childbearing potential (i.e., women with functioning ovaries who have a current documented tubal ligation, hysterectomy alone, hysterectomy and bilateral salpingo-oophorectomy, bilateral salpingo-oophorectomy alone or women who are post-menopausal); or b. childbearing potential (i.e., women with functioning ovaries and no documented impairment of oviductal or uterine function that would cause sterility; this category includes women with oligomenorrhea (severe), women who are perimenopausal, and young women who have begun to menstruate), has a negative serum pregnancy test at screening, and agrees to one of the following where considered acceptable to the local Institutional Review Board (IRB)/Independent Ethics Committee (IEC):\r\n* Double-barrier contraception (condom with spermicidal jelly, foam suppository, or film; diaphragm with spermicide; or male condom and diaphragm)\r\n* Abstinence from sexual intercourse from  weeks prior to administration of the investigational product, throughout the active study treatment period\r\n* Male partner who is sterile prior to the female subject's entry into the study and is the sole sexual partner for that female subject\r\n* Any intrauterine device (IUD)\r\n* Barrier methods including diaphragm or condom with a spermicide
Female subjects are eligible to enter the study if they are either:\r\n* Of non-childbearing potential (i.e., physiologically incapable of becoming pregnant) including any woman who:\r\n** Has had a hysterectomy, or\r\n** Has had a bilateral oophorectomy, or\r\n** Has had a bilateral tubal ligation, or\r\n** Is post-menopausal (demonstrates total cessation of menses for greater than or equal to  year) OR\r\n* Of childbearing potential, has a negative serum pregnancy test at screening, and agrees to one of the following contraceptives:\r\n** An intrauterine device (IUD) with a documented failure rate of less than % per year\r\n** Vasectomized partner who is sterile prior to the subjects entry and is the sole sexual partner for that woman\r\n** Complete abstinence from sexual intercourse for  days before exposure to investigational product, during the clinical trial, and for at least  days after the last dose of investigational product\r\n** Double barrier contraception defined as condom with spermicidal jelly, foam, suppository, or film; OR diaphragm with spermicide; OR male condom and diaphragm
Women of childbearing potential must have a negative B-Human chorionic gonadotropin (HCG) documented within  days prior to registration and must agree to practice adequate contraception as defined below. Non-childbearing potential (i.e., physiologically incapable of becoming pregnant), includes any female who has had:\r\n* A hysterectomy\r\n* A bilateral oophorectomy\r\n* A bilateral tubal ligation\r\n* Is post-menopausal: Subjects not using hormone replacement therapy (HRT) must have experienced total cessation of menses for >=  year and be greater than  years in age, OR, in questionable cases, have a follicle stimulating hormone (FSH) value >  mIU/mL and an estradiol value <  pg/mL (<  pmol/L).
A female is eligible to enter and participate in this study if she is of:\r\n* Non-childbearing potential (i.e., physiologically incapable of becoming pregnant), including any female who has had:\r\n** A hysterectomy\r\n** A bilateral oophorectomy (ovariectomy)\r\n** A bilateral tubal ligation\r\n** Is post-menopausal\r\n** Subjects not using hormone replacement therapy (HRT) must have experienced total cessation of menses for >=  year and be greater than  years in age, OR, in questionable cases, have a follicle stimulating hormone (FSH) value >  mIU/mL and an estradiol value <  pg/mL (<  pmol/L)\r\n** Subjects using HRT must have experienced total cessation of menses for >=  year and be greater than  years of age OR have had documented evidence of menopause based on FSH and estradiol concentrations prior to initiation of HRT\r\n* Childbearing potential, including any female who has had a negative serum pregnancy test, =<  days prior to registration\r\n* Agrees to use adequate contraception; acceptable contraceptive methods, when used consistently and in accordance with both the product label and the instructions of the physician, are as follows:\r\n** Complete abstinence from sexual intercourse for  days before exposure to investigational product, through the dosing period, and for at least  days after the last dose of investigational product\r\n** Oral contraceptive, either combined or progesterone alone\r\n** Intrauterine device (IUD) or intrauterine system (IUS) with a documented failure rate of less than % per year\r\n** Male partner sterilization (vasectomy with documentation of azoospermia) prior to the female subject's entry into the study, and this male is the sole partner for that subject\r\n** Double barrier method: condom and an occlusive cap (diaphragm or cervical/vault caps) with a vaginal spermicidal agent (foam/gel/film/cream/suppository)
A female patient is eligible to enter and participate in the study if she is:\r\n* Non-childbearing potential (i.e., physiologically incapable of becoming pregnant) including any woman who:\r\n ** Has had a hysterectomy, or\r\n ** Has had a bilateral oophorectomy (ovariectomy), or\r\n ** Has had a bilateral tubal ligation, or\r\n ** Is post-menopausal\r\n*** Patients not using hormone replacement therapy (HRT) must have experienced total cessation of menses for >=  year and be greater than  years in age, OR, in questionable cases, have a follicle stimulating hormone (FSH) value >  mIU/mL and an estradiol value <  pg/mL (<  pmol/L)\r\n*** Patients using HRT must have experienced total cessation of menses for >=  year and be greater than  years of age OR have had documented evidence of menopause based on FSH and estradiol concentrations prior to initiation of HRT\r\n* Childbearing potential, including any female who has a negative serum or urine pregnancy test within  days prior to the first dose of study treatment and agrees to one of the following:\r\n ** An intrauterine device with a documented failure rate of less than % per year.\r\n ** Vasectomized partner who is sterile prior to the patients entry and is the sole sexual partner for that woman.\r\n ** Complete abstinence from sexual intercourse for  days before exposure to investigation product, throughout the clinical trial, and for at least  days after the last dose of investigational product.\r\n ** Double barrier contraception defined as condom with spermicidal jelly, foam, suppository, or film; or diaphragm with spermicide; or male condom and diaphragm.\r\n ** Oral contraceptive, either combined or progestogen alone\r\n ** Injectable progestogen\r\n ** Implants of levonorgestrel\r\n ** Estrogenic vaginal ring\r\n ** Percutaneous contraceptive patches
A female is eligible to enter and participate in this study if she is of: \r\n* Non-childbearing potential (i.e., physiologically incapable of becoming pregnant), including any female who has had: \r\n** A hysterectomy \r\n** A bilateral oophorectomy (ovariectomy) \r\n** A bilateral tubal ligation, or \r\n** Is post-menopausal \r\n* Subjects not using hormone replacement therapy (HRT) must have experienced total cessation of menses for >=  year and be greater than  years in age, OR, in questionable cases, have a follicle stimulating hormone (FSH) value >  mIU/mL and an estradiol value <  pg/mL (<  pmol/L) \r\n* Subjects must discontinue HRT prior to study enrollment due to the potential for inhibition of cytochrome P (CYP) enzymes that metabolize estrogens and progestins; for most forms of HRT, at least - weeks must elapse between the cessation of HRT and determination of menopausal status; length of this interval depends on the type and dosage of HRT; if a female subject is determined not to be postmenopausal, they must use adequate contraception as defined immediately below during the trial and for  weeks after the last dose \r\n* Childbearing potential, including any female who has had a negative serum pregnancy test within  weeks prior to the first dose of study treatment, preferably as close to the first dose as possible, and agrees to use adequate contraception; acceptable contraceptive methods, when used consistently and in accordance with both the product label and the instructions of the physician, are as follows: an intrauterine device with a documented failure rate of less than % per year, vasectomized partner who is sterile prior to the female subjects entry and is the sole sexual partner for that female, double-barrier contraception (condom with spermicidal jelly, foam suppository, or film; diaphragm with spermicide; or male condom and diaphragm with spermicide); Note: Oral contraceptives are not reliable \r\n* Female subjects who are lactating should not be in the trial\r\n* A male with a female partner of childbearing potential is eligible to enter and participate in the study if he uses a barrier method of contraception or abstinence during the study
EXPANSION COHORT ONLY: A female is eligible to enter and participate in this study if she is of: \r\n* Non-childbearing potential (i.e., physiologically incapable of becoming pregnant), including any female who has had: \r\n** A hysterectomy \r\n** A bilateral oophorectomy (ovariectomy) \r\n** A bilateral tubal ligation, or \r\n** Is post-menopausal \r\n* Subjects not using hormone replacement therapy (HRT) must have experienced total cessation of menses for >=  year and be greater than  years in age, OR, in questionable cases, have a follicle stimulating hormone (FSH) value >  mIU/mL and an estradiol value <   pg/mL (<  pmol/L) \r\n* Subjects must discontinue HRT prior to study enrollment due to the potential for inhibition of cytochrome P (CYP) enzymes that metabolize estrogens and progestins; for most forms of HRT, at least - weeks must elapse between the cessation of HRT and determination of menopausal status; length of this interval depends on the type and dosage of HRT; if a female subject is determined not to be postmenopausal, they must use adequate contraception as defined immediately below during the trial and for  weeks after the last dose \r\n* Childbearing potential, including any female who has had a negative serum pregnancy test within  weeks prior to the first dose of study treatment, preferably as close to the first dose as possible, and agrees to use adequate contraception; acceptable contraceptive methods, when used consistently and in accordance with both the product label and the instructions of the physician, are as follows: an intrauterine device with a documented failure rate of less than % per year, vasectomized partner who is sterile prior to the female subjects entry and is the sole sexual partner for that female, double-barrier contraception (condom with spermicidal jelly, foam suppository, or film; diaphragm with spermicide; or male condom and diaphragm with spermicide); Note: Oral contraceptives are not reliable \r\n* Female subjects who are lactating not be included in the trial \r\n* A male with a female partner of childbearing potential is eligible to enter and participate in the study if he uses a barrier method of contraception or abstinence during the study
If female of childbearing potential (women who are post-menopausal <  year, not surgically sterilized, or not abstinent), pregnancy urine test is negative, and agrees to be consistent and correct use of one of the following acceptable methods of birth control: male partner who is sterile prior to the female subject entry into the study and is the sole sexual partner for that female subject; any intrauterine device (IUD) with a documented failure rate of less than % per year; oral contraception, or barrier methods, including diaphragm or condom with a spermicide
Female subjects are eligible to enter the study if they are either:\r\n* Of non-childbearing potential (i.e., physiologically incapable of becoming pregnant) including any woman who:\r\n** Has had a hysterectomy, or\r\n** Has had a bilateral oophorectomy (ovariectomy), or\r\n** Has had a bilateral tubal ligation, or\r\n** Is post-menopausal (demonstrates total cessation of menses for greater than or equal to  year)\r\nOR\r\n* Of childbearing potential, has a negative serum pregnancy test at screening, and agrees to one of the following contraceptives\r\n** An intrauterine device (IUD) with a documented failure rate of less than % per year\r\n** Vasectomized partner who is sterile prior to the subjects entry and is the sole sexual partner for that woman\r\n** Complete abstinence from sexual intercourse for  days before exposure to investigational product, during the clinical trial, and for at least  days after the last dose of investigational product\r\n** Double barrier contraception defined as condom with spermicidal jelly, foam, suppository, or film; OR diaphragm with spermicide; OR male condom and diaphragm
Childbearing potential, including any female who has had a negative serum pregnancy test within  weeks prior to the first dose of study treatment, preferably as close to the first dose as possible, and agrees to use adequate contraception; acceptable contraceptive methods, when used consistently and in accordance with both the product label and the instructions of the physician, are as follows:\r\n* An intrauterine device with a documented failure rate of less than % per year\r\n* Vasectomized partner who is sterile prior to the female subjects entry and is the sole sexual partner for that female\r\n* Complete abstinence from sexual intercourse for  days before exposure to investigational product, through the dosing period, and for at least  days after the last dose of investigational product\r\n* Double-barrier contraception (condom with spermicidal jelly, foam suppository, or film; diaphragm with spermicide; or male condom and diaphragm with spermicide)\r\n* Note: oral contraceptives are not reliable due to potential drug-drug interactions
Females are eligible to enter and participate in this study if she is of:\r\n* Non-childbearing potential (i.e., physiologically incapable of becoming pregnant), including any female who has had:\r\n** A hysterectomy\r\n** A bilateral oophorectomy (ovariectomy)\r\n** A bilateral tubal ligation\r\n** Is post-menopausal\r\n** Subjects not using hormone replacement therapy (HRT) must have experienced total cessation of menses for >=  year and be greater than  years in age, OR, in questionable cases, have a follicle stimulating hormone (FSH) value >  mIU/mL and an estradiol value < pg/mL (<  pmol/L)\r\n** Subjects using HRT must have experienced total cessation of menses for >=  year and be greater than  years of age OR have had documented evidence of menopause based on FSH and estradiol concentrations prior to initiation of HRT\r\n* Childbearing potential, including any female who has had a negative serum pregnancy test within  weeks prior to the first dose of study treatment, preferably as close to the first dose as possible, and agrees to use adequate contraception; GlaxoSmithKline (GSK) acceptable contraceptive methods, when used consistently and in accordance with both the product label and the instructions of the physician, are as follow:\r\n** An intrauterine device with a documented failure rate of less than % per year \r\n** Vasectomized partner who is sterile prior to the female subjects entry and is the sole sexual partner for that female\r\n** Complete abstinence from sexual intercourse for  days before exposure to investigational product, through the dosing period, and for at least  days after the last dose of investigational product\r\n** Double-barrier contraception (condom with spermicidal jelly, foam suppository, or film; diaphragm with spermicide; or male condom and diaphragm with spermicide)\r\n** Oral contraceptives