Tuberculosis
Conditions
Keywords
Ganfeborole, GSK3036656, Microgynon, Ethinylestradiol and Levonorgestrel, Drug-drug interaction (DDI), Non-childbearing potential, Tuberculosis (TB)
Brief summary
This study is designed to assess the pharmacokinetics (PK), safety, and tolerability of Ganfeborole and Microgynon, an oral contraceptive containing ethinylestradiol (EE) and levonorgestrel (LNG), when Microgynon is administered alone and in combination with Ganfeborole in healthy female participants of non-childbearing potential.
Interventions
DRUGGanfeborole
Participants receive Ganfeborole orally.
DRUGMicrogynon
Participants receive Microgynon orally.
Sponsors
GlaxoSmithKline
UNITE4TB consortium
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
This is an open-label study.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 64 Years
Healthy volunteers
Yes
Inclusion criteria
1. Participant is 18 to \<65 years of age, inclusive, at the time of signing the informed consent. 2. Participants who are healthy as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring (history and ECG). 3. A creatinine clearance of \>=75 mL/min. 4. Normal echocardiogram or echocardiogram with normal left ventricular function with at most trace to mild valvular regurgitation is allowed and no valvular stenosis. 5. Body weight \>=40.0 kg (99 pounds \[lbs\]) and body mass index within the range 18.5 up to 30.0 kg/m\^2 (inclusive). 6. Participant of Non-childbearing Potential. Participants in the following categories are considered female PONCBP: Postmenopausal female. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. * A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in individuals not using hormonal contraception or hormonal replacement therapy (HRT). However, in the absence of 12 months of amenorrhea, confirmation with more than one FSH measurement is required, within the Screening period. * Females on HRT and whose menopausal status is in doubt must discontinue HRT at least 30 days prior to the start of Treatment Period 1 to allow confirmation of postmenopausal status before study enrollment. 7. Participant is capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the Informed Consent Form (ICF) and in the protocol. 8. Additional inclusion criteria: * Two FSH tests * Negative pregnancy test
Exclusion criteria
1. History of known cardiac valve abnormalities 2. Medical history of fatty liver disease 3. Major health conditions (including ovarian, endometrial, cervical, and breast tumours as per the Microgynon label) 4. History of ovarian, endometrial, cervical and breast cancer 5. History of deep vein thrombosis (DVT) 6. Presence of hepatitis B surface antigen at Screening or within 3 months prior to starting study treatment. 7. Positive hepatitis C antibody test result at Screening or within 3 months prior to starting study treatment AND positive on reflex to hepatitis C RNA. 8. Positive HIV-1 and/or -2 antigen/antibody immunoassay at Screening. 9. Alanine aminotransferase (ALT) \>1.5×ULN. A single repeat of ALT is allowed within a single screening period to determine eligibility. 10. Bilirubin \>1.5×ULN (isolated bilirubin \>1.5×ULN is acceptable if bilirubin was fractionated and direct bilirubin \<35%). 11. Any acute laboratory abnormality at Screening which, in the opinion of the investigator, should preclude participation in the study of an investigational compound. 12. Participants with haemoglobin \<8.0 g/dL. 13. Any Grade 3 to 4 laboratory abnormality at Screening, inclusive of creatine phosphokinase and lipid abnormalities and ALT, excludes a participant from the study unless the investigator provided a compelling explanation for the laboratory result(s) and has the assent of the sponsor. A single repeat of any laboratory abnormality is allowed within a single screening period to determine eligibility. 14. A positive test result for drugs of abuse (including marijuana), alcohol, or cotinine (indicating active current smoking) at Screening or before the first dose of study treatment. 15. Unable to refrain from the use of prescription (including HRT), or non-prescription drugs including vitamins, herbal and dietary supplements (including St John's wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study treatment and for the duration of the study. Concomitant medications may be permitted on a case by case basis on the discretion of the medical monitor and the GSK Ganfeborole team. 16. Treatment with any vaccine within 30 days prior to receiving study treatment. 17. Unwillingness to abstain from excessive consumption of any food or drink containing caffeine, grapefruit or grapefruit juice, Seville oranges, blood oranges, or pomelos or their fruit juices within 7 days prior to the first dose of study treatment(s) until the end of the study. 18. The study will exclude participants who have undergone IVF or other assisted reproductive techniques within 9 months prior to screening or are participating in such programs at the time of screening, or who plan to undergo IVF or other assisted reproductive techniques during the following year. 19. Participation in another concurrent clinical study or prior clinical study (with the exception of imaging trials) prior to the first dosing day in the current study: 30 days, 5 half-lives plus 10 days, or twice the duration of the biological effect of the investigational product (whichever is longer). 20. Where participation in the study results in donation of blood or blood products in excess of 500 mL within 56 days. 21. Any significant arrhythmia or ECG finding which would interfere with the safety for the individual participant 22.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Cmax of EE and LNG, after repeat dose, alone and in the presence of Ganfeborole on Day 24 | On Day 24, at 30 minutes pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose |
| Area under the plasma concentration-time curve (AUC(0-tau)) over 24 hours of EE and LNG, after repeat dose, alone and in the presence of Ganfeborole on Day 10 | On Day 10 at 30 minutes pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose |
| AUC(0-tau) over 24 hours of EE and LNG, after repeat dose, alone and in the presence of Ganfeborole on Day 24 | On Day 24 at 30 minutes pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose |
| Maximum observed concentration (Cmax) of EE and LNG, after repeat dose, alone and in the presence of Ganfeborole on Day 10 | On Day 10, at 30 minutes pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with adverse events (AEs) of grade 3 severity or higher | From Day 1 to Day 25 | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. Grade 3 = severe, Grade 4 = life-threatening, Grade 5= death. |
| Number of participants with any AEs related to study interventions, overall and by each type of treatment (Microgynon and Ganfeborole) | From Day 1 to Day 25 | — |
| Number of participants withdrawn from the. treatment/study due to AEs | From Day 1 to Day 25 | — |
| Number of participants with electrocardiogram (ECG) values of potential clinical importance (PCI) | At Day 11 and Day 25 | — |
| Number of participants with clinical chemistry laboratory values of PCI | At Days 1, 7, 11, 21 and 25 | — |
| Number of participants with hematology laboratory values of PCI | At Days 1, 7, 11, 21 and 25 | — |
| Number of participants with vital signs parameters of systolic blood pressure (SBP), diastolic BP (DBP) and heart rate (HR) of PCI | At Days 1, 7, 11, 21 and 25 | — |
| Change in sex hormone binding globulin (SHBG) levels following repeat-dose administration of Microgynon | At Screening, Day 10 and Day 24 | — |
| AUC(0-tau) over 24 hours of Ganfeborole in the presence of EE and LNG | On Day 24, at 30 minutes pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose | — |
| Cmax of Ganfeborole in the presence of EE and LNG | On Days 16, 22 and 23, at 30 minutes pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose for each day, and on Days 24 and 25, at 30 minutes pre-dose and 24 hours post-dose for each day | — |
| Plasma concentration over 24 hours (Ctau) of Ganfeborole in the presence of EE and LNG | On Days 16, 22 and 23, at 30 minutes pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose for each day, and on Days 24 and 25, at 30 minutes pre-dose and 24 hours post-dose for each day | — |
| Time of maximum observed concentration (Tmax) of Ganfeborole in the presence of EE and LNG | On Days 16, 22 and 23, at 30 minutes pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose for each day, and on Days 24 and 25, at 30 minutes pre-dose and at 24 hours post-dose for each day | — |
| Tmax of EE and LNG alone and in the presence of Ganfeborole | On Days 8, 9, 22 and 23, at 30 minutes pre-dose and 24 hours post-dose for each day, and on Days 10, 24 and 25 at 30 minutes pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose for each day | — |
| Ctau over 24 hours of EE and LNG alone and in the presence of Ganfeborole | On Days 8, 9, 22 and 23, at 30 minutes pre-dose and 24 hours post-dose for each day, and on Days 10, 24 and 25 at 30 minutes pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose for each day | — |
| Number of participants with serious adverse events (SAEs) | From Day 1 to Day 25 | An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study participant, or other situations as per investigator's opinion. |
Contacts
CONTACTUS GSK Clinical Trials Call Center
CONTACTEU GSK Clinical Trials Call Center
Outcome results
None listed