A Study to Investigate the Pharmacokinetics of a Combined Oral Contraceptive When Given Alone and in Combination With GSK3036656 in Female Participants of Non-childbearing Potential Aged 18 to 65 Years of Age

Phase 1

Completed

• Conditions: Tuberculosis
• Interventions: Drug: EE/LNG; Drug: GSK3036656 Dose Level 1; Drug: GSK3036656 Dose Level 2

• Registration Number: NCT06354257
• Lead Sponsor: GlaxoSmithKline

Brief Summary

The purpose of this study is to provide data showing if there are any effects of GSK3036656 on a combined oral contraceptive containing Ethinyl Estradiol (EE) and Levonorgestrel (LNG), which will help inform future studies on suitable contraceptive measures to be used.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-04-03
• Study First Submitted QC: 2024-04-03
• Study Start: 2024-04-05
• Study First Posted: 2024-04-09
• Primary Completion: 2024-07-01
• Study Completion: 2024-07-01
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-24
• Last Update Posted: 2024-12-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 20

Inclusion Criteria

Age:

1. Participant is 18 to 65 years of age, inclusive, at the time of signing the informed consent.

   Type of Participant and Disease Characteristics:

2. Participants who are healthy or compensated 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 greater than or equal to (>=) 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.

   Weight:

5. Body weight >=45.0 kg (99 lbs) and body mass index within the range 18.5 to 31.0 kg/m2 (inclusive).

   Sex:

6. Female of Nonchildbearing Potential (WONCBP)

Women in the following categories are considered WONCBP:

1. Permanently sterile due to one of the following procedures:

   1. Documented hysterectomy.
   2. Documented bilateral salpingectomy.
   3. Documented bilateral oophorectomy.

2. 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 women not using hormonal contraception or hormone 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 enrolment.

Informed Consent:

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.

Exclusion Criteria

Medical History:

1. History of known cardiac valve abnormalities.

   Laboratory Assessments:

2. Presence of hepatitis B surface antigen at Screening or within 3 months prior to starting study treatment.

3. 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.

4. Positive HIV-1 and -2 antigen/antibody immunoassay at Screening.

5. Alanine aminotransferase (ALT) greater than (>) 1.5×ULN. A single repeat of ALT is allowed within a single screening period to determine eligibility.

6. Bilirubin >1.5×ULN (isolated bilirubin >1.5×ULN is acceptable if bilirubin was fractionated and direct bilirubin less than [<] 35%).

7. Any acute laboratory abnormality at Screening which, in the opinion of the investigator, should preclude participation in the study of an investigational compound.

8. Participants with haemoglobin <8.0 g/dL

9. Any Grade 2 to 4 laboratory abnormality at Screening, with the exception of creatine phosphokinase and lipid abnormalities and ALT (described above) 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.

10. A positive test result for drugs of abuse (including marijuana), alcohol, or cotinine at Screening or before the first dose of study treatment.

    Prior/Concomitant Therapy:

11. Unable to refrain from the use of prescription or non-prescription drugs including vitamins, herbal and dietary supplements (including St John's wort) within 7 days prior to the first dose of study treatment and for the duration of the study. Levothyroxine and omeprazole may also be used during the study providing the participant has been on a stable dose for at least one month prior to the start of Treatment Period 1 and they maintain the same dose throughout the study. The dose of Microgynon should be administered at least one hour after the dose of levothyroxine or omeprazole). Other concomitant medications may be permitted on a case by case basis on the discretion of the medical monitor and the GSK ganfeborole team.

12. Treatment with any vaccine within 30 days prior to receiving study treatment.

13. 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.

14. 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.

    Prior/Concurrent Clinical Study Experience:

15. Participation in another concurrent clinical study or prior clinical study 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).

16. Where participation in the study results in donation of blood or blood products in excess of 500 mL within 56 days.

    Diagnostic Assessments:

17. Any significant arrhythmia or ECG finding which, in the opinion of the investigator or GSK Medical Monitor, would interfere with the safety for the individual participant.

18. Exclusion criteria for screening ECG:

    Heart rate - <50 or >100 beats per minute. QTcF interval - >450 ms.

    Other Exclusion Criteria:

19. Participants with vitiligo.

20. Participants with hypertension or Type 2 diabetes that cannot be controlled with diet and exercise alone.

21. History of regular alcohol consumption within 6 months of the study defined as: an average weekly intake of >14 units.

22. Unable to refrain from tobacco- or nicotine-containing products within 3 months prior to Screening.

23. History of sensitivity to any of the study medications, or components thereof, or a history of drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates their participation.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Study Group	EE/LNG	Participants will receive Ethinyl Estradiol (EE) and Levonorgestrel (LNG) on Day 1 followed by GSK3036656 dose level (DL) 1 on Day 4, then GSK3036656 DL 2 daily from Day 5 to Day 14, followed by EE/LNG + GSK3036656 DL 2 on Day 15 and then GSK3036656 DL 2 daily from Day 16 to Day 17. Participants will be followed-up until Day 18 inclusive.
Study Group	GSK3036656 Dose Level 1	Participants will receive Ethinyl Estradiol (EE) and Levonorgestrel (LNG) on Day 1 followed by GSK3036656 dose level (DL) 1 on Day 4, then GSK3036656 DL 2 daily from Day 5 to Day 14, followed by EE/LNG + GSK3036656 DL 2 on Day 15 and then GSK3036656 DL 2 daily from Day 16 to Day 17. Participants will be followed-up until Day 18 inclusive.
Study Group	GSK3036656 Dose Level 2	Participants will receive Ethinyl Estradiol (EE) and Levonorgestrel (LNG) on Day 1 followed by GSK3036656 dose level (DL) 1 on Day 4, then GSK3036656 DL 2 daily from Day 5 to Day 14, followed by EE/LNG + GSK3036656 DL 2 on Day 15 and then GSK3036656 DL 2 daily from Day 16 to Day 17. Participants will be followed-up until Day 18 inclusive.

Primary Outcome Measures

Name	Time	Method
Area under the plasma drug concentration (AUC)-time curve from time zero to extrapolated to infinity (AUC[0-inf]) of EE after being administered with 14 days of GSK3036656 at DL 2	At Day 18
AUC(0-inf) of LNG after being administered with 14 days of GSK3036656 at DL 2	At Day 18
Maximum observed concentration (Cmax) of EE after being administered with 14 days of GSK3036656 at DL 2	At Day 18
Cmax of LNG after being administered with 14 days of GSK3036656 at DL 2	At Day 18

Secondary Outcome Measures

Name	Time	Method
AUC over the dosing interval (0-tau) of GSK3036656 after being administered with a single dose of EE/LNG	At Day 16
Tmax of EE/LNG after being administered with 14 days of GSK3036656 DL 2	At Day 18
Apparent terminal half-life (t1/2) of EE and LNG after a single dose of EE/LNG	At Day 4
Number of participants withdrawn from the treatment/study due to AEs	Day 1 to Day 3, Day 4 to Day 14 and Day 15 to Day 18	A participant may withdraw from the study at any time at the participant's own request, for any reason (or without providing any reason). A participant may be withdrawn at any time at the discretion of the investigator for safety, behavioural, compliance or administrative reasons.
Percentage of participants with clinical chemistry laboratory values of PCI	Day 1 to Day 3, Day 4 to Day 14 and Day 15 to Day 18
Percentage of participants with vital signs parameters of PCI	Day 1 to Day 3, Day 4 to Day 14 and Day 15 to Day 18	Vital signs parameters will include systolic blood pressure (SBP), diastolic blood pressure (DBP) and heat rate (HR).
Cmax of GSK3036656 after being administered with a single dose of EE/LNG	At Day 16
Tmax of GSK3036656 after being administered with a single dose of EE/LNG	At Day 18
Steady state assessment using trough plasma concentration (Ctau) of GSK3036656 after being administered with a single dose of EE/LNG	At Days 8, 10, 12, 15 and 16
AUC(0-t) of EE/LNG after being administered with 14 days of treatment with GSK3036656 at DL 2	At Day 18
t1/2 of EE and LNG after a single dose of EE/LNG in combination with 14 days of treatment with GSK3036656 at DL 2	At Day 18
Number of participants with serious adverse events (SAEs)	Day 1 to Day 3, Day 4 to Day 14 and Day 15 to Day 18	An SAE is defined as any untoward medical occurrence that, at any dose: results in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in in persistent or significant disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment.
Number of participants with drug-related AEs following the administration of GSK3036656	Day 1 to Day 3, Day 4 to Day 14 and Day 15 to Day 18	The drug-related AEs are assessed by the investigator to be possibly, probably or definitely related to the study interventions.
Percentage of participants with ECG values of Potential Clinical Importance (PCI)	Day 1 to Day 3, Day 4 to Day 14 and Day 15 to Day 18	The ECG values assessed include heart rate, PR, QRS, QT, and corrected QT (QTc).
AUC versus time curve (AUC[0-t]) of EE/LNG after being administered with a single dose of EE/LNG	At Day 4
Tmax of EE/LNG after being administered with a single dose of EE/LNG	At Day 4
Number of participants with Grade 3 or higher severity adverse events (AEs)	Day 1 to Day 3, Day 4 to Day 14 and Day 15 to Day 18	An AE is defined as 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. A severe AE is defined as a type of AE that interrupts usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention. It is described as an AE with grade 3 severity or higher.
Number of participants with drug-related AEs	Day 1 to Day 3, Day 4 to Day 14 and Day 15 to Day 18	The drug-related AEs are assessed by the investigator to be possibly, probably or definitely related to the study interventions.
Percentage of participants with haematology laboratory values of PCI	Day 1 to Day 3, Day 4 to Day 14 and Day 15 to Day 18

Trial Locations

Locations (1)

GSK Investigational Site; 🇪🇸 Madrid, Spain