Clinical trial NCT06354257: 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
Official title: A Phase 1, Open-label, Fixed Sequence, 1-way Drug-drug Interaction Study to Investigate the Pharmacokinetics of GSK3036656 and an Oral Contraceptive Containing Ethinyl Estradiol and Levonorgestrel When the Oral Contraceptive is Administered Alone and in Combination With GSK3036656 in Healthy Female Participants of Nonchildbearing Potential Aged 18-65 Years of Age
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Tuberculosis
Keywords: Oral contraceptive
GSK3036656
Fixed sequence
Ethinyl Estradiol
Levonorgestrel
Drug interaction
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2024-04-09
Enrollment: 20
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Fixed sequence
Primary purpose: PREVENTION

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.


Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: At Day 18
measure: Maximum observed concentration (Cmax) of EE after being administered with 14 days of GSK3036656 at DL 2
timeFrame: At Day 18
measure: AUC(0-inf) of LNG after being administered with 14 days of GSK3036656 at DL 2
timeFrame: At Day 18
measure: Cmax of LNG after being administered with 14 days of GSK3036656 at DL 2
timeFrame: At Day 18
Secondary outcomes:
measure: AUC over the dosing interval (0-tau) of GSK3036656 after being administered with a single dose of EE/LNG
timeFrame: At Day 16
measure: Cmax of GSK3036656 after being administered with a single dose of EE/LNG
timeFrame: At Day 16
measure: Steady state assessment using trough plasma concentration (Ctau) of GSK3036656 after being administered with a single dose of EE/LNG
timeFrame: At Days 8, 10, 12, 15 and 16
measure: Tmax of GSK3036656 after being administered with a single dose of EE/LNG
timeFrame: At Day 18
measure: AUC versus time curve (AUC[0-t]) of EE/LNG after being administered with a single dose of EE/LNG
timeFrame: At Day 4
measure: AUC(0-t) of EE/LNG after being administered with 14 days of treatment with GSK3036656 at DL 2
timeFrame: At Day 18
measure: Tmax of EE/LNG after being administered with a single dose of EE/LNG
timeFrame: At Day 4
measure: Tmax of EE/LNG after being administered with 14 days of GSK3036656 DL 2
timeFrame: At Day 18
measure: Apparent terminal half-life (t1/2) of EE and LNG after a single dose of EE/LNG
timeFrame: At Day 4
measure: 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
timeFrame: At Day 18
measure: Number of participants with serious adverse events (SAEs)
timeFrame: Day 1 to Day 3, Day 4 to Day 14 and Day 15 to Day 18
measure: Number of participants with Grade 3 or higher severity adverse events (AEs)
timeFrame: Day 1 to Day 3, Day 4 to Day 14 and Day 15 to Day 18
measure: Number of participants with drug-related AEs
timeFrame: Day 1 to Day 3, Day 4 to Day 14 and Day 15 to Day 18
measure: Number of participants with drug-related AEs following the administration of GSK3036656
timeFrame: Day 1 to Day 3, Day 4 to Day 14 and Day 15 to Day 18
measure: Number of participants withdrawn from the treatment/study due to AEs
timeFrame: Day 1 to Day 3, Day 4 to Day 14 and Day 15 to Day 18
measure: Percentage of participants with ECG values of Potential Clinical Importance (PCI)
timeFrame: Day 1 to Day 3, Day 4 to Day 14 and Day 15 to Day 18
measure: Percentage of participants with clinical chemistry laboratory values of PCI
timeFrame: Day 1 to Day 3, Day 4 to Day 14 and Day 15 to Day 18
measure: Percentage of participants with haematology laboratory values of PCI
timeFrame: Day 1 to Day 3, Day 4 to Day 14 and Day 15 to Day 18
measure: Percentage of participants with vital signs parameters of PCI
timeFrame: Day 1 to Day 3, Day 4 to Day 14 and Day 15 to Day 18
Other outcomes:
Locations:
city: Madrid
country: Spain
facility: GSK Investigational Site
Study officials:
References: