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

GlaxoSmithKline20 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

PREVENTION

Masking

NONE

Enrollment

Conditions

Tuberculosis

Interventions

MicrogynonDRUG

Participants received 1 dose of Microgynon (0.03 mg EE/0.15 mg LNG) on Day 1 of Treatment Period 1 and 1 dose co-administered with GSK3036656 20 mg on Day 15 of Treatment Period 3.

GSK3036656DRUG

Participants received 1 loading dose of 40 mg on Day 4 and a dose of 20 mg on Days 5 to 14 once daily in Treatment Period 2. In Treatment Period 3, participants received one 20 mg dose along with Microgynon (0.03 mg EE/0.15 mg LNG) on Day 15 after which a 20 mg dose on Days 17 and 18 once daily.

Eligibility

Sex: FEMALEMin age: 18 YearsMax age: 65 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: Age: 1. Participant was 18 to 65 years of age, inclusive, at the time of signing the informed consent. Type of Participant and Disease Characteristics: 2. Participants were 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. Creatinine clearance was \>= 75 mL/min. 4. Echocardiogram was normal or showed normal left ventricular function; at most trace to mild valvular regurgitation was allowed, with no valvular stenosis. Weight: 5. Body weight was \>= 45.0 kg (99 lbs), and body mass index was within the range 18.5 to 31.0 kg/m² (inclusive). Sex: 6. Female participants were of Nonchildbearing Potential (WONCBP). Women in the following categories were considered WONCBP: Permanently sterile due to one of the following procedures: 1. Documented hysterectomy. 2. Documented bilateral salpingectomy. 3. Documented bilateral oophorectomy. Postmenopausal females. A postmenopausal state was defined as no menses for 12 months without an alternative medical cause. * A high follicle-stimulating hormone (FSH) level in the postmenopausal range could have been 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 \>1 FSH measurement was required within the screening period. * Females on HRT and whose menopausal status was in doubt discontinued HRT \>= 30 days prior to the start of Treatment Period 1 to allow confirmation of postmenopausal status before study enrolment. Informed Consent: 7. Participant was capable of giving signed informed consent, which included 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) \> 1.5×ULN. A single repeat of ALT was allowed within a single screening period to determine eligibility. 6. Bilirubin \> 1.5×ULN (isolated bilirubin \> 1.5×ULN was acceptable if bilirubin was fractionated and direct bilirubin was \< 35%). 7. Any acute laboratory abnormality at Screening which, in the opinion of the investigator, should have precluded 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-except creatine phosphokinase, lipid abnormalities, and ALT (as above)-excluded a participant unless the investigator provided a compelling explanation and had sponsor assent. A single repeat of any laboratory abnormality was allowed within a single screening period. 10. Positive test result for drugs of abuse (including marijuana), alcohol, or cotinine at Screening or before the first study dose. Prior/Concomitant Therapy: 11. Participants were unable to refrain from using prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's wort), within 7 days prior to the first dose and throughout the study. Levothyroxine and omeprazole were allowed if participants had been on a stable dose for \>= 1 month prior to Treatment Period 1 and maintained the same dose. Microgynon was administered \>= 1 hour after levothyroxine or omeprazole. Other medications were allowed on a case-by-case basis with medical monitor and GSK ganfeborole team approval. 12. Participants received any vaccine within 30 days prior to study treatment. 13. Participants were unwilling to abstain from excessive consumption of caffeine, grapefruit, grapefruit juice, Seville oranges, blood oranges, pomelos, or their juices within 7 days prior to first dose through study end. 14. Participants who had undergone IVF or assisted reproductive techniques within 9 months prior to screening, were currently participating, or planned such procedures during the following year were excluded. Prior/Concurrent Clinical Study Experience: 15. Participants had taken part in another clinical study within 30 days, 5 half-lives + 10 days, or 2× duration of the investigational product's biological effect (whichever was longer). 16. Study participation resulted in donation of blood or blood products \> 500 mL within 56 days. Diagnostic Assessments: 17. Significant arrhythmia or ECG findings, in the opinion of the investigator or GSK Medical Monitor, would have interfered with participant safety. 18. Exclusion criteria for screening ECG: Heart rate \< 50 or \> 100 bpm QTcF interval \> 450 ms Other Exclusion Criteria: 19. Participants with vitiligo. 20. Participants with hypertension or Type 2 diabetes that could not 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 \> 14 units. 22. Use of tobacco- or nicotine-containing products within 3 months prior to Screening. 23. History of sensitivity to any study medications or components, or any allergy that, in the investigator's or medical monitor's opinion, contraindicated participation.

Locations (1)

GSK Investigational Site

Madrid, Spain

Outcomes

Primary Outcomes

Area Under the Plasma Drug Concentration (AUC) From Time Zero Extrapolated to Infinity (AUC[0-inf]) After a Single Dose of EE and LNG

AUC(0-inf) is defined as the area under the concentration-time curve from time 0 extrapolated to infinity and was calculated by using a non-compartmental analysis.

Time frame: At Day 1 for the Treatment Period 1: Microgynon Group and at Day 15 for the Treatment Period 3: Microgynon + GSK3036656 Group

Maximum Observed Plasma Concentration (Cmax) After a Single Dose of EE and LNG

Cmax is defined as the maximum observed plasma concentration determined directly from the concentration-time data and was calculated by using a non-compartmental analysis.

Time frame: At Day 1 for the Treatment Period 1: Microgynon Group and at Day 15 for the Treatment Period 3: Microgynon + GSK3036656 Group

Secondary Outcomes

AUC Versus Time Curve From Time Zero During a Dosage Interval of Time at Steady State [AUC(0-tau)] of GSK3036656 With EE/LNG

AUC(0-tau) is defined as the area under the concentration-time curve over a dosing interval and was calculated by using a non-compartmental analysis.

Time frame: At Day 15

Cmax at Steady State of GSK3036656 With EE/LNG

Cmax is defined as the maximum observed plasma concentration determined directly from the concentration-time data and was calculated by using a non-compartmental analysis.

Time frame: At Day 15

Trough Plasma Concentration (Ctau) at Steady State of GSK3036656 With EE/LNG and GSK3036656 Alone

Ctau is defined as the concentration reached by the drug immediately before the next dose is administered.

Time frame: At Day 8, 10, 12, 15 and 16

Time to Maximum Observed Plasma Drug Concentration (Tmax) at Steady State of GSK3036656 With EE/LNG

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.