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
Summary
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Area Under the Plasma Drug Concentration (AUC) From Time Zero Extrapolated to Infinity (AUC[0-inf]) After a Single Dose of EE and LNG |
627.11; 552.01; 24651.76; 30334.48 | — |
| PRIMARY Maximum Observed Plasma Concentration (Cmax) After a Single Dose of EE and LNG |
50.86; 48.96; 2599.85; 2828.17 | — |
| SECONDARY AUC Versus Time Curve From Time Zero During a Dosage Interval of Time at Steady State [AUC(0-tau)] of GSK3036656 With EE/LNG |
8372.42 | — |
| SECONDARY Cmax at Steady State of GSK3036656 With EE/LNG |
600.62 | — |
| SECONDARY Trough Plasma Concentration (Ctau) at Steady State of GSK3036656 With EE/LNG and GSK3036656 Alone |
226.92; 235.54; 243.40; 251.26; 254.91 | — |
| SECONDARY Time to Maximum Observed Plasma Drug Concentration (Tmax) at Steady State of GSK3036656 With EE/LNG |
0.95 | — |
| SECONDARY AUC Versus Time Curve (AUC[0-t]) of EE and LNG Alone and With GSK3036656 |
447.10; 363.00; 21182.61; 23287.77 | — |
| SECONDARY Tmax of EE and LNG Alone and With GSK3036656 |
0.967; 1.433; 0.967; 0.967 | — |
| SECONDARY Apparent Terminal Half-life (t1/2) of EE and LNG Alone and With GSK3036656 |
19.180; 10.867; 41.315; 34.697 | — |
| SECONDARY Number of Participants With Serious Adverse Events (SAEs) |
0; 0; 0 | — |
| SECONDARY Number of Participants With Grade 3 or Higher Severity Adverse Events (AEs) |
0; 0; 0 | — |
| SECONDARY Number of Participants With Drug-related AEs Following Administration of Microgynon and Following the Administration of GSK3036656 |
0; 0; 0 | — |
| SECONDARY Number of Participants Withdrawn From the Treatment Due to AEs |
0; 1; 0 | — |
| SECONDARY Number of Participants Withdrawn From the Study Due to AEs |
0; 1; 0 | — |
| SECONDARY Number of Participants With Electrocardiogram (ECG) Values of Potential Clinical Importance (PCI) |
0; 0; 0; 20; 19; 18 | — |
| SECONDARY Number of Participants With Clinical Chemistry Laboratory Values of PCI |
0; 0; 0; 19; 19; 15 | — |
| SECONDARY Number of Participants With Haematology Laboratory Values of PCI |
7; 1; 1; 13; 17; 16 | — |
| SECONDARY Number of Participants With Vital Signs Parameters of PCI |
0; 0; 0; 20; 19; 18 | — |
Eligibility Criteria
Inclusion Criteria
Age:
- Participant was 18 to 65 years of age, inclusive, at the time of signing the informed consent.
Type of Participant and Disease Characteristics:
- 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).
- Creatinine clearance was >= 75 mL/min.
- Echocardiogram was normal or showed normal left ventricular function; at most trace to mild valvular regurgitation was allowed, with no valvular stenosis.
Weight:
- 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:
- Female participants were of Nonchildbearing Potential (WONCBP).
Women in the following categories were considered WONCBP:
Permanently sterile due to one of the following procedures:
- Documented hysterectomy.
- Documented bilateral salpingectomy.
- 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:
- 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:
- History of known cardiac valve abnormalities.
Laboratory Assessments:
- Presence of hepatitis B surface antigen at Screening or within 3 months prior to starting study treatment.
- 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.
- Positive HIV-1 and -2 antigen/antibody immunoassay at Screening.
- Alanine aminotransferase (ALT) > 1.5×ULN. A single repeat of ALT was allowed within a single screening period to determine eligibility.
- Bilirubin > 1.5×ULN (isolated bilirubin > 1.5×ULN was acceptable if bilirubin was fractionated and direct bilirubin was = 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.
- Participants received any vaccine within 30 days prior to study treatment.
- 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.
- 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:
- 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).
- Study participation resulted in donation of blood or blood products > 500 mL within 56 days.
Diagnostic Assessments:
- Significant arrhythmia or ECG findings, in the opinion of the investigator or GSK Medical Monitor, would have interfered with participant safety.
- Exclusion criteria for screening ECG:
Heart rate 100 bpm
QTcF interval > 450 ms
Other Exclusio
Data sourced from ClinicalTrials.gov (NCT06354257). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.