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This open-label, fixed-sequence crossover study aims to evaluate the effect of GSK1265744 (744) oral administration on the pharmacokinetics (PK) and pharmacodynamics (PD) of a commonly used oral contraceptive (OC) product (combination of ethinyl estradiol and levonorgestrel), in 20 healthy female subjects. Each subject will participate in a Run-in Period (if needed), followed by a single-sequence Treatment Period. Subjects will receive oral contraceptive containing Levonorgestrel and Ethinyl Estradiol on Days 1 to 21 and be OC free on Days 22 to 28, during which withdrawal menses should occur. Subjects will receive OC alone on Days 1 to 10. Levonorgestrel (LNG) and ethinyl estradiol (EE) PK will be determined on Day 10. Subjects will then co-administer 744 and OC on Days 11 to 21. Levonorgestrel and ethinyl estradiol PK will be determined again on Day 21 to assess if co-administration with 744 results in a significant change in OC exposure compared to OC alone. Subjects will return to the study center for final follow-up evaluations 7 to 14 days after the last dose of study medication (Days 28 to 35).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| OC containing levonorgestrel and ethinyl estradiol + GSK126574 | Experimental | Eligible subjects will enter a run-in-period of 21 days (may extend to 49 days) to stabilize on OC containing levonorgestrel and ethinyl estradiol in order to synchronize the menstrual cycles of multiple subjects. Subjects completing run-in-period will enter Treatment period 1 and will be dosed OC once daily on Days 1 to 10. At day 11 subjects will enter Treatment period 2 and will be dosed with OC containing levonorgestrel and ethinyl estradiol + 744 once daily on Day 12 to 19. Subjects completing Treatment period 2 will have 7 OC free days (Day 22 to 28) during which withdrawal menses should occur. Subjects will then be followed up for 7 to 14 days (Day 28 to 35/49). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ethinyl Estadiol | Drug | EE is available as a combination of EE 0.03 mg and LNG 0.15mg, a monophasic oral contraceptive tablet to be taken along with 240 mL water |
|
| Measure | Description | Time Frame |
|---|---|---|
| Plasma (AUC[0-tau]) | Blood samples will be collected to estimate the area under the concentration-time curve over the dosing interval (AUC[0-tau]) of LNG and EE following OC with and without 744 | Period 1: Predose on Day 9 and on Day 10: predose, and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, and 24 hours postdose. Period 2: Predose on Day 20 and on Day 21 predose, and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, and 24 hours postdose |
| Measure | Description | Time Frame |
|---|---|---|
| Safety and tolerability of 744 when given with and without OC as assessed by adverse events (AE) | Safety and tolerability as assessed by number of participants with AEs | Up to 72 days |
| Safety and tolerability of 744 when given with and without OC as assessed by clinical laboratory tests |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | ViiV Healthcare | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | London | SE1 1YR | United Kingdom |
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| Levonorgestrel | Drug | LNG is available as a combination of EE 0.03 mg and LNG 0.15mg, a monophasic oral contraceptive tablet to be taken along with 240 mL water |
|
| GSK1265744 | Drug | GSK1265744 is available as 30 mg tablet to be taken along with 240 mL water |
|
Safety laboratory parameters included hematology and clinical chemistry analysis and ECG |
| Up to 72 days |
| Safety and tolerability of 744 when given with and without OC as assessed by Electrocardiogram (ECG) | Up to 72 days |
| Safety and tolerability of 744 when given with and without OC as assessed by vital signs | Vital signs will include pulse rate and blood pressure measurements | Up to 72 days |
| Composite of plasma pharmacokinetic (PK) parameters of 744 | Maximum observed plasma concentration (Cmax), plasma concentration at the end of the dosing interval (Ctau), time to maximum drug concentration (tmax), and oral clearance (CL/F) CL/F will be used to evaluate the pharmacokinetics of LNG and EE after OC alone and after OC with 744. | Period 1: Predose on Day 9 and on Day 10: predose, and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, and 24 hours postdose. Period 2: Predose on Day 20 and on Day 21 predose, and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, and 24 hours postdose |
| Predose serum levels of Progesterone, Luteinizing hormone (LH) and follicle stimulating hormone (FSH) | To assess the impact of 744 on the pharmacodynamic effects of OC on endogenous LH, FSH, and progesterone levels when given in combination compared with these parameters when OC is administered alone | At Screening and predose on Days 1, 10, 11, 21, and 22 |
| Composite of plasma PK parameters of 744 - AUC(0-tau), Cmax, tmax, Ctau and CL/F | To evaluate the PK of 744 when co-administered with LNG and EE | Predose on Day 20 and on Day 21: predose and at 1, 2, 3, 4, 6, 8, 12, and 24 hours post dose on Day 22 |
| ID | Term |
|---|---|
| D007239 | Infections |
| D000163 | Acquired Immunodeficiency Syndrome |
| D006505 | Hepatitis |
| ID | Term |
|---|---|
| D015658 | HIV Infections |
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D015229 | Sexually Transmitted Diseases, Viral |
| D012749 | Sexually Transmitted Diseases |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D012897 | Slow Virus Diseases |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
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| ID | Term |
|---|---|
| D016912 | Levonorgestrel |
| C584914 | cabotegravir |
| ID | Term |
|---|---|
| D009644 | Norgestrel |
| D009652 | Norpregnenes |
| D009650 | Norpregnanes |
| D009654 | Norsteroids |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
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