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).
Study Type
INTERVENTIONAL
Allocation
NA
Masking
NONE
Enrollment
20
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
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 is available as 30 mg tablet to be taken along with 240 mL water
GSK Investigational Site
London, United Kingdom
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
Time frame: 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
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
Time frame: Up to 72 days
Safety and tolerability of 744 when given with and without OC as assessed by clinical laboratory tests
Safety laboratory parameters included hematology and clinical chemistry analysis and ECG
Time frame: Up to 72 days
Safety and tolerability of 744 when given with and without OC as assessed by Electrocardiogram (ECG)
Time frame: 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
Time frame: 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.
Time frame: 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
Time frame: 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
Time frame: 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
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