Infections, Human Immunodeficiency Virus and Hepatitis
Conditions
Keywords
ethinyl estradiol, GSK1265744, pharmacokinetics, oral contraceptive, oral contraceptive containing levonorgestrel and ethinyl estradiol, levonorgestrel
Brief summary
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).
Interventions
DRUGEthinyl Estadiol
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
DRUGLevonorgestrel
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
DRUGGSK1265744
GSK1265744 is available as 30 mg tablet to be taken along with 240 mL water
Sponsors
ViiV Healthcare
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy female subjects, as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. * Females aged between 18 and 45 years of age inclusive, at the time of signing the informed consent. * A female subject is eligible to participate if she is of: Child-bearing potential with negative pregnancy test as determined by serum hCG test at screening AND agrees to use one of the contraception methods listed in the protocol in addition to OC (containing levonorgestrel and ethinyl estradiol ) from Day 1 of the Run-In Period (if required) or Day 1 of Treatment Period 1 until 14 days after the last dose of study drug to sufficiently minimize the risk of pregnancy. Female subjects must agree to use an additional form of contraception throughout the study and for the subsequent post-study follow-up period OR Has only same-sex partners, when this is her preferred and usual lifestyle. * Female subject's with a body mass index (BMI) of 18to 30 kilogram per meter square (kg/m\^2) and body weight \>=50 kg (110 pounds \[lbs\]) and \<114 kg (\<250 lbs). * Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form * Alanine transaminase (ALT), alkaline phosphatase and bilirubin \<=1.5x upper limit of normal (ULN) (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).
Exclusion criteria
* History of any condition that would contraindicate OC administration (which may include hypertension, stroke, ischemic heart disease, venous thromboembolism or family history of thromboembolism, known factor V Leiden mutation or other gene mutations associated with increased risk of thromboembolism, migraine headaches, carcinoma of the breast, liver or endometrium, gallbladder disease, history of undiagnosed abnormal uterine bleeding, etc.). * Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). * History of regular alcohol consumption within 6 months of the study defined as: an average weekly intake of \>14 units for females. One unit is equivalent to 8 grams of alcohol: a half-pint (\ 240 milliliter \[mL\]) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits. * 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 GlaxoSmithKline (GSK) Medical Monitor, contraindicates their participation. * A positive pre-study Hepatitis B surface antigen (or positive Hepatitis B core antibody with negative hepatitis B surface antibody) or positive Hepatitis C antibody result within 3 months of screening * A positive pre-study drug/alcohol screen. * A positive test for Human immunodeficiency virus (HIV) antibody. * The subject's systolic blood pressure is outside the range of 80-140 millimeter of mercury (mmHg), or diastolic blood pressure is outside the range of 45-90mmHg. *
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Plasma (AUC[0-tau]) | 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 | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety and tolerability of 744 when given with and without OC as assessed by clinical laboratory tests | Up to 72 days | Safety laboratory parameters included hematology and clinical chemistry analysis and ECG |
| 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 | Up to 72 days | Vital signs will include pulse rate and blood pressure measurements |
| Safety and tolerability of 744 when given with and without OC as assessed by adverse events (AE) | Up to 72 days | Safety and tolerability as assessed by number of participants with AEs |
| Predose serum levels of Progesterone, Luteinizing hormone (LH) and follicle stimulating hormone (FSH) | At Screening and predose on Days 1, 10, 11, 21, and 22 | 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 |
| Composite of plasma PK parameters of 744 - AUC(0-tau), Cmax, tmax, Ctau and CL/F | 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 | To evaluate the PK of 744 when co-administered with LNG and EE |
| Composite of plasma pharmacokinetic (PK) parameters of 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 | 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. |
Countries
United Kingdom
Outcome results
None listed