Dolutegravir (DTG, GSK1349572 is an integrase inhibitor that is currently in Phase 3 clinical development for the treatment of HIV infection. DTG will likely be used in women on oral contraceptives (OC) for birth control. Based on accumulated non-clinical and clinical drug metabolism and pharmacokinetic data, there is a low likelihood of drug interaction between DTG and most widely used OC drugs. The primary objective of this study is to evaluate the effect of DTG administration on the pharmacokinetics and pharmacodynamics of a commonly used oral contraceptive product, Ortho-Cyclen (combination of norgestimate and ethinyl estradiol), in healthy female subjects. Each subject will participate in a Run-in period (if needed), followed by two treatment periods. Approximately 16 subjects will be randomized in a cross-over fashion to either Ortho-Cyclen with DTG or Ortho-Cyclen with Placebo for 10 days and switch to the alternate treatment for another 10 days. Subjects will return to the study center for final follow up evaluations 7 - 14 days after the final dose of study medication.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
DOUBLE
Enrollment
16
Ortho-cyclen is an oral contraceptive.
Dolutegravir is an experimental HIV drug
Placebo is a tablet with no drug in it
GSK Investigational Site
Miami, Florida, United States
AUC(0-tau) of norelgestromin and ethinylestradiol after Ortho-Cyclen alone and after Ortho-Cyclen with dolutegravir
Samples will be collected at predose and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, and 24 hours postdose on Days 10 and 21
Time frame: Up to 24 hours post-dose
Safety and tolerability of all treatments as assessed by vital signs, AEs, and clinical laboratory tests
Time frame: Up to 8 weeks
Composite of norelgestromin pharmacokinetic parameters on Day 10 and Day 21: Cmax, Cmin, tmax, tmin and half life
Samples will be collected at predose and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, and 24 hours postdose on Days 10 and 21
Time frame: Up to 24 hours post dose
Predose serum levels of luteinizing hormone and follicle stimulating hormone from Periods 1 and 2
Samples will be collected at predose on Days 1, 10, 11, 21 and 22
Time frame: predose on Days 1, 10, 11, 21 and 22
Predose serum levels of progesterone from Periods 1 and 2
Samples will be collected at predose on Days 1, 10, 11, 21 and 22
Time frame: predose on Days 1, 10, 11, 21 and 22
Composite of dolutegravir pharmacokinetic parameters on Day 10 and Day 21: AUC(0-t), Cmax, tmax, Cmin, C0, Ct and CL/F
Samples will be collected at predose and at 1, 2, 3, 4, 6, 8, and 12 hours post dose on Day 10 and Day 21
Time frame: Up to 12 hours post dose
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