Study of Combined Oral Contraceptive Effects in Female Subjects

Study Overview
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Brief Summary
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The purpose of this study is to assess the effect of BMS-955176 on the pharmacokinetics of coadministered oral contraceptives.

Official Title
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The Effect of Coadministration of BMS-955176 on the Pharmacokinetics of a Combined Oral Contraceptive Containing Ethinyl Estradiol and Norgestimate in Female Subjects

Conditions
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Infection, Human Immunodeficiency Virus

Intervention / Treatment
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* Drug: BMS-955176
* Drug: Ortho Cyclen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed Written Informed Consent a) The signed informed consent form Target population a) Healthy female subjects as determined by no clinically significant deviation from normal in medical history, physical examination findings, vital sign measurements, 12-lead ECG measurements, physical measurements, and clinical laboratory test results b) Body Mass Index (BMI) of 18.0 to 32.0 kg/m2, inclusive, at screening and Day -1. BMI = weight (kg)/[height (m)]2 c) Weight greater than or equal to 45 kg d) Subject Reenrollment: This study permits the reenrollment of a subject that has discontinued study as a pretreatment failure (ie, has not been treated). If reenrolled, the subject must be reconsented Age and Reproductive Status a) Women, 18 to 40 years of age, inclusive b) Women of childbearing potential (WOCBP) with intact ovarian function as determined by medical history and history of regular menstrual cycles, and who have been on a stable regimen of Ortho Cyclen for at least 2 consecutive months without evidence of breakthrough bleeding or spotting, or subjects who have been using a stable regimen of another combination oral contraceptive containing EE for at least two months prior to dosing on Day 1 of Cycle 1 and willing to switch to Ortho Cyclen for the total duration of the study (approximately 78 days) c) Women must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin) within 24 hours prior to dosing on Day 1 of Cycle 1 d) Women must not be breastfeeding Exclusion Criteria: Medical History and Concurrent Diseases a) Any significant acute or chronic medical illness b) History of biliary disorders, including Gilbert's disease or Dubin-Johnson disease c) Current or recent (within 3 months of dosing on Day 1 of Cycle 1) gastrointestinal disease d) Any major surgery within 4 weeks of dosing on Day 1 of Cycle 1 e) Any gastrointestinal surgery (including cholecystectomy) that could impact upon the absorption of study drug f) Donation of > 400 mL to a blood bank or in a clinical study (except a screening visit) within 8 weeks of dosing on Day 1 of Cycle 1 g) Blood transfusion within 4 weeks of dosing on Day 1 of Cycle 1 h) Inability to tolerate oral medication i) Inability to be venipunctured and/or tolerate venous access j) Smokers (those who currently smoke, as well as those who have stopped smoking less than 6 months prior to dosing on Day 1 of Cycle 1) k) Recent (within 6 months of dosing on Day 1 of Cycle 1) drug or alcohol abuse as defined in Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM IV), Diagnostic Criteria for Drug and Alcohol Abuse l) Any other sound medical, psychiatric, and/or social reason as determined by the investigator

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1: NGMN/EE + BMS-955176<br>Cycle 1- Active Ortho Cyclen QD on Days 1 to 21. Inert Ortho Cyclen tablets on Days 22 to 28 Cycle 2- Active Ortho Cyclen QD alone on Days 29 to 39 (11 days), followed by concomitant administration of active Ortho Cyclen QD + BMS-955176 80 mg QD on Days 40 to 49 (10 days) | Drug: BMS-955176<br> <br> Drug: Ortho Cyclen<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serial blood samples for plasma Ethinyl Estradiol and Norelgestromin determination |  | Before dosing (0 hour) through 24 hours after administration on Days 21 and 49 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum progesterone measurements |  | Day 14, 21, 35, and 42 | 
| Trough blood samples collected for BMS-955716 |  | Days 48, 49, 50 | 
| Safety assessments based on review of adverse events, vital sign measurements, electrocardiograms, physical examinations, and clinical laboratory tests. |  | Two to three months |