Study of Combined Oral Contraceptive Effects in Female Subjects

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

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

Study Overview

• Status: Completed
• Conditions: Infection, Human Immunodeficiency Virus
• Intervention / Treatment: Drug: BMS-955176; Drug: Ortho Cyclen

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Signed Written Informed Consent a) The signed informed consent form

2. 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

3. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Arm 1: NGMN/EE + BMS-955176; 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; Drug: Ortho Cyclen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: ViiV Healthcare
• Collaborators: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 2, 2014
• Primary Completion (ACTUAL): August 25, 2014
• Study Completion (ACTUAL): August 25, 2014

Study Registration Dates

• First Submitted: June 2, 2014
• First Submitted That Met QC Criteria: June 4, 2014
• First Posted (ESTIMATE): June 6, 2014

Study Record Updates

• Last Update Posted (ACTUAL): April 17, 2018
• Last Update Submitted That Met QC Criteria: April 13, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral, Combined; Contraceptives, Oral; Contraceptive Agents, Female; Moxifloxacin; Norgestimate, ethinyl estradiol drug combination; BMS-955176
• Other Study ID Numbers: 206293; AI468-041 (OTHER: Bristol-Myers Squibb)