Study of Drug Combination on Pharmacokinetics in Healthy Volunteers

Effect of a Combination of Daclatasvir, Asunaprevir, and BMS-791325 on the Pharmacokinetics of Selective Serotonin Reuptake Inhibitors in Healthy Subjects

The purpose of this study is to assess the effect of Daclatasvir, Asunaprevir, and BMS-791325 on the pharmacokinetics of selective serotonin reuptake inhibitors.

Study Overview

• Status: Completed
• Conditions: Hepatitis C Infection
• Intervention / Treatment: Drug: Sertraline; Drug: DCV 3DAA FDC; Drug: BMS-791325; Drug: Escitalopram

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Signed Informed Consent Form

   a) Signed written informed consent must be obtained from the subjects in accordance with requirements of the study center's IRB or IEC before the initiation of any protocol-required procedures.

2. Target Population

   a) Healthy subjects as determined by no clinically significant deviation from normal in medical history, psychiatric history, physical examination findings, vital sign measurements, 12-lead ECG measurements, physical measurements, and clinical laboratory test results.

3. Age and Reproductive Status

   1. Males and females, ages 25 to 55 years, inclusive.
   2. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of study drug.
   3. Women must not be breastfeeding.

Exclusion Criteria:

1. Any significant acute or chronic medical illness.
2. Current or recent (within 3 months of study drug administration) gastrointestinal disease that could impact upon the absorption of study drug (appendectomies with no complications are allowed at the investigator's discretion).
3. Any major surgery within 4 weeks of study drug administration.
4. Smokers (those who currently smoke, as well as those who have stopped smoking less than 6 months prior to the start of study drug administration).
5. 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: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 2; Sertraline (50 milligrams each morning) day 1-7, DCV 3DAA FDC + 75 mg BMS-791325 twice daily days 13 to 22, DCV 3DAA FDC + 75 mg BMS-791325 twice daily + Sertraline (50 milligrams each morning) days 23-29	Drug: Sertraline; 50 milligrams administered each morning; Other Names: Zoloft; Drug: DCV 3DAA FDC; Fixed dose combination (daclatasvir [DCV] 30 milligrams, asunaprevir [ASV] 200 milligrams, and BMS-791325 75 milligrams) one tablet administered twice daily; Drug: BMS-791325; 75 milligrams single-agent film coated oral tablet administered twice daily
Experimental: Cohort 1; Escitalopram (10 milligrams each morning) day 1-7, DCV 3DAA FDC + 75 mg BMS-791325 twice daily days 13 to 22, DCV 3DAA FDC + 75 mg BMS-791325 twice daily + Escitalopram (10 milligrams each morning) days 23-29	Drug: DCV 3DAA FDC; Fixed dose combination (daclatasvir [DCV] 30 milligrams, asunaprevir [ASV] 200 milligrams, and BMS-791325 75 milligrams) one tablet administered twice daily; Drug: BMS-791325; 75 milligrams single-agent film coated oral tablet administered twice daily; Drug: Escitalopram; 10 milligrams administered each morning; Other Names: Lexapro

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Serial blood samples for plasma SSRI (selective serotonin reuptake inhibitor) of escitalopram or sertraline	Before dosing (0 hour) through 24 hours after SSRI administration on day 7 and day 29
Serial blood samples for determination of plasma concentrations of DCV (daclatasvir), ASV (asunaprevir), BMS-791325, and the metabolite BMS-794712	Before dosing (0 hour) through 12 hours after SSRI administration on day 22 and day 29

Secondary Outcome Measures

Outcome Measure	Time Frame
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: Bristol-Myers Squibb
• Investigators: Principal Investigator: Ikenna Ogbaa, MD, PPD

Study record dates

Study Major Dates

• Study Start: June 1, 2014
• Primary Completion (Actual): August 1, 2014

Study Registration Dates

• First Submitted: June 24, 2014
• First Submitted That Met QC Criteria: June 24, 2014
• First Posted (Estimate): June 26, 2014

Study Record Updates

• Last Update Posted (Estimate): February 10, 2015
• Last Update Submitted That Met QC Criteria: February 9, 2015
• Last Verified: February 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Hepatitis; Hepatitis C; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Antidepressive Agents, Second-Generation; Sertraline; Citalopram
• Other Study ID Numbers: AI443-116