A Bioequivalence Study of Daclatasvir Tablets and Bioavailability Studies of Daclatasvir and Asunaprevir

A Bioequivalence Study of the 90-mg Daclatasvir Tablet Relative to the 3 × 30-mg Daclatasvir Phase 3 Tablets, and Relative Bioavailability Studies of Chewable Pediatric Tablets of Daclatasvir and Asunaprevir in Healthy Adult Subjects

Grps 1, 2, 3 "This study will be testing the performance of ASV and DCV pediatric chewable tablets.

Grp #4 The purpose of this group is to support the marketing authorization of a DCV 90-mg tablet

Study Overview

• Status: Completed
• Conditions: Hepatitis C Infection
• Intervention / Treatment: Drug: Daclatasvir; Drug: Daclatasvir; Drug: Daclatasvir; Drug: Asunaprevir

• Study Type: Interventional
• Enrollment (Actual): 88
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 49 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Signed Written Informed Consent must be obtained from the subjects in accordance with requirements of the study center's Institutional review Board (IRB)/ Institutional Ethics Committee (IEC)
2. Target Population: Healthy subjects as determined by no clinically significant deviation from normal in medical history, physical examination, ECGs, and clinical laboratory determinations.
3. Age and Reproductive Status : Males and females, ages 18 to 49 years, inclusive. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 24 hours prior to the start of study drug and must be using an acceptable method of contraception for 4 weeks prior to study drug administration. Women must not be breastfeeding.

Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for duration of treatment with study drug females must still undergo pregnancy testing as described in this section.

Exclusion Criteria:

1. Medical History and Concurrent Diseases : Any significant acute or chronic medical illness. Current or recent (within 3 months of study drug administration) gastrointestinal disease that could impact upon the absorption of study drug. Any major surgery within 4 weeks of study drug administration. Any gastrointestinal surgery that could impact upon the absorption of study drug (appendectomies with no complications are allowed at the investigator's discretion). Inability to tolerate oral medication, smokers or recent durg or alcohol abuse and Any other sound medical, psychiatric, and/or social reason as determined by the investigator.
2. Physical and Laboratory Test Findings: Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs, ECG, or clinical laboratory determinations beyond what is consistent with the target population, positive urine screen for drugs, positive blood screen for hepatitis C antibody, hepatitis B surface antigen, or HIV-1, -2 antibodies.
3. Allergies and Adverse Drug Reaction : History of allergy to DCV, ASV, Hepatitis C virus (HCV) NS3 protease inhibitors, HCV NS5A replication cofactors, or related compounds.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1: Daclatasvir; Single oral dose of Daclatasvir (DCV) tablet and single oral dose of DCV pediatric chewable tablet	Drug: Daclatasvir; Treatment A= single oral dose of Daclatasvir (DCV) tablet and Treatment B= single oral dose of DCV pediatric chewable tablet; Drug: Daclatasvir; Treatment C= single oral dose of Daclatasvir (DCV) pediatric chewable tablet and Treatment D= single oral dose of DCV pediatric chewable tablet; Drug: Daclatasvir; Treatment H= single oral dose of Daclatasvir (DCV) tablet and Treatment I= single oral dose of DCV tablets
Experimental: Group 2: Daclatasvir; Single oral dose of Daclatasvir (DCV) pediatric chewable tablet and single oral dose of DCV pediatric chewable tablet	Drug: Daclatasvir; Treatment A= single oral dose of Daclatasvir (DCV) tablet and Treatment B= single oral dose of DCV pediatric chewable tablet; Drug: Daclatasvir; Treatment C= single oral dose of Daclatasvir (DCV) pediatric chewable tablet and Treatment D= single oral dose of DCV pediatric chewable tablet; Drug: Daclatasvir; Treatment H= single oral dose of Daclatasvir (DCV) tablet and Treatment I= single oral dose of DCV tablets
Experimental: Group 3: Asunaprevir; Single oral dose of Asunaprevir (ASV) tablet, single oral dose of ASV pediatric chewable tablet and single oral dose of ASV pediatric chewable tablets	Drug: Asunaprevir; Treatment E= single oral dose of Asunaprevir (ASV) tablet and Treatment F= single oral dose of ASV pediatric chewable tablet and Treatment G= single oral dose of of ASV pediatric chewable tablet
Experimental: Group 4: Daclatasvir; Single oral dose of Daclatasvir (DCV) tablet and single oral dose of DCV tablets	Drug: Daclatasvir; Treatment A= single oral dose of Daclatasvir (DCV) tablet and Treatment B= single oral dose of DCV pediatric chewable tablet; Drug: Daclatasvir; Treatment C= single oral dose of Daclatasvir (DCV) pediatric chewable tablet and Treatment D= single oral dose of DCV pediatric chewable tablet; Drug: Daclatasvir; Treatment H= single oral dose of Daclatasvir (DCV) tablet and Treatment I= single oral dose of DCV tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum observed plasma concentration [Cmax]	Before dosing through 96 hours
Area under the concentration-time curve [AUC] from time zero extrapolated to infinite time [AUC(INF)]	Before dosing through 96 hours
AUC from time zero to the time of last quantifiable concentration [AUC(0-T)]	Before dosing through 96 hours
Time of maximum observed plasma concentration [Tmax]	Before dosing through 96 hours
Terminal plasma half life [T-HALF])	Before dosing through 96 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Event reports	Safety assessments based on review of adverse events, vital sign measurements, electrocardiograms, physical examinations, and clinical laboratory tests.	30 days after last dose
Vital sign measurements		30 days after last dose
ECGs		30 days after last dose
Physical examinations		30 days after last dose
Clinical laboratory tests		30 days after last dose
The incidence of reported AEs will be tabulated and reviewed for potential significance and clinical importance.		30 days after last dose

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb
• Investigators: Principal Investigator: Rebecca N Wood-Horrall, MD, PPD

Study record dates

Study Major Dates

• Study Start: December 1, 2014
• Primary Completion (Actual): February 1, 2015
• Study Completion (Actual): February 1, 2015

Study Registration Dates

• First Submitted: December 9, 2014
• First Submitted That Met QC Criteria: December 18, 2014
• First Posted (Estimate): December 23, 2014

Study Record Updates

• Last Update Posted (Estimate): February 24, 2015
• Last Update Submitted That Met QC Criteria: February 23, 2015
• Last Verified: December 1, 2014

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; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Asunaprevir
• Other Study ID Numbers: AI447-111