Study Assessing the Effects of Darunavir/Ritonavir or Lopinavir/Ritonavir on the Pharmacokinetics of Daclatasvir in Healthy Participants

A Phase 1 Clinical Study to Assess the Effect of Darunavir/Ritonavir or Lopinavir/Ritonavir on the Pharmacokinetics of Daclatasvir in Healthy Subjects

The purpose of this study is to determine whether multiple doses of darunavir/ritonavir or lopinavir/ritonavir affect the pharmacokinetics of daclatasvir in healthy participants.

Study Overview

• Status: Completed
• Conditions: Hepatitis C
• Intervention / Treatment: Drug: Ritonavir; Drug: Lopinavir/Ritonavir; Drug: Daclatasvir; Drug: Darunavir

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • San Antonio, Texas, United States, 78209
      • Healthcare Discoveries, Llc D/B/A Icon Development Solutions

Participation Criteria

Eligibility Criteria

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

Description

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Key Inclusion Criteria:

• Healthy male and female participants, aged 18 to 49, as determined by medical history, physical examination, 12 lead electrocardiogram, vital signs, and clinical laboratory evaluations

Key Exclusion Criteria:

• Any significant acute or chronic medical illness; donation of blood to a blood bank or in a clinical study (except a screening visit) within 4 weeks of study drug administration (within 2 weeks for plasma only); or blood screen findings positive for hepatitis C antibody, hepatitis B surface antigen, or HIV-1 and HIV-2 antibodies

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1: Daclatasvir and Darunavir/Ritonavir; Treatment A: Daclatasvir oral tablet on specific days Treatment B: Daclatasvir tablet and Darunavir Tablet/Ritonavir capsule orally on specific days	Drug: Ritonavir; Other Names: Norvir; Drug: Daclatasvir; Other Names: BMS-790052; Drug: Darunavir; Other Names: Prezista
Experimental: Group 2: Daclatasvir and Lopinavir/Ritonavir; Treatment C: Daclatasvir oral tablet on specific days Treatment D: Daclatasvir tablet and Lopinavir/Ritonavir tablet orally on specific days	Drug: Ritonavir; Other Names: Norvir; Drug: Lopinavir/Ritonavir; Drug: Daclatasvir; Other Names: BMS-790052

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Plasma Concentration (Cmax) for Daclatasvir	Cmax was obtained from concentration-time plot using a noncompartmental method and a validated pharmacokinetic analysis program.	Predose (0 hour) on Day 2, 3 and 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24 hours on Day 4 (Period 1); Predose (0 hour) on Day 12, 13 and 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24 hour on Day 14 (Period 2)
Area Under the Concentration-Time Curve in 1 Dosing Interval (AUC[TAU]) for Daclatasvir	AUC(TAU) was the area under the curve from time zero to end of dosing interval. AUC(TAU) was obtained from concentration-time plot of daclatasvir using noncompartmental method and a validated pharmacokinetic analysis program.	Predose (0 hour) on Day 2, 3 and 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24 hours on Day 4 (Period 1); Predose (0 hour) on Day 12, 13 and 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24 hour on Day 14 (Period 2)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time of Maximum Observed Plasma Concentration (Tmax) of Daclatasvir	Tmax was obtained from concentration-time plot of daclatasvir by using non-compartmental method by a validated pharmacokinetic analysis program.	Predose (0 hour) on Day 2, 3 and 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24 hours on Day 4 (Period 1); Predose (0 hour) on Day 12, 13 and 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24 hour on Day 14 (Period 2)
Plasma Concentration Observed at 24 Hours Postdose (C24) of Daclatasvir	C24 was obtained from concentration time plot of daclatasvir by using noncompartmental method by a validated pharmacokinetic analysis program.	Predose (0 hour) on Day 2, 3 and 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24 hours on Day 4 (Period 1); Predose (0 hour) on Day 12, 13 and 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24 hour on Day 14 (Period 2)
Dose-normalized Maximum Observed Plasma Concentration (Cmax/D) and Dose-normalized Plasma Concentration Observed at 24 Hours Postdose (C24/D) of Daclatasvir	Cmax/D and C24/D are obtained from concentration-time plot of daclatasvir by using noncompartmental method by a validated pharmacokinetic analysis program.	Predose (0 hour) on Day 2, 3 and 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24 hours on Day 4 (Period 1); Predose (0 hour) on Day 12, 13 and 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24 hour on Day 14 (Period 2)
Dose-normalized Area Under the Concentration-Time Curve in 1 Dosing Interval (AUC[TAU]/D) of Daclatasvir	AUC(TAU)/D was obtained from concentration-time plot of daclatasvir by using noncompartmental method by a validated pharmacokinetic analysis program.	Predose (0 hour) on Day 2, 3 and 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24 hours on Day 4 (Period 1); Predose (0 hour) on Day 12, 13 and 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24 hour on Day 14 (Period 2)
Number of Participants With Serious Adverse Events (SAEs) and Discontinuations Due to Adverse Events (AEs) and Who Died	AE was defined as any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship with treatment. SAE was defined as a medical event that at any dose resulted in death, persistent or significant disability/incapacity, or drug dependency/abuse; was life threatening, an important medical event, or a congenital anomaly/birth defect; or required or prolonged hospitalization.	From start of study treatment (Day 1) to study discharge for AEs (up to 15 days); Day 1 to 30 days after last dose of study treatment for SAEs (up to 44 days)
Number of Participants With Abnormalities in Vital Sign Measurements	Criteria for abnormalities in vital sign measurements: Diastolic blood pressure: Value >90 and change from baseline > 0 or value < 55 and change from baseline <-10. Systolic blood pressure: Value >140 and change from baseline >20 or value <90 and change from baseline <-20. Heart rate: Value >100 and change from baseline >30 or value <55 and change from baseline <-15. Respiration: Value >16 or change from baseline >10. Temperature: Value >38.3°C or change from baseline >1.6°C.	From start of study treatment (Day 1) to study discharge (up to 15 days)
Number of Participants With Abnormalities in Electrocardiogram (ECG) Findings	Abnormalities in ECG findings included: PR ≥210 msec, QRS ≥120 msec, QT ≥500 msec, QTcF ≥450 msec, and second- or third-degree heart block.	From start of study treatment (Day 1) to study discharge (up to 15 days)
Number of Participants With Marked Abnormalities in Hematology Laboratory Test Results	Criteria for marked abnormalities in test results: Platelet count >1.5*upper limits of normal (ULN) value, >1.5*ULN if pretreatment (PreRx) value is missing, <0.85*lower limit of normal (LLN) if PreRx ≥LLN, <0.85*LLN if PreRx is missing, <0.85*PreRx if PreRx <LLN. Leukocytes >1.2*ULN if LLN ≤PreRx ≤ULN, >1.2*ULN if PreRx is missing, >1.5*PreRx if PreRx >ULN, >ULN if PreRx <LLN, <0.85*PreRx if PreRx <LLN, <0.9*LLN if LLN ≤PreRx ≤ULN, <0.9*LLN if PreRx is missing and <LLN if PreRx >ULN. Lymphocytes >7.5*10^3 c/uL and <0.75*10^3 c/uL. Neutrophils <0.85*PreRx if PreRx <1.5*ULN, <1.5*ULN if PreRx ≥1.5*ULN and <1.5*ULN if PreRx is missing.	From start of study treatment (Day 1) to study discharge (up to 15 days)
Number of Participants With Abnormalities in Urinalysis and Other Chemistry Testing Results	Criteria for marked abnormalities on laboratory test results: urinary dipstick blood: ≥2 if pretreatment (PreRx) <1, ≥2 if PreRx is missing or ≥2*PreRx if PreRx ≥1. Urinary microscopic red blood cell (RBC): ≥2 if PreRx <2, ≥2 if PreRx is missing or ≥4 if PreRx ≥2. Urinary microscopic white blood cell (WBC): ≥2 if PreRx <2, ≥2 if PreRx is missing or ≥4 if PreRx ≥2. Lactate dehydrogenase >1.25*upper limit of normal (ULN) if PreRx ≤ULN, >1.25*ULN if PreRx is missing and >1.5*PreRx if PreRx >ULN.	From start of study treatment (Day 1) to study discharge (up to 15 days)

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS clinical trial educational resource

Study record dates

Study Major Dates

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

Study Registration Dates

• First Submitted: June 6, 2014
• First Submitted That Met QC Criteria: June 6, 2014
• First Posted (Estimate): June 9, 2014

Study Record Updates

• Last Update Posted (Estimate): November 30, 2015
• Last Update Submitted That Met QC Criteria: October 29, 2015
• Last Verified: October 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; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Ritonavir; Lopinavir; Darunavir
• Other Study ID Numbers: AI444-093