A Phase 1 Clinical Study to Assess the Effect of Darunavir/Ritonavir or Lopinavir/Ritonavir on the Pharmacokinetics of Daclatasvir in Healthy Subjects
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Enrollment
- 49
- Locations
- 1
- Primary Endpoint
- Maximum Observed Plasma Concentration (Cmax) for Daclatasvir
Study Overview
Brief Summary
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 Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 49 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
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
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
Arms & Interventions
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
Intervention: Darunavir (Drug)
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
Intervention: Daclatasvir (Drug)
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
Intervention: Ritonavir (Drug)
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
Intervention: Daclatasvir (Drug)
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
Intervention: Ritonavir (Drug)
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
Intervention: Lopinavir/Ritonavir (Drug)
Outcomes
Primary Outcomes
Maximum Observed Plasma Concentration (Cmax) for Daclatasvir
Time Frame: 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)
Cmax was obtained from concentration-time plot using a noncompartmental method and a validated pharmacokinetic analysis program.
Area Under the Concentration-Time Curve in 1 Dosing Interval (AUC[TAU]) for Daclatasvir
Time Frame: 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)
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.
Secondary Outcomes
- Time of Maximum Observed Plasma Concentration (Tmax) of Daclatasvir(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(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(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(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(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(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(From start of study treatment (Day 1) to study discharge (up to 15 days))
- Number of Participants With Abnormalities in Electrocardiogram (ECG) Findings(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(From start of study treatment (Day 1) to study discharge (up to 15 days))