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

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ClinicalTrials.gov Identifier: NCT02159352
Recruitment Status : Completed
First Posted : June 9, 2014
Results First Posted : November 30, 2015
Last Update Posted : November 30, 2015
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb

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.

Condition or disease Intervention/treatment Phase
Hepatitis C Drug: Daclatasvir Drug: Darunavir Drug: Ritonavir Drug: Lopinavir/Ritonavir Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 49 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Official Title: A Phase 1 Clinical Study to Assess the Effect of Darunavir/Ritonavir or Lopinavir/Ritonavir on the Pharmacokinetics of Daclatasvir in Healthy Subjects
Study Start Date : June 2014
Actual Primary Completion Date : July 2014
Actual Study Completion Date : July 2014

Resource links provided by the National Library of Medicine


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: Daclatasvir
Other Name: BMS-790052

Drug: Darunavir
Other Name: Prezista

Drug: Ritonavir
Other Name: Norvir

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: Daclatasvir
Other Name: BMS-790052

Drug: Ritonavir
Other Name: Norvir

Drug: Lopinavir/Ritonavir



Primary Outcome Measures :
  1. 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.

  2. 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 Outcome Measures :
  1. Time of Maximum Observed Plasma Concentration (Tmax) of 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) ]
    Tmax was obtained from concentration-time plot of daclatasvir by using non-compartmental method by a validated pharmacokinetic analysis program.

  2. Plasma Concentration Observed at 24 Hours Postdose (C24) of 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) ]
    C24 was obtained from concentration time plot of daclatasvir by using noncompartmental method by a validated pharmacokinetic analysis program.

  3. Dose-normalized Maximum Observed Plasma Concentration (Cmax/D) and Dose-normalized Plasma Concentration Observed at 24 Hours Postdose (C24/D) of 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/D and C24/D are obtained from concentration-time plot of daclatasvir by using noncompartmental method by a validated pharmacokinetic analysis program.

  4. Dose-normalized Area Under the Concentration-Time Curve in 1 Dosing Interval (AUC[TAU]/D) of 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)/D was obtained from concentration-time plot of daclatasvir by using noncompartmental method by a validated pharmacokinetic analysis program.

  5. Number of Participants With Serious Adverse Events (SAEs) and Discontinuations Due to Adverse Events (AEs) and Who Died [ Time Frame: 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) ]
    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.

  6. Number of Participants With Abnormalities in Vital Sign Measurements [ Time Frame: From start of study treatment (Day 1) to study discharge (up to 15 days) ]
    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.

  7. Number of Participants With Abnormalities in Electrocardiogram (ECG) Findings [ Time Frame: From start of study treatment (Day 1) to study discharge (up to 15 days) ]
    Abnormalities in ECG findings included: PR ≥210 msec, QRS ≥120 msec, QT ≥500 msec, QTcF ≥450 msec, and second- or third-degree heart block.

  8. Number of Participants With Marked Abnormalities in Hematology Laboratory Test Results [ Time Frame: From start of study treatment (Day 1) to study discharge (up to 15 days) ]
    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.

  9. Number of Participants With Abnormalities in Urinalysis and Other Chemistry Testing Results [ Time Frame: From start of study treatment (Day 1) to study discharge (up to 15 days) ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 49 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02159352


Locations
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United States, Texas
Healthcare Discoveries, Llc D/B/A Icon Development Solutions
San Antonio, Texas, United States, 78209
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
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Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
Additional Information:
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Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT02159352    
Other Study ID Numbers: AI444-093
First Posted: June 9, 2014    Key Record Dates
Results First Posted: November 30, 2015
Last Update Posted: November 30, 2015
Last Verified: October 2015
Additional relevant MeSH terms:
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Hepatitis C
Hepatitis
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Flaviviridae Infections
RNA Virus Infections
Ritonavir
Lopinavir
Darunavir
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors