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

Hepatitis C Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02159352
• Other study ID #: AI444-093
• Status: Completed
• Phase: Phase 1
• First received: June 6, 2014
• Last updated: October 29, 2015
• Start date: June 2014
• Est. completion date: July 2014

Study information

• Verified date: October 2015
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: July 2014
• Est. primary completion date: July 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 49 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Hepatitis C

Intervention

Drug:
• Daclatasvir

• Darunavir

• Ritonavir

• Lopinavir/Ritonavir

Locations

Country	Name	City	State
United States	Healthcare Discoveries, Llc D/B/A Icon Development Solutions	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	No
Primary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	Yes
Secondary	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)	Yes
Secondary	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)	Yes
Secondary	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	From start of study treatment (Day 1) to study discharge (up to 15 days)	Yes
Secondary	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)	Yes

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