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Trial record 93 of 243 for:    "Viral Infectious Disease" | "Lopinavir"

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

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label)
Condition Hepatitis C
Interventions Drug: Daclatasvir
Drug: Darunavir
Drug: Ritonavir
Drug: Lopinavir/Ritonavir
Enrollment 49
Recruitment Details Participants were enrolled at 1 site in the United States of America.
Pre-assignment Details Of 49 participants enrolled, 28 were randomized to receive treatment. Of the 21 who were not randomized, 16 no longer met study criteria and 5 discontinued due to other reasons.
Arm/Group Title Daclatasvir + Darunavir/Ritonavir Daclatasvir + Lopinavir/Ritonavir
Hide Arm/Group Description Participants received a 60-mg daclatasvir tablet once daily on Days 1 through 4 and a 30-mg daclatasvir tablet once daily, along with an 800-mg darunavir tablet and a 100-mg ritonavir capsule once daily on Days 5 through 14. Participants received a 60-mg daclatasvir tablet once daily on Days 1 through 4 and a 30-mg daclatasvir tablet once daily, along with 2 200-mg lopinavir/50-mg ritonavir tablets twice daily on Days 5 through 14.
Period Title: Overall Study
Started 14 14
Phase 1 (Day 1- 4) 14 14
Phase 2 (Day 5-14) 11 12
Completed 11 12
Not Completed 3 2
Reason Not Completed
Adverse Event             3             1
Withdrawal by Subject             0             1
Arm/Group Title Daclatasvir + Darunavir/Ritonavir Daclatasvir + Lopinavir/Ritonavir Total
Hide Arm/Group Description Participants received a 60-mg daclatasvir tablet once daily on Days 1 through 4 and a 30-mg daclatasvir tablet once daily, along with an 800-mg darunavir tablet and a 100-mg ritonavir capsule once daily on Days 5 through 14. Participants received a 60-mg daclatasvir tablet once daily on Days 1 through 4 and a 30-mg daclatasvir tablet once daily, along with 2 200-mg lopinavir/50-mg ritonavir tablets twice daily on Days 5 through 14. Total of all reporting groups
Overall Number of Baseline Participants 14 14 28
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Between 18 and 65 years Number Analyzed 14 participants 14 participants 28 participants
14 14 28
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 14 participants 14 participants 28 participants
Female
5
  35.7%
4
  28.6%
9
  32.1%
Male
9
  64.3%
10
  71.4%
19
  67.9%
1.Primary Outcome
Title Maximum Observed Plasma Concentration (Cmax) for Daclatasvir
Hide Description Cmax was obtained from concentration-time plot using a noncompartmental method and a validated pharmacokinetic analysis program.
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)
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants with adequate pharmacokinetic profiles.
Arm/Group Title Group 1: Daclatasvir (60 mg) Group 1: Daclatasvir (30 mg) + Darunavir/Ritonavir Group 2: Daclatasvir (60 mg) Group 2: Daclatasvir (30 mg) + Lopinavir/Ritonavir
Hide Arm/Group Description:
Participants received a 60-mg daclatasvir tablet once daily on Days 1 through 4.
Participants received a 30-mg daclatasvir tablet once daily, along with an 800-mg darunavir tablet, and a 100-mg ritonavir capsule once daily on Days 5 through 14.
Participants received a 60-mg daclatasvir tablet once daily on Days 5 through 14.
Participants received a 30-mg daclatasvir tablet once daily along with 2 200-mg lopinavir/50-mg ritonavir tablets twice daily Days 5 through 14.
Overall Number of Participants Analyzed 14 11 14 13
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
1335
(38%)
493
(36%)
1412
(28%)
476
(21%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group 1: Daclatasvir (60 mg), Group 1: Daclatasvir (30 mg) + Darunavir/Ritonavir
Comments A general linear mixed effect model (restricted maximum likelihood) with treatment as fixed effect and measurements within each participant as repeated measures was fitted to the log-transformed Cmax.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Geometric Mean Ratio
Estimated Value 0.384
Confidence Interval (2-Sided) 90%
0.348 to 0.423
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Group 2: Daclatasvir (60 mg), Group 2: Daclatasvir (30 mg) + Lopinavir/Ritonavir
Comments A general linear mixed effect model (restricted maximum likelihood) with treatment as fixed effect and measurements within each participant as repeated measures was fitted to the log-transformed Cmax.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Geometric Mean Ratio
Estimated Value 0.337
Confidence Interval (2-Sided) 90%
0.306 to 0.371
Estimation Comments [Not Specified]
2.Primary Outcome
Title Area Under the Concentration-Time Curve in 1 Dosing Interval (AUC[TAU]) for Daclatasvir
Hide Description 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.
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)
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants with adequate pharmacokinetic profiles. Number of participants analyzed (N) signifies number of participants evaluable for this outcome measure.
Arm/Group Title Daclatasvir (60 mg) Days 1-4 Daclatasvir (30 mg) + Darunavir/Ritonavir Days 5-14 Daclatasvir (60 mg) Days 5-14 Daclatasvir (30 mg) + Lopinavir/Ritonavir Days 5-14
Hide Arm/Group Description:
Participants received a 60-mg daclatasvir tablet once daily on Days 1 through 4.
Participants received a 30-mg daclatasvir tablet once daily along with an 800-mg darunavir tablet and a 100-mg ritonavir capsule once daily on Days 5 through 14.
Participants received a 60-mg daclatasvir tablet once daily on Days 5 through 14.
Participants received a 30-mg daclatasvir tablet once daily along with 2 200-mg lopinavir/50-mg ritonavir tablets twice daily Days 5 through 14.
Overall Number of Participants Analyzed 14 11 14 12
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*h/mL
12677
(41%)
8295
(39%)
13799
(26%)
7855
(23%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Daclatasvir (60 mg) Days 1-4, Daclatasvir (30 mg) + Darunavir/Ritonavir Days 5-14
Comments A general linear mixed effect model (restricted maximum likelihood) with treatment as fixed effect and measurements within each participant as repeated measures was fitted to the log-transformed AUC(TAU).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Geometric Mean Ratio
Estimated Value 0.703
Confidence Interval (2-Sided) 90%
0.658 to 0.750
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Daclatasvir (60 mg) Days 5-14, Daclatasvir (30 mg) + Lopinavir/Ritonavir Days 5-14
Comments A general linear mixed effect model (restricted maximum likelihood) with treatment as fixed effect and measurements within each participant as repeated measures was fitted to the log-transformed AUC(TAU).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Geometric Mean Ratio
Estimated Value 0.577
Confidence Interval (2-Sided) 90%
0.535 to 0.622
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Time of Maximum Observed Plasma Concentration (Tmax) of Daclatasvir
Hide Description Tmax was obtained from concentration-time plot of daclatasvir by using non-compartmental method by a validated pharmacokinetic analysis program.
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)
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants with adequate pharmacokinetic profile. Here, N signifies number of participants evaluable for this outcome measure.
Arm/Group Title Group 1: Daclatasvir (60 mg) Group 1: Daclatasvir (30 mg) + Darunavir/Ritonavir Group 2: Daclatasvir (60 mg) Group 2: Daclatasvir (30 mg) + Lopinavir/Ritonavir
Hide Arm/Group Description:
Participants received a 60-mg daclatasvir tablet once daily on Days 1 through 4.
Participants received a 30-mg daclatasvir tablet once daily along with an 800-mg darunavir tablet and a 100-mg ritonavir capsule once daily on Days 5 through 14.
Participants received a 60-mg daclatasvir tablet once daily on Days 1 through 4.
Participants received a 30-mg daclatasvir tablet once daily along with 2 200-mg lopinavir/50-mg ritonavir tablets twice daily on Days 5 through 14.
Overall Number of Participants Analyzed 14 11 14 13
Median (Full Range)
Unit of Measure: hours
2.00
(1.00 to 6.00)
3.00
(1.00 to 6.00)
2.00
(1.00 to 6.00)
2.00
(1.00 to 11.93)
4.Secondary Outcome
Title Plasma Concentration Observed at 24 Hours Postdose (C24) of Daclatasvir
Hide Description C24 was obtained from concentration time plot of daclatasvir by using noncompartmental method by a validated pharmacokinetic analysis program.
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)
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants with adequate pharmacokinetic profile. Here, N signifies number of participants evaluable for this outcome measure.
Arm/Group Title Group 1: Daclatasvir (60 mg) Group 1: Daclatasvir (30 mg) + Darunavir/Ritonavir Group 2: Daclatasvir (60 mg) Group 2: Daclatasvir (30 mg) + Lopinavir/Ritonavir
Hide Arm/Group Description:
Participants received a 60-mg daclatasvir tablet once daily on Days 1 through 4.
Participants received a 30-mg daclatasvir tablet once daily along with an 800-mg darunavir tablet and a 100-mg ritonavir capsule once daily on Days 5 through 14.
Participants received 60 mg of daclatasvir tablet once daily from Day 1 through 4.
Participants received a 30-mg daclatasvir tablet once daily along with 2 200-mg lopinavir/50-mg ritonavir tablets twice daily on Days 5 through 14.
Overall Number of Participants Analyzed 14 11 14 12
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
225
(54%)
250
(45%)
225
(36%)
280
(29%)
5.Secondary Outcome
Title Dose-normalized Maximum Observed Plasma Concentration (Cmax/D) and Dose-normalized Plasma Concentration Observed at 24 Hours Postdose (C24/D) of Daclatasvir
Hide Description Cmax/D and C24/D are obtained from concentration-time plot of daclatasvir by using noncompartmental method by a validated pharmacokinetic analysis program.
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)
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants with adequate pharmacokinetic profile.
Arm/Group Title Group 1: Daclatasvir (60 mg) Group 1: Daclatasvir (30 mg) + Darunavir/Ritonavir Group 2: Daclatasvir (60 mg) Group 2: Daclatasvir (30 mg) + Lopinavir/Ritonavir
Hide Arm/Group Description:
Participants received a 60-mg daclatasvir tablet once daily on Days 1 through 4.
Participants received a 30-mg daclatasvir tablet once daily along with an 800-mg darunavir tablet and a 100-mg ritonavir capsule once daily on Days 5 through 14.
Participants received 60 mg of daclatasvir tablet once daily from Day 1 through 4.
Participants received a 30-mg daclatasvir tablet once daily along with 2 200-mg lopinavir/ 50-mg ritonavir tablets twice daily on Days 5 through 14.
Overall Number of Participants Analyzed 14 11 14 13
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL/mg
Cmax/D
22.2
(38%)
16.4
(36%)
23.5
(28%)
15.9
(21%)
C24/D
3.75
(54%)
8.34
(45%)
3.76
(36%)
9.33
(29%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group 1: Daclatasvir (60 mg), Group 1: Daclatasvir (30 mg) + Darunavir/Ritonavir
Comments A general linear mixed effect model (restricted maximum likelihood) with treatment as fixed effect and measurements within each participant as repeated measures was fitted to the log-transformed Cmax/D.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Geometric Mean Ratio
Estimated Value 0.768
Confidence Interval (2-Sided) 90%
0.697 to 0.846
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Group 2: Daclatasvir (60 mg), Group 2: Daclatasvir (30 mg) + Lopinavir/Ritonavir
Comments A general linear mixed effect model (restricted maximum likelihood) with treatment as fixed effect and measurements within each participant as repeated measures was fitted to the log-transformed Cmax/D.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Geometric Mean Ratio
Estimated Value 0.673
Confidence Interval (2-Sided) 90%
0.611 to 0.742
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Dose-normalized Area Under the Concentration-Time Curve in 1 Dosing Interval (AUC[TAU]/D) of Daclatasvir
Hide Description AUC(TAU)/D was obtained from concentration-time plot of daclatasvir by using noncompartmental method by a validated pharmacokinetic analysis program.
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)
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants with adequate pharmacokinetic profile. Here, N signifies number of participants evaluable for this outcome measure.
Arm/Group Title Group 1: Daclatasvir (60 mg) Group 1: Daclatasvir (30 mg) + Darunavir/Ritonavir Group 2: Daclatasvir (60 mg) Group 2: Daclatasvir (30 mg) + Lopinavir/Ritonavir
Hide Arm/Group Description:
Participants received a 60-mg daclatasvir tablet once daily on Days 1 through 4.
Participants received a 30-mg daclatasvir tablet once daily along with an 800-mg darunavir tablet and a 100-mg ritonavir capsule once daily on Days 5 through 14.
Participants received a 60-mg daclatasvir tablet once daily on Days 1 through 4.
Participants received a 30-mg daclatasvir tablet once daily along with 2 200-mg lopinavir/50-mg ritonavir tablets twice daily on Days 5 through 14.
Overall Number of Participants Analyzed 14 11 14 12
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: (ng*h/mL)/mg
211
(41%)
276
(39%)
230
(26%)
262
(23%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group 1: Daclatasvir (60 mg), Group 1: Daclatasvir (30 mg) + Darunavir/Ritonavir
Comments A general linear mixed effect model (restricted maximum likelihood) with treatment as fixed effect and measurements within each participant as repeated measures was fitted to the log-transformed (AUC(TAU)/D).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Geometric Mean Ratio
Estimated Value 1.406
Confidence Interval (2-Sided) 90%
1.317 to 1.501
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Group 2: Daclatasvir (60 mg), Group 2: Daclatasvir (30 mg) + Lopinavir/Ritonavir
Comments A general linear mixed effect model (restricted maximum likelihood) with treatment as fixed effect and measurements within each participant as repeated measures was fitted to the log-transformed (AUC(TAU)/D).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Geometric Mean Ratio
Estimated Value 1.154
Confidence Interval (2-Sided) 90%
1.070 to 1.244
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Number of Participants With Serious Adverse Events (SAEs) and Discontinuations Due to Adverse Events (AEs) and Who Died
Hide Description 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.
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)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose of study drug
Arm/Group Title Group 1: Daclatasvir (60 mg) Group 1: Daclatasvir (30 mg) + Darunavir/Ritonavir Group 2: Daclatasvir (60 mg) Group 2: Daclatasvir (30 mg) + Lopinavir/Ritonavir
Hide Arm/Group Description:
Participants received a 60-mg daclatasvir tablet once daily on Days 1 through 4.
Participants received a 30-mg daclatasvir tablet once daily along with an 800-mg darunavir tablet and a 100-mg ritonavir capsule once daily on Days 5 through 14.
Participants received a 60-mg daclatasvir tablet once daily on Days 1 through 4.
Participants received a 30-mg daclatasvir tablet once daily along with 2 -mg lopinavir/50-mg ritonavir tablets twice daily on Days 5 through 14.
Overall Number of Participants Analyzed 14 14 14 14
Measure Type: Number
Unit of Measure: participants
SAE 0 0 0 0
Discontinued due to AEs 0 3 0 1
Death 0 0 0 0
8.Secondary Outcome
Title Number of Participants With Abnormalities in Vital Sign Measurements
Hide Description 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.
Time Frame From start of study treatment (Day 1) to study discharge (up to 15 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study drug
Arm/Group Title Group 1: Daclatasvir + Darunavir/Ritonavir Group 2: Daclatasvir + Lopinavir/Ritonavir
Hide Arm/Group Description:
Participants received a 60-mg daclatasvir tablet once daily on Days 1 through 4 and a 30-mg daclatasvir tablet once daily along with an 800-mg darunavir tablet and a 100-mg ritonavir capsule once daily on Days 5 through 14.
Participants received a 60-mg daclatasvir tablet once daily on Days 1 through 4 and a 30-mg daclatasvir tablet once daily, along with 2 200-mg lopinavir/50-mg ritonavir tablets twice daily on Days 5 through 14.
Overall Number of Participants Analyzed 14 14
Measure Type: Number
Unit of Measure: participants
3 2
9.Secondary Outcome
Title Number of Participants With Abnormalities in Electrocardiogram (ECG) Findings
Hide Description Abnormalities in ECG findings included: PR ≥210 msec, QRS ≥120 msec, QT ≥500 msec, QTcF ≥450 msec, and second- or third-degree heart block.
Time Frame From start of study treatment (Day 1) to study discharge (up to 15 days)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose of study drug
Arm/Group Title Group 1: Daclatasvir (60 mg) Group 1: Daclatasvir (30 mg) + Darunavir/Ritonavir Group 2: Daclatasvir (60 mg) Group 2: Daclatasvir (30 mg) + Lopinavir/Ritonavir
Hide Arm/Group Description:
Participants received a 60-mg daclatasvir tablet once daily on Days 1 through 4.
Participants received a 30-mg daclatasvir tablet once daily along with an 800-mg darunavir tablet and 100-mg ritonavir capsule once daily on Days 5 through 14.
Participants received a 60-mg daclatasvir tablet once daily on Days 1 through 4.
Participants received a 30-mg daclatasvir tablet once daily along with 2 200-mg lopinavir/ 50-mg ritonavir tablets twice daily on Days 5 through 14.
Overall Number of Participants Analyzed 14 14 14 14
Measure Type: Number
Unit of Measure: participants
PR >210 2 4 0 1
QRS >120 0 0 0 0
QT >500 0 0 0 0
QTcF >450 0 1 0 0
10.Secondary Outcome
Title Number of Participants With Marked Abnormalities in Hematology Laboratory Test Results
Hide Description 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.
Time Frame From start of study treatment (Day 1) to study discharge (up to 15 days)
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants.
Arm/Group Title Group 1: Daclatasvir (60 mg) Group 1: Daclatasvir (30 mg) + Darunavir/Ritonavir Group 2: Daclatasvir (60 mg) Group 2: Daclatasvir (30 mg) + Lopinavir/Ritonavir
Hide Arm/Group Description:
Participants received a 60-mg daclatasvir tablet once daily on Days 1 through 4.
Participants received a 30-mg daclatasvir tablet once daily along with an 800-mg darunavir tablet and a 100-mg ritonavir capsule once daily on Days 5 through 14.
Participants received a 60-mg daclatasvir tablet once daily on Days 1 through 4.
Participants received a 30-mg daclatasvir tablet once daily along with 2 200-mg lopinavir/ 50-mg ritonavir tablets twice daily on Days 5 through 14.
Overall Number of Participants Analyzed 14 14 14 14
Measure Type: Number
Unit of Measure: participants
Platelet Count 1 0 0 0
Leukocytes 0 1 1 1
Neutrophils (absolute) 0 2 1 0
Lymphocytes (absolute) 0 1 0 0
11.Secondary Outcome
Title Number of Participants With Abnormalities in Urinalysis and Other Chemistry Testing Results
Hide Description 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.
Time Frame From start of study treatment (Day 1) to study discharge (up to 15 days)
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants.
Arm/Group Title Group 1: Daclatasvir (60 mg) Group 1: Daclatasvir (30 mg) + Darunavir/Ritonavir Group 2: Daclatasvir (60 mg) Group 2: Daclatasvir (30 mg) + Lopinavir/Ritonavir
Hide Arm/Group Description:
Participants received a 60-mg daclatasvir tablet once daily on Days 1 through 4.
Participants received a 30-mg daclatasvir tablet once daily along with an 800-mg darunavir tablet and a 100-mg ritonavir capsule once daily on Days 5 through 14.
Participants received a 60-mg daclatasvir tablet once daily on Days 1 through 4.
Participants received a 30-mg daclatasvir tablet once daily along with 2 200-mg lopinavir/50-mg ritonavir tablets twice daily on Days 5 through 14.
Overall Number of Participants Analyzed 14 14 14 14
Measure Type: Number
Unit of Measure: participants
Blood, urine 2 1 1 0
RBC, urine 1 1 0 0
WBC, urine 1 3 0 0
Lactate dehydrogenase 2 2 1 1
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)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Group 1: Total Group 1: Daclatasvir (60 mg) Group 1: Daclatasvir (30 mg) + Darunavir/Ritonavir Group 2: Total Group 2: Daclatasvir (60 mg) Group 2: Daclatasvir (30 mg) + Lopinavir/Ritonavir
Hide Arm/Group Description Participants received a 60-mg daclatasvir tablet once daily on Days 1 through 4 and 30 mg daclatasvir tablet once daily along with an 800-mg darunavir tablet and a 100-mg of ritonavir capsule once daily on Days 5 through 14. Participants received a 60-mg daclatasvir tablet once daily on Days 1 through 4. Participants received a 30-mg daclatasvir tablet once daily along with an 800-mg darunavir tablet and a 100-mg of ritonavir capsule once daily on Days 5 through 14. Participants received a 60-mg daclatasvir tablet once daily on Days 1 through 4 and a 30-mg daclatasvir tablet once daily along with an 800-mg darunavir tablet and a 100­-mg ritonavir capsule once daily on Days 5 through 14. Participants received a 60-mg daclatasvir tablet once daily on Days 1 through 4. Participants received a 30-mg daclatasvir tablet once daily along with 2 200-mg lopinavir/ 50-mg ritonavir tablets twice daily on Days 5 through 14.
All-Cause Mortality
Group 1: Total Group 1: Daclatasvir (60 mg) Group 1: Daclatasvir (30 mg) + Darunavir/Ritonavir Group 2: Total Group 2: Daclatasvir (60 mg) Group 2: Daclatasvir (30 mg) + Lopinavir/Ritonavir
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Group 1: Total Group 1: Daclatasvir (60 mg) Group 1: Daclatasvir (30 mg) + Darunavir/Ritonavir Group 2: Total Group 2: Daclatasvir (60 mg) Group 2: Daclatasvir (30 mg) + Lopinavir/Ritonavir
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/14 (0.00%)   0/14 (0.00%)   0/14 (0.00%)   0/14 (0.00%)   0/14 (0.00%)   0/14 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Group 1: Total Group 1: Daclatasvir (60 mg) Group 1: Daclatasvir (30 mg) + Darunavir/Ritonavir Group 2: Total Group 2: Daclatasvir (60 mg) Group 2: Daclatasvir (30 mg) + Lopinavir/Ritonavir
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   6/14 (42.86%)   1/14 (7.14%)   6/14 (42.86%)   8/14 (57.14%)   3/14 (21.43%)   8/14 (57.14%) 
Eye disorders             
Vitreous floaters  1  1/14 (7.14%)  1/14 (7.14%)  0/14 (0.00%)  0/14 (0.00%)  0/14 (0.00%)  0/14 (0.00%) 
Gastrointestinal disorders             
Diarrhoea  1  2/14 (14.29%)  0/14 (0.00%)  2/14 (14.29%)  5/14 (35.71%)  0/14 (0.00%)  5/14 (35.71%) 
Constipation  1  0/14 (0.00%)  0/14 (0.00%)  0/14 (0.00%)  1/14 (7.14%)  0/14 (0.00%)  1/14 (7.14%) 
Nausea  1  0/14 (0.00%)  0/14 (0.00%)  0/14 (0.00%)  4/14 (28.57%)  2/14 (14.29%)  2/14 (14.29%) 
Dyspepsia  1  0/14 (0.00%)  0/14 (0.00%)  0/14 (0.00%)  1/14 (7.14%)  0/14 (0.00%)  1/14 (7.14%) 
General disorders             
Chest discomfort  1  0/14 (0.00%)  0/14 (0.00%)  0/14 (0.00%)  1/14 (7.14%)  0/14 (0.00%)  1/14 (7.14%) 
Injury, poisoning and procedural complications             
Soft tissue injury  1  0/14 (0.00%)  0/14 (0.00%)  0/14 (0.00%)  1/14 (7.14%)  0/14 (0.00%)  1/14 (7.14%) 
Investigations             
Electrocardiogram PR prolongation  1  1/14 (7.14%)  0/14 (0.00%)  1/14 (7.14%)  0/14 (0.00%)  0/14 (0.00%)  0/14 (0.00%) 
Metabolism and nutrition disorders             
Decreased appetite  1  0/14 (0.00%)  0/14 (0.00%)  0/14 (0.00%)  2/14 (14.29%)  1/14 (7.14%)  1/14 (7.14%) 
Nervous system disorders             
Presyncope  1  0/14 (0.00%)  0/14 (0.00%)  0/14 (0.00%)  1/14 (7.14%)  0/14 (0.00%)  1/14 (7.14%) 
Headache  1  1/14 (7.14%)  0/14 (0.00%)  1/14 (7.14%)  3/14 (21.43%)  2/14 (14.29%)  1/14 (7.14%) 
Respiratory, thoracic and mediastinal disorders             
Cough  1  0/14 (0.00%)  0/14 (0.00%)  0/14 (0.00%)  1/14 (7.14%)  1/14 (7.14%)  0/14 (0.00%) 
Skin and subcutaneous tissue disorders             
Rash  1  1/14 (7.14%)  0/14 (0.00%)  1/14 (7.14%)  0/14 (0.00%)  0/14 (0.00%)  0/14 (0.00%) 
Drug eruption  1  2/14 (14.29%)  0/14 (0.00%)  2/14 (14.29%)  1/14 (7.14%)  0/14 (0.00%)  1/14 (7.14%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial’s primary publication.
Results Point of Contact
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Name/Title: Bristol-Myers Squibb Study Director
Organization: Bristol-Myers Squibb
EMail: Clinical.Trials@bms.com
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Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT02159352     History of Changes
Other Study ID Numbers: AI444-093
First Submitted: June 6, 2014
First Posted: June 9, 2014
Results First Submitted: August 21, 2015
Results First Posted: November 30, 2015
Last Update Posted: November 30, 2015