Trial Outcomes & Findings for Study Assessing the Effects of Darunavir/Ritonavir or Lopinavir/Ritonavir on the Pharmacokinetics of Daclatasvir in Healthy Participants (NCT NCT02159352)
NCT ID: NCT02159352
Last Updated: 2015-11-30
Results Overview
Cmax was obtained from concentration-time plot using a noncompartmental method and a validated pharmacokinetic analysis program.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
49 participants
Primary outcome timeframe
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)
Results posted on
2015-11-30
Participant Flow
Participants were enrolled at 1 site in the United States of America.
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.
Participant milestones
| Measure |
Daclatasvir + Darunavir/Ritonavir
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.
|
Daclatasvir + Lopinavir/Ritonavir
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 Study
STARTED
|
14
|
14
|
|
Overall Study
Phase 1 (Day 1- 4)
|
14
|
14
|
|
Overall Study
Phase 2 (Day 5-14)
|
11
|
12
|
|
Overall Study
COMPLETED
|
11
|
12
|
|
Overall Study
NOT COMPLETED
|
3
|
2
|
Reasons for withdrawal
| Measure |
Daclatasvir + Darunavir/Ritonavir
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.
|
Daclatasvir + Lopinavir/Ritonavir
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 Study
Adverse Event
|
3
|
1
|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
Baseline Characteristics
Study Assessing the Effects of Darunavir/Ritonavir or Lopinavir/Ritonavir on the Pharmacokinetics of Daclatasvir in Healthy Participants
Baseline characteristics by cohort
| Measure |
Daclatasvir + Darunavir/Ritonavir
n=14 Participants
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.
|
Daclatasvir + Lopinavir/Ritonavir
n=14 Participants
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
n=28 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Customized
Between 18 and 65 years
|
14 participants
n=5 Participants
|
14 participants
n=7 Participants
|
28 participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
9 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
19 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 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)Population: All treated participants with adequate pharmacokinetic profiles.
Cmax was obtained from concentration-time plot using a noncompartmental method and a validated pharmacokinetic analysis program.
Outcome measures
| Measure |
Group 2: Daclatasvir (30 mg) + Lopinavir/Ritonavir
n=13 Participants
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.
|
Group 1: Daclatasvir (60 mg)
n=14 Participants
Participants received a 60-mg daclatasvir tablet once daily on Days 1 through 4.
|
Group 1: Daclatasvir (30 mg) + Darunavir/Ritonavir
n=11 Participants
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.
|
Group 2: Daclatasvir (60 mg)
n=14 Participants
Participants received 60 mg of daclatasvir tablet once daily from Day 1 through 4.
|
|---|---|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) for Daclatasvir
|
476 ng/mL
Geometric Coefficient of Variation 21
|
1335 ng/mL
Geometric Coefficient of Variation 38
|
493 ng/mL
Geometric Coefficient of Variation 36
|
1412 ng/mL
Geometric Coefficient of Variation 28
|
PRIMARY outcome
Timeframe: 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)Population: All treated participants with adequate pharmacokinetic profiles. Number of participants analyzed (N) signifies number of participants evaluable for this outcome measure.
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.
Outcome measures
| Measure |
Group 2: Daclatasvir (30 mg) + Lopinavir/Ritonavir
n=12 Participants
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.
|
Group 1: Daclatasvir (60 mg)
n=14 Participants
Participants received a 60-mg daclatasvir tablet once daily on Days 1 through 4.
|
Group 1: Daclatasvir (30 mg) + Darunavir/Ritonavir
n=11 Participants
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.
|
Group 2: Daclatasvir (60 mg)
n=14 Participants
Participants received 60 mg of daclatasvir tablet once daily from Day 1 through 4.
|
|---|---|---|---|---|
|
Area Under the Concentration-Time Curve in 1 Dosing Interval (AUC[TAU]) for Daclatasvir
|
7855 ng*h/mL
Geometric Coefficient of Variation 23
|
12677 ng*h/mL
Geometric Coefficient of Variation 41
|
8295 ng*h/mL
Geometric Coefficient of Variation 39
|
13799 ng*h/mL
Geometric Coefficient of Variation 26
|
SECONDARY outcome
Timeframe: 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)Population: All treated participants with adequate pharmacokinetic profile. Here, N signifies number of participants evaluable for this outcome measure.
Tmax was obtained from concentration-time plot of daclatasvir by using non-compartmental method by a validated pharmacokinetic analysis program.
Outcome measures
| Measure |
Group 2: Daclatasvir (30 mg) + Lopinavir/Ritonavir
n=13 Participants
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.
|
Group 1: Daclatasvir (60 mg)
n=14 Participants
Participants received a 60-mg daclatasvir tablet once daily on Days 1 through 4.
|
Group 1: Daclatasvir (30 mg) + Darunavir/Ritonavir
n=11 Participants
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.
|
Group 2: Daclatasvir (60 mg)
n=14 Participants
Participants received 60 mg of daclatasvir tablet once daily from Day 1 through 4.
|
|---|---|---|---|---|
|
Time of Maximum Observed Plasma Concentration (Tmax) of Daclatasvir
|
2.00 hours
Interval 1.0 to 11.93
|
2.00 hours
Interval 1.0 to 6.0
|
3.00 hours
Interval 1.0 to 6.0
|
2.00 hours
Interval 1.0 to 6.0
|
SECONDARY outcome
Timeframe: 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)Population: All treated participants with adequate pharmacokinetic profile. Here, N signifies number of participants evaluable for this outcome measure.
C24 was obtained from concentration time plot of daclatasvir by using noncompartmental method by a validated pharmacokinetic analysis program.
Outcome measures
| Measure |
Group 2: Daclatasvir (30 mg) + Lopinavir/Ritonavir
n=12 Participants
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.
|
Group 1: Daclatasvir (60 mg)
n=14 Participants
Participants received a 60-mg daclatasvir tablet once daily on Days 1 through 4.
|
Group 1: Daclatasvir (30 mg) + Darunavir/Ritonavir
n=11 Participants
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.
|
Group 2: Daclatasvir (60 mg)
n=14 Participants
Participants received 60 mg of daclatasvir tablet once daily from Day 1 through 4.
|
|---|---|---|---|---|
|
Plasma Concentration Observed at 24 Hours Postdose (C24) of Daclatasvir
|
280 ng/mL
Geometric Coefficient of Variation 29
|
225 ng/mL
Geometric Coefficient of Variation 54
|
250 ng/mL
Geometric Coefficient of Variation 45
|
225 ng/mL
Geometric Coefficient of Variation 36
|
SECONDARY outcome
Timeframe: 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)Population: All treated participants with adequate pharmacokinetic profile.
Cmax/D and C24/D are obtained from concentration-time plot of daclatasvir by using noncompartmental method by a validated pharmacokinetic analysis program.
Outcome measures
| Measure |
Group 2: Daclatasvir (30 mg) + Lopinavir/Ritonavir
n=13 Participants
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.
|
Group 1: Daclatasvir (60 mg)
n=14 Participants
Participants received a 60-mg daclatasvir tablet once daily on Days 1 through 4.
|
Group 1: Daclatasvir (30 mg) + Darunavir/Ritonavir
n=11 Participants
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.
|
Group 2: Daclatasvir (60 mg)
n=14 Participants
Participants received 60 mg of daclatasvir tablet once daily from Day 1 through 4.
|
|---|---|---|---|---|
|
Dose-normalized Maximum Observed Plasma Concentration (Cmax/D) and Dose-normalized Plasma Concentration Observed at 24 Hours Postdose (C24/D) of Daclatasvir
Cmax/D
|
15.9 ng/mL/mg
Geometric Coefficient of Variation 21
|
22.2 ng/mL/mg
Geometric Coefficient of Variation 38
|
16.4 ng/mL/mg
Geometric Coefficient of Variation 36
|
23.5 ng/mL/mg
Geometric Coefficient of Variation 28
|
|
Dose-normalized Maximum Observed Plasma Concentration (Cmax/D) and Dose-normalized Plasma Concentration Observed at 24 Hours Postdose (C24/D) of Daclatasvir
C24/D
|
9.33 ng/mL/mg
Geometric Coefficient of Variation 29
|
3.75 ng/mL/mg
Geometric Coefficient of Variation 54
|
8.34 ng/mL/mg
Geometric Coefficient of Variation 45
|
3.76 ng/mL/mg
Geometric Coefficient of Variation 36
|
SECONDARY outcome
Timeframe: 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)Population: All treated participants with adequate pharmacokinetic profile. Here, N signifies number of participants evaluable for this outcome measure.
AUC(TAU)/D was obtained from concentration-time plot of daclatasvir by using noncompartmental method by a validated pharmacokinetic analysis program.
Outcome measures
| Measure |
Group 2: Daclatasvir (30 mg) + Lopinavir/Ritonavir
n=12 Participants
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.
|
Group 1: Daclatasvir (60 mg)
n=14 Participants
Participants received a 60-mg daclatasvir tablet once daily on Days 1 through 4.
|
Group 1: Daclatasvir (30 mg) + Darunavir/Ritonavir
n=11 Participants
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.
|
Group 2: Daclatasvir (60 mg)
n=14 Participants
Participants received 60 mg of daclatasvir tablet once daily from Day 1 through 4.
|
|---|---|---|---|---|
|
Dose-normalized Area Under the Concentration-Time Curve in 1 Dosing Interval (AUC[TAU]/D) of Daclatasvir
|
262 (ng*h/mL)/mg
Geometric Coefficient of Variation 23
|
211 (ng*h/mL)/mg
Geometric Coefficient of Variation 41
|
276 (ng*h/mL)/mg
Geometric Coefficient of Variation 39
|
230 (ng*h/mL)/mg
Geometric Coefficient of Variation 26
|
SECONDARY outcome
Timeframe: 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)Population: All participants who received at least 1 dose of study drug
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.
Outcome measures
| Measure |
Group 2: Daclatasvir (30 mg) + Lopinavir/Ritonavir
n=14 Participants
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.
|
Group 1: Daclatasvir (60 mg)
n=14 Participants
Participants received a 60-mg daclatasvir tablet once daily on Days 1 through 4.
|
Group 1: Daclatasvir (30 mg) + Darunavir/Ritonavir
n=14 Participants
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.
|
Group 2: Daclatasvir (60 mg)
n=14 Participants
Participants received 60 mg of daclatasvir tablet once daily from Day 1 through 4.
|
|---|---|---|---|---|
|
Number of Participants With Serious Adverse Events (SAEs) and Discontinuations Due to Adverse Events (AEs) and Who Died
Death
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Serious Adverse Events (SAEs) and Discontinuations Due to Adverse Events (AEs) and Who Died
SAE
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Serious Adverse Events (SAEs) and Discontinuations Due to Adverse Events (AEs) and Who Died
Discontinued due to AEs
|
1 participants
|
0 participants
|
3 participants
|
0 participants
|
SECONDARY outcome
Timeframe: From start of study treatment (Day 1) to study discharge (up to 15 days)Population: Participants who received at least 1 dose of study drug
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.
Outcome measures
| Measure |
Group 2: Daclatasvir (30 mg) + Lopinavir/Ritonavir
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.
|
Group 1: Daclatasvir (60 mg)
n=14 Participants
Participants received a 60-mg daclatasvir tablet once daily on Days 1 through 4.
|
Group 1: Daclatasvir (30 mg) + Darunavir/Ritonavir
n=14 Participants
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.
|
Group 2: Daclatasvir (60 mg)
Participants received 60 mg of daclatasvir tablet once daily from Day 1 through 4.
|
|---|---|---|---|---|
|
Number of Participants With Abnormalities in Vital Sign Measurements
|
—
|
3 participants
|
2 participants
|
—
|
SECONDARY outcome
Timeframe: From start of study treatment (Day 1) to study discharge (up to 15 days)Population: All participants who received at least 1 dose of study drug
Abnormalities in ECG findings included: PR ≥210 msec, QRS ≥120 msec, QT ≥500 msec, QTcF ≥450 msec, and second- or third-degree heart block.
Outcome measures
| Measure |
Group 2: Daclatasvir (30 mg) + Lopinavir/Ritonavir
n=14 Participants
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.
|
Group 1: Daclatasvir (60 mg)
n=14 Participants
Participants received a 60-mg daclatasvir tablet once daily on Days 1 through 4.
|
Group 1: Daclatasvir (30 mg) + Darunavir/Ritonavir
n=14 Participants
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.
|
Group 2: Daclatasvir (60 mg)
n=14 Participants
Participants received 60 mg of daclatasvir tablet once daily from Day 1 through 4.
|
|---|---|---|---|---|
|
Number of Participants With Abnormalities in Electrocardiogram (ECG) Findings
PR >210
|
1 participants
|
2 participants
|
4 participants
|
0 participants
|
|
Number of Participants With Abnormalities in Electrocardiogram (ECG) Findings
QRS >120
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Abnormalities in Electrocardiogram (ECG) Findings
QT >500
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Abnormalities in Electrocardiogram (ECG) Findings
QTcF >450
|
0 participants
|
0 participants
|
1 participants
|
0 participants
|
SECONDARY outcome
Timeframe: From start of study treatment (Day 1) to study discharge (up to 15 days)Population: All treated participants.
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.
Outcome measures
| Measure |
Group 2: Daclatasvir (30 mg) + Lopinavir/Ritonavir
n=14 Participants
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.
|
Group 1: Daclatasvir (60 mg)
n=14 Participants
Participants received a 60-mg daclatasvir tablet once daily on Days 1 through 4.
|
Group 1: Daclatasvir (30 mg) + Darunavir/Ritonavir
n=14 Participants
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.
|
Group 2: Daclatasvir (60 mg)
n=14 Participants
Participants received 60 mg of daclatasvir tablet once daily from Day 1 through 4.
|
|---|---|---|---|---|
|
Number of Participants With Marked Abnormalities in Hematology Laboratory Test Results
Platelet Count
|
0 participants
|
1 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Marked Abnormalities in Hematology Laboratory Test Results
Leukocytes
|
1 participants
|
0 participants
|
1 participants
|
1 participants
|
|
Number of Participants With Marked Abnormalities in Hematology Laboratory Test Results
Neutrophils (absolute)
|
0 participants
|
0 participants
|
2 participants
|
1 participants
|
|
Number of Participants With Marked Abnormalities in Hematology Laboratory Test Results
Lymphocytes (absolute)
|
0 participants
|
0 participants
|
1 participants
|
0 participants
|
SECONDARY outcome
Timeframe: From start of study treatment (Day 1) to study discharge (up to 15 days)Population: All treated participants.
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.
Outcome measures
| Measure |
Group 2: Daclatasvir (30 mg) + Lopinavir/Ritonavir
n=14 Participants
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.
|
Group 1: Daclatasvir (60 mg)
n=14 Participants
Participants received a 60-mg daclatasvir tablet once daily on Days 1 through 4.
|
Group 1: Daclatasvir (30 mg) + Darunavir/Ritonavir
n=14 Participants
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.
|
Group 2: Daclatasvir (60 mg)
n=14 Participants
Participants received 60 mg of daclatasvir tablet once daily from Day 1 through 4.
|
|---|---|---|---|---|
|
Number of Participants With Abnormalities in Urinalysis and Other Chemistry Testing Results
Blood, urine
|
0 participants
|
2 participants
|
1 participants
|
1 participants
|
|
Number of Participants With Abnormalities in Urinalysis and Other Chemistry Testing Results
RBC, urine
|
0 participants
|
1 participants
|
1 participants
|
0 participants
|
|
Number of Participants With Abnormalities in Urinalysis and Other Chemistry Testing Results
WBC, urine
|
0 participants
|
1 participants
|
3 participants
|
0 participants
|
|
Number of Participants With Abnormalities in Urinalysis and Other Chemistry Testing Results
Lactate dehydrogenase
|
1 participants
|
2 participants
|
2 participants
|
1 participants
|
Adverse Events
Group 1: Total
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Group 1: Daclatasvir (60 mg)
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Group 1: Daclatasvir (30 mg) + Darunavir/Ritonavir
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Group 2: Total
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
Group 2: Daclatasvir (60 mg)
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Group 2: Daclatasvir (30 mg) + Lopinavir/Ritonavir
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Group 1: Total
n=14 participants at risk
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.
|
Group 1: Daclatasvir (60 mg)
n=14 participants at risk
Participants received a 60-mg daclatasvir tablet once daily on Days 1 through 4.
|
Group 1: Daclatasvir (30 mg) + Darunavir/Ritonavir
n=14 participants at risk
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.
|
Group 2: Total
n=14 participants at risk
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.
|
Group 2: Daclatasvir (60 mg)
n=14 participants at risk
Participants received a 60-mg daclatasvir tablet once daily on Days 1 through 4.
|
Group 2: Daclatasvir (30 mg) + Lopinavir/Ritonavir
n=14 participants at risk
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.
|
|---|---|---|---|---|---|---|
|
Investigations
Electrocardiogram PR prolongation
|
7.1%
1/14 • 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)
|
0.00%
0/14 • 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)
|
7.1%
1/14 • 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)
|
0.00%
0/14 • 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)
|
0.00%
0/14 • 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)
|
0.00%
0/14 • 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)
|
|
General disorders
Chest discomfort
|
0.00%
0/14 • 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)
|
0.00%
0/14 • 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)
|
0.00%
0/14 • 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)
|
7.1%
1/14 • 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)
|
0.00%
0/14 • 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)
|
7.1%
1/14 • 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)
|
|
Injury, poisoning and procedural complications
Soft tissue injury
|
0.00%
0/14 • 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)
|
0.00%
0/14 • 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)
|
0.00%
0/14 • 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)
|
7.1%
1/14 • 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)
|
0.00%
0/14 • 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)
|
7.1%
1/14 • 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)
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/14 • 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)
|
0.00%
0/14 • 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)
|
0.00%
0/14 • 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)
|
7.1%
1/14 • 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)
|
7.1%
1/14 • 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)
|
0.00%
0/14 • 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)
|
|
Gastrointestinal disorders
Diarrhoea
|
14.3%
2/14 • 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)
|
0.00%
0/14 • 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)
|
14.3%
2/14 • 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)
|
35.7%
5/14 • 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)
|
0.00%
0/14 • 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)
|
35.7%
5/14 • 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)
|
|
Nervous system disorders
Presyncope
|
0.00%
0/14 • 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)
|
0.00%
0/14 • 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)
|
0.00%
0/14 • 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)
|
7.1%
1/14 • 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)
|
0.00%
0/14 • 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)
|
7.1%
1/14 • 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)
|
|
Skin and subcutaneous tissue disorders
Rash
|
7.1%
1/14 • 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)
|
0.00%
0/14 • 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)
|
7.1%
1/14 • 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)
|
0.00%
0/14 • 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)
|
0.00%
0/14 • 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)
|
0.00%
0/14 • 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)
|
|
Eye disorders
Vitreous floaters
|
7.1%
1/14 • 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)
|
7.1%
1/14 • 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)
|
0.00%
0/14 • 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)
|
0.00%
0/14 • 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)
|
0.00%
0/14 • 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)
|
0.00%
0/14 • 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)
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/14 • 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)
|
0.00%
0/14 • 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)
|
0.00%
0/14 • 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)
|
7.1%
1/14 • 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)
|
0.00%
0/14 • 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)
|
7.1%
1/14 • 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)
|
|
Skin and subcutaneous tissue disorders
Drug eruption
|
14.3%
2/14 • 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)
|
0.00%
0/14 • 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)
|
14.3%
2/14 • 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)
|
7.1%
1/14 • 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)
|
0.00%
0/14 • 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)
|
7.1%
1/14 • 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)
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/14 • 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)
|
0.00%
0/14 • 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)
|
0.00%
0/14 • 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)
|
28.6%
4/14 • 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)
|
14.3%
2/14 • 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)
|
14.3%
2/14 • 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)
|
|
Nervous system disorders
Headache
|
7.1%
1/14 • 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)
|
0.00%
0/14 • 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)
|
7.1%
1/14 • 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)
|
21.4%
3/14 • 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)
|
14.3%
2/14 • 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)
|
7.1%
1/14 • 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)
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.00%
0/14 • 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)
|
0.00%
0/14 • 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)
|
0.00%
0/14 • 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)
|
14.3%
2/14 • 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)
|
7.1%
1/14 • 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)
|
7.1%
1/14 • 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)
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/14 • 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)
|
0.00%
0/14 • 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)
|
0.00%
0/14 • 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)
|
7.1%
1/14 • 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)
|
0.00%
0/14 • 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)
|
7.1%
1/14 • 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)
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER