Trial Outcomes & Findings for A Single Ascending Dose Study of Daclatasvir (BMS-790052) in Hepatitis C Virus Infected Subjects (NCT NCT00546715)

NCT ID: NCT00546715

Last Updated: 2015-11-18

Results Overview

AEs were defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding) or disease which either occurs during study, whether or not related to the study drug. SAEs were defined as any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgement of investigators represent significant hazards.

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 95 participants
• Primary outcome timeframe: Day 1 up to Day 7 for non-SAEs and Day 1 to 30 days after study discontinuation for SAEs
• Results posted on: 2015-11-18

Participant Flow

The study was conducted at 7 centers in United States.

A total of 95 participants were enrolled, of which 18 received treatment. Remaining 77 participants were not randomized (participants either no longer met study criteria by the time of randomization or were no longer needed as an adequate number of study participants had already been dosed in each dose panel).

Participant milestones

Measure	Daclatasvir-1 mg Participants received single dose of daclatasvir 1 mg as oral solution at concentration of 1 mg/mL daily, after fasting for at least 10 hours pre-dose and 4 hours post-dose.	Daclatasvir-10 mg Participants received single dose of daclatasvir 10 mg as oral solution at concentration of 1 mg/mL daily, after fasting for at least 10 hours pre-dose and 4 hours post-dose.	Daclatasvir-100 mg Participants received single dose of daclatasvir 100 mg as oral solution at concentration of 50 mg/mL daily, after fasting for at least 10 hours pre-dose and 4 hours post-dose.	Placebo Participants received single dose of placebo matched to daclatasvir daily, after fasting for at least 10 hours pre-dose and 4 hours post-dose.
Overall Study STARTED	6	5	5	2
Overall Study COMPLETED	6	4	5	2
Overall Study NOT COMPLETED	0	1	0	0

Reasons for withdrawal

Measure	Daclatasvir-1 mg Participants received single dose of daclatasvir 1 mg as oral solution at concentration of 1 mg/mL daily, after fasting for at least 10 hours pre-dose and 4 hours post-dose.	Daclatasvir-10 mg Participants received single dose of daclatasvir 10 mg as oral solution at concentration of 1 mg/mL daily, after fasting for at least 10 hours pre-dose and 4 hours post-dose.	Daclatasvir-100 mg Participants received single dose of daclatasvir 100 mg as oral solution at concentration of 50 mg/mL daily, after fasting for at least 10 hours pre-dose and 4 hours post-dose.	Placebo Participants received single dose of placebo matched to daclatasvir daily, after fasting for at least 10 hours pre-dose and 4 hours post-dose.
Overall Study Withdrawal by Subject	0	1	0	0

Baseline Characteristics

A Single Ascending Dose Study of Daclatasvir (BMS-790052) in Hepatitis C Virus Infected Subjects

Baseline characteristics by cohort

Measure	Daclatasvir-1 mg n=6 Participants Participants received single dose of daclatasvir 1 mg as oral solution at concentration of 1 mg/mL daily, after fasting for at least 10 hours pre-dose and 4 hours post-dose.	Daclatasvir-10 mg n=5 Participants Participants received single dose of daclatasvir 10 mg as oral solution at concentration of 1 mg/mL daily, after fasting for at least 10 hours pre-dose and 4 hours post-dose.	Daclatasvir-100 mg n=5 Participants Participants received single dose of daclatasvir 100 mg as oral solution at concentration of 50 mg/mL daily, after fasting for at least 10 hours pre-dose and 4 hours post-dose.	Placebo n=2 Participants Participants received single dose of placebo matched to daclatasvir daily, after fasting for at least 10 hours pre-dose and 4 hours post-dose.	Total n=18 Participants Total of all reporting groups
Age, Continuous	43.5 years n=5 Participants	46 years n=7 Participants	44 years n=5 Participants	28 years n=4 Participants	44 years n=21 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants	0 Participants n=4 Participants	8 Participants n=21 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants	10 Participants n=21 Participants

PRIMARY outcome

Timeframe: Day 1 up to Day 7 for non-SAEs and Day 1 to 30 days after study discontinuation for SAEs

Population: Analysis was performed in safety population defined as all participants who received any study drug treatment.

AEs were defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding) or disease which either occurs during study, whether or not related to the study drug. SAEs were defined as any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgement of investigators represent significant hazards.

Outcome measures

Measure	Daclatasvir-1 mg n=6 Participants Participants received single dose of daclatasvir 1 mg as oral solution at concentration of 1 mg/mL daily, after fasting for at least 10 hours pre-dose and 4 hours post-dose.	Daclatasvir-10 mg n=5 Participants Participants received single dose of daclatasvir 10 mg as oral solution at concentration of 1 mg/mL daily, after fasting for at least 10 hours pre-dose and 4 hours post-dose.	Daclatasvir-100 mg n=5 Participants Participants received single dose of daclatasvir 100 mg as oral solution at concentration of 50 mg/mL daily, after fasting for at least 10 hours pre-dose and 4 hours post-dose.	Placebo n=2 Participants Participants received single dose of placebo matched to daclatasvir daily, after fasting for at least 10 hours pre-dose and 4 hours post-dose.
Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs) and Who Died SAEs	0 participants	0 participants	0 participants	0 participants
Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs) and Who Died Discontinuations due to AEs	0 participants	0 participants	0 participants	0 participants
Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs) and Who Died Death	0 participants	0 participants	0 participants	0 participants

PRIMARY outcome

Timeframe: Day 1 up to Day 7 or Discharge

Population: The analysis was performed in the safety population.

Participants were assessed by investigator for any clinically significant changes in vital parameters like body temperature, respiratory rate, blood pressure, heart rate and weight. The assessment was performed by a calibrated sphygmomanometer and thermometer for blood pressure and temperature, respectively. Blood pressure and heart rate were measured after at least 5 minutes quiet seating of the subject. Weight was measured at the discharge. The criteria for clinically significant change was as per the investigators discretion.

Outcome measures

Measure	Daclatasvir-1 mg n=6 Participants Participants received single dose of daclatasvir 1 mg as oral solution at concentration of 1 mg/mL daily, after fasting for at least 10 hours pre-dose and 4 hours post-dose.	Daclatasvir-10 mg n=5 Participants Participants received single dose of daclatasvir 10 mg as oral solution at concentration of 1 mg/mL daily, after fasting for at least 10 hours pre-dose and 4 hours post-dose.	Daclatasvir-100 mg n=5 Participants Participants received single dose of daclatasvir 100 mg as oral solution at concentration of 50 mg/mL daily, after fasting for at least 10 hours pre-dose and 4 hours post-dose.	Placebo n=2 Participants Participants received single dose of placebo matched to daclatasvir daily, after fasting for at least 10 hours pre-dose and 4 hours post-dose.
Number of Participants With Clinically Significant Change From Baseline in Vital Sign Measurements and Physical Examination Findings Systolic blood pressure	0 participants	0 participants	0 participants	0 participants
Number of Participants With Clinically Significant Change From Baseline in Vital Sign Measurements and Physical Examination Findings Diastolic blood pressure	0 participants	0 participants	0 participants	0 participants
Number of Participants With Clinically Significant Change From Baseline in Vital Sign Measurements and Physical Examination Findings Pulse rate	0 participants	0 participants	0 participants	0 participants
Number of Participants With Clinically Significant Change From Baseline in Vital Sign Measurements and Physical Examination Findings Respiration rate	0 participants	0 participants	0 participants	0 participants
Number of Participants With Clinically Significant Change From Baseline in Vital Sign Measurements and Physical Examination Findings Temperature	0 participants	0 participants	0 participants	0 participants
Number of Participants With Clinically Significant Change From Baseline in Vital Sign Measurements and Physical Examination Findings Weight	0 participants	0 participants	0 participants	0 participants

PRIMARY outcome

Timeframe: Day 1 up to Day 7

Population: The analysis was performed in the safety population.

Laboratory marked abnormalities were defined as Hematocrit (low) as <0.85*pre-treatment value, Leukocytes (low) as <0.9*lower limit of normal, Aspartate Aminotransferase (high) as >1.25*upper limit of normal, Creatinine (high) as >1.33*pre-treatment value, Bicarbonate (high) as >1.2*upper limit of normal, Total Protein (high) as >1.1*upper limit of normal, Creatinine Kinase (high) as >1.5*upper limit of normal, Blood in Urine (high) as ≥ 2*upper limit of normal. Participants were fasted for at least 10 hours prior to the collection of blood specimens for clinical laboratory tests.

Outcome measures

Measure	Daclatasvir-1 mg n=6 Participants Participants received single dose of daclatasvir 1 mg as oral solution at concentration of 1 mg/mL daily, after fasting for at least 10 hours pre-dose and 4 hours post-dose.	Daclatasvir-10 mg n=5 Participants Participants received single dose of daclatasvir 10 mg as oral solution at concentration of 1 mg/mL daily, after fasting for at least 10 hours pre-dose and 4 hours post-dose.	Daclatasvir-100 mg n=5 Participants Participants received single dose of daclatasvir 100 mg as oral solution at concentration of 50 mg/mL daily, after fasting for at least 10 hours pre-dose and 4 hours post-dose.	Placebo n=2 Participants Participants received single dose of placebo matched to daclatasvir daily, after fasting for at least 10 hours pre-dose and 4 hours post-dose.
Number of Participants With Marked Abnormalities in Laboratory Findings Hematocrit (Low)	1 participants	0 participants	0 participants	0 participants
Number of Participants With Marked Abnormalities in Laboratory Findings Leukocytes (Low)	0 participants	0 participants	1 participants	0 participants
Number of Participants With Marked Abnormalities in Laboratory Findings Aspartate Aminotransferase (High)	1 participants	0 participants	0 participants	0 participants
Number of Participants With Marked Abnormalities in Laboratory Findings Total Protein (High)	1 participants	0 participants	1 participants	0 participants
Number of Participants With Marked Abnormalities in Laboratory Findings Creatinine (High)	1 participants	1 participants	1 participants	1 participants
Number of Participants With Marked Abnormalities in Laboratory Findings Bicarbonate (High)	0 participants	1 participants	0 participants	0 participants
Number of Participants With Marked Abnormalities in Laboratory Findings Creatinine Kinase (High)	1 participants	0 participants	0 participants	0 participants
Number of Participants With Marked Abnormalities in Laboratory Findings Blood in Urine (High)	0 participants	0 participants	1 participants	0 participants

SECONDARY outcome

Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 48 and 72 hours post-dosing on Day 1

Population: The analysis was performed in the pharmacokinetic (PK) set population defined as all participants who received at least single dose of daclatasvir with available valid data.

Maximum observed plasma concentration following drug administration from the raw plasma concentration-time data. C-12 and C-24 were defined as observed plasma concentration of daclatasvir at 12 hours and 24 hours, respectively. The plasma samples were analyzed for daclatasvir using a validated liquid chromatography-tandem mass spectrometric assay.

Outcome measures

Measure	Daclatasvir-1 mg n=6 Participants Participants received single dose of daclatasvir 1 mg as oral solution at concentration of 1 mg/mL daily, after fasting for at least 10 hours pre-dose and 4 hours post-dose.	Daclatasvir-10 mg n=5 Participants Participants received single dose of daclatasvir 10 mg as oral solution at concentration of 1 mg/mL daily, after fasting for at least 10 hours pre-dose and 4 hours post-dose.	Daclatasvir-100 mg n=5 Participants Participants received single dose of daclatasvir 100 mg as oral solution at concentration of 50 mg/mL daily, after fasting for at least 10 hours pre-dose and 4 hours post-dose.	Placebo Participants received single dose of placebo matched to daclatasvir daily, after fasting for at least 10 hours pre-dose and 4 hours post-dose.
Maximum Observed Plasma Concentration (Cmax) and Observed Plasma Concentration at 12 Hours (C-12) and 24 Hours (C-24) Cmax	15.7 ng/mL Geometric Coefficient of Variation 56	177.6 ng/mL Geometric Coefficient of Variation 52	2416.5 ng/mL Geometric Coefficient of Variation 27	—
Maximum Observed Plasma Concentration (Cmax) and Observed Plasma Concentration at 12 Hours (C-12) and 24 Hours (C-24) C-12	2.7 ng/mL Geometric Coefficient of Variation 49	32.2 ng/mL Geometric Coefficient of Variation 28	706.7 ng/mL Geometric Coefficient of Variation 51	—
Maximum Observed Plasma Concentration (Cmax) and Observed Plasma Concentration at 12 Hours (C-12) and 24 Hours (C-24) C-24	1.1 ng/mL Geometric Coefficient of Variation 65	14.2 ng/mL Geometric Coefficient of Variation 44	363.2 ng/mL Geometric Coefficient of Variation 55	—

SECONDARY outcome

Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 48 and 72 hours post-dosing on Day 1

Population: The analysis was performed in the PK set population.

Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration. It was calculated as the sum of linear trapezoids using non-compartmental analysis. Area under the plasma concentration-time curve from time zero extrapolated to infinite time was estimated as sum of AUC(0-T) and the extrapolated area, computed by the quotient of the last observable concentration and λ, where λ was the slopes of the terminal phases of the plasma concentration-time profiles. The plasma samples were analyzed for daclatasvir using a validated liquid chromatography-tandem mass spectrometric assay.

Outcome measures

Measure	Daclatasvir-1 mg n=6 Participants Participants received single dose of daclatasvir 1 mg as oral solution at concentration of 1 mg/mL daily, after fasting for at least 10 hours pre-dose and 4 hours post-dose.	Daclatasvir-10 mg n=5 Participants Participants received single dose of daclatasvir 10 mg as oral solution at concentration of 1 mg/mL daily, after fasting for at least 10 hours pre-dose and 4 hours post-dose.	Daclatasvir-100 mg n=5 Participants Participants received single dose of daclatasvir 100 mg as oral solution at concentration of 50 mg/mL daily, after fasting for at least 10 hours pre-dose and 4 hours post-dose.	Placebo Participants received single dose of placebo matched to daclatasvir daily, after fasting for at least 10 hours pre-dose and 4 hours post-dose.
Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUC[0-T]), Area Under the Plasma Concentration-time Curve From Time Zero (AUC[INF]) Extrapolated to Infinite Time AUC(0-T)	126.8 ng*h/mL Geometric Coefficient of Variation 49	1413.9 ng*h/mL Geometric Coefficient of Variation 45	28239.1 ng*h/mL Geometric Coefficient of Variation 48	—
Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUC[0-T]), Area Under the Plasma Concentration-time Curve From Time Zero (AUC[INF]) Extrapolated to Infinite Time AUC(0-INF)	129.1 ng*h/mL Geometric Coefficient of Variation 49	1431.1 ng*h/mL Geometric Coefficient of Variation 45	29256.1 ng*h/mL Geometric Coefficient of Variation 53	—

SECONDARY outcome

Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 48 and 72 hours post-dosing on Day 1

Population: The analysis was performed in the PK set population.

Tmax was defined as the time required to reach maximum observed plasma concentration. The plasma samples were analyzed for daclatasvir using a validated liquid chromatography-tandem mass spectrometric assay.

Outcome measures

Measure	Daclatasvir-1 mg n=6 Participants Participants received single dose of daclatasvir 1 mg as oral solution at concentration of 1 mg/mL daily, after fasting for at least 10 hours pre-dose and 4 hours post-dose.	Daclatasvir-10 mg n=5 Participants Participants received single dose of daclatasvir 10 mg as oral solution at concentration of 1 mg/mL daily, after fasting for at least 10 hours pre-dose and 4 hours post-dose.	Daclatasvir-100 mg n=5 Participants Participants received single dose of daclatasvir 100 mg as oral solution at concentration of 50 mg/mL daily, after fasting for at least 10 hours pre-dose and 4 hours post-dose.	Placebo Participants received single dose of placebo matched to daclatasvir daily, after fasting for at least 10 hours pre-dose and 4 hours post-dose.
Time to Reach Maximum Plasma Concentration (Tmax)	1 hours Interval 0.5 to 3.0	1 hours Interval 1.0 to 1.5	1.5 hours Interval 1.0 to 3.0	—

SECONDARY outcome

Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 48 and 72 hours post-dosing on Day 1

Population: The analysis was performed in the PK set population.

Plasma half-life was defined as the time required for one half of the total amount of administered drug eliminated from the body. The plasma samples were analyzed for daclatasvir using a validated liquid chromatography-tandem mass spectrometric assay.

Outcome measures

Measure	Daclatasvir-1 mg n=6 Participants Participants received single dose of daclatasvir 1 mg as oral solution at concentration of 1 mg/mL daily, after fasting for at least 10 hours pre-dose and 4 hours post-dose.	Daclatasvir-10 mg n=5 Participants Participants received single dose of daclatasvir 10 mg as oral solution at concentration of 1 mg/mL daily, after fasting for at least 10 hours pre-dose and 4 hours post-dose.	Daclatasvir-100 mg n=5 Participants Participants received single dose of daclatasvir 100 mg as oral solution at concentration of 50 mg/mL daily, after fasting for at least 10 hours pre-dose and 4 hours post-dose.	Placebo Participants received single dose of placebo matched to daclatasvir daily, after fasting for at least 10 hours pre-dose and 4 hours post-dose.
Plasma Half-life (T-half)	9.7 hours Standard Deviation 2.65	12.1 hours Standard Deviation 1.97	14.0 hours Standard Deviation 6.43	—

SECONDARY outcome

Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 48 and 72 hours post-dosing on Day 1

Population: The analysis was performed in the PK set population.

Apparent total body clearance (CLT/F) was calculated as Dose/AUC(INF), where CLT was the clearance of the drug and F was the absolute oral bioavailability. The plasma samples were analyzed for daclatasvir using a validated liquid chromatography-tandem mass spectrometric assay.

Outcome measures

Measure	Daclatasvir-1 mg n=6 Participants Participants received single dose of daclatasvir 1 mg as oral solution at concentration of 1 mg/mL daily, after fasting for at least 10 hours pre-dose and 4 hours post-dose.	Daclatasvir-10 mg n=5 Participants Participants received single dose of daclatasvir 10 mg as oral solution at concentration of 1 mg/mL daily, after fasting for at least 10 hours pre-dose and 4 hours post-dose.	Daclatasvir-100 mg n=5 Participants Participants received single dose of daclatasvir 100 mg as oral solution at concentration of 50 mg/mL daily, after fasting for at least 10 hours pre-dose and 4 hours post-dose.	Placebo Participants received single dose of placebo matched to daclatasvir daily, after fasting for at least 10 hours pre-dose and 4 hours post-dose.
Apparent Total Body Clearance (CLT/F)	129.1 mL/min Geometric Coefficient of Variation 48	116.5 mL/min Geometric Coefficient of Variation 43	57.0 mL/min Geometric Coefficient of Variation 49	—

SECONDARY outcome

Timeframe: Pre-dose, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 144 hours post-dose on Day 1

Population: The analysis was performed in the pharmacodynamic (PD) population defined as participants who received at least one dose of study medication with available valid data.

The Roche TaqMan HCV quantitative assay was used for analysis with detection limit of 10 IU/mL. Positive value indicated reduction from baseline in HCV RNA while negative value indicated an increase from baseline in HCV RNA. Baseline HCV RNA was defined as the pre-dose value on Day 1 log10 HCV RNA.

Outcome measures

Measure	Daclatasvir-1 mg n=5 Participants Participants received single dose of daclatasvir 1 mg as oral solution at concentration of 1 mg/mL daily, after fasting for at least 10 hours pre-dose and 4 hours post-dose.	Daclatasvir-10 mg n=5 Participants Participants received single dose of daclatasvir 10 mg as oral solution at concentration of 1 mg/mL daily, after fasting for at least 10 hours pre-dose and 4 hours post-dose.	Daclatasvir-100 mg n=5 Participants Participants received single dose of daclatasvir 100 mg as oral solution at concentration of 50 mg/mL daily, after fasting for at least 10 hours pre-dose and 4 hours post-dose.	Placebo n=2 Participants Participants received single dose of placebo matched to daclatasvir daily, after fasting for at least 10 hours pre-dose and 4 hours post-dose.
Decline From Baseline in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Decline From Baseline to 24 hours	2.12 log IU/mL Standard Deviation 0.57	3.24 log IU/mL Standard Deviation 0.51	3.28 log IU/mL Standard Deviation 0.35	-0.12 log IU/mL Standard Deviation 0.29
Decline From Baseline in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Maximum Decline	2.44 log IU/mL Standard Deviation 0.80	3.12 log IU/mL Standard Deviation 0.66	4.06 log IU/mL Standard Deviation 0.53	0.06 log IU/mL Standard Deviation 0.11

SECONDARY outcome

Timeframe: Pre-dose, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 144 hours post-dose on Day 1

Population: The analysis was performed in the PD population defined as participants who received at least one dose of study medication with available valid data.

Participants were assessed for time to reach maximum decrease in log10 hepatitis C virus RNA level. Baseline HCV RNA was defined as the pre-dose value on Day 1 log10 HCV RNA.

Outcome measures

Measure	Daclatasvir-1 mg n=5 Participants Participants received single dose of daclatasvir 1 mg as oral solution at concentration of 1 mg/mL daily, after fasting for at least 10 hours pre-dose and 4 hours post-dose.	Daclatasvir-10 mg n=5 Participants Participants received single dose of daclatasvir 10 mg as oral solution at concentration of 1 mg/mL daily, after fasting for at least 10 hours pre-dose and 4 hours post-dose.	Daclatasvir-100 mg n=5 Participants Participants received single dose of daclatasvir 100 mg as oral solution at concentration of 50 mg/mL daily, after fasting for at least 10 hours pre-dose and 4 hours post-dose.	Placebo n=2 Participants Participants received single dose of placebo matched to daclatasvir daily, after fasting for at least 10 hours pre-dose and 4 hours post-dose.
Time to Reach Maximum Decline in Plasma Hepatitis C Virus RNA Levels From Baseline	16.4 hours Standard Deviation 7.8	43.2 hours Standard Deviation 56.74	105.60 hours Standard Deviation 55.25	144 hours Standard Deviation 0

SECONDARY outcome

Timeframe: Baseline (Day 1), Day 7 or Discharge

Population: The analysis was performed in the safety population.

Changes in heart rate from baseline were measured after the participants were supine for at least 5 minutes. Baseline was defined as the Day 1 pre-dose measurement. The normal heart rate lies between 60-90 beats per minute (bpm), below 60 bpm and above 90 bpm were considered as bradycardia and tachycardia, respectively.

Outcome measures

Measure	Daclatasvir-1 mg n=6 Participants Participants received single dose of daclatasvir 1 mg as oral solution at concentration of 1 mg/mL daily, after fasting for at least 10 hours pre-dose and 4 hours post-dose.	Daclatasvir-10 mg n=5 Participants Participants received single dose of daclatasvir 10 mg as oral solution at concentration of 1 mg/mL daily, after fasting for at least 10 hours pre-dose and 4 hours post-dose.	Daclatasvir-100 mg n=5 Participants Participants received single dose of daclatasvir 100 mg as oral solution at concentration of 50 mg/mL daily, after fasting for at least 10 hours pre-dose and 4 hours post-dose.	Placebo n=2 Participants Participants received single dose of placebo matched to daclatasvir daily, after fasting for at least 10 hours pre-dose and 4 hours post-dose.
Change From Baseline in Heart Rate to Day 7 or Discharge	7.3 bpm Standard Deviation 16.2	7.6 bpm Standard Deviation 9.3	1.6 bpm Standard Deviation 8.5	14 bpm Standard Deviation 1.4

SECONDARY outcome

Timeframe: Baseline (Day 1), Day 7 or Discharge

Population: The analysis was performed in the safety population.

The ECG was recorded after the participant was in a supine position for at least 5 minutes. Baseline was defined as the Day 1 pre-dose measurement. The PR interval was defined as the beginning of the P wave to the beginning of the QRS complex, and represents the time taken by electrical impulse to travel from the sinus node through the atrioventricular (AV) node. The QRS complex represented the rapid depolarization of the right and left ventricles. The QT interval was defined as the time from the start of the Q wave to the end of the T wave, and represents the time taken for ventricular depolarization and repolarization. QTc was defined as corrected QT interval at a heart rate of 60 bpm. QTc was estimated using Bazett's formula and Fredericia's formula.

Outcome measures

Measure	Daclatasvir-1 mg n=6 Participants Participants received single dose of daclatasvir 1 mg as oral solution at concentration of 1 mg/mL daily, after fasting for at least 10 hours pre-dose and 4 hours post-dose.	Daclatasvir-10 mg n=5 Participants Participants received single dose of daclatasvir 10 mg as oral solution at concentration of 1 mg/mL daily, after fasting for at least 10 hours pre-dose and 4 hours post-dose.	Daclatasvir-100 mg n=5 Participants Participants received single dose of daclatasvir 100 mg as oral solution at concentration of 50 mg/mL daily, after fasting for at least 10 hours pre-dose and 4 hours post-dose.	Placebo n=2 Participants Participants received single dose of placebo matched to daclatasvir daily, after fasting for at least 10 hours pre-dose and 4 hours post-dose.
Change From Baseline in Electrocardiogram (ECG) Parameters (PR, QRS, QT, and QTc Intervals) to Day 7 or Discharge QT Interval	-27.5 msec Standard Deviation 32.7	-18.6 msec Standard Deviation 29.2	-1.2 msec Standard Deviation 27.8	-36 msec Standard Deviation 14.1
Change From Baseline in Electrocardiogram (ECG) Parameters (PR, QRS, QT, and QTc Intervals) to Day 7 or Discharge QTc Fridericia Interval	-13.3 msec Standard Deviation 10.5	-5.6 msec Standard Deviation 14.7	0.4 msec Standard Deviation 11.4	-12.5 msec Standard Deviation 19.1
Change From Baseline in Electrocardiogram (ECG) Parameters (PR, QRS, QT, and QTc Intervals) to Day 7 or Discharge QRS Width	-2.3 msec Standard Deviation 4.7	1 msec Standard Deviation 11.3	-3.6 msec Standard Deviation 8.2	0 msec Standard Deviation 0
Change From Baseline in Electrocardiogram (ECG) Parameters (PR, QRS, QT, and QTc Intervals) to Day 7 or Discharge QTc Bazett Interval	-5.5 msec Standard Deviation 21.0	1.2 msec Standard Deviation 12.7	1.8 msec Standard Deviation 7.2	1 msec Standard Deviation 21.2
Change From Baseline in Electrocardiogram (ECG) Parameters (PR, QRS, QT, and QTc Intervals) to Day 7 or Discharge PR Interval	-6.7 msec Standard Deviation 9.9	2.4 msec Standard Deviation 10.3	-4.4 msec Standard Deviation 11.2	-7 msec Standard Deviation 7.1

SECONDARY outcome

Timeframe: Baseline (Day 1), Day 7 or Discharge

Changes in blood pressure from baseline were measured after the participants were supine for at least 5 minutes. Baseline was defined as the Day 1 pre-dose measurement.

Outcome measures

Measure	Daclatasvir-1 mg n=5 Participants Participants received single dose of daclatasvir 1 mg as oral solution at concentration of 1 mg/mL daily, after fasting for at least 10 hours pre-dose and 4 hours post-dose.	Daclatasvir-10 mg n=4 Participants Participants received single dose of daclatasvir 10 mg as oral solution at concentration of 1 mg/mL daily, after fasting for at least 10 hours pre-dose and 4 hours post-dose.	Daclatasvir-100 mg n=3 Participants Participants received single dose of daclatasvir 100 mg as oral solution at concentration of 50 mg/mL daily, after fasting for at least 10 hours pre-dose and 4 hours post-dose.	Placebo n=1 Participants Participants received single dose of placebo matched to daclatasvir daily, after fasting for at least 10 hours pre-dose and 4 hours post-dose.
Change From Baseline in Blood Pressure to Day 7 or Discharge Systolic blood pressure	14 mmHg Standard Deviation 4.4	1 mmHg Standard Deviation 15.7	6 mmHg Standard Deviation 17.5	-2 mmHg Standard Deviation NA Only 1 participant was available for assessment, hence value of standard deviation is not applicable.
Change From Baseline in Blood Pressure to Day 7 or Discharge Diastolic blood pressure	9.6 mmHg Standard Deviation 7.3	4.3 mmHg Standard Deviation 5.9	3.7 mmHg Standard Deviation 12.7	1 mmHg Standard Deviation NA Only 1 participant was available for assessment, hence value of standard deviation is not applicable.

Adverse Events

Daclatasvir-1 mg

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Daclatasvir-10 mg

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Daclatasvir-100 mg

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Daclatasvir-1 mg n=6 participants at risk Participants received single dose of daclatasvir 1 mg as oral solution at concentration of 1 mg/mL daily, after fasting for at least 10 hours pre-dose and 4 hours post-dose.	Daclatasvir-10 mg n=5 participants at risk Participants received single dose of daclatasvir 10 mg as oral solution at concentration of 1 mg/mL daily, after fasting for at least 10 hours pre-dose and 4 hours post-dose.	Daclatasvir-100 mg n=5 participants at risk Participants received single dose of daclatasvir 100 mg as oral solution at concentration of 50 mg/mL daily, after fasting for at least 10 hours pre-dose and 4 hours post-dose.	Placebo n=2 participants at risk Participants received single dose of placebo matched to daclatasvir daily, after fasting for at least 10 hours pre-dose and 4 hours post-dose.
Gastrointestinal disorders Diarrhoea	0.00% 0/6 • Day 1 up to Day 7 (for non-SAEs), Day 1 to 30 days after study discontinuation (for SAEs) On-treatment period	20.0% 1/5 • Day 1 up to Day 7 (for non-SAEs), Day 1 to 30 days after study discontinuation (for SAEs) On-treatment period	0.00% 0/5 • Day 1 up to Day 7 (for non-SAEs), Day 1 to 30 days after study discontinuation (for SAEs) On-treatment period	0.00% 0/2 • Day 1 up to Day 7 (for non-SAEs), Day 1 to 30 days after study discontinuation (for SAEs) On-treatment period
Nervous system disorders Memory impairment	16.7% 1/6 • Day 1 up to Day 7 (for non-SAEs), Day 1 to 30 days after study discontinuation (for SAEs) On-treatment period	0.00% 0/5 • Day 1 up to Day 7 (for non-SAEs), Day 1 to 30 days after study discontinuation (for SAEs) On-treatment period	0.00% 0/5 • Day 1 up to Day 7 (for non-SAEs), Day 1 to 30 days after study discontinuation (for SAEs) On-treatment period	0.00% 0/2 • Day 1 up to Day 7 (for non-SAEs), Day 1 to 30 days after study discontinuation (for SAEs) On-treatment period
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.00% 0/6 • Day 1 up to Day 7 (for non-SAEs), Day 1 to 30 days after study discontinuation (for SAEs) On-treatment period	0.00% 0/5 • Day 1 up to Day 7 (for non-SAEs), Day 1 to 30 days after study discontinuation (for SAEs) On-treatment period	20.0% 1/5 • Day 1 up to Day 7 (for non-SAEs), Day 1 to 30 days after study discontinuation (for SAEs) On-treatment period	0.00% 0/2 • Day 1 up to Day 7 (for non-SAEs), Day 1 to 30 days after study discontinuation (for SAEs) On-treatment period
Gastrointestinal disorders Nausea	16.7% 1/6 • Day 1 up to Day 7 (for non-SAEs), Day 1 to 30 days after study discontinuation (for SAEs) On-treatment period	0.00% 0/5 • Day 1 up to Day 7 (for non-SAEs), Day 1 to 30 days after study discontinuation (for SAEs) On-treatment period	0.00% 0/5 • Day 1 up to Day 7 (for non-SAEs), Day 1 to 30 days after study discontinuation (for SAEs) On-treatment period	0.00% 0/2 • Day 1 up to Day 7 (for non-SAEs), Day 1 to 30 days after study discontinuation (for SAEs) On-treatment period
Nervous system disorders Paraesthesia	16.7% 1/6 • Day 1 up to Day 7 (for non-SAEs), Day 1 to 30 days after study discontinuation (for SAEs) On-treatment period	0.00% 0/5 • Day 1 up to Day 7 (for non-SAEs), Day 1 to 30 days after study discontinuation (for SAEs) On-treatment period	0.00% 0/5 • Day 1 up to Day 7 (for non-SAEs), Day 1 to 30 days after study discontinuation (for SAEs) On-treatment period	0.00% 0/2 • Day 1 up to Day 7 (for non-SAEs), Day 1 to 30 days after study discontinuation (for SAEs) On-treatment period
Gastrointestinal disorders Flatulence	0.00% 0/6 • Day 1 up to Day 7 (for non-SAEs), Day 1 to 30 days after study discontinuation (for SAEs) On-treatment period	20.0% 1/5 • Day 1 up to Day 7 (for non-SAEs), Day 1 to 30 days after study discontinuation (for SAEs) On-treatment period	0.00% 0/5 • Day 1 up to Day 7 (for non-SAEs), Day 1 to 30 days after study discontinuation (for SAEs) On-treatment period	0.00% 0/2 • Day 1 up to Day 7 (for non-SAEs), Day 1 to 30 days after study discontinuation (for SAEs) On-treatment period
Gastrointestinal disorders Abdominal pain	16.7% 1/6 • Day 1 up to Day 7 (for non-SAEs), Day 1 to 30 days after study discontinuation (for SAEs) On-treatment period	0.00% 0/5 • Day 1 up to Day 7 (for non-SAEs), Day 1 to 30 days after study discontinuation (for SAEs) On-treatment period	0.00% 0/5 • Day 1 up to Day 7 (for non-SAEs), Day 1 to 30 days after study discontinuation (for SAEs) On-treatment period	0.00% 0/2 • Day 1 up to Day 7 (for non-SAEs), Day 1 to 30 days after study discontinuation (for SAEs) On-treatment period
Investigations Blood creatine phosphokinase increased	16.7% 1/6 • Day 1 up to Day 7 (for non-SAEs), Day 1 to 30 days after study discontinuation (for SAEs) On-treatment period	0.00% 0/5 • Day 1 up to Day 7 (for non-SAEs), Day 1 to 30 days after study discontinuation (for SAEs) On-treatment period	0.00% 0/5 • Day 1 up to Day 7 (for non-SAEs), Day 1 to 30 days after study discontinuation (for SAEs) On-treatment period	0.00% 0/2 • Day 1 up to Day 7 (for non-SAEs), Day 1 to 30 days after study discontinuation (for SAEs) On-treatment period
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/6 • Day 1 up to Day 7 (for non-SAEs), Day 1 to 30 days after study discontinuation (for SAEs) On-treatment period	20.0% 1/5 • Day 1 up to Day 7 (for non-SAEs), Day 1 to 30 days after study discontinuation (for SAEs) On-treatment period	0.00% 0/5 • Day 1 up to Day 7 (for non-SAEs), Day 1 to 30 days after study discontinuation (for SAEs) On-treatment period	0.00% 0/2 • Day 1 up to Day 7 (for non-SAEs), Day 1 to 30 days after study discontinuation (for SAEs) On-treatment period
Psychiatric disorders Abnormal dreams	0.00% 0/6 • Day 1 up to Day 7 (for non-SAEs), Day 1 to 30 days after study discontinuation (for SAEs) On-treatment period	20.0% 1/5 • Day 1 up to Day 7 (for non-SAEs), Day 1 to 30 days after study discontinuation (for SAEs) On-treatment period	0.00% 0/5 • Day 1 up to Day 7 (for non-SAEs), Day 1 to 30 days after study discontinuation (for SAEs) On-treatment period	0.00% 0/2 • Day 1 up to Day 7 (for non-SAEs), Day 1 to 30 days after study discontinuation (for SAEs) On-treatment period
Nervous system disorders Headache	33.3% 2/6 • Day 1 up to Day 7 (for non-SAEs), Day 1 to 30 days after study discontinuation (for SAEs) On-treatment period	40.0% 2/5 • Day 1 up to Day 7 (for non-SAEs), Day 1 to 30 days after study discontinuation (for SAEs) On-treatment period	0.00% 0/5 • Day 1 up to Day 7 (for non-SAEs), Day 1 to 30 days after study discontinuation (for SAEs) On-treatment period	0.00% 0/2 • Day 1 up to Day 7 (for non-SAEs), Day 1 to 30 days after study discontinuation (for SAEs) On-treatment period

Additional Information

Bristol-Myers Squibb Study Director

Bristol-Myers Squibb

Email: Clinical.Trials@bms.com

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