Trial Outcomes & Findings for Study of Daclatasvir (BMS-790052) Add-on to Standard of Care in Treatment- naïve Patients (NCT NCT01125189)

NCT ID: NCT01125189

Last Updated: 2015-10-23

Results Overview

eRVR was defined as HCV RNA \<lower limit of quantitation and target not detected at both Weeks 4 and 12 on treatment.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

558 participants

Primary outcome timeframe

Weeks 4 and 12

Results posted on

2015-10-23

Participant Flow

Participants were enrolled at 64 sites in 11 countries.

A total of 558 participants were enrolled in this study, and 395 participants were randomized and treated.

Participant milestones

Participant milestones
Measure	Daclatasvir (20 mg) + Peg-interferon Alfa-2a + Ribavirin Participants received daclatasvir tablets 20 mg orally, once daily with pegylated-interferon alfa-2a solution for injection 180 µg per 0.5 mL subcutaneously, once weekly, and ribavirin tablets 1000-1200 mg orally, twice daily for a total duration of 12 weeks. After Week 12, additional treatment was provided with interferon and ribavirin for a total of 24 or 48 weeks of therapy depending on whether or not the participant achieved an on-treatment response as defined in protocol.	Daclatasvir (60 mg) + Peg-interferon Alfa-2a + Ribavirin Participants received daclatasvir tablets 60 mg orally, once daily with pegylated-interferon alfa-2a solution for injection 180 µg per 0.5 mL subcutaneously, once weekly, and ribavirin tablets 1000-1200 mg orally, twice daily for a total duration of 12 weeks. After Week 12, additional treatment was provided with interferon and ribavirin for a total of 24 or 48 weeks of therapy depending on whether or not the participant achieved an on-treatment response as defined in protocol.	Placebo + Peg-interferon Alfa-2a + Ribavirin Participants received placebo matched with daclatasvir tablets orally, once daily with pegylated-interferon alfa-2a solution for injection 180 µg per 0.5 mL subcutaneously, once weekly, and ribavirin tablets 1000-1200 mg orally, twice daily, for a total duration of 24 weeks and pegylated-interferon alfa-2a and ribavirin, for a total duration of 48 weeks.
Treatment Period STARTED	159	158	78
Treatment Period COMPLETED	128	123	37
Treatment Period NOT COMPLETED	31	35	41
Follow up Period STARTED	152	153	74
Follow up Period COMPLETED	132	138	58
Follow up Period NOT COMPLETED	20	15	16

Reasons for withdrawal

Reasons for withdrawal
Measure	Daclatasvir (20 mg) + Peg-interferon Alfa-2a + Ribavirin Participants received daclatasvir tablets 20 mg orally, once daily with pegylated-interferon alfa-2a solution for injection 180 µg per 0.5 mL subcutaneously, once weekly, and ribavirin tablets 1000-1200 mg orally, twice daily for a total duration of 12 weeks. After Week 12, additional treatment was provided with interferon and ribavirin for a total of 24 or 48 weeks of therapy depending on whether or not the participant achieved an on-treatment response as defined in protocol.	Daclatasvir (60 mg) + Peg-interferon Alfa-2a + Ribavirin Participants received daclatasvir tablets 60 mg orally, once daily with pegylated-interferon alfa-2a solution for injection 180 µg per 0.5 mL subcutaneously, once weekly, and ribavirin tablets 1000-1200 mg orally, twice daily for a total duration of 12 weeks. After Week 12, additional treatment was provided with interferon and ribavirin for a total of 24 or 48 weeks of therapy depending on whether or not the participant achieved an on-treatment response as defined in protocol.	Placebo + Peg-interferon Alfa-2a + Ribavirin Participants received placebo matched with daclatasvir tablets orally, once daily with pegylated-interferon alfa-2a solution for injection 180 µg per 0.5 mL subcutaneously, once weekly, and ribavirin tablets 1000-1200 mg orally, twice daily, for a total duration of 24 weeks and pegylated-interferon alfa-2a and ribavirin, for a total duration of 48 weeks.
Treatment Period Lack of Efficacy	15	18	25
Treatment Period Adverse Event	7	8	8
Treatment Period Withdrawal by Subject	3	1	1
Treatment Period Death	1	0	0
Treatment Period Lost to Follow-up	1	2	1
Treatment Period Poor compliance/noncompliance	0	1	0
Treatment Period Participants requested to discontinue	1	3	4
Treatment Period Other reasons	1	1	0
Treatment Period Completed 24 week treatment period only	2	1	2
Follow up Period Withdrawal by Subject	3	2	5
Follow up Period Death	1	0	0
Follow up Period Lost to Follow-up	12	9	6
Follow up Period Other reasons	4	4	5

Baseline Characteristics

Study of Daclatasvir (BMS-790052) Add-on to Standard of Care in Treatment- naïve Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Daclatasvir (20 mg) + Peg-interferon Alfa-2a + Ribavirin n=159 Participants Participants received daclatasvir tablets 20 mg orally, once daily with pegylated-interferon alfa-2a solution for injection 180 µg per 0.5 mL subcutaneously, once weekly, and ribavirin tablets 1000-1200 mg orally, twice daily for a total duration of 12 weeks. After Week 12, additional treatment was provided with interferon and ribavirin for a total of 24 or 48 weeks of therapy depending on whether or not the participant achieved an on-treatment response as defined in protocol.	Daclatasvir (60 mg) + Peg-interferon Alfa-2a + Ribavirin n=158 Participants Participants received daclatasvir tablets 60 mg orally, once daily with pegylated-interferon alfa-2a solution for injection 180 µg per 0.5 mL subcutaneously, once weekly, and ribavirin tablets 1000-1200 mg orally, twice daily for a total duration of 12 weeks. After Week 12, additional treatment was provided with interferon and ribavirin for a total of 24 or 48 weeks of therapy depending on whether or not the participant achieved an on-treatment response as defined in protocol.	Placebo + Peg-interferon Alfa-2a + Ribavirin n=78 Participants Participants received placebo matched with daclatasvir tablets orally, once daily with pegylated-interferon alfa-2a solution for injection 180 µg per 0.5 mL subcutaneously, once weekly, and ribavirin tablets 1000-1200 mg orally, twice daily, for a total duration of 24 weeks and pegylated-interferon alfa-2a and ribavirin, for a total duration of 48 weeks.	Total n=395 Participants Total of all reporting groups
Age, Customized <65 years	154 participants n=5 Participants	154 participants n=7 Participants	77 participants n=5 Participants	385 participants n=4 Participants
Age, Customized ≥65 years	5 participants n=5 Participants	4 participants n=7 Participants	1 participants n=5 Participants	10 participants n=4 Participants
Sex: Female, Male Female	52 Participants n=5 Participants	55 Participants n=7 Participants	23 Participants n=5 Participants	130 Participants n=4 Participants
Sex: Female, Male Male	107 Participants n=5 Participants	103 Participants n=7 Participants	55 Participants n=5 Participants	265 Participants n=4 Participants
Hepatitis C Virus RNA Distribution <800,000 IU/mL	26 participants n=5 Participants	35 participants n=7 Participants	17 participants n=5 Participants	78 participants n=4 Participants
Hepatitis C Virus RNA Distribution ≥800,000 IU/mL	133 participants n=5 Participants	123 participants n=7 Participants	61 participants n=5 Participants	317 participants n=4 Participants
IL-28B Genotype CC genotype	53 participants n=5 Participants	44 participants n=7 Participants	23 participants n=5 Participants	120 participants n=4 Participants
IL-28B Genotype CT genotype	82 participants n=5 Participants	86 participants n=7 Participants	38 participants n=5 Participants	206 participants n=4 Participants
IL-28B Genotype TT genotype	17 participants n=5 Participants	18 participants n=7 Participants	11 participants n=5 Participants	46 participants n=4 Participants
IL-28B Genotype Missing	7 participants n=5 Participants	10 participants n=7 Participants	6 participants n=5 Participants	23 participants n=4 Participants

PRIMARY outcome

Timeframe: Weeks 4 and 12

Population: All treated participants. Here, 'number of participants' analyzed (N) signifies number of participants evaluable for this outcome measure.

eRVR was defined as HCV RNA \<lower limit of quantitation and target not detected at both Weeks 4 and 12 on treatment.

Outcome measures

Outcome measures
Measure	Daclatasvir (20 mg) + Peg-interferon Alfa-2a + Ribavirin n=147 Participants Participants received daclatasvir tablets 20 mg orally, once daily with pegylated-interferon alfa-2a solution for injection 180 µg per 0.5 mL subcutaneously, once weekly, and ribavirin tablets 1000-1200 mg orally, twice daily for a total duration of 12 weeks. After Week 12, additional treatment was provided with interferon and ribavirin for a total of 24 or 48 weeks of therapy depending on whether or not the participant achieved an on-treatment response as defined in protocol.	Daclatasvir (60 mg) + Peg-interferon Alfa-2a + Ribavirin n=146 Participants Participants received daclatasvir tablets 60 mg orally, once daily with pegylated-interferon alfa-2a solution for injection 180 µg per 0.5 mL subcutaneously, once weekly, and ribavirin tablets 1000-1200 mg orally, twice daily for a total duration of 12 weeks. After Week 12, additional treatment was provided with interferon and ribavirin for a total of 24 or 48 weeks of therapy depending on whether or not the participant achieved an on-treatment response as defined in protocol.	Placebo + Peg-interferon Alfa-2a + Ribavirin n=72 Participants Participants received placebo matched with daclatasvir tablets orally, once daily with pegylated-interferon alfa-2a solution for injection 180 µg per 0.5 mL subcutaneously, once weekly, and ribavirin tablets 1000-1200 mg orally, twice daily, for a total duration of 24 weeks and pegylated-interferon alfa-2a and ribavirin, for a total duration of 48 weeks.
Percentage of Hepatitis C Virus (HCV) Genotype 1 Participants With Extended Rapid Virologic Response (eRVR)	54.4 percentage of participants Interval 49.2 to 59.7	54.1 percentage of participants Interval 48.8 to 59.4	13.9 percentage of participants Interval 8.7 to 19.1

PRIMARY outcome

Timeframe: Follow-up Week 24

Population: All treated participants. Here, N signifies number of participants evaluable for this outcome measure.

SVR24 was defined as HCV \<lower limit of quantitation (LLOQ) and target not detected (TND) at follow-up Week 24. The LLOQ was 25 IU/mL, and \<LLOQ, TND was 10 IU/mL. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory.

Outcome measures

Outcome measures
Measure	Daclatasvir (20 mg) + Peg-interferon Alfa-2a + Ribavirin n=147 Participants Participants received daclatasvir tablets 20 mg orally, once daily with pegylated-interferon alfa-2a solution for injection 180 µg per 0.5 mL subcutaneously, once weekly, and ribavirin tablets 1000-1200 mg orally, twice daily for a total duration of 12 weeks. After Week 12, additional treatment was provided with interferon and ribavirin for a total of 24 or 48 weeks of therapy depending on whether or not the participant achieved an on-treatment response as defined in protocol.	Daclatasvir (60 mg) + Peg-interferon Alfa-2a + Ribavirin n=146 Participants Participants received daclatasvir tablets 60 mg orally, once daily with pegylated-interferon alfa-2a solution for injection 180 µg per 0.5 mL subcutaneously, once weekly, and ribavirin tablets 1000-1200 mg orally, twice daily for a total duration of 12 weeks. After Week 12, additional treatment was provided with interferon and ribavirin for a total of 24 or 48 weeks of therapy depending on whether or not the participant achieved an on-treatment response as defined in protocol.	Placebo + Peg-interferon Alfa-2a + Ribavirin n=72 Participants Participants received placebo matched with daclatasvir tablets orally, once daily with pegylated-interferon alfa-2a solution for injection 180 µg per 0.5 mL subcutaneously, once weekly, and ribavirin tablets 1000-1200 mg orally, twice daily, for a total duration of 24 weeks and pegylated-interferon alfa-2a and ribavirin, for a total duration of 48 weeks.
Percentage of Hepatitis C Virus (HCV) Genotype 1 Participants With Sustained Virologic Response (SVR24)	59.2 percentage of participants Interval 54.0 to 64.4	59.6 percentage of participants Interval 54.4 to 64.8	37.5 percentage of participants Interval 30.2 to 44.8

PRIMARY outcome

Timeframe: From start of study treatment (day 1) up to follow-up Week 48

Population: All treated participants.

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

Outcome measures
Measure	Daclatasvir (20 mg) + Peg-interferon Alfa-2a + Ribavirin n=159 Participants Participants received daclatasvir tablets 20 mg orally, once daily with pegylated-interferon alfa-2a solution for injection 180 µg per 0.5 mL subcutaneously, once weekly, and ribavirin tablets 1000-1200 mg orally, twice daily for a total duration of 12 weeks. After Week 12, additional treatment was provided with interferon and ribavirin for a total of 24 or 48 weeks of therapy depending on whether or not the participant achieved an on-treatment response as defined in protocol.	Daclatasvir (60 mg) + Peg-interferon Alfa-2a + Ribavirin n=158 Participants Participants received daclatasvir tablets 60 mg orally, once daily with pegylated-interferon alfa-2a solution for injection 180 µg per 0.5 mL subcutaneously, once weekly, and ribavirin tablets 1000-1200 mg orally, twice daily for a total duration of 12 weeks. After Week 12, additional treatment was provided with interferon and ribavirin for a total of 24 or 48 weeks of therapy depending on whether or not the participant achieved an on-treatment response as defined in protocol.	Placebo + Peg-interferon Alfa-2a + Ribavirin n=78 Participants Participants received placebo matched with daclatasvir tablets orally, once daily with pegylated-interferon alfa-2a solution for injection 180 µg per 0.5 mL subcutaneously, once weekly, and ribavirin tablets 1000-1200 mg orally, twice daily, for a total duration of 24 weeks and pegylated-interferon alfa-2a and ribavirin, for a total duration of 48 weeks.
Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), and Who Died SAEs	12 participants	13 participants	6 participants
Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), and Who Died Discontinuations Due to AEs	7 participants	7 participants	8 participants
Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), and Who Died Death	2 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: Week 4

Population: All treated participants. Here, N signifies number of participants evaluable for this outcome measure.

RVR was defined as undetectable RNA (HCV RNA \<lower limit of quantitation \[LLOQ\], target not detected \[TND\]) at Week 4. The LLOQ was 25 IU/mL, and \<LLOQ, TND was 10 IU/mL. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. N=Number of participants analyzed for this outcome.

Outcome measures

Outcome measures
Measure	Daclatasvir (20 mg) + Peg-interferon Alfa-2a + Ribavirin n=147 Participants Participants received daclatasvir tablets 20 mg orally, once daily with pegylated-interferon alfa-2a solution for injection 180 µg per 0.5 mL subcutaneously, once weekly, and ribavirin tablets 1000-1200 mg orally, twice daily for a total duration of 12 weeks. After Week 12, additional treatment was provided with interferon and ribavirin for a total of 24 or 48 weeks of therapy depending on whether or not the participant achieved an on-treatment response as defined in protocol.	Daclatasvir (60 mg) + Peg-interferon Alfa-2a + Ribavirin n=146 Participants Participants received daclatasvir tablets 60 mg orally, once daily with pegylated-interferon alfa-2a solution for injection 180 µg per 0.5 mL subcutaneously, once weekly, and ribavirin tablets 1000-1200 mg orally, twice daily for a total duration of 12 weeks. After Week 12, additional treatment was provided with interferon and ribavirin for a total of 24 or 48 weeks of therapy depending on whether or not the participant achieved an on-treatment response as defined in protocol.	Placebo + Peg-interferon Alfa-2a + Ribavirin n=72 Participants Participants received placebo matched with daclatasvir tablets orally, once daily with pegylated-interferon alfa-2a solution for injection 180 µg per 0.5 mL subcutaneously, once weekly, and ribavirin tablets 1000-1200 mg orally, twice daily, for a total duration of 24 weeks and pegylated-interferon alfa-2a and ribavirin, for a total duration of 48 weeks.
Percentage of Hepatitis C Virus (HCV) Genotype 1 Participants With Rapid Virologic Response (RVR)	59.9 percentage of participants Interval 54.7 to 65.0	56.8 percentage of participants Interval 51.6 to 62.1	15.3 percentage of participants Interval 9.8 to 20.7

SECONDARY outcome

Timeframe: Week 12

Population: All treated participants. Here, N signifies number of participants evaluable for this outcome measure.

cEVR was defined as undetectable RNA (HCV RNA \<lower limit of quantitation \[LLOQ\], target not detected \[TND\]) at Week 12. The LLOQ was 25 IU/mL, and \<LLOQ, TND was 10 IU/mL. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. N=Number of participants analyzed for this outcome.

Outcome measures

Outcome measures
Measure	Daclatasvir (20 mg) + Peg-interferon Alfa-2a + Ribavirin n=147 Participants Participants received daclatasvir tablets 20 mg orally, once daily with pegylated-interferon alfa-2a solution for injection 180 µg per 0.5 mL subcutaneously, once weekly, and ribavirin tablets 1000-1200 mg orally, twice daily for a total duration of 12 weeks. After Week 12, additional treatment was provided with interferon and ribavirin for a total of 24 or 48 weeks of therapy depending on whether or not the participant achieved an on-treatment response as defined in protocol.	Daclatasvir (60 mg) + Peg-interferon Alfa-2a + Ribavirin n=146 Participants Participants received daclatasvir tablets 60 mg orally, once daily with pegylated-interferon alfa-2a solution for injection 180 µg per 0.5 mL subcutaneously, once weekly, and ribavirin tablets 1000-1200 mg orally, twice daily for a total duration of 12 weeks. After Week 12, additional treatment was provided with interferon and ribavirin for a total of 24 or 48 weeks of therapy depending on whether or not the participant achieved an on-treatment response as defined in protocol.	Placebo + Peg-interferon Alfa-2a + Ribavirin n=72 Participants Participants received placebo matched with daclatasvir tablets orally, once daily with pegylated-interferon alfa-2a solution for injection 180 µg per 0.5 mL subcutaneously, once weekly, and ribavirin tablets 1000-1200 mg orally, twice daily, for a total duration of 24 weeks and pegylated-interferon alfa-2a and ribavirin, for a total duration of 48 weeks.
Percentage of Hepatitis C Virus (HCV) Genotype 1 Participants With Complete Early Virologic Response (cEVR)	77.6 percentage of participants Interval 73.1 to 82.0	75.3 percentage of participants Interval 70.8 to 79.9	43.1 percentage of participants Interval 35.6 to 50.5

SECONDARY outcome

Timeframe: Follow-up Week 12

Population: All treated participants. Here, N signifies number of participants evaluable for this outcome measure.

SVR12 was defined as undetectable RNA (HCV RNA \< lower limit of quantitation (LLOQ), target not detected (TND) at follow-up Week 12. The LLOQ was 25 IU/mL, and \<LLOQ, TND was 10 IU/mL. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. N=Number of participants analyzed for this outcome.

Outcome measures

Outcome measures
Measure	Daclatasvir (20 mg) + Peg-interferon Alfa-2a + Ribavirin n=147 Participants Participants received daclatasvir tablets 20 mg orally, once daily with pegylated-interferon alfa-2a solution for injection 180 µg per 0.5 mL subcutaneously, once weekly, and ribavirin tablets 1000-1200 mg orally, twice daily for a total duration of 12 weeks. After Week 12, additional treatment was provided with interferon and ribavirin for a total of 24 or 48 weeks of therapy depending on whether or not the participant achieved an on-treatment response as defined in protocol.	Daclatasvir (60 mg) + Peg-interferon Alfa-2a + Ribavirin n=146 Participants Participants received daclatasvir tablets 60 mg orally, once daily with pegylated-interferon alfa-2a solution for injection 180 µg per 0.5 mL subcutaneously, once weekly, and ribavirin tablets 1000-1200 mg orally, twice daily for a total duration of 12 weeks. After Week 12, additional treatment was provided with interferon and ribavirin for a total of 24 or 48 weeks of therapy depending on whether or not the participant achieved an on-treatment response as defined in protocol.	Placebo + Peg-interferon Alfa-2a + Ribavirin n=72 Participants Participants received placebo matched with daclatasvir tablets orally, once daily with pegylated-interferon alfa-2a solution for injection 180 µg per 0.5 mL subcutaneously, once weekly, and ribavirin tablets 1000-1200 mg orally, twice daily, for a total duration of 24 weeks and pegylated-interferon alfa-2a and ribavirin, for a total duration of 48 weeks.
Percentage of Hepatitis C Virus (HCV) Genotype 1 Participants With 12-week Sustained Virologic Response (SVR12)	64.6 percentage of participants Interval 59.6 to 69.7	60.3 percentage of participants Interval 55.1 to 65.5	36.1 percentage of participants Interval 28.9 to 43.4

SECONDARY outcome

Timeframe: Follow-up Week 48

Population: All treated participants. Here, N signifies number of participants evaluable for this outcome measure.

Virologic failure was defined as: 1. Virologic breakthrough: confirmed \>1 log10 increase in hepatitis C virus (HCV) RNA over nadir or confirmed RNA ≥lower limit of quantitation (LLOQ) after confirmed HCV RNA \<LLOQ, target not detected (TND) while on treatment 2. \<1 log10 decrease in HCV RNA from baseline at Week 4 of treatment 3. Failure to achieve early virologic response: \<2 log10 decrease in HCV RNA from baseline and HCV RNA ≥LLOQ at Week 12 of treatment 4. HCV RNA \< LLOQ, TD or ≥ LLOQ at Week 12 and ≥ LLOQ at Week 24 5. HCV RNA ≥LLOQ or \<LLOQ, target detected (TD) at the end of treatment (EOT) (including early discontinuation) 6. Relapse, defined as HCV RNA ≥LLOQ or \<LLOQ, TD during follow-up, after HCV RNA \< LLOQ, TND at EOT. The LLOQ was 25 IU/mL, and \<LLOQ, TND was 10 IU/mL. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. N=Number of participants analyzed for this outcome.

Outcome measures

Outcome measures
Measure	Daclatasvir (20 mg) + Peg-interferon Alfa-2a + Ribavirin n=147 Participants Participants received daclatasvir tablets 20 mg orally, once daily with pegylated-interferon alfa-2a solution for injection 180 µg per 0.5 mL subcutaneously, once weekly, and ribavirin tablets 1000-1200 mg orally, twice daily for a total duration of 12 weeks. After Week 12, additional treatment was provided with interferon and ribavirin for a total of 24 or 48 weeks of therapy depending on whether or not the participant achieved an on-treatment response as defined in protocol.	Daclatasvir (60 mg) + Peg-interferon Alfa-2a + Ribavirin n=146 Participants Participants received daclatasvir tablets 60 mg orally, once daily with pegylated-interferon alfa-2a solution for injection 180 µg per 0.5 mL subcutaneously, once weekly, and ribavirin tablets 1000-1200 mg orally, twice daily for a total duration of 12 weeks. After Week 12, additional treatment was provided with interferon and ribavirin for a total of 24 or 48 weeks of therapy depending on whether or not the participant achieved an on-treatment response as defined in protocol.	Placebo + Peg-interferon Alfa-2a + Ribavirin n=72 Participants Participants received placebo matched with daclatasvir tablets orally, once daily with pegylated-interferon alfa-2a solution for injection 180 µg per 0.5 mL subcutaneously, once weekly, and ribavirin tablets 1000-1200 mg orally, twice daily, for a total duration of 24 weeks and pegylated-interferon alfa-2a and ribavirin, for a total duration of 48 weeks.
Percentage of Resistant Variants Associated With Virologic Failure Virologic Breakthrough	8.2 percentage of participants	10.3 percentage of participants	2.8 percentage of participants
Percentage of Resistant Variants Associated With Virologic Failure Week 4 Futility Rule	2.0 percentage of participants	2.1 percentage of participants	25.0 percentage of participants
Percentage of Resistant Variants Associated With Virologic Failure Detectable HCV RNA at EOT	7.5 percentage of participants	6.8 percentage of participants	5.6 percentage of participants
Percentage of Resistant Variants Associated With Virologic Failure Other Criteria	1.4 percentage of participants	0.1 percentage of participants	6.9 percentage of participants
Percentage of Resistant Variants Associated With Virologic Failure Relapse	18.5 percentage of participants	19.0 percentage of participants	22.0 percentage of participants

Adverse Events

Daclatasvir (20 mg) + Peg-interferon Alfa-2a + Ribavirin

Serious events: 12 serious events

Other events: 156 other events

Deaths: 0 deaths

Daclatasvir (60 mg) + Peg-interferon Alfa-2a + Ribavirin

Serious events: 13 serious events

Other events: 155 other events

Deaths: 0 deaths

Placebo + Peg-interferon Alfa-2a + Ribavirin

Serious events: 6 serious events

Other events: 76 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Bristol-Myers Squibb Study Director

Bristol-Myers Squibb

Email: [email protected]

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

Measure	Daclatasvir (20 mg) + Peg-interferon Alfa-2a + Ribavirin n=159 participants at risk Participants received daclatasvir tablets 20 mg orally, once daily with pegylated--interferon alfa-2a solution for injection 180 µg per 0.5 mL subcutaneously, once weekly, and ribavirin tablets 1000-1200 mg orally, twice daily for a total duration of 12 weeks. After Week 12, additional treatment was provided with interferon and ribavirin for a total of 24 or 48 weeks of therapy depending on whether or not the patient achieved an on-treatment response as defined in protocol.	Daclatasvir (60 mg) + Peg-interferon Alfa-2a + Ribavirin n=158 participants at risk Participants received daclatasvir tablets 60 mg orally, once daily with pegylated-interferon alfa-2a solution for injection 180 µg per 0.5 mL subcutaneously, once weekly, and ribavirin tablets 1000-1200 mg orally, twice daily for a total duration of 12 weeks. After Week 12, additional treatment was provided with interferon and ribavirin for a total of 24 or 48 weeks of therapy depending on whether or not the patient achieved an on-treatment response as defined in protocol.	Placebo + Peg-interferon Alfa-2a + Ribavirin n=78 participants at risk Participants received placebo matched with daclatasvir tablets orally, once daily with pegylated-interferon alfa-2a solution for injection 180 µg per 0.5 mL subcutaneously, once weekly, and ribavirin tablets 1000-1200 mg orally, twice daily, for a total duration of 24 weeks and pegylated-interferon alfa-2a and ribavirin, for a total duration of 48 weeks.
Injury, poisoning and procedural complications Accidental overdose	0.63% 1/159 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.00% 0/158 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.00% 0/78 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.
Psychiatric disorders Adjustment disorder	0.63% 1/159 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.00% 0/158 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.00% 0/78 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.
Blood and lymphatic system disorders Anaemia	0.00% 0/159 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.63% 1/158 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	2.6% 2/78 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.
Musculoskeletal and connective tissue disorders Bursitis	0.63% 1/159 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.00% 0/158 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.00% 0/78 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/159 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.63% 1/158 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.00% 0/78 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.
Gastrointestinal disorders Gastritis	0.63% 1/159 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.00% 0/158 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.00% 0/78 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.
Musculoskeletal and connective tissue disorders Rhabdomyolysis	0.63% 1/159 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.00% 0/158 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.00% 0/78 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.
Infections and infestations Clostridium difficile colitis	0.00% 0/159 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.63% 1/158 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.00% 0/78 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.
General disorders Death	0.63% 1/159 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.00% 0/158 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.00% 0/78 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/159 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.00% 0/158 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	1.3% 1/78 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.
Infections and infestations Furuncle	0.00% 0/159 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.63% 1/158 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.00% 0/78 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.
Psychiatric disorders Hypomania	0.63% 1/159 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.00% 0/158 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.00% 0/78 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.
Musculoskeletal and connective tissue disorders Muscle spasms	0.63% 1/159 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.00% 0/158 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.00% 0/78 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.
Psychiatric disorders Mental disorder	0.00% 0/159 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.63% 1/158 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.00% 0/78 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.
Skin and subcutaneous tissue disorders Rash generalised	0.63% 1/159 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.00% 0/158 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.00% 0/78 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.
Nervous system disorders Aphasia	0.00% 0/159 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.00% 0/158 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	1.3% 1/78 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.
Blood and lymphatic system disorders Aplastic anaemia	0.00% 0/159 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.63% 1/158 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.00% 0/78 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.
Cardiac disorders Atrial fibrillation	0.00% 0/159 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.00% 0/158 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	1.3% 1/78 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.
Ear and labyrinth disorders Auricular perichondritis	0.00% 0/159 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.63% 1/158 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.00% 0/78 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.
Infections and infestations Carbuncle	0.00% 0/159 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.63% 1/158 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.00% 0/78 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.
Musculoskeletal and connective tissue disorders Costochondritis	0.63% 1/159 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.00% 0/158 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.00% 0/78 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.
Psychiatric disorders Depression	0.63% 1/159 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.63% 1/158 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.00% 0/78 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.
Investigations Electrocardiogram change	0.00% 0/159 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.00% 0/158 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	1.3% 1/78 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.
Investigations Haemoglobin decreased	0.00% 0/159 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.00% 0/158 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	1.3% 1/78 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.
Investigations Neutrophil count decreased	0.00% 0/159 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.00% 0/158 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	1.3% 1/78 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.
Nervous system disorders Syncope	0.63% 1/159 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.00% 0/158 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.00% 0/78 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.
Nervous system disorders Dizziness	0.63% 1/159 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.00% 0/158 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.00% 0/78 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.
Infections and infestations Peritonitis	0.00% 0/159 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.63% 1/158 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.00% 0/78 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.
Psychiatric disorders Suicidal ideation	0.63% 1/159 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.63% 1/158 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.00% 0/78 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.
Hepatobiliary disorders Bile duct stone	0.00% 0/159 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.63% 1/158 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.00% 0/78 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.
General disorders Chest pain	0.63% 1/159 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.00% 0/158 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.00% 0/78 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.63% 1/159 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.00% 0/158 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.00% 0/78 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.
Injury, poisoning and procedural complications Fall	0.00% 0/159 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	1.3% 2/158 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.00% 0/78 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.
Nervous system disorders Paraesthesia	0.00% 0/159 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.00% 0/158 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	1.3% 1/78 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.
Infections and infestations Pneumonia	0.00% 0/159 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	1.3% 2/158 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	1.3% 1/78 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.
Psychiatric disorders Substance-induced psychotic disorder	0.63% 1/159 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.00% 0/158 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.00% 0/78 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.
Infections and infestations Bronchitis	0.63% 1/159 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.00% 0/158 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.00% 0/78 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/159 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.00% 0/158 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	1.3% 1/78 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.
Injury, poisoning and procedural complications Overdose	0.63% 1/159 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.00% 0/158 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.00% 0/78 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.
Psychiatric disorders Schizophrenia, paranoid type	0.00% 0/159 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.63% 1/158 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.00% 0/78 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.
Gastrointestinal disorders Abdominal pain	0.00% 0/159 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.63% 1/158 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.00% 0/78 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.
Gastrointestinal disorders Gastric ulcer haemorrhage	0.00% 0/159 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	1.3% 2/158 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.00% 0/78 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.
Nervous system disorders Loss of consciousness	0.63% 1/159 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.00% 0/158 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.00% 0/78 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.
Infections and infestations Oral herpes	0.00% 0/159 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.63% 1/158 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.00% 0/78 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.
Infections and infestations Pyelonephritis	0.00% 0/159 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	0.00% 0/158 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.	1.3% 1/78 • From start of study treatment (day 1) up to 7 days post last dose of study treatment (Week 24) On-treatment period.