Safety and Efficacy of Daclatasvir (BMS-790052) Plus Standard of Care (Pegylated-interferon Alpha-2b and Ribavirin) in Japanese Patients

• Sponsor: Bristol-Myers Squibb (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01016912
• Collaborator: (none)
• Enrollment: 51
• Locations: 6
• Arms: 5
• Duration (Months): 9
• Patients Per Site: 8.5
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

The purpose of this study is to identify at least 1 dose of daclatasvir that is safe, well tolerated, and efficacious when combined with peginterferon-alfa and ribavirin for the treatment of hepatitis C virus genotype 1 in chronically infected patients who are treatment-naïve and nonresponsive to the standard of care

Condition or Disease	Intervention/Treatment	Phase
Hepatitis C Infection	Drug: BMS-790052; Drug: BMS-790052; Drug: Placebo; Drug: Peginterferon alfa-2b; Drug: Ribavirin	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 51 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 2a Study of BMS-790052 in Combination With Peginterferon Alfa-2b (PegIntron®) and Ribavirin (Rebetol®) in Japanese Subjects With Genotype 1 Chronic Hepatitis C Virus (HCV) Infection
• Study Start Date: Dec 1, 2009
• Actual Primary Completion Date: Sep 1, 2010
• Actual Study Completion Date: Sep 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A (BMS-790052, plus Peginterferon alfa-2b, Ribavirin) Treatment Naive	Drug: BMS-790052; Tablets, Oral, 10 mg, daily, 24-48 weeks; Drug: Peginterferon alfa-2b; Syringe, Subcutaneous, 180µg, weekly, 24-48 weeks; Other Names: PegIntron® ; Drug: Ribavirin; Capsules, Oral, 600 to 1000 mg based on weight, daily, 24-48 weeks; Other Names: Rebetol®
Experimental: Arm B (BMS-790052, plus Peginterferon alfa-2b, Ribavirin) Treatment Naive	Drug: BMS-790052; Tablets, Oral, 60 mg, daily, 24-48 weeks; Drug: Peginterferon alfa-2b; Syringe, Subcutaneous, 180µg, weekly, 24-48 weeks; Other Names: PegIntron® ; Drug: Ribavirin; Capsules, Oral, 600 to 1000 mg based on weight, daily, 24-48 weeks; Other Names: Rebetol®
Placebo Comparator: Arm C (Placebo, plus Peginterferon alfa-2b, Ribavirin) Treatment Naive	Drug: Placebo; Tablets, Oral, 0 mg, daily, 48 weeks; Drug: Peginterferon alfa-2b; Syringe, Subcutaneous, 180µg, weekly, 24-48 weeks; Other Names: PegIntron® ; Drug: Ribavirin; Capsules, Oral, 600 to 1000 mg based on weight, daily, 24-48 weeks; Other Names: Rebetol®
Experimental: Arm D (BMS-790052, plus peginterferon alfa-2b, Ribavirin) Non-Responder	Drug: BMS-790052; Tablets, Oral, 10 mg, daily, 24-48 weeks; Drug: Peginterferon alfa-2b; Syringe, Subcutaneous, 180µg, weekly, 24-48 weeks; Other Names: PegIntron® ; Drug: Ribavirin; Capsules, Oral, 600 to 1000 mg based on weight, daily, 24-48 weeks; Other Names: Rebetol®
Experimental: Arm E (BMS-790052, plus Peginterferon alfa-2b, Ribavirin) Non-Responder	Drug: BMS-790052; Tablets, Oral, 60 mg, daily, 24-48 weeks; Drug: Peginterferon alfa-2b; Syringe, Subcutaneous, 180µg, weekly, 24-48 weeks; Other Names: PegIntron® ; Drug: Ribavirin; Capsules, Oral, 600 to 1000 mg based on weight, daily, 24-48 weeks; Other Names: Rebetol®

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Extended Rapid Virologic Response (eRVR) [At Weeks 4 and 12 on treatment]

   eRVR was defined as undetectable hepatitis C virus (HCV) RNA (ie, HCV RNA <15 IU/mL, the lower limit of detection, target not detected) at both Weeks 4 and 12. HCV RNA levels were measured by Tobas TaqMan HCV Auto from the central laboratory.

Secondary Outcome Measures

1. Percentage of Participants With Rapid Virologic Response (RVR) [At Week 4 on treatment]

   RVR was defined as undetectable hepatitis C virus (HCV) RNA (ie, HCV RNA <15 IU/mL, the lower limit of detection, target not detected) at Week 4. HCV RNA levels were measured by CobasTaqMan HCV Auto from the central laboratory .

2. Percentage of Participants With Complete Early Virologic Response (cEVR) [At Week 12 on treatment]

   cEVR was defined as undetectable hepatitis C virus (HCV) RNA (ie, HCV RNA <15 IU/mL, the lower limit of detection, target not detected) at Week 12 on treatment. HCV RNA levels were measured by Cobas TaqMan HCV Auto from the central laboratory

3. Percentage of Participants With a Sustained Virologic Response (SVR) at Weeks 4, 12, and 24 [Follow-up Weeks 4, 12, and 24]

   SVR at follow-up Week 4 (SVR4), follow-up Week 12 (SVR12), and follow-up Week 24 (SVR24) is defined as undetectable hepatitis C virus (HCV) RNA (ie, HCV RNA <15 IU/mL, the lower limit of detection, target not detected) at each of these timepoints. HCV RNA levels were measured by Cobas TaqMan HCV Auto from the central laboratory .

4. Percentage of Participants With Virologic Failure [From on-treatment Week 1 to Follow-up Week 24]

   Virologic failure is defined by the following 6 categories: 1.Virologic breakthrough, defined as confirmed >1 log10 increase in hepatitis C virus (HCV) RNA over nadir or confirmed HCV RNA ≥limit of quantitation (LOQ) after confirmed undetectable HCV RNA while on treatment. 2. <1 log10 decrease in HCV RNA from baseline at Week 4 of treatment. 3. Failure to achieve early virologic response, defined as <2 log10 decrease in HCV RNA from baseline at Week 12 of treatment. 4. Detectable HCV RNA at Week 12, and HCV RNA ≥LOQ at Week 24 of treatment. 5. Detectable HCV RNA at end of treatment (including early discontinuation). 6 Relapse, defined as detectable HCV RNA during follow-up after undetectable HCV RNA levels at end of treatment.

Other Outcome Measures

1. Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), Treatment-related AEs, and Death as Outcome [From baseline to 30 days after last dose of study drug]

   AE was defined as any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not has 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. Treatment-related AE was defined as an AE that had certain, probable, possible, or unknown relationship to study drug.

2. Number of Participants With Grade 3 to 4 Abnormalities on Laboratory Test Results [From baseline to 30 days after last dose of study drug]

   Clinically significant marked abnormalities in laboratory test results graded by the Division of AIDS grading table, 2004. Hemoglobin: Grade 3= <7.0 to 8.9 g/dL, Grade 4= <7.0 g/dL. Lymphocytes: Grade 3= 350-499 cells/mm^3, Grade 4= <350 cells/mm^3. Neutrophils: Grade 3= 500-999 cells/mm^3, Grade 4= <500 cells/mm^3. White blood cells (WBC): Grade 3= 1000-1499 cells/mm^3, Grade 4= <1000 cells/mm^3. Alanine aminotransferase (ALT): Grade 3= 5.1-10*upper limit of normal (ULN), Grade 4= >10.0*ULN. Aspartate aminotransferase (AST): Grade 3= 5.1-10*ULN, Grade 4= >10.0*ULN. Total bilirubin: Grade 3= 2.6-5*ULN, Grade 4= >5.0*ULN.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Key Inclusion Criteria:

• Patients chronically infected with hepatitis C virus (HCV) genotype 1

• HCV RNA viral load ≥105 IU/mL at screening

• Naïve or nonresponsive to the current standard of care

Key Exclusion Criteria:

• Cirrhosis

• Hepatocellular carcinoma

• Coinfection with hepatitis B virus, HIV-1 or HIV-2

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Local Institution	Hiroshima City	Hiroshima	Japan	734-0037
2	Local Institution	Sapporo-Shi	Hokkaido	Japan	060-0033
3	Local Institution	Kawasaki-Shi	Kanagawa	Japan	2138587
4	Local Institution	Suita-Shi	Osaka	Japan	5650871
5	Local Institution	Iruma-Gun	Saitama	Japan	3500495
6	Local Institution	Minato-Ku	Tokyo	Japan	105-0001

Sponsors and Collaborators

• Bristol-Myers Squibb

Investigators

• Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Bristol-Myers Squibb
• ClinicalTrials.gov Identifier: NCT01016912
• Other Study ID Numbers: AI444-021
• First Posted: Nov 20, 2009
• Last Update Posted: Oct 12, 2015
• Last Verified: Sep 1, 2015

• Additional relevant MeSH terms: Infections; Hepatitis C; Hepatitis; Ribavirin; Peginterferon alfa-2b

Study Results

Participant Flow

Recruitment Details	The study was conducted at 6 sites in Japan.
Pre-assignment Detail	A total of 51 participants were enrolled, of which 45 were randomized to receive treatment and 6 were discontinued for no longer meeting study criteria.

Arm/Group Title	Placebo + pegIFNα + Ribavirin (Treatment-naive)	Daclatasvir 10- mg + pegIFNα + Ribavirin (Treatment-naive)	Daclatasvir 60- mg + pegIFNα + Ribavirin (Treatment-naive)	Daclatasvir 10- mg + pegIFNα+ Ribavirin (Nonresponders)	Daclatasvir 60- mg + pegIFNα + Ribavirin (Nonresponders)
Arm/Group Description	Participants received a matching placebo of daclatasvir tablet, once daily coadministered with ribavirin, twice daily, and peginterferon alpha (pegIFNα) injection, once weekly. Treatment-naive participants were those who had never been exposed to any hepatitis C virus (HCV) therapy with interferon IFNα-containing regimens, including pegIFNα/ribavirin.	Participants received 10 mg of daclatasvir, once daily, coadministered with ribavirin, twice daily, and peginterferon alpha-2b (pegIFNα) injection, once weekly. Treatment-naive participants were those who had never been exposed to any hepatitis C virus (HCV) therapy with interferon IFNα-containing regimens, including pegIFNα/ribavirin.	Participants received 60 mg of daclatasvir, once daily, coadministered with ribavirin, twice daily, and pegIFNα injection, once weekly. Treatment-naive participants were those who had never been exposed to any HCV therapy with interferon IFNα-containing regimens, including pegIFNα/ribavirin.	Participants received 10 mg of daclatasvir, once daily, coadministered with ribavirin, twice daily, and pegIFNα injection once weekly. Nonresponders were participants who had never attained undetectable HCV RNA levels, after at least 12 weeks of the current standard of care, pegIFNα/ribavirin.	Participants received 60 mg of daclatasvir, once daily, coadministered with ribavirin, twice daily, and pegIFNα injection once weekly. Nonresponders were participants who had never attained undetectable HCV RNA levels, after at least 12 weeks of the current standard of care pegIFNα/ribavirin.
Period Title: End of Treatment Period
STARTED	8	9	10	9	9
Received Treatment	8	9	10	9	9
COMPLETED	8	6	9	5	5
NOT COMPLETED	0	3	1	4	4
Period Title: End of Treatment Period
STARTED	8	9	10	9	9
COMPLETED	8	9	9	8	9
NOT COMPLETED	0	0	1	1	0

Baseline Characteristics

Arm/Group Title	Placebo + pegIFNα + Ribavirin (Treatment-naive)	Daclatasvir 10- mg + pegIFNα- + Ribavirin (Treatment-naive)	Daclatasvir 60- mg + pegIFNα + Ribavirin (Treatment-naive)	Daclatasvir 10- mg + pegIFNα + Ribavirin (Nonresponders)	Daclatasvir 60- mg + pegIFNα + Ribavirin (Nonresponders)	Total
Arm/Group Description	Participants received a matching placebo of daclatasvir tablet, once daily coadministered with ribavirin, twice daily, and peginterferon alpha-2b (pegIFNα) injection, once weekly. Treatment-naive participants were those who had never been exposed to any hepatitis C virus (HCV) therapy with interferon IFNα-containing regimens, including pegIFNα/ribavirin.	Participants received 10 mg of daclatasvir, once daily, coadministered with ribavirin, twice daily, and pegIFNα injection, once weekly. Treatment-naive participants were those who had never been exposed to any HCV therapy with interferon IFNα-containing regimens, including pegIFNα/ribavirin.	Participants received 60 mg of daclatasvir, once daily, coadministered with ribavirin, twice daily, and pegIFNα injection, once weekly. Treatment-naive participants were those who had never been exposed to any HCV therapy with interferon IFNα-containing regimens, including pegIFNα/ribavirin.	Participants received 10 mg of daclatasvir, once daily, coadministered with ribavirin, twice daily, and pegIFNα injection once weekly. Nonresponders were participants who had never attained undetectable HCV RNA levels, after at least 12 weeks of the current standard of care, pegIFNα/ribavirin.	Participants received 60 mg of daclatasvir, once daily, coadministered with ribavirin, twice daily, and pegIFNα injection once weekly. Nonresponders were participants who had never attained undetectable HCV RNA levels, after at least 12 weeks of the current standard of care pegIFNα/ribavirin.	Total of all reporting groups
Overall Participants	8	9	10	9	9	45
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	52.6 (8.78)	49.1 (15.09)	53.2 (9.96)	57.4 (6.11)	58.8 (9.46)	54.2 (10.46)
Sex: Female, Male (Count of Participants)
Female	4 50%	7 77.8%	4 40%	6 66.7%	6 66.7%	27 60%
Male	4 50%	2 22.2%	6 60%	3 33.3%	3 33.3%	18 40%

Outcome Measures

1. Other Pre-specified Outcome

Title	Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), Treatment-related AEs, and Death as Outcome
Description	AE was defined as any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not has 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. Treatment-related AE was defined as an AE that had certain, probable, possible, or unknown relationship to study drug.
Time Frame	From baseline to 30 days after last dose of study drug

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study therapy.

Arm/Group Title	Placebo + pegIFNα + Ribavirin (Treatment-naive)	Daclatasvir 10- mg + pegIFNα- + Ribavirin (Treatment-naive)	Daclatasvir 60- mg + pegIFNα + Ribavirin (Treatment-naive)	Daclatasvir 10- mg+ pegIFNα + Ribavirin (Nonresponders)	Daclatasvir 60- mg + pegIFNα- + Ribavirin (Nonresponders)
Arm/Group Description	Participants received a matching placebo of daclatasvir tablet, once daily coadministered with ribavirin, twice daily, and peginterferon alpha(pegIFNα) injection, once weekly. Treatment-naive participants were those who had never been exposed to any hepatitis C virus (HCV) therapy with interferon IFNα-containing regimens, including pegIFNα/ribavirin.	Participants received 10 mg of daclatasvir, once daily, coadministered with ribavirin, twice daily, and pegIFNα injection, once weekly. Treatment-naive participants were those who had never been exposed to any HCV therapy with interferon IFNα-containing regimens, including pegIFNα/ribavirin.	Participants received 60 mg of daclatasvir, once daily, coadministered with ribavirin, twice daily, and pegIFNα injection, once weekly. Treatment-naive participants were those who had never been exposed to any HCV therapy with interferon IFNα-containing regimens, including pegIFNα/ribavirin..	Participants received 10 mg of daclatasvir, once daily, coadministered with ribavirin, twice daily, and pegIFNα injection once weekly. Nonresponders were participants who had never attained undetectable HCV RNA levels, after at least 12 weeks of the current standard of care pegIFNα/ribavirin.	Participants received 60 mg of daclatasvir, once daily, coadministered with ribavirin, twice daily, and pegIFNα injection once weekly. Nonresponders were participants who had never attained undetectable HCV RNA levels, after at least 12 weeks of the current standard of care pegIFNα/ribavirin.
Measure Participants	8	9	10	9	9
SAEs	0 0%	0 0%	0 0%	1 11.1%	0 0%
Discontinuation due to AEs	0 0%	1 11.1%	1 10%	0 0%	0 0%
Treatment-related AEs	8 100%	9 100%	10 100%	9 100%	9 100%
Death	0 0%	0 0%	0 0%	0 0%	0 0%

2. Other Pre-specified Outcome

Title	Number of Participants With Grade 3 to 4 Abnormalities on Laboratory Test Results
Description	Clinically significant marked abnormalities in laboratory test results graded by the Division of AIDS grading table, 2004. Hemoglobin: Grade 3= <7.0 to 8.9 g/dL, Grade 4= <7.0 g/dL. Lymphocytes: Grade 3= 350-499 cells/mm^3, Grade 4= <350 cells/mm^3. Neutrophils: Grade 3= 500-999 cells/mm^3, Grade 4= <500 cells/mm^3. White blood cells (WBC): Grade 3= 1000-1499 cells/mm^3, Grade 4= <1000 cells/mm^3. Alanine aminotransferase (ALT): Grade 3= 5.1-10*upper limit of normal (ULN), Grade 4= >10.0*ULN. Aspartate aminotransferase (AST): Grade 3= 5.1-10*ULN, Grade 4= >10.0*ULN. Total bilirubin: Grade 3= 2.6-5*ULN, Grade 4= >5.0*ULN.
Time Frame	From baseline to 30 days after last dose of study drug

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study therapy.

Arm/Group Title	Placebo + pegIFNα + Ribavirin (Treatment-naive)	Daclatasvir 10- mg + pegIFNα + Ribavirin (Treatment-naive)	Daclatasvir 60- mg + pegIFNα- + Ribavirin (Treatment-naive)	Daclatasvir 10- mg + pegIFNα + Ribavirin (Nonresponders)	Daclatasvir 60- mg + pegIFNα- + Ribavirin (Nonresponders)
Arm/Group Description	Participants received a matching placebo of daclatasvir tablet, once daily coadministered with ribavirin, twice daily, and peginterferon alpha (pegIFNα) injection, once weekly. Treatment-naive participants were those who had never been exposed to any hepatitis C virus (HCV) therapy with interferon IFNα-containing regimens, including pegIFNα/ribavirin..	Participants received 10 mg of daclatasvir, once daily, coadministered with ribavirin, twice daily, and pegIFNα injection, once weekly. Treatment-naive participants were those who had never been exposed to any HCV therapy with interferon IFNα-containing regimens, including pegIFNα/ribavirin..	Participants received 60 mg of daclatasvir, once daily, coadministered with ribavirin, twice daily, and pegIFNα injection, once weekly. Treatment-naive participants were those who had never been exposed to any HCV therapy with interferon IFNα-containing regimens, including pegIFNα/ribavirin.	Participants received 10 mg of daclatasvir, once daily, coadministered with ribavirin, twice daily, and pegIFNα injection once weekly. Nonresponders were participants who had never attained undetectable HCV RNA levels, after at least 12 weeks of the current standard of care, pegIFNα/ribavirin.	Participants received 60 mg of daclatasvir, once daily, coadministered with ribavirin, twice daily, and pegIFNα injection once weekly. Nonresponders were participants who had never attained undetectable HCV RNA levels, after at least 12 weeks of the current standard of care, pegIFNα/ribavirin.
Measure Participants	8	9	10	9	9
Hemoglobin	1 12.5%	0 0%	1 10%	3 33.3%	0 0%
Lymphocytes	2 25%	2 22.2%	3 30%	3 33.3%	2 22.2%
Neutrophils	2 25%	4 44.4%	2 20%	2 22.2%	0 0%
WBC	1 12.5%	1 11.1%	0 0%	2 22.2%	0 0%
ALT	0 0%	1 11.1%	0 0%	0 0%	1 11.1%
AST	0 0%	1 11.1%	0 0%	0 0%	1 11.1%
Total bilirubin	0 0%	1 11.1%	0 0%	0 0%	0 0%

3. Primary Outcome

Title	Percentage of Participants With Extended Rapid Virologic Response (eRVR)
Description	eRVR was defined as undetectable hepatitis C virus (HCV) RNA (ie, HCV RNA <15 IU/mL, the lower limit of detection, target not detected) at both Weeks 4 and 12. HCV RNA levels were measured by Tobas TaqMan HCV Auto from the central laboratory.
Time Frame	At Weeks 4 and 12 on treatment

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study therapy.

Arm/Group Title	Placebo + pegIFNα + Ribavirin (Treatment-naive)	Daclatasvir 10- mg + pegIFNα + Ribavirin (Treatment-naive)	Daclatasvir 60- mg + pegIFNα + Ribavirin (Treatment Naive)	Daclatasvir 10- mg + pegINFα + Ribavirin (Nonresponders)	Daclatasvir 60- mg + pegIFNα + Ribavirin (Nonresponders)
Arm/Group Description	Participants received a matching placebo of daclatasvir tablet, once daily coadministered with ribavirin, twice daily, and peginterferon alpha (pegIFNα) injection, once weekly. Treatment-naive participants were those who had never been exposed to any hepatitis C virus (HCV) therapy with interferon IFNα-containing regimens, including pegIFNα/ribavirin.	Participants received 10 mg of daclatasvir, once daily, coadministered with ribavirin, twice daily, and pegIFNα injection, once weekly. Treatment-naive participants were those who had never been exposed to any HCV therapy with interferon IFNα-containing regimens, including pegIFNα/ribavirin	Participants received 60 mg of daclatasvir, once daily, coadministered with ribavirin, twice daily, and pegIFNα injection, once weekly. Treatment-naive participants were those who had never been exposed to any HCV therapy with interferon IFNα-containing regimens, including pegIFNα/ribavirin.	Participants received 10 mg of daclatasvir, once daily, coadministered with ribavirin, twice daily, and pegIFNα injection once weekly. Nonresponders were participants who had never attained undetectable HCV RNA levels, after at least 12 weeks of the current standard of care, pegIFNα/ribavirin.	Participants received 60 mg of daclatasvir, once daily, coadministered with ribavirin, twice daily, and pegIFNα injection once weekly. Nonresponders were participants who had never attained undetectable HCV RNA levels, after at least 12 weeks of the current standard of care pegIFNα/ribavirin.
Measure Participants	8	9	10	9	9
Number (80% Confidence Interval) [percentage of participants]	0 0%	66.7 741.1%	80.0 800%	55.6 617.8%	22.2 246.7%

4. Secondary Outcome

Title	Percentage of Participants With Rapid Virologic Response (RVR)
Description	RVR was defined as undetectable hepatitis C virus (HCV) RNA (ie, HCV RNA <15 IU/mL, the lower limit of detection, target not detected) at Week 4. HCV RNA levels were measured by CobasTaqMan HCV Auto from the central laboratory .
Time Frame	At Week 4 on treatment

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study therapy.

Arm/Group Title	Placebo + pegIFNα + Ribavirin (Treatment-naive)	Daclatasvir 10 mg + pegIFNα + Ribavirin (Treatment-naive)	Daclatasvir 60 mg + pegIFNα + Ribavirin (Treatment-naive)	Daclatasvir 10 mg + pegIFNα + Ribavirin (Nonresponders)	Daclatasvir 60 mg + pegIFNα + Ribavirin (Nonresponders)
Arm/Group Description	Participants received a matching placebo of daclatasvir tablet, once daily coadministered with ribavirin, twice daily, and peginterferon alpha(pegIFNα) injection, once weekly. Treatment-naive participants were those who had never been exposed to any hepatitis C virus (HCV) therapy with interferon IFNα-containing regimens, including pegIFNα/ribavirin	Participants received 10 mg of daclatasvir, once daily, coadministered with ribavirin, twice daily, and pegIFNα injection, once weekly. Treatment-naive participants were those who had never been exposed to any HCV therapy with interferon IFNα-containing regimens, including pegIFNα/ribavirin.	Participants received 60 mg of daclatasvir, once daily, coadministered with ribavirin, twice daily, and pegIFNα injection, once weekly. Treatment-naive participants were those who had never been exposed to any HCV therapy with interferon IFNα-containing regimens, including pegIFNα/ribavirin.	Participants received 10 mg of daclatasvir, once daily, coadministered with ribavirin, twice daily, and pegIFNα injection once weekly. Nonresponders were participants who had never attained undetectable HCV RNA levels, after at least 12 weeks of the current standard of care, pegIFNα/ribavirin..	Participants received 60 mg of daclatasvir, once daily, coadministered with ribavirin, twice daily, and pegIFNα injection once weekly. Nonresponders were participants who had never attained undetectable HCV RNA levels, after at least 12 weeks of the current standard of care pegIFNα/ribavirin.
Measure Participants	8	9	10	9	9
Number (80% Confidence Interval) [percentage of participants]	0 0%	77.8 864.4%	80.0 800%	55.6 617.8%	33.3 370%

5. Secondary Outcome

Title	Percentage of Participants With Complete Early Virologic Response (cEVR)
Description	cEVR was defined as undetectable hepatitis C virus (HCV) RNA (ie, HCV RNA <15 IU/mL, the lower limit of detection, target not detected) at Week 12 on treatment. HCV RNA levels were measured by Cobas TaqMan HCV Auto from the central laboratory
Time Frame	At Week 12 on treatment

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study therapy.

Arm/Group Title	Placebo + pegIFNα + Ribavirin (Treatment-naive)	Daclatasvir 10 mg + pegIFNα + Ribavirin (Treatment-naive)	Daclatasvir 60 mg + pegIFNα + Ribavirin (Treatment-naive)	Daclatasvir 10 mg + pegIFNα + Ribavirin (Nonreponders)	Daclatasvir 60 mg + pegIFNα + Ribavirin (Nonresponders)
Arm/Group Description	Participants received a matching placebo of daclatasvir tablet, once daily coadministered with ribavirin, twice daily, and peginterferon alpha (pegIFNα) injection, once weekly. Treatment-naive participants were those who had never been exposed to any hepatitis C virus (HCV) therapy with interferon IFNα-containing regimens, including pegIFNα/ribavirin.	Participants received 10 mg of daclatasvir, once daily, coadministered with ribavirin, twice daily, and pegIFNα injection, once weekly. Treatment-naive participants were those who had never been exposed to any HCV therapy with interferon IFNα-containing regimens, including pegIFNα/ribavirin.	Participants received 60 mg of daclatasvir, once daily, coadministered with ribavirin, twice daily, and pegIFNα injection, once weekly. Treatment-naive participants were those who had never been exposed to any HCV therapy with interferon IFNα-containing regimens, including pegIFNα/ribavirin.	Participants received 10 mg of daclatasvir, once daily, coadministered with ribavirin, twice daily, and pegIFNα injection once weekly. Nonresponders were participants who had never attained undetectable HCV RNA levels, after at least 12 weeks of the current standard of care, pegIFNα/ribavirin.	Participants received 60 mg of daclatasvir, once daily, coadministered with ribavirin, twice daily, and pegIFNα injection once weekly. Nonresponders were participants who had never attained undetectable HCV RNA levels, after at least 12 weeks of the current standard of care pegIFNα/ribavirin.
Measure Participants	8	9	10	9	9
Number (80% Confidence Interval) [percentage of participants]	62.5 781.3%	77.8 864.4%	100.0 1000%	55.6 617.8%	55.6 617.8%

6. Secondary Outcome

Title	Percentage of Participants With a Sustained Virologic Response (SVR) at Weeks 4, 12, and 24
Description	SVR at follow-up Week 4 (SVR4), follow-up Week 12 (SVR12), and follow-up Week 24 (SVR24) is defined as undetectable hepatitis C virus (HCV) RNA (ie, HCV RNA <15 IU/mL, the lower limit of detection, target not detected) at each of these timepoints. HCV RNA levels were measured by Cobas TaqMan HCV Auto from the central laboratory .
Time Frame	Follow-up Weeks 4, 12, and 24

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study therapy.

Arm/Group Title	Placebo + pegIFNα + Ribavirin (Treatment-naive)	Daclatasvir 10 mg + pegIFNα + Ribavirin (Treatment-naive)	Daclatasvir 60 mg + pegIFNα + Ribavirin (Treatment-naive)	Daclatasvir 10 mg + pegIFNα + Ribavirin (Nonresponders)	Daclatasvir 60 mg + pegIFNα + Ribavirin (Nonresponders)
Arm/Group Description	Participants received a matching placebo of daclatasvir tablet, once daily coadministered with ribavirin, twice daily, and peginterferon alpha (pegIFNα) injection, once weekly. Treatment-naive participants were those who had never been exposed to any hepatitis C virus (HCV) therapy with interferon IFNα-containing regimens, including pegIFNα/ribavirin.	Participants received 10 mg of daclatasvir, once daily, coadministered with ribavirin, twice daily, and pegIFNα injection, once weekly. Treatment-naive participants were those who had never been exposed to any HCV therapy with interferon IFNα-containing regimens, including pegIFNα/ribavirin.	Participants received 60 mg of daclatasvir, once daily, coadministered with ribavirin, twice daily, and pegIFNα injection, once weekly. Treatment-naive participants were those who had never been exposed to any HCV therapy with interferon IFNα-containing regimens, including pegIFNα/ribavirin.	Participants received 10 mg of daclatasvir, once daily, coadministered with ribavirin, twice daily, and pegIFNα injection once weekly. Nonresponders were participants who had never attained undetectable HCV RNA levels, after at least 12 weeks of the current standard of care, pegIFNα/ribavirin.	Participants received 60 mg of daclatasvir, once daily, coadministered with ribavirin, twice daily, and pegIFNα injection once weekly. Nonresponders were participants who had never attained undetectable HCV RNA levels, after at least 12 weeks of the current standard of care, pegIFNα/ribavirin
Measure Participants	8	9	10	9	9
SVR4: Follow-up Week 4	75.0 937.5%	66.7 741.1%	90.0 900%	22.2 246.7%	33.3 370%
SVR12: Follow-up Week 12	62.5 781.3%	66.7 741.1%	90.0 900%	22.2 246.7%	33.3 370%
SVR24: Follow-up Week 24	62.5 781.3%	66.7 741.1%	90.0 900%	22.2 246.7%	33.3 370%

7. Secondary Outcome

Title	Percentage of Participants With Virologic Failure
Description	Virologic failure is defined by the following 6 categories: 1.Virologic breakthrough, defined as confirmed >1 log10 increase in hepatitis C virus (HCV) RNA over nadir or confirmed HCV RNA ≥limit of quantitation (LOQ) after confirmed undetectable HCV RNA while on treatment. 2. <1 log10 decrease in HCV RNA from baseline at Week 4 of treatment. 3. Failure to achieve early virologic response, defined as <2 log10 decrease in HCV RNA from baseline at Week 12 of treatment. 4. Detectable HCV RNA at Week 12, and HCV RNA ≥LOQ at Week 24 of treatment. 5. Detectable HCV RNA at end of treatment (including early discontinuation). 6 Relapse, defined as detectable HCV RNA during follow-up after undetectable HCV RNA levels at end of treatment.
Time Frame	From on-treatment Week 1 to Follow-up Week 24

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study therapy.

Arm/Group Title	Placebo + pegIFNα + Ribavirin (Treatment-naive)	Daclatasvir 10 mg + pegIFNα + Ribavirin (Treatment-naive)	Daclatasvir 60 mg + Peg-IFNα + Ribavirin (Treatment-naive)	Daclatasvir 10 mg + pegIFNα + Ribavirin (Nonresponders)	Daclatasvir 60 mg + pegIFNα + Ribavirin (Nonresponders)
Arm/Group Description	Participants received a matching placebo of daclatasvir tablet, once daily coadministered with ribavirin, twice daily, and peginterferon alpha(pegIFNα) injection, once weekly. Treatment-naive participants were those who had never been exposed to any hepatitis C virus (HCV) therapy with interferon IFNα-containing regimens, including pegIFNα/ribavirin	Participants received 10 mg of daclatasvir, once daily, coadministered with ribavirin, twice daily, and pegIFNα injection, once weekly. Treatment-naive participants were those who had never been exposed to any HCV therapy with interferon IFNα-containing regimens, including pegIFNα/ribavirin	received 60 mg of daclatasvir, once daily, coadministered with ribavirin, twice daily, and pegIFNα injection, once weekly. Treatment-naive participants were those who had never been exposed to any HCV therapy with interferon IFNα-containing regimens, including pegIFNα/ribavirin.	Participants received 10 mg of daclatasvir, once daily, coadministered with ribavirin, twice daily, and pegIFNα injection once weekly. Nonresponders were participants who had never attained undetectable HCV RNA levels, after at least 12 weeks of the current standard of care, pegIFNα/ribavirin.	Participants received 60 mg of daclatasvir, once daily, coadministered with ribavirin, twice daily, and pegIFNα injection once weekly. Nonresponders were participants who had never attained undetectable HCV RNA levels, after at least 12 weeks of the current standard of care pegIFNα/ribavirin.
Measure Participants	8	9	10	9	9
Virologic failure	37.5 468.8%	33.3 370%	10.0 100%	77.8 864.4%	66.7 741.1%
Virologic breakthrough	12.5 156.3%	11.1 123.3%	0.0 0%	44.4 493.3%	44.4 493.3%
Relapse	25.0 312.5%	11.1 123.3%	10.0 100%	33.3 370%	22.2 246.7%

Adverse Events

Time Frame	From baseline up to 30 days after last dose of study drug
Arm/Group Title	Placebo+pegIFNα +Ribavirin (Treatment Naive)		Daclatasvir 10- mg+pegIFNα+Ribavirin (Treatment Naive)		Daclatasvir 60- mg+pegIFNα+Ribavirin (Treatment Naive)		Daclatasvir 10- mg+pegIFNα+Ribavirin (Non--Responders)		Daclatasvir 60- mg+pegIFNα+Ribavirin (Non--Responders)
Arm/Group Description	Participants received a matching placebo of daclatasvir tablet, orally, once daily (OD) with peginterferon alpha-2a (pegIFNα) subcutaneously once weekly and ribavirin orally, twice daily (BID). Treatment naive participants were those who had never been exposed to any Hepatitis C Virus (HCV) therapy with interferon IFNα containing regimens including pegIFNα-2b/ribavirin.		Participants received 10 mg of daclatasvir OD coadministered with pegIFNα subcutaneously once weekly and ribavirin orally BID. Treatment naive participants were defined as those who had never been exposed to any HCV therapy with IFNα containing regimens including pegIFNα-2b/ribavirin.		Participants received 60 mg of daclatasvir OD in coadministration with pegIFNα administered subcutaneously once weekly and ribavirin administered orally BID. Treatment naive participants were defined as those who had never been exposed to any HCV therapy with IFNα containing regimens including pegIFNα-2b/ribavirin.		Participants received 10 mg of daclatasvir OD coadministered with pegIFNα subcutaneously once weekly and ribavirin orally BID. Non-responders were participants who had never attained undetectable HCV RNA levels, after at least 12 weeks of the current standard of care pegIFNα-2b/ribavirin.		Participants received 60 mg of daclatasvir OD in coadministration with pegIFNα administered subcutaneously once weekly and ribavirin administered orally BID. Non-responders were participants who had never attained undetectable HCV RNA levels, after at least 12 weeks of the current standard of care pegIFNα-2b/ribavirin.
All Cause Mortality
	Placebo+pegIFNα +Ribavirin (Treatment Naive)		Daclatasvir 10- mg+pegIFNα+Ribavirin (Treatment Naive)		Daclatasvir 60- mg+pegIFNα+Ribavirin (Treatment Naive)		Daclatasvir 10- mg+pegIFNα+Ribavirin (Non--Responders)		Daclatasvir 60- mg+pegIFNα+Ribavirin (Non--Responders)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo+pegIFNα +Ribavirin (Treatment Naive)		Daclatasvir 10- mg+pegIFNα+Ribavirin (Treatment Naive)		Daclatasvir 60- mg+pegIFNα+Ribavirin (Treatment Naive)		Daclatasvir 10- mg+pegIFNα+Ribavirin (Non--Responders)		Daclatasvir 60- mg+pegIFNα+Ribavirin (Non--Responders)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/9 (0%)		0/10 (0%)		1/9 (11.1%)		0/9 (0%)
Infections and infestations
Gastroenteritis	0/8 (0%)		0/9 (0%)		0/10 (0%)		1/9 (11.1%)		0/9 (0%)
Other (Not Including Serious) Adverse Events
	Placebo+pegIFNα +Ribavirin (Treatment Naive)		Daclatasvir 10- mg+pegIFNα+Ribavirin (Treatment Naive)		Daclatasvir 60- mg+pegIFNα+Ribavirin (Treatment Naive)		Daclatasvir 10- mg+pegIFNα+Ribavirin (Non--Responders)		Daclatasvir 60- mg+pegIFNα+Ribavirin (Non--Responders)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/8 (100%)		9/9 (100%)		10/10 (100%)		9/9 (100%)		9/9 (100%)
Blood and lymphatic system disorders
Neutropenia	2/8 (25%)		4/9 (44.4%)		2/10 (20%)		2/9 (22.2%)		0/9 (0%)
Lymphopenia	2/8 (25%)		2/9 (22.2%)		3/10 (30%)		3/9 (33.3%)		2/9 (22.2%)
Anaemia	5/8 (62.5%)		2/9 (22.2%)		2/10 (20%)		5/9 (55.6%)		1/9 (11.1%)
Leukopenia	1/8 (12.5%)		1/9 (11.1%)		0/10 (0%)		2/9 (22.2%)		0/9 (0%)
Thrombocytopenia	0/8 (0%)		0/9 (0%)		0/10 (0%)		0/9 (0%)		1/9 (11.1%)
Cardiac disorders
Ventricular extrasystoles	0/8 (0%)		1/9 (11.1%)		0/10 (0%)		0/9 (0%)		0/9 (0%)
Tachycardia	0/8 (0%)		0/9 (0%)		0/10 (0%)		0/9 (0%)		1/9 (11.1%)
Ear and labyrinth disorders
Vertigo	0/8 (0%)		0/9 (0%)		0/10 (0%)		0/9 (0%)		1/9 (11.1%)
Ear pain	0/8 (0%)		0/9 (0%)		1/10 (10%)		0/9 (0%)		0/9 (0%)
Inner ear disorder	0/8 (0%)		0/9 (0%)		1/10 (10%)		0/9 (0%)		0/9 (0%)
Tinnitus	0/8 (0%)		0/9 (0%)		2/10 (20%)		0/9 (0%)		1/9 (11.1%)
Endocrine disorders
Hypothyroidism	0/8 (0%)		0/9 (0%)		0/10 (0%)		1/9 (11.1%)		1/9 (11.1%)
Basedow's disease	0/8 (0%)		1/9 (11.1%)		0/10 (0%)		0/9 (0%)		0/9 (0%)
Eye disorders
Eye pain	0/8 (0%)		0/9 (0%)		0/10 (0%)		0/9 (0%)		1/9 (11.1%)
Retinal tear	1/8 (12.5%)		0/9 (0%)		0/10 (0%)		0/9 (0%)		0/9 (0%)
Retinopathy	1/8 (12.5%)		0/9 (0%)		0/10 (0%)		0/9 (0%)		0/9 (0%)
Blepharitis	0/8 (0%)		1/9 (11.1%)		1/10 (10%)		0/9 (0%)		0/9 (0%)
Conjunctivitis	0/8 (0%)		1/9 (11.1%)		0/10 (0%)		0/9 (0%)		0/9 (0%)
Retinal disorder	1/8 (12.5%)		0/9 (0%)		0/10 (0%)		0/9 (0%)		0/9 (0%)
Phosphenes	1/8 (12.5%)		0/9 (0%)		0/10 (0%)		0/9 (0%)		0/9 (0%)
Retinal haemorrhage	0/8 (0%)		0/9 (0%)		0/10 (0%)		1/9 (11.1%)		0/9 (0%)
Dry eye	1/8 (12.5%)		0/9 (0%)		0/10 (0%)		0/9 (0%)		1/9 (11.1%)
Retinal exudates	0/8 (0%)		0/9 (0%)		1/10 (10%)		0/9 (0%)		0/9 (0%)
Gastrointestinal disorders
Diarrhoea	1/8 (12.5%)		3/9 (33.3%)		4/10 (40%)		3/9 (33.3%)		1/9 (11.1%)
Dry mouth	0/8 (0%)		0/9 (0%)		1/10 (10%)		1/9 (11.1%)		0/9 (0%)
Epigastric discomfort	0/8 (0%)		0/9 (0%)		0/10 (0%)		0/9 (0%)		1/9 (11.1%)
Abdominal pain	0/8 (0%)		1/9 (11.1%)		0/10 (0%)		0/9 (0%)		0/9 (0%)
Dyspepsia	1/8 (12.5%)		0/9 (0%)		0/10 (0%)		0/9 (0%)		0/9 (0%)
Abdominal distension	1/8 (12.5%)		1/9 (11.1%)		0/10 (0%)		0/9 (0%)		1/9 (11.1%)
Cheilitis	0/8 (0%)		2/9 (22.2%)		3/10 (30%)		0/9 (0%)		0/9 (0%)
Vomiting	0/8 (0%)		0/9 (0%)		2/10 (20%)		2/9 (22.2%)		2/9 (22.2%)
Constipation	3/8 (37.5%)		1/9 (11.1%)		1/10 (10%)		1/9 (11.1%)		2/9 (22.2%)
Dental caries	0/8 (0%)		0/9 (0%)		0/10 (0%)		0/9 (0%)		1/9 (11.1%)
Nausea	3/8 (37.5%)		1/9 (11.1%)		1/10 (10%)		2/9 (22.2%)		0/9 (0%)
Abdominal discomfort	1/8 (12.5%)		2/9 (22.2%)		3/10 (30%)		1/9 (11.1%)		1/9 (11.1%)
Abdominal pain upper	0/8 (0%)		2/9 (22.2%)		0/10 (0%)		0/9 (0%)		1/9 (11.1%)
Enterocolitis	1/8 (12.5%)		0/9 (0%)		0/10 (0%)		0/9 (0%)		0/9 (0%)
Lip dry	1/8 (12.5%)		0/9 (0%)		1/10 (10%)		0/9 (0%)		0/9 (0%)
Periodontitis	0/8 (0%)		0/9 (0%)		0/10 (0%)		0/9 (0%)		1/9 (11.1%)
Stomatitis	1/8 (12.5%)		3/9 (33.3%)		3/10 (30%)		1/9 (11.1%)		1/9 (11.1%)
Gingivitis	0/8 (0%)		0/9 (0%)		1/10 (10%)		0/9 (0%)		0/9 (0%)
General disorders
Fatigue	3/8 (37.5%)		0/9 (0%)		3/10 (30%)		3/9 (33.3%)		1/9 (11.1%)
Feeling abnormal	0/8 (0%)		0/9 (0%)		1/10 (10%)		0/9 (0%)		0/9 (0%)
Injection site rash	0/8 (0%)		0/9 (0%)		1/10 (10%)		0/9 (0%)		0/9 (0%)
Vessel puncture site pain	0/8 (0%)		0/9 (0%)		0/10 (0%)		1/9 (11.1%)		0/9 (0%)
Injection site reaction	1/8 (12.5%)		1/9 (11.1%)		2/10 (20%)		2/9 (22.2%)		1/9 (11.1%)
Chills	0/8 (0%)		0/9 (0%)		2/10 (20%)		1/9 (11.1%)		0/9 (0%)
Influenza like illness	0/8 (0%)		1/9 (11.1%)		1/10 (10%)		2/9 (22.2%)		1/9 (11.1%)
Vessel puncture site reaction	1/8 (12.5%)		0/9 (0%)		0/10 (0%)		0/9 (0%)		0/9 (0%)
Chest pain	0/8 (0%)		0/9 (0%)		0/10 (0%)		1/9 (11.1%)		0/9 (0%)
Injection site injury	0/8 (0%)		0/9 (0%)		1/10 (10%)		0/9 (0%)		0/9 (0%)
Pyrexia	5/8 (62.5%)		8/9 (88.9%)		9/10 (90%)		6/9 (66.7%)		8/9 (88.9%)
Injection site erythema	1/8 (12.5%)		2/9 (22.2%)		0/10 (0%)		0/9 (0%)		0/9 (0%)
Injection site pruritus	2/8 (25%)		3/9 (33.3%)		3/10 (30%)		2/9 (22.2%)		1/9 (11.1%)
Malaise	2/8 (25%)		7/9 (77.8%)		2/10 (20%)		2/9 (22.2%)		1/9 (11.1%)
Vessel puncture site pruritus	0/8 (0%)		0/9 (0%)		1/10 (10%)		0/9 (0%)		0/9 (0%)
Infections and infestations
Gastroenteritis	0/8 (0%)		0/9 (0%)		0/10 (0%)		1/9 (11.1%)		0/9 (0%)
Folliculitis	1/8 (12.5%)		0/9 (0%)		0/10 (0%)		0/9 (0%)		0/9 (0%)
Nasopharyngitis	2/8 (25%)		5/9 (55.6%)		3/10 (30%)		0/9 (0%)		2/9 (22.2%)
Bronchitis	0/8 (0%)		1/9 (11.1%)		0/10 (0%)		0/9 (0%)		0/9 (0%)
Cystitis	0/8 (0%)		0/9 (0%)		0/10 (0%)		2/9 (22.2%)		2/9 (22.2%)
Otitis externa	0/8 (0%)		0/9 (0%)		2/10 (20%)		0/9 (0%)		0/9 (0%)
Pharyngitis	0/8 (0%)		0/9 (0%)		0/10 (0%)		0/9 (0%)		1/9 (11.1%)
Atypical mycobacterial infection	0/8 (0%)		0/9 (0%)		0/10 (0%)		0/9 (0%)		1/9 (11.1%)
Otitis media	0/8 (0%)		0/9 (0%)		1/10 (10%)		0/9 (0%)		0/9 (0%)
Oral herpes	0/8 (0%)		0/9 (0%)		0/10 (0%)		0/9 (0%)		1/9 (11.1%)
Injury, poisoning and procedural complications
Fall	1/8 (12.5%)		0/9 (0%)		0/10 (0%)		0/9 (0%)		1/9 (11.1%)
Thermal burn	0/8 (0%)		0/9 (0%)		0/10 (0%)		1/9 (11.1%)		0/9 (0%)
Arthropod sting	0/8 (0%)		0/9 (0%)		1/10 (10%)		0/9 (0%)		0/9 (0%)
Contusion	2/8 (25%)		0/9 (0%)		0/10 (0%)		0/9 (0%)		1/9 (11.1%)
Investigations
Blood thyroid stimulating hormone increased	2/8 (25%)		0/9 (0%)		0/10 (0%)		0/9 (0%)		0/9 (0%)
Blood bilirubin increased	0/8 (0%)		1/9 (11.1%)		0/10 (0%)		0/9 (0%)		0/9 (0%)
Gamma-glutamyltransferase increased	0/8 (0%)		1/9 (11.1%)		0/10 (0%)		0/9 (0%)		0/9 (0%)
Weight decreased	3/8 (37.5%)		0/9 (0%)		0/10 (0%)		1/9 (11.1%)		1/9 (11.1%)
Alanine aminotransferase increased	0/8 (0%)		1/9 (11.1%)		0/10 (0%)		0/9 (0%)		0/9 (0%)
Aspartate aminotransferase increased	0/8 (0%)		1/9 (11.1%)		0/10 (0%)		0/9 (0%)		0/9 (0%)
Blood triglycerides increased	0/8 (0%)		0/9 (0%)		0/10 (0%)		1/9 (11.1%)		0/9 (0%)
Blood phosphorus decreased	0/8 (0%)		0/9 (0%)		1/10 (10%)		0/9 (0%)		0/9 (0%)
Blood pressure increased	1/8 (12.5%)		0/9 (0%)		0/10 (0%)		0/9 (0%)		1/9 (11.1%)
Lipase increased	1/8 (12.5%)		0/9 (0%)		0/10 (0%)		0/9 (0%)		1/9 (11.1%)
Metabolism and nutrition disorders
Decreased appetite	1/8 (12.5%)		3/9 (33.3%)		3/10 (30%)		5/9 (55.6%)		2/9 (22.2%)
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion	0/8 (0%)		1/9 (11.1%)		1/10 (10%)		0/9 (0%)		0/9 (0%)
Temporomandibular joint syndrome	0/8 (0%)		0/9 (0%)		0/10 (0%)		0/9 (0%)		1/9 (11.1%)
Neck mass	0/8 (0%)		0/9 (0%)		1/10 (10%)		0/9 (0%)		0/9 (0%)
Arthralgia	3/8 (37.5%)		2/9 (22.2%)		0/10 (0%)		0/9 (0%)		0/9 (0%)
Muscle spasms	1/8 (12.5%)		0/9 (0%)		0/10 (0%)		0/9 (0%)		0/9 (0%)
Musculoskeletal stiffness	1/8 (12.5%)		0/9 (0%)		1/10 (10%)		0/9 (0%)		1/9 (11.1%)
Musculoskeletal pain	0/8 (0%)		0/9 (0%)		0/10 (0%)		0/9 (0%)		1/9 (11.1%)
Back pain	1/8 (12.5%)		0/9 (0%)		3/10 (30%)		5/9 (55.6%)		0/9 (0%)
Myalgia	2/8 (25%)		0/9 (0%)		1/10 (10%)		0/9 (0%)		0/9 (0%)
Pain in extremity	0/8 (0%)		0/9 (0%)		1/10 (10%)		0/9 (0%)		0/9 (0%)
Nervous system disorders
Dizziness	0/8 (0%)		0/9 (0%)		1/10 (10%)		2/9 (22.2%)		1/9 (11.1%)
Dysgeusia	0/8 (0%)		0/9 (0%)		3/10 (30%)		3/9 (33.3%)		0/9 (0%)
Neuropathy peripheral	0/8 (0%)		0/9 (0%)		1/10 (10%)		0/9 (0%)		0/9 (0%)
Carpal tunnel syndrome	0/8 (0%)		1/9 (11.1%)		0/10 (0%)		0/9 (0%)		0/9 (0%)
Migraine	0/8 (0%)		0/9 (0%)		2/10 (20%)		0/9 (0%)		0/9 (0%)
Poor quality sleep	0/8 (0%)		0/9 (0%)		0/10 (0%)		1/9 (11.1%)		0/9 (0%)
Dizziness postural	0/8 (0%)		0/9 (0%)		1/10 (10%)		0/9 (0%)		0/9 (0%)
Syncope	0/8 (0%)		0/9 (0%)		0/10 (0%)		1/9 (11.1%)		0/9 (0%)
Headache	5/8 (62.5%)		6/9 (66.7%)		4/10 (40%)		5/9 (55.6%)		3/9 (33.3%)
Psychiatric disorders
Anxiety disorder	0/8 (0%)		0/9 (0%)		0/10 (0%)		0/9 (0%)		1/9 (11.1%)
Depressed mood	1/8 (12.5%)		0/9 (0%)		0/10 (0%)		0/9 (0%)		0/9 (0%)
Depression	0/8 (0%)		0/9 (0%)		1/10 (10%)		0/9 (0%)		0/9 (0%)
Insomnia	2/8 (25%)		2/9 (22.2%)		3/10 (30%)		0/9 (0%)		0/9 (0%)
Renal and urinary disorders
Nephrolithiasis	1/8 (12.5%)		0/9 (0%)		0/10 (0%)		0/9 (0%)		0/9 (0%)
Reproductive system and breast disorders
Amenorrhoea	0/8 (0%)		0/9 (0%)		0/10 (0%)		1/9 (11.1%)		0/9 (0%)
Respiratory, thoracic and mediastinal disorders
Laryngeal inflammation	0/8 (0%)		1/9 (11.1%)		0/10 (0%)		0/9 (0%)		0/9 (0%)
Nasal congestion	0/8 (0%)		0/9 (0%)		1/10 (10%)		0/9 (0%)		0/9 (0%)
Dyspnoea exertional	0/8 (0%)		0/9 (0%)		0/10 (0%)		1/9 (11.1%)		0/9 (0%)
Oropharyngeal discomfort	1/8 (12.5%)		1/9 (11.1%)		0/10 (0%)		0/9 (0%)		0/9 (0%)
Rhinitis allergic	0/8 (0%)		1/9 (11.1%)		0/10 (0%)		0/9 (0%)		0/9 (0%)
Dyspnoea	0/8 (0%)		0/9 (0%)		0/10 (0%)		0/9 (0%)		1/9 (11.1%)
Oropharyngeal pain	0/8 (0%)		1/9 (11.1%)		0/10 (0%)		0/9 (0%)		0/9 (0%)
Upper respiratory tract inflammation	1/8 (12.5%)		0/9 (0%)		0/10 (0%)		0/9 (0%)		0/9 (0%)
Cough	1/8 (12.5%)		0/9 (0%)		2/10 (20%)		0/9 (0%)		1/9 (11.1%)
Sputum retention	0/8 (0%)		1/9 (11.1%)		0/10 (0%)		0/9 (0%)		0/9 (0%)
Skin and subcutaneous tissue disorders
Dermatitis acneiform	0/8 (0%)		0/9 (0%)		1/10 (10%)		0/9 (0%)		0/9 (0%)
Dermatitis atopic	0/8 (0%)		0/9 (0%)		1/10 (10%)		0/9 (0%)		0/9 (0%)
Erythema	0/8 (0%)		1/9 (11.1%)		0/10 (0%)		0/9 (0%)		0/9 (0%)
Nail disorder	0/8 (0%)		0/9 (0%)		1/10 (10%)		0/9 (0%)		0/9 (0%)
Prurigo	0/8 (0%)		0/9 (0%)		0/10 (0%)		0/9 (0%)		1/9 (11.1%)
Rash	3/8 (37.5%)		2/9 (22.2%)		5/10 (50%)		0/9 (0%)		1/9 (11.1%)
Pruritus	3/8 (37.5%)		3/9 (33.3%)		2/10 (20%)		1/9 (11.1%)		5/9 (55.6%)
Pruritus generalised	0/8 (0%)		0/9 (0%)		1/10 (10%)		2/9 (22.2%)		0/9 (0%)
Urticaria	1/8 (12.5%)		0/9 (0%)		0/10 (0%)		0/9 (0%)		1/9 (11.1%)
Dry skin	1/8 (12.5%)		0/9 (0%)		1/10 (10%)		0/9 (0%)		0/9 (0%)
Eczema asteatotic	0/8 (0%)		0/9 (0%)		1/10 (10%)		0/9 (0%)		0/9 (0%)
Alopecia	3/8 (37.5%)		3/9 (33.3%)		7/10 (70%)		3/9 (33.3%)		3/9 (33.3%)
Drug eruption	0/8 (0%)		0/9 (0%)		0/10 (0%)		1/9 (11.1%)		0/9 (0%)
Eczema	1/8 (12.5%)		1/9 (11.1%)		2/10 (20%)		2/9 (22.2%)		0/9 (0%)
Heat rash	0/8 (0%)		0/9 (0%)		0/10 (0%)		1/9 (11.1%)		0/9 (0%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.