COMMAND-3: Study Comparing Daclatasvir (BMS-790052) With Telaprevir Combined With Peginterferon Alfa-2a and Ribavirin in Patients With Chronic Hepatitis C Virus Infection

• Sponsor: Bristol-Myers Squibb (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01492426
• Collaborator: (none)
• Enrollment: 605
• Locations: 91
• Arms: 2
• Duration (Months): 26
• Patients Per Site: 6.6
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The purpose of this study is to compare the effectiveness of BMS-790052 (Daclatasvir) and Telaprevir when given in combination with Peginterferon alfa-2a and Ribavirin in genotype 1b patients

Condition or Disease	Intervention/Treatment	Phase
Hepatitis C	Drug: Daclatasvir; Drug: Telaprevir; Drug: Peginterferon alfa-2a; Drug: Ribavirin	Phase 3

Detailed Description

Allocation: Randomized Stratified

Study Design

• Study Type: Interventional
• Actual Enrollment: 605 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 3 Evaluation of BMS-790052 (Daclatasvir) Compared With Telaprevir in Combination With Peginterferon Alfa-2a and Ribavirin in Treatment-Naive Patients With Chronic Hepatitis C
• Study Start Date: Jan 1, 2012
• Actual Primary Completion Date: Dec 1, 2013
• Actual Study Completion Date: Mar 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Daclatasvir + Peginterferon alfa-2a + Ribavirin	Drug: Daclatasvir; Film-coated tablet, oral, 60 mg, once daily, 24 weeks; Other Names: BMS-790052 ; Drug: Peginterferon alfa-2a; Solution for injection, subcutaneous injection, 180 μg, weekly; Other Names: Pegasys® ; Drug: Ribavirin; Film-coated tablet, oral, in a body weight stratified dose range of 1000-1200 mg per day; Other Names: Copegus®
Experimental: Telaprevir + Peginterferon alfa-2a + Ribavirin	Drug: Telaprevir; Film-coated tablet, oral, 750 mg, 3 times daily; Other Names: Incivek® ; Drug: Peginterferon alfa-2a; Solution for injection, subcutaneous injection, 180 μg, weekly; Other Names: Pegasys® ; Drug: Ribavirin; Film-coated tablet, oral, in a body weight stratified dose range of 1000-1200 mg per day; Other Names: Copegus®

Outcome Measures

Primary Outcome Measures

1. Percentage of Genotype 1b Participants With Sustained Virologic Response at Follow-up Week 12 (SVR12) [Week 12 (Follow-up period)]

   SVR12 was defined as hepatitis C virus RNA levels to be lower than the limit of quantitation, ie, 25 IU/mL target detected or target not detected at follow-up Week 12.

Secondary Outcome Measures

1. Percentage of Genotype 1b Participants With Rapid Virologic Response (RVR) at Week 4 [Week 4]

   RVR was defined as hepatitis c virus RNA levels lower than lower limit of quantitation, ie, 25 IU/mL target not detected at Week 4 of treatment.

2. Percentage of Genotype 1b Participants With Extended Rapid Virologic Response (eRVR) at Both Week 4 and Week 12 [Week 4, Week 12]

   eRVR was defined as hepatitis C virus RNA levels lower than the lower limit of quantitation, ie, 25 IU/mL target not detected at both Weeks 4 and 12 of treatment.

3. Percentage of Genotype 1b Participants With Complete Early Virologic Response (cEVR) [Week 12]

   cEVR was defined as hepatitis C virus RNA levels lower than the lower limit of quantitation, ie, 25 IU/mL target not detected at Week 12 of treatment.

4. Percentage of Genotype 1b Participants With Sustained Virologic Response at Follow-up Week 24 (SVR24) [Week 24 (Follow-up period)]

   SVR24 was defined as hepatitis C virus RNA levels lower than the lower limit of quantitation, ie, 25 IU/mL target detected or target not detected at follow-up week 24 of treatment.

5. Percentage of Genotype 1a Participants With Sustained Virologic Response at Follow-up Week 12 (SVR12) [Week 12 (Follow-up period)]

   SVR12 was defined as hepatitis C virus RNA levels lower than the lower limit of quantitation, ie, 25 IU/mL target detected or target not detected at follow-up week 12 of treatment.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Key Inclusion Criteria:

• Participants chronically infected with hepatitis C virus (HCV) genotype 1a or 1b

• HCV RNA viral load ≥10,000 IU/mL

• No prior treatment including but not limited to interferon, ribavirin, and direct-acting antivirals

• No history of cirrhosis liver biopsy within 3 years or Fibroscan® within 1 year

• Body mass index of 18 to 35 kg/m^2

• Negative for HIV and hepatitis B virus

Key Exclusion Criteria:

• Evidence of decompensated liver disease

• Evidence of medical condition other than HCV contributing to chronic liver disease

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Kirklin Clinic	Birmingham	Alabama	United States	35294
2	Mayo Clinic Arizona	Phoenix	Arizona	United States	85054
3	Va Long Beach Healthcare System	Long Beach	California	United States	90822
4	Medical Associates Research Group	San Diego	California	United States	92123
5	Yale University School Of Medicine	New Haven	Connecticut	United States	06520-8019
6	Orlando Immunology Center	Orlando	Florida	United States	32803
7	Atlanta Medical Center	Atlanta	Georgia	United States	30312
8	Gastrointestinal Specialists Of Georgia	Marietta	Georgia	United States	30060
9	Northwestern University	Chicago	Illinois	United States	60611
10	Rush University Medical Center	Chicago	Illinois	United States	60612
11	University Of Maryland	Baltimore	Maryland	United States	21201-1595
12	Johns Hopkins University	Lutherville	Maryland	United States	21093
13	Minnesota Gastroenterology, P.A.	Saint Paul	Minnesota	United States	55114
14	Saint Louis University Gastroenterology & Hepatology	St. Louis	Missouri	United States	63104
15	Weill Cornell Medical College	New York	New York	United States	10021
16	University Of North Carolina At Chapel Hill School Of Med	Chapel Hill	North Carolina	United States	27599-7584
17	Carolinas Medical Center	Charlotte	North Carolina	United States	28203
18	Duke University Medical Center	Durham	North Carolina	United States	27710
19	Albert Einstein Medical Center	Philadelphia	Pennsylvania	United States	19141
20	University Gastroenterology	Providence	Rhode Island	United States	02905
21	The Miriam Hospital	Providence	Rhode Island	United States	02906
22	Brooke Army Medical Center	Ft. Sam Houston	Texas	United States	78234
23	Baylor College Of Medicine	Houston	Texas	United States	77030
24	Research Specialists Of Texas	Houston	Texas	United States	77030
25	Alamo Medical Research	San Antonio	Texas	United States	78215
26	Local Institution	Ciudad De Buenos Aires	Buenos Aires	Argentina	C1121ABE
27	Local Institution	Ciudad De Buenos Aires	Buenos Aires	Argentina	C1181ACH
28	Local Institution	Prov. Buenos Aires	Buenos Aires	Argentina	1629
29	Local Institution	Prov De Santa Fe	Santa Fe	Argentina	2000
30	Local Institution	Camperdown	New South Wales	Australia	2050
31	Local Institution	Penrith	New South Wales	Australia	2750
32	Local Institution	Westmead Nsw	New South Wales	Australia	2145
33	Local Institution	Greenslopes Qld	Queensland	Australia	4120
34	Local Institution	Adelaide	South Australia	Australia	5000
35	Local Institution	Fitzroy	Victoria	Australia	3065 VIC
36	Local Institution	Prahran	Victoria	Australia	3181
37	Local Institution	Linz		Austria	4010
38	Local Institution	Wien		Austria	1090
39	Local Institution	Wien		Austria	1160
40	Local Institution	Sao Paulo		Brazil	04023-062
41	Local Institution	Calgary	Alberta	Canada	T2N 4Z6
42	Local Institution	Edmonton	Alberta	Canada	T6G 2B7
43	Local Institution	Vancouver	British Columbia	Canada	V6Z 2K5
44	Local Institution	Winnipeg	Manitoba	Canada	R3E 3P4
45	Local Institution	Ottawa	Ontario	Canada	K1H 8L6
46	Local Institution	Toronto	Ontario	Canada	M5G 2N2
47	Local Institution	Hvidovre		Denmark	2650
48	Local Institution	Odense		Denmark	5000
49	Local Institution	Besancon		France	25000
50	Local Institution	Bondy Cedex		France	93143
51	Local Institution	Grenoble Cedex 09		France	38043
52	Local Institution	Lille Cedex		France	59037
53	Local Institution	Paris Cedex 12		France	75571
54	Local Institution	Paris Cedex 13		France	75651
55	Local Institution	Pessac		France	33600
56	Local Institution	Strasbourg		France	67090
57	Local Institution	Berlin		Germany	10969
58	Local Institution	Berlin		Germany	13353
59	Local Institution	Essen		Germany	45122
60	Local Institution	Frankfurt		Germany	60590
61	Local Institution	Freiburg		Germany	79106
62	Local Institution	Hamburg		Germany	20246
63	Local Institution	Hannover		Germany	30625
64	Local Institution	Koeln		Germany	50937
65	Local Institution	Haifa		Israel	31096
66	Local Institution	Nazareth		Israel	16100
67	Local Institution	Tel Aviv		Israel	64239
68	Local Institution	Zefat		Israel	13110
69	Local Institution	Bergamo		Italy	24127
70	Local Institution	Cisanello (pisa)		Italy	56124
71	Local Institution	Firenze		Italy	50134
72	Local Institution	Napoli		Italy	80131
73	Local Institution	Torino		Italy	10100
74	Local Institution	Bialystok		Poland	15-540
75	Local Institution	Chorzow		Poland	41-500
76	Local Institution	Kielce		Poland	25-317
77	Local Institution	Myslowice		Poland	41-400
78	Local Institution	Raciborz		Poland	47-400
79	Local Institution	Wroclaw		Poland	50-220
80	Local Institution	Moscow		Russian Federation	109240
81	Local Institution	Moscow		Russian Federation	119991
82	Local Institution	Moscow		Russian Federation	121170
83	Local Institution	Alcorcon		Spain	28922
84	Local Institution	Barcelona		Spain	08003
85	Local Institution	Barcelona		Spain	08036
86	Local Institution	Valencia		Spain	46010
87	Local Institution	Zurich		Switzerland	8091
88	Local Institution	London	Greater London	United Kingdom	SE5 9RS
89	Local Institution	Edinburgh	Scotland	United Kingdom	EH4 2XU
90	Local Institution	Glasgow	Scotland	United Kingdom	G12 0YN
91	Local Institution	Birmingham	West Midlands	United Kingdom	B15 2TH

Sponsors and Collaborators

• Bristol-Myers Squibb

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• BMS clinical trial educational resource

Publications

None provided.

• Responsible Party: Bristol-Myers Squibb
• ClinicalTrials.gov Identifier: NCT01492426
• Other Study ID Numbers: AI444-052; 2011-004237-14
• First Posted: Dec 15, 2011
• Last Update Posted: Jun 3, 2016
• Last Verified: Apr 1, 2016

• Keywords provided by Bristol-Myers Squibb: Hepatitis C Virus
• Additional relevant MeSH terms: Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis; Ribavirin; Peginterferon alfa-2a

Study Results

Participant Flow

Recruitment Details	A total of 793 participants were recruited at 90 sites in 15 countries.
Pre-assignment Detail	Of the 793 participants, 605 were randomized to treatment. A total of 191 enrolled subjects did not enter the treatment period as they no longer met study entry criteria and a 602 participants were received treatment.

Arm/Group Title	Daclatasvir + PEG-IFN Alpha-2a + Ribavirin	Telaprevir + PEG-IFN Alpha-2a + Ribavirin
Arm/Group Description	Participants received daclatasvir 60-mg tablet orally once daily for 24 weeks in combination with pegylated interferon alpha-2a (PEG-IFN alpha-2a)180 µg administered subcutaneously once a week for 24 or 48 weeks and ribavarin administered in a body weight stratified dose range of 1000-1200 mg per day (for participants weighing less than 75 kg, the total dose was 1000 mg per day and for those weighing greater than or equal to 75 kg, the dose was 1200 mg per day).	Participants received 2 telaprevir 375-mg tablets orally 3 times a day for 12 weeks. PEG-IFN alpha-2a 180 µg was coadministered subcutaneously once a week for 24 or 48 weeks depending on response, and ribavirin in a body weight stratified dose range of 1000-1200 mg per day was administered twice daily with food.
Period Title: Treatment
STARTED	402	200
COMPLETED	319	160
NOT COMPLETED	83	40
Period Title: Treatment
STARTED	384	191
COMPLETED	359	181
NOT COMPLETED	25	10

Baseline Characteristics

Arm/Group Title	Daclatasvir + PEG-IFN Alpha-2a + Ribavirin	Telaprevir + PEG-IFN Alpha-2a + Ribavirin	Total
Arm/Group Description	Participants received daclatasvir 60-mg tablet orally once daily for 24 weeks in combination with pegylated interferon alpha-2a (PEG-IFN alpha-2a)180 µg administered subcutaneously once a week for 24 or 48 weeks and ribavarin administered in a body weight stratified dose range of 1000-1200 mg per day (for participants weighing less than 75 kg, the total dose was 1000 mg per day and for those weighing greater than or equal to 75 kg, the dose was 1200 mg per day).	Participants received 2 telaprevir 375-mg tablets orally 3 times a day for 12 weeks. PEG-IFN alpha-2a 180 µg was coadministered subcutaneously once a week for 24 or 48 weeks depending on response, and ribavirin in a body weight stratified dose range of 1000-1200 mg per day was administered twice daily with food.	Total of all reporting groups
Overall Participants	402	200	602
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	46.5 (12.12)	47.6 (12.29)	46.9 (12.18)
Age, Customized (participants) [Number]
Younger than 65 years	387 96.3%	188 94%	575 95.5%
65 years and older	15 3.7%	12 6%	27 4.5%
Sex: Female, Male (Count of Participants)
Female	145 36.1%	81 40.5%	226 37.5%
Male	257 63.9%	119 59.5%	376 62.5%

Outcome Measures

1. Primary Outcome

Title	Percentage of Genotype 1b Participants With Sustained Virologic Response at Follow-up Week 12 (SVR12)
Description	SVR12 was defined as hepatitis C virus RNA levels to be lower than the limit of quantitation, ie, 25 IU/mL target detected or target not detected at follow-up Week 12.
Time Frame	Week 12 (Follow-up period)

Outcome Measure Data

Analysis Population Description

The analysis was performed in all treated participants who received at least 1 dose of active study therapy. Here, 'Number of participants analysed' signifies Genotype 1b participants assessed for SVR12 response.

Arm/Group Title	Daclatasvir + PEG-IFN Alpha-2a + Ribavirin	Telaprevir + PEG-IFN Alpha-2a + Ribavirin
Arm/Group Description	Participants received daclatasvir 60-mg tablet orally once daily for 24 weeks in combination with pegylated interferon alpha-2a (PEG-IFN alpha-2a) 180 µg administered subcutaneously once a week for 24 or 48 weeks and ribavarin administered in a body weight stratified dose range of 1000-1200 mg per day (for participants weighing less than 75 kg, the total dose was 1000 mg per day and for those weighing greater than or equal to 75 kg, the dose was 1200 mg per day).	Participants received 2 telaprevir 375-mg tablets orally 3 times a day for 12 weeks. PEG-IFN alpha-2a 180 µg was coadministered subcutaneously once a week for 24 or 48 weeks depending on response, and ribavirin in a body weight stratified dose range of 1000-1200 mg per day was administered twice daily with food.
Measure Participants	268	134
Number (95% Confidence Interval) [Percentage of participants]	85.1 21.2%	81.3 40.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Daclatasvir + PEG-IFN Alpha-2a + Ribavirin, Telaprevir + PEG-IFN Alpha-2a + Ribavirin
	Comments	Percentage difference between SVR12 rate in the experimental and control arms was computed using a stratum-adjusted Mantel-Haenszel confidence interval (95% level) for the difference in rates. The stratification factors were IL28B rs1297860 single nucleotide polymorphism (CC or non-CC) and baseline cirrhosis status (absent or present), unless otherwise indicated.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Test of noninferiority was based on noninferiority margin of -12% and 2-sided alpha level of 5%. That is, if the lower bound of the 95% CI > -12%, the Daclatasvir arm would be considered nonnferior to the telaprevir arm.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage difference
	Estimated Value	4.3
	Confidence Interval	(2-Sided) 95%; -3.3 to 11.9
	Parameter Dispersion	Type: Standard Deviation; Value: 3.885
	Estimation Comments

2. Secondary Outcome

Title	Percentage of Genotype 1b Participants With Rapid Virologic Response (RVR) at Week 4
Description	RVR was defined as hepatitis c virus RNA levels lower than lower limit of quantitation, ie, 25 IU/mL target not detected at Week 4 of treatment.
Time Frame	Week 4

Outcome Measure Data

Analysis Population Description

The analysis was performed in all treated participants who received at least 1 dose of active study therapy. Here, 'Number of participants analysed' signifies Genotype 1b participants assessed for RVR response.

Arm/Group Title	Daclatasvir + PEG-IFN Alpha-2a + Ribavirin	Telaprevir + PEG-IFN Alpha-2a + Ribavirin
Arm/Group Description	Participants received daclatasvir 60-mg tablet orally once daily for 24 weeks in combination with pegylated interferon alpha-2a (PEG-IFN alpha-2a) 180 µg administered subcutaneously once a week for 24 or 48 weeks and ribavarin administered in a body weight stratified dose range of 1000 - 1200 mg per day (for participants weighing less than 75 kg, the total dose was 1000 mg per day and for those weighing greater than or equal to 75 kg, the dose was 1200 mg per day).	Participants received 2 telaprevir 375-mg tablets orally 3 times a day for 12 weeks. PEG-IFN alpha-2a 180 µg was coadministered subcutaneously once a week for 24 or 48 weeks depending on response, and ribavirin in a body weight stratified dose range of 1000-1200 mg per day was administered twice daily with food.
Measure Participants	268	134
Number (95% Confidence Interval) [Percentage of participants]	77.2 19.2%	79.1 39.6%

3. Secondary Outcome

Title	Percentage of Genotype 1b Participants With Extended Rapid Virologic Response (eRVR) at Both Week 4 and Week 12
Description	eRVR was defined as hepatitis C virus RNA levels lower than the lower limit of quantitation, ie, 25 IU/mL target not detected at both Weeks 4 and 12 of treatment.
Time Frame	Week 4, Week 12

Outcome Measure Data

Analysis Population Description

The analysis was performed in all treated participants who received at least 1 dose of active study therapy. Here, 'Number of participants analysed' signifies Genotype 1b participants assessed for eRVR response.

Arm/Group Title	Daclatasvir + PEG-IFN Alpha-2a + Ribavirin	Telaprevir + PEG-IFN Alpha-2a + Ribavirin
Arm/Group Description	Participants received daclatasvir 60-mg tablet orally once daily for 24 weeks in combination with pegylated interferon alpha-2a (PEG-IFN alpha-2a) 180 µg administered subcutaneously once a week for 24 or 48 weeks and ribavarin administered in a body weight stratified dose range of 1000-1200 mg per day (for participants weighing less than 75 kg, the total dose was 1000 mg per day and for those weighing greater than or equal to 75 kg, the dose was 1200 mg per day).	Participants received 2 telaprevir 375-mg tablets orally 3 times a day for 12 weeks. PEG-IFN alpha-2a 180 µg was coadministered subcutaneously once a week for 24 or 48 weeks depending on response, and ribavirin in a body weight stratified dose range of 1000-1200mg per day was administered twice daily with food.
Measure Participants	268	134
Number (95% Confidence Interval) [Percentage of participants]	75.0 18.7%	73.1 36.6%

4. Secondary Outcome

Title	Percentage of Genotype 1b Participants With Complete Early Virologic Response (cEVR)
Description	cEVR was defined as hepatitis C virus RNA levels lower than the lower limit of quantitation, ie, 25 IU/mL target not detected at Week 12 of treatment.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

The analysis was performed in all treated participants who received at least 1 dose of active study therapy. Here, 'Number of participants analysed' signifies Genotype 1b participants assessed for cEVR response.

Arm/Group Title	Daclatasvir + PEG-IFN Alpha-2a+ Ribavirin	Telaprevir + PEG-IFN Alpha-2a + Ribavirin
Arm/Group Description	Participants received daclatasvir 60-mg tablet orally once daily for 24 weeks in combination with pegylated interferon alpha-2a (PEG-IFN alpha-2a)180 µg administered subcutaneously once a week for 24 or 48 weeks and ribavarin administered in a body weight stratified dose range of 1000-1200 mg per day (for participants weighing less than 75 kg, the total dose was 1000 mg per day and for those weighing greater than or equal to 75 kg, the dose was 1200 mg per day).	Participants received 2 telaprevir 375-mg tablets orally 3 times a day for 12 weeks. PEG-IFN alpha-2a 180 µg was coadministered subcutaneously once a week for 24 or 48 weeks depending on response, and ribavirin in a body weight stratified dose range of 1000-1200 mg per day was administered twice daily with food.
Measure Participants	268	134
Number (95% Confidence Interval) [percentage of participants]	90.7 22.6%	90.03 45%

5. Secondary Outcome

Title	Percentage of Genotype 1b Participants With Sustained Virologic Response at Follow-up Week 24 (SVR24)
Description	SVR24 was defined as hepatitis C virus RNA levels lower than the lower limit of quantitation, ie, 25 IU/mL target detected or target not detected at follow-up week 24 of treatment.
Time Frame	Week 24 (Follow-up period)

Outcome Measure Data

Analysis Population Description

The analysis was performed in all treated participants who received at least 1 dose of active study therapy. Here, 'Number of participants analysed' signifies Genotype 1b participants assessed for SVR24 response.

Arm/Group Title	Daclatasvir + PEG-IFN Alpha-2a+ Ribavirin	Telaprevir + PEG-IFN Alpha-2a + Ribavirin
Arm/Group Description	Participants received daclatasvir 60-mg tablet orally once daily for 24 weeks in combination with pegylated interferon alpha-2a (PEG-IFN alpha-2a)180 µg administered subcutaneously once a week for 24 or 48 weeks and ribavarin administered in a body weight stratified dose range of 1000-1200 mg per day (for participants weighing less than 75 kg, the total dose was 1000 mg per day and for those weighing greater than or equal to 75 kg, the dose was 1200 mg per day).	Participants received 2 telaprevir 375-mg tablets orally 3 times a day for 12 weeks. PEG-IFN alpha-2a 180 µg was coadministered subcutaneously once a week for 24 or 48 weeks depending on response, and ribavirin in a body weight stratified dose range of 1000-1200 mg per day was administered twice daily with food.
Measure Participants	268	134
Number (95% Confidence Interval) [Percentage of participants]	84.3 21%	80.6 40.3%

6. Secondary Outcome

Title	Percentage of Genotype 1a Participants With Sustained Virologic Response at Follow-up Week 12 (SVR12)
Description	SVR12 was defined as hepatitis C virus RNA levels lower than the lower limit of quantitation, ie, 25 IU/mL target detected or target not detected at follow-up week 12 of treatment.
Time Frame	Week 12 (Follow-up period)

Outcome Measure Data

Analysis Population Description

The analysis was performed in all treated participants who received at least 1 dose of active study therapy. Here, 'Number of participants analysed' signifies Genotype 1a participants assessed for SVR12 response.

Arm/Group Title	Daclatasvir + PEG-IFN Alpha-2a + Ribavirin	Telaprevir + PEG-IFN Alpha-2a + Ribavirin
Arm/Group Description	Participants received daclatasvir 60-mg tablet orally once daily for 24 weeks in combination with pegylated interferon alpha-2a (PEG-IFN alpha-2a)180 µg administered subcutaneously once a week for 24 or 48 weeks and ribavarin administered in a body weight stratified dose range of 1000-1200 mg per day (for participants weighing less than 75 kg, the total dose was 1000 mg per day and for those weighing greater than or equal to 75 kg, the dose was 1200 mg per day).	Participants received 2 telaprevir 375-mg tablets orally 3 times a day for 12 weeks. PEG-IFN alpha-2a 180 µg was coadministered subcutaneously once a week for 24 or 48 weeks depending on response, and ribavirin in a body weight stratified dose range of 1000-1200 mg per day was administered twice daily with food.
Measure Participants	134	66
Number (95% Confidence Interval) [Percentage of participants]	64.9 16.1%	69.7 34.9%

Adverse Events

Arm/Group Title	Daclatasvir + PEG-IFN Alpha-2a + Ribavirin		Telaprevir + PEG-IFN Alpha-2a + Ribavirin
Arm/Group Description	Participants received daclatasvir 60-mg tablet orally once daily for 24 weeks in combination with pegylated interferon alpha-2a (PEG-IFN alpha-2a) 180 µg administered subcutaneously once a week for 24 or 48 weeks and ribavarin administered in a body weight stratified dose range of 1000-1200 mg per day (for participants weighing less than 75 kg, the total dose was 1000 mg per day and for those weighing greater than or equal to 75 kg, the dose was 1200 mg per day)		Participants received 2 telaprevir 375-mg tablets orally 3 times a day for 12 weeks. PEG-IFN alpha-2a 180 µg was coadministered subcutaneously once a week for 24 or 48 weeks depending on response, and ribavirin in a body weight stratified dose range of 1000-1200 mg per day was administered twice daily with food
All Cause Mortality
	Daclatasvir + PEG-IFN Alpha-2a + Ribavirin		Telaprevir + PEG-IFN Alpha-2a + Ribavirin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Daclatasvir + PEG-IFN Alpha-2a + Ribavirin		Telaprevir + PEG-IFN Alpha-2a + Ribavirin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	26/402 (6.5%)		20/200 (10%)
Blood and lymphatic system disorders
Haemolytic anaemia	1/402 (0.2%)		0/200 (0%)
Anaemia	0/402 (0%)		5/200 (2.5%)
Cardiac disorders
Palpitations	0/402 (0%)		1/200 (0.5%)
Coronary artery disease	1/402 (0.2%)		0/200 (0%)
Gastrointestinal disorders
Duodenitis	1/402 (0.2%)		0/200 (0%)
Ileus	1/402 (0.2%)		0/200 (0%)
Vomiting	0/402 (0%)		1/200 (0.5%)
Haemorrhoids	1/402 (0.2%)		1/200 (0.5%)
Gastrointestinal haemorrhage	0/402 (0%)		1/200 (0.5%)
Pancreatitis	0/402 (0%)		1/200 (0.5%)
Hepatobiliary disorders
Cholecystitis acute	0/402 (0%)		1/200 (0.5%)
Cholelithiasis	1/402 (0.2%)		0/200 (0%)
Infections and infestations
Pneumonia	3/402 (0.7%)		0/200 (0%)
Bronchopneumonia	0/402 (0%)		1/200 (0.5%)
Cellulitis	2/402 (0.5%)		0/200 (0%)
Proctitis infectious	0/402 (0%)		1/200 (0.5%)
Peritonsillar abscess	1/402 (0.2%)		0/200 (0%)
Sepsis	0/402 (0%)		1/200 (0.5%)
Bursitis infective	1/402 (0.2%)		0/200 (0%)
Lung infection	1/402 (0.2%)		0/200 (0%)
Pneumococcal sepsis	1/402 (0.2%)		0/200 (0%)
Bacteraemia	0/402 (0%)		1/200 (0.5%)
Pneumonia mycoplasmal	1/402 (0.2%)		0/200 (0%)
Tonsillitis	1/402 (0.2%)		0/200 (0%)
Injury, poisoning and procedural complications
Anaemia postoperative	1/402 (0.2%)		0/200 (0%)
Overdose	1/402 (0.2%)		0/200 (0%)
Concussion	1/402 (0.2%)		0/200 (0%)
Intentional overdose	0/402 (0%)		1/200 (0.5%)
Metabolism and nutrition disorders
Hypokalaemia	1/402 (0.2%)		1/200 (0.5%)
Musculoskeletal and connective tissue disorders
Bursitis	1/402 (0.2%)		0/200 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	1/402 (0.2%)		0/200 (0%)
Lung adenocarcinoma	1/402 (0.2%)		0/200 (0%)
Nervous system disorders
Headache	0/402 (0%)		1/200 (0.5%)
Syncope	1/402 (0.2%)		1/200 (0.5%)
Convulsion	0/402 (0%)		1/200 (0.5%)
Psychiatric disorders
Psychotic disorder	0/402 (0%)		1/200 (0.5%)
Mental status changes	0/402 (0%)		1/200 (0.5%)
Bipolar I disorder	1/402 (0.2%)		0/200 (0%)
Panic attack	1/402 (0.2%)		0/200 (0%)
Suicidal ideation	0/402 (0%)		1/200 (0.5%)
Depression	0/402 (0%)		2/200 (1%)
Panic disorder	0/402 (0%)		1/200 (0.5%)
Renal and urinary disorders
Renal failure acute	0/402 (0%)		2/200 (1%)
Respiratory, thoracic and mediastinal disorders
Haemothorax	1/402 (0.2%)		0/200 (0%)
Lung infiltration	1/402 (0.2%)		0/200 (0%)
Pulmonary oedema	0/402 (0%)		1/200 (0.5%)
Skin and subcutaneous tissue disorders
Dry skin	1/402 (0.2%)		0/200 (0%)
Rash generalised	1/402 (0.2%)		0/200 (0%)
Rash	1/402 (0.2%)		0/200 (0%)
Drug reaction with eosinophilia and systemic symptoms	1/402 (0.2%)		1/200 (0.5%)
Drug eruption	0/402 (0%)		1/200 (0.5%)
Vascular disorders
Circulatory collapse	0/402 (0%)		1/200 (0.5%)
Venous thrombosis	0/402 (0%)		1/200 (0.5%)
Other (Not Including Serious) Adverse Events
	Daclatasvir + PEG-IFN Alpha-2a + Ribavirin		Telaprevir + PEG-IFN Alpha-2a + Ribavirin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	384/402 (95.5%)		193/200 (96.5%)
Blood and lymphatic system disorders
Anaemia	96/402 (23.9%)		98/200 (49%)
Neutropenia	87/402 (21.6%)		27/200 (13.5%)
Thrombocytopenia	19/402 (4.7%)		14/200 (7%)
Ear and labyrinth disorders
Vertigo	18/402 (4.5%)		12/200 (6%)
Gastrointestinal disorders
Diarrhoea	63/402 (15.7%)		35/200 (17.5%)
Vomiting	26/402 (6.5%)		23/200 (11.5%)
Abdominal pain upper	24/402 (6%)		15/200 (7.5%)
Anorectal discomfort	3/402 (0.7%)		19/200 (9.5%)
Nausea	88/402 (21.9%)		74/200 (37%)
Haemorrhoids	7/402 (1.7%)		11/200 (5.5%)
Dyspepsia	17/402 (4.2%)		16/200 (8%)
Anal pruritus	3/402 (0.7%)		25/200 (12.5%)
Proctalgia	2/402 (0.5%)		11/200 (5.5%)
General disorders
Fatigue	140/402 (34.8%)		81/200 (40.5%)
Pyrexia	80/402 (19.9%)		42/200 (21%)
Chills	31/402 (7.7%)		18/200 (9%)
Influenza like illness	85/402 (21.1%)		38/200 (19%)
Injection site erythema	21/402 (5.2%)		7/200 (3.5%)
Injection site reaction	22/402 (5.5%)		5/200 (2.5%)
Asthenia	109/402 (27.1%)		53/200 (26.5%)
Infections and infestations
Urinary tract infection	7/402 (1.7%)		10/200 (5%)
Metabolism and nutrition disorders
Decreased appetite	61/402 (15.2%)		39/200 (19.5%)
Musculoskeletal and connective tissue disorders
Arthralgia	55/402 (13.7%)		14/200 (7%)
Myalgia	61/402 (15.2%)		23/200 (11.5%)
Muscle spasms	7/402 (1.7%)		11/200 (5.5%)
Back pain	27/402 (6.7%)		14/200 (7%)
Nervous system disorders
Disturbance in attention	22/402 (5.5%)		10/200 (5%)
Dizziness	32/402 (8%)		18/200 (9%)
Dysgeusia	23/402 (5.7%)		21/200 (10.5%)
Headache	137/402 (34.1%)		57/200 (28.5%)
Psychiatric disorders
Insomnia	71/402 (17.7%)		35/200 (17.5%)
Anxiety	10/402 (2.5%)		16/200 (8%)
Irritability	43/402 (10.7%)		27/200 (13.5%)
Depression	29/402 (7.2%)		12/200 (6%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	48/402 (11.9%)		25/200 (12.5%)
Cough	76/402 (18.9%)		31/200 (15.5%)
Oropharyngeal pain	22/402 (5.5%)		11/200 (5.5%)
Skin and subcutaneous tissue disorders
Dry skin	84/402 (20.9%)		34/200 (17%)
Pruritus	107/402 (26.6%)		75/200 (37.5%)
Rash	93/402 (23.1%)		69/200 (34.5%)
Alopecia	86/402 (21.4%)		32/200 (16%)
Erythema	16/402 (4%)		10/200 (5%)

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.