ATTAIN: TMC435HPC3001 - An Efficacy, Safety and Tolerability Study for TMC435 vs Telaprevir in Combination With PegINFα-2a and Ribavirin in Chronic Hepatitis C Patients Who Were Null or Partial Responders to Prior PegINFα-2a and Ribavirin Therapy

• Sponsor: Janssen R&D Ireland (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01485991
• Collaborator: (none)
• Enrollment: 771
• Locations: 142
• Arms: 2
• Duration (Months): 26
• Patients Per Site: 5.4
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to demonstrate the efficacy of TMC435 in combination with peginterferon (PegIFN) + ribavirin (RBV) by means of establishing its non- inferiority compared to an approved regimen of telaprevir + PegIFN + RBV in patients who have previously failed PegIFN.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis C	Drug: TMC435; Drug: TVR	Phase 3

Detailed Description

This study is a randomized (study drug assigned by chance like flipping a coin), double-blind (neither physician nor patient knows the name of the assigned drug), double-dummy (patients receive both active and inactive pills also called placebo), 2-arm, multicenter Phase III clinical study in adult treatment experienced Chronic Hepatitis C (CHC) genotype-1 infected patients who failed to respond during at least 1 previous course of PegINFα-2a/ RBV therapy. The purpose of the trial is to study the efficacy of TMC435 in combination with PegINFα-2a and RBV for 48 weeks of treatment compared to the approved regimen of telaprevir in combination with PegINFα-2a and RBV for 48 weeks of treatment. The study will consist of a screening period (maximum 6 weeks), treatment period (48 weeks) and post-treatment period (until 72 weeks after the start of treatment). For the first 12 weeks one group of patients will take TMC435 and TVR placebo, plus PegINFα-2a and RBV. The other group will take TMC435 placebo and TVR, plus PegINFα-2a and RBV. After 12 weeks, patients in both arms will only take PegINFα-2a and RBV up to week 48. After patients stop taking study medication, they will continue to go to the doctor's office for study visits until a total of 72 weeks after they start study treatment. Patients will be monitored for safety throughout the study. Study assessments at each study visit may include, but are not limited to: blood and urine collection for testing, electrocardiogram (ECG) assessments (a measurement of the electrical activity of your heart), patient questionnaires, and physical examinations.

Study Design

• Study Type: Interventional
• Actual Enrollment: 771 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Phase III in Partial and Null Responders
• Study Start Date: Feb 1, 2012
• Actual Primary Completion Date: Apr 1, 2014
• Actual Study Completion Date: Apr 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: TMC435/PR	Drug: TMC435; TMC435 Type=exact number, unit=mg, number=150, form=capsule, route=oral use. TVR placebo Form=tablet, route=oral use. TMC435 capsule is taken once daily in addition to 2 TVR placebo tablets 3 times a day for 12 weeks, and peginterferon alfa-2a and ribavirin for 48 weeks.
Active Comparator: TVR/PR	Drug: TVR; TVR Type=exact number, unit=mg, number=375, form=tablet, route=oral use. TMC435 placebo Form=capsule, route=oral use. 2 TVR tablets are taken 3 times a day together with 150 mg TMC435 placebo capsule once daily for 12 weeks, in addition to peginterferon alfa-2a and ribavirin for 48 weeks

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Sustained Virologic Response 12 Weeks After the Planned End of Treatment (SVR12) [12 Weeks After the Planned End of Treatment (EOT: Week 48)]

   Participants are considered to have reached SVR12 if both conditions below are met: 1) HCV RNA levels less than (<) 25 International unit per milliliter (IU/mL) undetectable; 2) HCV RNA levels <25 IU/mL undetectable or HCV RNA levels <25 IU/mL detectable.

Secondary Outcome Measures

1. Percentage of Participants With Sustained Virologic Response 24 Weeks After the Planned End of Treatment (SVR24) [24 Weeks After the Planned EOT (Week 48)]

   Participants are considered to have reached SVR24 if both conditions below are met: 1) HCV RNA levels less than <25 International unit per milliliter (IU/mL) undetectable (at the actual end of treatment);2) HCV RNA levels <25 IU/mL undetectable or HCV RNA levels <25 IU/mL detectable (24 weeks after the planned EOT).

2. Percentage of Participants With Viral Relapse [End of Treatment (Week 48) up to Follow-up Period (until Week 72)]

   Participants are considered to have a viral relapse if both conditions as specified are met: 1) <25 IU/mL undetectable HCV RNA at the actual end of study drug treatment; 2) confirmed HCV RNA greater than or equal to (>=) 25 IU/mL during follow-up.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patient must have had a liver biopsy before screening (or between the screening and baseline visit), unless patient cannot undergo such a procedure or has evidence of portal hypertension not associated with cirrhosis. For patients who had a liver biopsy performed more than 2 years prior to screening or without a biopsy (because of a contraindication or portal hypertension), a non-invasive staging assessment needs to be available. Non-invasive staging assessments include FibroScan, MR-Elastography, or FibroTest/FibroSure and must not be older than 6 months prior to screening

• Chronicity of hepatitis C virus (HCV) infection, as confirmed by one or both of the following: presence of anti-HCV antibody and/or HCV ribonucleic acid (RNA) at least 6 months prior to the screening visit and/or presence of fibrosis on biopsy

• Genotype 1 HCV infection with plasma HCV RNA of >10,000 IU/mL (both confirmed at screening)

• Patient must have had at least 1 documented previous course of treatment with PegINFα-2a or PegINFα-2b in combination with ribavirin (RBV) (at least 12 weeks for null responder and 20 weeks for partial responder)

Exclusion Criteria:

• Hepatic decompensation (impaired functioning of the liver), as indicated by significant laboratory abnormalities or other active diseases

• Infection with Human Immunodeficiency Virus (HIV) or non genotype 1 hepatitis C

• Liver disease not related to hepatitis C infection

• Previous chronic hepatitis C treatment, other than PegIFN and RBV

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Bakersfield	California	United States
2		San Diego	California	United States
3		Aurora	Colorado	United States
4		Washington	District of Columbia	United States
5		Jacksonville	Florida	United States
6		Orlando	Florida	United States
7		West Palm Beach	Florida	United States
8		Atlanta	Georgia	United States
9		Honolulu	Hawaii	United States
10		Chicago	Illinois	United States
11		Crestview Hills	Kentucky	United States
12		New Orleans	Louisiana	United States
13		Chevy Chase	Maryland	United States
14		Jackson	Mississippi	United States
15		Tupelo	Mississippi	United States
16		Kansas City	Missouri	United States
17		Missoula	Montana	United States
18		Newark	New Jersey	United States
19		New York	New York	United States
20		Rochester	New York	United States
21		Cincinnati	Ohio	United States
22		Cleveland	Ohio	United States
23		Allentown	Pennsylvania	United States
24		Philadelphia	Pennsylvania	United States
25		Pittsburgh	Pennsylvania	United States
26		Arlington	Texas	United States
27		Houston	Texas	United States
28		Odessa	Texas	United States
29		San Antonio	Texas	United States
30		Falls Church	Virginia	United States
31		Bellevue	Washington	United States
32		Seattle	Washington	United States
33		Buenos Aires N/A		Argentina
34		Buenos Aires		Argentina
35		Rosario, Santa Fe		Argentina
36		Darlinghurst		Australia
37		Greenslopes		Australia
38		Kingswood		Australia
39		Melbourne		Australia
40		Parkville - Vic		Australia
41		Perth		Australia
42		Sydney		Australia
43		Woolloongabba N/A		Australia
44		Linz		Austria
45		Wien		Austria
46		Brussels		Belgium
47		Brussel		Belgium
48		Haine-Saint-Paul, La Louviere		Belgium
49		Leuven		Belgium
50		Liège		Belgium
51		Campinas		Brazil
52		Ribeirão Preto		Brazil
53		Salvador		Brazil
54		Sao Paulo		Brazil
55		Sofia		Bulgaria
56		Varna		Bulgaria
57		Calgary	Alberta	Canada
58		Edmonton	Alberta	Canada
59		Vancouver	British Columbia	Canada
60		Toronto	Ontario	Canada
61		Montreal	Quebec	Canada
62		Brno		Czech Republic
63		Karlovy Vary		Czech Republic
64		Plzen		Czech Republic
65		Praha 2		Czech Republic
66		Praha 4		Czech Republic
67		Copenhagen		Denmark
68		Hvidovre N/A		Denmark
69		Odense N/A		Denmark
70		Grenoble		France
71		Lyon		France
72		Marseille		France
73		Nice		France
74		Paris Cedex 12		France
75		Paris		France
76		Pessac		France
77		Vandoeuvre Les Nancy		France
78		Berlin		Germany
79		Frankfurt N/A		Germany
80		Freiburg		Germany
81		Hamburg		Germany
82		Hannover		Germany
83		Heidelberg		Germany
84		Kiel		Germany
85		Mainz		Germany
86		München		Germany
87		Stuttgart		Germany
88		Ulm		Germany
89		Würzburg		Germany
90		Alexandroupolis		Greece
91		Athens		Greece
92		Larissa		Greece
93		Budapest		Hungary
94		Debrecen		Hungary
95		Kaposvár		Hungary
96		Pecs		Hungary
97		Szeged N/A		Hungary
98		Haifa		Israel
99		Jerusalem		Israel
100		Petah Tiqva		Israel
101		Ramat-Gan		Israel
102		Tel-Aviv		Israel
103		Zefat		Israel
104		Fredrikstad		Norway
105		Nordbyhagen		Norway
106		Stavanger		Norway
107		Tromsø		Norway
108		Bydgoszcz		Poland
109		Chorzow		Poland
110		Kielce		Poland
111		Lodz		Poland
112		Lublin		Poland
113		Myslowice		Poland
114		Raciborz		Poland
115		Warszawa		Poland
116		Lisboa		Portugal
117		Lisbon		Portugal
118		Porto		Portugal
119		Santurce		Puerto Rico
120		Bucuresti		Romania
121		Constanta		Romania
122		Iasi		Romania
123		Timisoara		Romania
124		Barcelona		Spain
125		Madrid		Spain
126		Santander N/A		Spain
127		Sevilla N/A		Spain
128		Valencia		Spain
129		Göteborg		Sweden
130		Lund		Sweden
131		Malmö		Sweden
132		Stockholm		Sweden
133		Örebro		Sweden
134		Lugano		Switzerland
135		St Gallen		Switzerland
136		Zurich N/A		Switzerland
137		Glasgow		United Kingdom
138		Leeds		United Kingdom
139		London		United Kingdom
140		Newcastle Upon Tyne		United Kingdom
141		Plymouth		United Kingdom
142		Southampton		United Kingdom

Sponsors and Collaborators

• Janssen R&D Ireland

Investigators

• Study Director: Tibotec Pharmaceuticals Limited Clinical Trial, Tibotec Pharmaceutical Limited

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Janssen R&D Ireland
• ClinicalTrials.gov Identifier: NCT01485991
• Other Study ID Numbers: CR100677; TMC435HPC3001
• First Posted: Dec 6, 2011
• Last Update Posted: Apr 26, 2016
• Last Verified: Mar 1, 2016

• Keywords provided by Janssen R&D Ireland: Hepatitis C; TMC435HPC3001; TMC435; Hepatitis C Virus (HCV); HEP C; Genotype 1; Treatment experienced; Null responders; Partial responders
• Additional relevant MeSH terms: Hepatitis A; Hepatitis C; Hepatitis; Simeprevir

Study Results

Participant Flow

Arm/Group Title	Simeprevir+Placebo+Peginterferon Alfa-2a+Ribavirin	Telaprevir+Placebo+Peginterferon Alfa-2a+Ribavirin
Arm/Group Description	Simeprevir (TMC435) 150 milligram (mg) capsule, orally, once daily for 12 weeks, along with 2 telaprevir (TVR) matched placebo tablets 3 times a day for 12 weeks, and peginterferon alfa-2a and ribavirin for 48 weeks.	2 Telaprevir (TVR) tablets, orally, 3 times a day along with 150 mg TMC435 matched placebo capsule once daily for 12 weeks, in addition to peginterferon alfa-2a and ribavirin for 48 weeks.
Period Title: Overall Study
STARTED	385	386
Treated	379	384
COMPLETED	353	350
NOT COMPLETED	32	36

Baseline Characteristics

Arm/Group Title	Simeprevir+Placebo+Peginterferon Alfa-2a+Ribavirin	Telaprevir+Placebo+Peginterferon Alfa-2a+Ribavirin	Total
Arm/Group Description	Simeprevir (TMC435) 150 milligram (mg) capsule, orally, once daily for 12 weeks, along with 2 telaprevir (TVR) matched placebo tablets 3 times a day for 12 weeks, and peginterferon alfa-2a and ribavirin for 48 weeks.	2 Telaprevir (TVR) tablets, orally, 3 times a day along with 150 mg TMC435 matched placebo capsule once daily for 12 weeks, in addition to peginterferon alfa-2a and ribavirin for 48 weeks.	Total of all reporting groups
Overall Participants	379	384	763
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	50	52	51
Sex: Female, Male (Count of Participants)
Female	136 35.9%	161 41.9%	297 38.9%
Male	243 64.1%	223 58.1%	466 61.1%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Sustained Virologic Response 12 Weeks After the Planned End of Treatment (SVR12)
Description	Participants are considered to have reached SVR12 if both conditions below are met: 1) HCV RNA levels less than (<) 25 International unit per milliliter (IU/mL) undetectable; 2) HCV RNA levels <25 IU/mL undetectable or HCV RNA levels <25 IU/mL detectable.
Time Frame	12 Weeks After the Planned End of Treatment (EOT: Week 48)

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population included all randomized participants who took at least 1 dose of study medication.

Arm/Group Title	Simeprevir+Placebo+Peginterferon Alfa-2a+Ribavirin	Telaprevir+Placebo+Peginterferon Alfa-2a+Ribavirin
Arm/Group Description	Simeprevir (TMC435) 150 milligram (mg) capsule, orally, once daily for 12 weeks, along with 2 telaprevir (TVR) matched placebo tablets 3 times a day for 12 weeks, and peginterferon alfa-2a and ribavirin for 48 weeks.	2 Telaprevir (TVR) tablets, orally, 3 times a day along with 150 mg TMC435 matched placebo capsule once daily for 12 weeks, in addition to peginterferon alfa-2a and ribavirin for 48 weeks.
Measure Participants	379	384
Number [percentage of participants]	53.6 14.1%	54.7 14.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Simeprevir+Placebo+Peginterferon Alfa-2a+Ribavirin, Telaprevir+Placebo+Peginterferon Alfa-2a+Ribavirin
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments	based on the asymptotic distribution of the generalized Cochran-Mantel-Haenszel statistic controlling for stratification factors, using a non-inferiority margin of 12 percent
	Method	Stratified Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Difference in proportions
	Estimated Value	-1.1
	Confidence Interval	(2-Sided) 95%; -7.8 to 5.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Percentage of Participants With Sustained Virologic Response 24 Weeks After the Planned End of Treatment (SVR24)
Description	Participants are considered to have reached SVR24 if both conditions below are met: 1) HCV RNA levels less than <25 International unit per milliliter (IU/mL) undetectable (at the actual end of treatment);2) HCV RNA levels <25 IU/mL undetectable or HCV RNA levels <25 IU/mL detectable (24 weeks after the planned EOT).
Time Frame	24 Weeks After the Planned EOT (Week 48)

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who took at least 1 dose of study medication.

Arm/Group Title	Simeprevir+Placebo+Peginterferon Alfa-2a+Ribavirin	Telaprevir+Placebo+Peginterferon Alfa-2a+Ribavirin
Arm/Group Description	Simeprevir (TMC435) 150 milligram (mg) capsule, orally, once daily for 12 weeks, along with 2 telaprevir (TVR) matched placebo tablets 3 times a day for 12 weeks, and peginterferon alfa-2a and ribavirin for 48 weeks.	2 Telaprevir (TVR) tablets, orally, 3 times a day along with 150 mg TMC435 matched placebo capsule once daily for 12 weeks, in addition to peginterferon alfa-2a and ribavirin for 48 weeks.
Measure Participants	379	384
Number [percentage of participants]	53.3 14.1%	55.2 14.4%

3. Secondary Outcome

Title	Percentage of Participants With Viral Relapse
Description	Participants are considered to have a viral relapse if both conditions as specified are met: 1) <25 IU/mL undetectable HCV RNA at the actual end of study drug treatment; 2) confirmed HCV RNA greater than or equal to (>=) 25 IU/mL during follow-up.
Time Frame	End of Treatment (Week 48) up to Follow-up Period (until Week 72)

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who took at least 1 dose of study drug. Here 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.

Arm/Group Title	Simeprevir+Placebo+Peginterferon Alfa-2a+Ribavirin	Telaprevir+Placebo+Peginterferon Alfa-2a+Ribavirin
Arm/Group Description	Simeprevir (TMC435) 150 milligram (mg) capsule, orally, once daily for 12 weeks, along with 2 telaprevir (TVR) matched placebo tablets 3 times a day for 12 weeks, and peginterferon alfa-2a and ribavirin for 48 weeks.	2 Telaprevir (TVR) tablets, orally, 3 times a day along with 150 mg TMC435 matched placebo capsule once daily for 12 weeks, in addition to peginterferon alfa-2a and ribavirin for 48 weeks.
Measure Participants	246	256
Number [percentage of participants]	17.9 4.7%	16.4 4.3%

Adverse Events

Time Frame	Baseline up to Follow-up (Week 72)
Arm/Group Title	Simeprevir+Placebo+Peginterferon Alfa-2a+Ribavirin		Telaprevir+Placebo+Peginterferon Alfa-2a+Ribavirin
Arm/Group Description	Simeprevir (TMC435) 150 milligram (mg) capsule, orally, once daily for 12 weeks, along with 2 telaprevir (TVR) matched placebo tablets 3 times a day for 12 weeks, and peginterferon alfa-2a and ribavirin for 48 weeks.		2 Telaprevir (TVR) tablets, orally, 3 times a day along with 150 mg TMC435 matched placebo capsule once daily for 12 weeks, in addition to peginterferon alfa-2a and ribavirin for 48 weeks.
All Cause Mortality
	Simeprevir+Placebo+Peginterferon Alfa-2a+Ribavirin		Telaprevir+Placebo+Peginterferon Alfa-2a+Ribavirin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Simeprevir+Placebo+Peginterferon Alfa-2a+Ribavirin		Telaprevir+Placebo+Peginterferon Alfa-2a+Ribavirin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	22/379 (5.8%)		54/384 (14.1%)
Blood and lymphatic system disorders
Anaemia	2/379 (0.5%)		16/384 (4.2%)
Neutropenia	2/379 (0.5%)		3/384 (0.8%)
Pancytopenia	1/379 (0.3%)		1/384 (0.3%)
Thrombocytopenia	1/379 (0.3%)		1/384 (0.3%)
Haemorrhagic diathesis	1/379 (0.3%)		0/384 (0%)
Leukopenia	1/379 (0.3%)		0/384 (0%)
Splenic vein thrombosis	0/379 (0%)		1/384 (0.3%)
Cardiac disorders
Angina unstable	1/379 (0.3%)		0/384 (0%)
Acute myocardial infarction	0/379 (0%)		1/384 (0.3%)
Angina pectoris	0/379 (0%)		1/384 (0.3%)
Myocardial infarction	0/379 (0%)		1/384 (0.3%)
Eye disorders
Visual impairment	0/379 (0%)		1/384 (0.3%)
Gastrointestinal disorders
Haemorrhoids	1/379 (0.3%)		0/384 (0%)
Nausea	1/379 (0.3%)		0/384 (0%)
Oesophageal varices haemorrhage	1/379 (0.3%)		0/384 (0%)
Abdominal pain	0/379 (0%)		1/384 (0.3%)
Ascites	0/379 (0%)		1/384 (0.3%)
Haemorrhoidal haemorrhage	0/379 (0%)		1/384 (0.3%)
Mesenteric vein thrombosis	0/379 (0%)		1/384 (0.3%)
Pancreatitis	0/379 (0%)		1/384 (0.3%)
Pancreatitis acute	0/379 (0%)		1/384 (0.3%)
General disorders
Pyrexia	2/379 (0.5%)		0/384 (0%)
Fatigue	0/379 (0%)		1/384 (0.3%)
Hepatobiliary disorders
Hepatic failure	1/379 (0.3%)		0/384 (0%)
Cholelithiasis	0/379 (0%)		1/384 (0.3%)
Portal vein thrombosis	0/379 (0%)		1/384 (0.3%)
Infections and infestations
Pneumonia	0/379 (0%)		4/384 (1%)
Appendicitis	2/379 (0.5%)		1/384 (0.3%)
Acute sinusitis	1/379 (0.3%)		0/384 (0%)
Bronchitis	1/379 (0.3%)		0/384 (0%)
Cellulitis	1/379 (0.3%)		0/384 (0%)
Cholecystitis infective	1/379 (0.3%)		0/384 (0%)
Gastroenteritis viral	1/379 (0.3%)		0/384 (0%)
Superinfection	1/379 (0.3%)		0/384 (0%)
Candidiasis	0/379 (0%)		1/384 (0.3%)
Impetigo	0/379 (0%)		1/384 (0.3%)
Lower respiratory tract infection	0/379 (0%)		1/384 (0.3%)
Pharyngitis	0/379 (0%)		1/384 (0.3%)
Pneumonia legionella	0/379 (0%)		1/384 (0.3%)
Pneumonia pneumococcal	0/379 (0%)		1/384 (0.3%)
Sepsis	0/379 (0%)		1/384 (0.3%)
Septic shock	0/379 (0%)		1/384 (0.3%)
Urinary tract infection	0/379 (0%)		1/384 (0.3%)
Injury, poisoning and procedural complications
Chemical peritonitis	1/379 (0.3%)		0/384 (0%)
Meniscus lesion	1/379 (0.3%)		0/384 (0%)
Concussion	0/379 (0%)		1/384 (0.3%)
Investigations
Neutrophil count decreased	0/379 (0%)		1/384 (0.3%)
Metabolism and nutrition disorders
Hyperglycaemia	0/379 (0%)		1/384 (0.3%)
Metabolic acidosis	0/379 (0%)		1/384 (0.3%)
Musculoskeletal and connective tissue disorders
Arthritis	0/379 (0%)		1/384 (0.3%)
Back pain	0/379 (0%)		1/384 (0.3%)
Bursitis	0/379 (0%)		1/384 (0.3%)
Muscle haemorrhage	0/379 (0%)		1/384 (0.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hepatic neoplasm malignant	0/379 (0%)		1/384 (0.3%)
Nervous system disorders
Syncope	2/379 (0.5%)		0/384 (0%)
Haemorrhage intracranial	1/379 (0.3%)		0/384 (0%)
Transient ischaemic attack	1/379 (0.3%)		0/384 (0%)
Convulsion	0/379 (0%)		1/384 (0.3%)
Critical illness polyneuropathy	0/379 (0%)		1/384 (0.3%)
Headache	0/379 (0%)		1/384 (0.3%)
Loss of consciousness	0/379 (0%)		1/384 (0.3%)
Mononeuropathy	0/379 (0%)		1/384 (0.3%)
Psychiatric disorders
Depression	1/379 (0.3%)		1/384 (0.3%)
Suicide attempt	1/379 (0.3%)		0/384 (0%)
Panic attack	0/379 (0%)		1/384 (0.3%)
Substance-induced psychotic disorder	0/379 (0%)		1/384 (0.3%)
Renal and urinary disorders
Renal failure	0/379 (0%)		1/384 (0.3%)
Renal failure acute	0/379 (0%)		1/384 (0.3%)
Reproductive system and breast disorders
Benign prostatic hyperplasia	0/379 (0%)		1/384 (0.3%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	2/379 (0.5%)		0/384 (0%)
Pleurisy	1/379 (0.3%)		0/384 (0%)
Pneumonia aspiration	0/379 (0%)		1/384 (0.3%)
Pulmonary embolism	0/379 (0%)		1/384 (0.3%)
Skin and subcutaneous tissue disorders
Dermatitis atopic	1/379 (0.3%)		0/384 (0%)
Drug rash with eosinophilia and systemic symptoms	0/379 (0%)		1/384 (0.3%)
Rash	0/379 (0%)		1/384 (0.3%)
Rash generalised	0/379 (0%)		1/384 (0.3%)
Toxic skin eruption	0/379 (0%)		1/384 (0.3%)
Vascular disorders
Hypertension	1/379 (0.3%)		1/384 (0.3%)
Deep vein thrombosis	0/379 (0%)		2/384 (0.5%)
Thrombophlebitis	1/379 (0.3%)		0/384 (0%)
Other (Not Including Serious) Adverse Events
	Simeprevir+Placebo+Peginterferon Alfa-2a+Ribavirin		Telaprevir+Placebo+Peginterferon Alfa-2a+Ribavirin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	349/379 (92.1%)		369/384 (96.1%)
Blood and lymphatic system disorders
Anaemia	95/379 (25.1%)		157/384 (40.9%)
Neutropenia	82/379 (21.6%)		78/384 (20.3%)
Thrombocytopenia	40/379 (10.6%)		46/384 (12%)
Gastrointestinal disorders
Nausea	74/379 (19.5%)		110/384 (28.6%)
Diarrhoea	51/379 (13.5%)		60/384 (15.6%)
Dyspepsia	25/379 (6.6%)		29/384 (7.6%)
Abdominal pain upper	24/379 (6.3%)		25/384 (6.5%)
Vomiting	23/379 (6.1%)		36/384 (9.4%)
Constipation	21/379 (5.5%)		10/384 (2.6%)
Abdominal pain	11/379 (2.9%)		22/384 (5.7%)
Dry mouth	11/379 (2.9%)		25/384 (6.5%)
Anorectal discomfort	10/379 (2.6%)		32/384 (8.3%)
Anal pruritus	9/379 (2.4%)		42/384 (10.9%)
Haemorrhoids	6/379 (1.6%)		38/384 (9.9%)
General disorders
Fatigue	132/379 (34.8%)		155/384 (40.4%)
Pyrexia	86/379 (22.7%)		101/384 (26.3%)
Asthenia	80/379 (21.1%)		69/384 (18%)
Influenza like illness	64/379 (16.9%)		66/384 (17.2%)
Chills	22/379 (5.8%)		40/384 (10.4%)
Injection site erythema	14/379 (3.7%)		27/384 (7%)
Infections and infestations
Urinary tract infection	12/379 (3.2%)		21/384 (5.5%)
Metabolism and nutrition disorders
Decreased appetite	54/379 (14.2%)		64/384 (16.7%)
Hyperuricaemia	3/379 (0.8%)		28/384 (7.3%)
Musculoskeletal and connective tissue disorders
Myalgia	47/379 (12.4%)		63/384 (16.4%)
Arthralgia	41/379 (10.8%)		45/384 (11.7%)
Back pain	18/379 (4.7%)		30/384 (7.8%)
Nervous system disorders
Headache	103/379 (27.2%)		120/384 (31.3%)
Dizziness	26/379 (6.9%)		43/384 (11.2%)
Dysgeusia	15/379 (4%)		36/384 (9.4%)
Psychiatric disorders
Insomnia	53/379 (14%)		73/384 (19%)
Depression	35/379 (9.2%)		20/384 (5.2%)
Mood altered	35/379 (9.2%)		32/384 (8.3%)
Respiratory, thoracic and mediastinal disorders
Cough	66/379 (17.4%)		53/384 (13.8%)
Dyspnoea	30/379 (7.9%)		40/384 (10.4%)
Skin and subcutaneous tissue disorders
Pruritus	142/379 (37.5%)		179/384 (46.6%)
Rash	66/379 (17.4%)		100/384 (26%)
Dry skin	39/379 (10.3%)		30/384 (7.8%)
Alopecia	33/379 (8.7%)		59/384 (15.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

A copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested in writing, such publication will be withheld for up to an additional 60 days.