Taribavirin Phase 2 Dose Finding Study for the Treatment of Hepatitis C Virus (HCV)

• Sponsor: Bausch Health Americas, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00446134
• Collaborator: (none)
• Enrollment: 278
• Location: 1
• Arms: 4
• Duration (Months): 25
• Patients Per Site Per Month: 11.1

Study Details

Study Description

Brief Summary

The objective of the study is to select an optimal dose of taribavirin by comparing the efficacy and safety of 3 taribavirin dose levels, 20, 25, and 30 mg/kg/day, versus ribavirin 800 to 1400 mg/day based on body weight, both administered in combination with peginterferon alfa-2b to therapy-naive patients with chronic Hepatitis C Virus (HCV) genotype 1 infection.

Condition or Disease	Intervention/Treatment	Phase
Chronic Hepatitis C	Drug: Taribavirin; Drug: Taribavirin; Drug: Taribavirin; Drug: Ribavirin	Phase 2

Detailed Description

The objective of the study is to select an optimal dose of taribavirin by comparing the efficacy and safety of 3 taribavirin dose levels, 20, 25, and 30 mg/kg/day, versus ribavirin 800 mg/day to 1400 mg/day based on subject body weight, with both drugs administered in combination with peginterferon alfa-2b to therapy-naive patients with chronic Hepatitis C Virus genotype 1 infection.

Study Design

• Study Type: Interventional
• Actual Enrollment: 278 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 2 Comparison of Weight-based Doses of Taribavirin Combined With Peginterferon Alfa-2b Versus Ribavirin Combined With Peginterferon Alfa-2b in Therapy-naïve Patients With Chronic Hepatitis C Virus Genotype 1 Infection
• Study Start Date: Mar 1, 2007
• Actual Primary Completion Date: Apr 1, 2008
• Actual Study Completion Date: Apr 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group 1: Drug Oral taribavirin tablet 20 mg/kg/day (Actual doses were 20-24 mg/kg/day) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk)	Drug: Taribavirin; Oral (200 mg) Tablet: 20mg/kg/day BID, patients will be treated for a total of 48 weeks. in addition, all patients will receive peginterferon alfa-2b (PEG-Intron) by weekly subcutaneous injection. Patients who complete treatment with study drug or discontinue treatment prematurely will enter a 24-week follow-up period.; Other Names: Viramidine RNA003142-204
Experimental: Group 2: Drug Oral taribavirin tablet 25 mg/kg/day (Actual doses were 25-29 mg/kg/day) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk)	Drug: Taribavirin; Oral (200 mg) Tablet: 25mg/kg/day BID, patients will be treated for a total of 48 weeks. in addition, all patients will receive peginterferon alfa-2b (PEG-Intron) by weekly subcutaneous injection. Patients who complete treatment with study drug or discontinue treatment prematurely will enter a 24-week follow-up period.; Other Names: Viramidine RNA003142-204
Experimental: Group 3: Drug Oral taribavirin 30 mg/kg/day (Actual doses were 30-34 mg/kg/day) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk)	Drug: Taribavirin; Oral (200mg)Tablet: 30mg/kg/day BID, patients will be treated for a total of 48 weeks. in addition, all patients will receive peginterferon alfa-2b (PEG-Intron) by weekly subcutaneous injection. Patients who complete treatment with study drug or discontinue treatment prematurely will enter a 24-week follow-up period.; Other Names: Viramidine RNA003142-204
Active Comparator: Group 4: Drug Oral ribavirin 800 mg/day (body weight <65 kg), 1000 mg/day (body weight 65-84 kg), 1200 mg/day (body weight 85-104 kg) or 1400 mg/day (body weight greater than or equal to 105 kg) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk)	Drug: Ribavirin; Oral (200mg)Tablet: 800 mg/day, 1000 mg/day, 1200 mg/day, or 1400 mg/day BID, patients will be treated for a total of 48 weeks. in addition, all patients will receive peginterferon alfa-2b (PEG-Intron) by weekly subcutaneous injection. Patients who complete treatment with study drug or discontinue treatment prematurely will enter a 24-week follow-up period.; Other Names: Rebetol Copegus Ribasphere Virazole

Outcome Measures

Primary Outcome Measures

1. Patients With Either Undetectable Serum HCV RNA (<100 Copies/ml) or at Least a 2-log Decrease From Baseline in Serum Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Treatment Week 12. [Treatment Week 12]

   The primary efficacy endpoint was the numbers of responders at Treatment Week (TW) 12. Responders are defined as patients achieving either viral negativity or a partial response (PR). Viral negativity is defined as <100 copies/mL serum HCV RNA. A PR is defined as < 100 copies/mL serum HCV RNA and at least a 2-log decrease from baseline in serum HCV RNA levels. Responder rates with corresponding 95% confidence intervals were estimated for each treatment group.

Secondary Outcome Measures

1. Patients With Anemia (Hemoglobin <10 g/dL) Up to Follow-up Week 24 [Treatment Week Follow-Up 24]

   The primary safety endpoint will be the numbers of patients with hemoglobin <10 g/dL (anemia) at any time during the treatment period. The comparison of anemia rates between taribavirin and ribavirin groups will be carried out using the Fisher's exact test or Chi-square test. The 95% confidence interval of the difference in proportion will be analyzed.

2. Patients With Undetected Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) (<100 Copies/mL) at Treatment Week Follow-Up 24 [Treatment Week Follow-Up 24]

3. Relapsers at Follow-Up Visit 24 [Follow-Up Week 24]

   Includes patients who had undetectable Hepatitis Virus C (HVC) Ribonucleic Acid (RNA) at their last visit on drug.

Eligibility Criteria

Criteria

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

Subject Inclusion Criteria

To be eligible for enrollment, patients must meet all of the following criteria:

1. At least 18 years of age

2. Diagnosed with compensated chronic HCV genotype 1 infection that has not been treated with interferon, peginterferon, ribavirin or any experimental therapy for >28 days

2a Serum HCV RNA >2000 copies/mL (780 IU/mL) 2b Liver biopsy performed within 3 years prior to screening consistent with chronic HCV infection 2c Criteria for compensated HCV infection, including normal prothrombin time, serum albumin and bilirubin levels (unless due to non-hepatitis factors) and no history or evidence of bleeding esophageal varices, ascites, or hepatic encephalopathy

3 History of alanine aminotransferase (ALT) elevation either within 6 months prior to screening, at screening, or on retest 2 weeks after a negative screening test, or histologic evidence of HCV infection and a detectable viral load

4 Platelet count ≥90,000/mm3

5 Absolute neutrophil count ≥1200/mm3

6 Hemoglobin ≥12.0 g/dL for females or ≥13.0 g/dL for males

7 Antinuclear antibody (ANA) titer ≤1:320

8 Serum creatinine <1.5 mg/dL

9 HbA1c ≤8.5% for diabetic patients

10 Normal or adequately controlled TSH on prescription medication

11 Alpha fetoprotein (AFP) <20 ng/mL or hepatocellular carcinoma ruled out (ultrasound, CT or MRI scan) within 6 months prior to the study (Patients with an AFP >20 ng/mL must have ongoing hepatocellular carcinoma screening during study as part of the patient's routine medical care)

12 All other clinical laboratory values within normal limits, unless judged not clinically significant by the investigator

13 Sterile or infertile (defined as vasectomy, tubal ligation, postmenopausal, or hysterectomy), or willing to use an approved method of double-barrier contraception (hormonal plus barrier or barrier plus barrier, eg, diaphragm plus condom) from the time of first dose administration until 6 months after the last dose

14 Capable of understanding instructions, adhering to study schedules and requirements, and willing to provided informed consent

Subject Exclusion Criteria

Patients who have any of the following during the screening or Day 1 visit are not eligible for enrollment in this study:

1. Positive HIV or HbsAg serology

2. Severe psychiatric or neuropsychiatric disorders including severe depression, history of suicidal ideations or suicide attempt(s). (This would include patients with a history of suicidal ideations or suicide attempt(s) that occurred when the patient was a minor or many years ago; if the event occurred while under the influence of alcohol or drugs; if the suicidal ideations or suicide attempt(s) were connected to a traumatic event; if the patient was not hospitalized or treated; if the patient has obtained psychiatric clearance for treatment)

3. History or clinical manifestations of significant metabolic, hematological, pulmonary, ischemic or unstable heart disease, gastrointestinal, neurological, renal, urological, endocrine, ophthalmologic (including severe retinopathy), or immune mediated disease

4. History of thalassemia or other hemoglobinopathies (even if the hemoglobin is normal)

5. Chronic hepatic disease other than hepatitis C

6. Organ or bone marrow transplant

7. Chronic (greater than 30 days) use of immunosuppressive medications including steroids in doses equivalent to 10 mg of prednisone or higher, 30 days prior to and anytime during the course of the study

8. Female patients who are breast-feeding or have a positive pregnancy test at any time during the study

9. Males whose female partners are pregnant

10. Patients who have had a malignancy diagnosed and/or treated within the past 5 years, except for localized squamous or basal cell cancers treated by local excision

11. Patients who have participated in a clinical trial and have received an investigational drug within 30 days prior to screening

12. History of alcoholism or drug addiction 1 year prior to screening

13. The use of methadone, buprenorphine or any similar drug, regardless of the prescribed indication or the length of time the patient has been on the drug

14. Chronic (>4 weeks duration) diarrhea, including irritable bowel disease

15. Fibrosis score F4 (cirrhosis) based on Metavir or equivalent index

16. Weight >128 kg or <40 kg

17. Patients infected with mixed HCV genotypes

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cedars-Sinai Medical Center, 8635 W. 3rd Street, Suite 590W	Los Angeles	California	United States	90048

Sponsors and Collaborators

• Bausch Health Americas, Inc.

Investigators

• Principal Investigator: Fred Poordad, MD, Cedars-Sinai Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Bausch Health Americas, Inc.
• ClinicalTrials.gov Identifier: NCT00446134
• Other Study ID Numbers: RNA003142-204
• First Posted: Mar 12, 2007
• Last Update Posted: Jul 27, 2012
• Last Verified: Jun 1, 2012

• Keywords provided by Bausch Health Americas, Inc.: Phase 2b Dose-Ranging Study
• Additional relevant MeSH terms: Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis; Hepatitis, Chronic; Ribavirin; Taribavirin

Study Results

Participant Flow

Recruitment Details	Patients who met all entry criteria and signed an informed consent were randomized in a 1:1:1:1 ratio to one of the 4 arms by a central randomization schedule. A total of 51 clinical centers in the United States participated in the study. 278 patients were randomized; 275 patients who receive one dose of study drug were included in all analyses.
Pre-assignment Detail	Randomization was stratified by screening HCV RNA viral load less than or = to 2 or greater than (>) 2 million copies/mL and body weight (BW) (less than or = 75 or >75 kg). A cap of 70% was set for patients with BWs >75 kg so that at least 30% of the patients in each group have BWs less than or = to 75 kg.

Arm/Group Title	Taribavirin 20 mg/kg/Day	Taribavirin 25 mg/kg/Day	Taribavirin 30 mg/kg/Day	Ribavirin 800 mg/Day
Arm/Group Description	Oral taribavirin 20 mg/kg/day (actual doses were 20-24 mg/kg/day) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk)	Oral taribavirin tablet 25 mg/kg/day actual doses were 25-29 mg/kg/day) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk)	Oral taribavirin 30 mg/kg/day actual doses were 30-34 mg/kg/day) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk)	Oral ribavirin 800 mg/day (body weight <65 kg), 1000 mg/day (body weight 65-84 kg), 1200 mg/day (body weight 85-104 kg) or 1400 mg/day (body weight greater than or equal to 105 kg) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk)
Period Title: Overall Study
STARTED	69	70	69	70
COMPLETED	35	25	26	25
NOT COMPLETED	34	45	43	45

Baseline Characteristics

Arm/Group Title	Taribavirin 20 mg/kg/Day	Taribavirin 25 mg/kg/Day	Taribavirin 30 mg/kg/Day	Ribavirin 800 mg/Day	Total
Arm/Group Description	Oral taribavirin 20 mg/kg/day (actual doses were 20-24 mg/kg/day) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk)	Oral taribavirin tablet 25 mg/kg/day actual doses were 25-29 mg/kg/day) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk)	Oral taribavirin 30 mg/kg/day actual doses were 30-34 mg/kg/day) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk)	Oral ribavirin 800 mg/day (body weight <65 kg), 1000 mg/day (body weight 65-84 kg), 1200 mg/day (body weight 85-104 kg) or 1400 mg/day (body weight greater than or equal to 105 kg) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk)	Total of all reporting groups
Overall Participants	67	70	68	70	275
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	48.5 (9.39)	47.5 (9.42)	49.6 (7.24)	49.7 (8.30)	48.8 (8.63)
Sex: Female, Male (Count of Participants)
Female	35 52.2%	25 35.7%	25 36.8%	22 31.4%	107 38.9%
Male	32 47.8%	45 64.3%	43 63.2%	48 68.6%	168 61.1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	2 3%	4 5.7%	3 4.4%	2 2.9%	11 4%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	10 14.9%	14 20%	13 19.1%	12 17.1%	49 17.8%
White	50 74.6%	41 58.6%	42 61.8%	45 64.3%	178 64.7%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	5 7.5%	11 15.7%	10 14.7%	11 15.7%	37 13.5%
Weight (kilograms) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilograms]	81.5 (16.9)	82.6 (16.8)	82.2 (18.0)	82.3 (17.1)	82.1 (17.09)
Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) (log 10) (Copies/mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Copies/mL]	6.6 (0.71)	6.6 (0.78)	6.6 (0.78)	6.5 (0.84)	6.6 (0.77)

Outcome Measures

1. Primary Outcome

Title	Patients With Either Undetectable Serum HCV RNA (<100 Copies/ml) or at Least a 2-log Decrease From Baseline in Serum Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Treatment Week 12.
Description	The primary efficacy endpoint was the numbers of responders at Treatment Week (TW) 12. Responders are defined as patients achieving either viral negativity or a partial response (PR). Viral negativity is defined as <100 copies/mL serum HCV RNA. A PR is defined as < 100 copies/mL serum HCV RNA and at least a 2-log decrease from baseline in serum HCV RNA levels. Responder rates with corresponding 95% confidence intervals were estimated for each treatment group.
Time Frame	Treatment Week 12

Outcome Measure Data

Analysis Population Description

The primary efficacy analysis was performed using the Intent-to-Treat (ITT) population and 275 patients who received at least one dose of study drug were analyzed for efficacy.

Arm/Group Title	Taribavirin 20 mg/kg/Day	Taribavirin 25 mg/kg/Day	Taribavirin 30 mg/kg/Day	Ribavirin 800 mg/Day
Arm/Group Description	Oral taribavirin 20 mg/kg/day (actual doses were 20-24 mg/kg/day) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk)	Oral taribavirin tablet 25 mg/kg/day actual doses were 25-29 mg/kg/day) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk)	Oral taribavirin 30 mg/kg/day actual doses were 30-34 mg/kg/day) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk)	Oral ribavirin 800 mg/day (body weight <65 kg), 1000 mg/day (body weight 65-84 kg), 1200 mg/day (body weight 85-104 kg) or 1400 mg/day (body weight greater than or equal to 105 kg) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk)
Measure Participants	67	70	68	70
Early Virologic Response (EVR) (less than 100)	43 64.2%	40 57.1%	37 54.4%	36 51.4%
No EVR (non-responder, Total)	24 35.8%	30 42.9%	31 45.6%	34 48.6%
Detectable (greater than 100 copies/mL at TW 12)	17 25.4%	17 24.3%	21 30.9%	19 27.1%
Discontinued (Prior to TW 12)	7 10.4%	12 17.1%	10 14.7%	15 21.4%
Missing (No value at TW 12)	0 0%	1 1.4%	0 0%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Taribavirin 20 mg/kg/Day, Ribavirin 800 mg/Day
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The study will have 70% to detect non-inferiority of taribavirin versus ribavirin using a non-inferiority margin of 12%.
Statistical Test of Hypothesis	p-Value	0.167
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Other
	Estimated Value	12.75
	Confidence Interval	(2-Sided) 95%; -3.65 to 29.15
	Parameter Dispersion	Type: Standard Deviation; Value: 5
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Taribavirin 25 mg/kg/Day, Ribavirin 800 mg/Day
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The study will have 70% to detect non-inferiority of taribavirin versus ribavirin using a non-inferiority margin of 12%.
Statistical Test of Hypothesis	p-Value	0.611
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Difference of Proportion
	Estimated Value	5.71
	Confidence Interval	(2-Sided) 95%; -10.76 to 22.19
	Parameter Dispersion	Type: Standard Deviation; Value: 5
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Taribavirin 30 mg/kg/Day, Ribavirin 800 mg/Day
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The study will have 70% to detect non-inferiority of taribavirin versus ribavirin using a non-inferiority margin of 12%.
Statistical Test of Hypothesis	p-Value	0.736
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Difference of Proportion
	Estimated Value	2.98
	Confidence Interval	(2-Sided) 95%; -13.67 to 19.63
	Parameter Dispersion	Type: Standard Deviation; Value: 5
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Taribavirin 20 mg/kg/Day, Taribavirin 25 mg/kg/Day
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The study will have 70% to detect non-inferiority of taribavirin versus taribavirin using a non-inferiority margin of 12%.
Statistical Test of Hypothesis	p-Value	0.485
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Difference of Proportion
	Estimated Value	7.04
	Confidence Interval	(2-Sided) 95%; -9.28 to 23.35
	Parameter Dispersion	Type: Standard Deviation; Value: 5
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Taribavirin 20 mg/kg/Day, Taribavirin 30 mg/kg/Day
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The study will have 70% to detect non-inferiority of taribavirin versus taribavirin using a non-inferiority margin of 12%.
Statistical Test of Hypothesis	p-Value	0.295
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Difference of Proportion
	Estimated Value	9.77
	Confidence Interval	(2-Sided) 95%; -6.72 to 26.26
	Parameter Dispersion	Type: Standard Deviation; Value: 5
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Taribavirin 25 mg/kg/Day, Taribavirin 30 mg/kg/Day
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The study will have 70% to detect non-inferiority of taribavirin versus taribavirin using a non-inferiority margin of 12%.
Statistical Test of Hypothesis	p-Value	0.864
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Difference of Proportion
	Estimated Value	2.73
	Confidence Interval	(2-Sided) 95%; -13.84 to 19.3
	Parameter Dispersion	Type: Standard Deviation; Value: 5
	Estimation Comments

2. Secondary Outcome

Title	Patients With Anemia (Hemoglobin <10 g/dL) Up to Follow-up Week 24
Description	The primary safety endpoint will be the numbers of patients with hemoglobin <10 g/dL (anemia) at any time during the treatment period. The comparison of anemia rates between taribavirin and ribavirin groups will be carried out using the Fisher's exact test or Chi-square test. The 95% confidence interval of the difference in proportion will be analyzed.
Time Frame	Treatment Week Follow-Up 24

Outcome Measure Data

Analysis Population Description

The secondary analysis was performed using the Safety Population and 275 patients who received at least one dose of study drug were analyzed for safety.

Arm/Group Title	Taribavirin 20 mg/kg/Day	Taribavirin 25 mg/kg/Day	Taribavirin 30 mg/kg/Day	Ribavirin 800 mg/Day
Arm/Group Description	Oral taribavirin 20 mg/kg/day (actual doses were 20-24 mg/kg/day) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk)	Oral taribavirin tablet 25 mg/kg/day actual doses were 25-29 mg/kg/day) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk)	Oral taribavirin 30 mg/kg/day actual doses were 30-34 mg/kg/day) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk)	Oral ribavirin 800 mg/day (body weight <65 kg), 1000 mg/day (body weight 65-84 kg), 1200 mg/day (body weight 85-104 kg) or 1400 mg/day (body weight greater than or equal to 105 kg) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk)
Measure Participants	67	70	68	70
Number [Participants]	11 16.4%	11 15.7%	19 27.9%	23 32.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Taribavirin 20 mg/kg/Day, Ribavirin 800 mg/Day
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0304
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	16.4
	Confidence Interval	(2-Sided) 95%; 2.31 to 30.57
	Parameter Dispersion	Type: Standard Deviation; Value: 5
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Taribavirin 25 mg/kg/Day, Ribavirin 800 mg/Day
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0293
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	17.1
	Confidence Interval	(2-Sided) 95%; 3.22 to 31.06
	Parameter Dispersion	Type: Standard Deviation; Value: 5
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Taribavirin 30 mg/kg/Day, Ribavirin 800 mg/Day
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5816
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	4.9
	Confidence Interval	(2-Sided) 95%; -10.41 to 20.24
	Parameter Dispersion	Type: Standard Deviation; Value: 5
	Estimation Comments

3. Secondary Outcome

Title	Patients With Undetected Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) (<100 Copies/mL) at Treatment Week Follow-Up 24
Time Frame	Treatment Week Follow-Up 24

Outcome Measure Data

Analysis Population Description

This analysis was performed using the Intent-to-Treat Population (ITT); undetectable HCV RNA defined as <100 copies/mL;Patients with a missing value at TW 12, TW 24 were considered Non-responders (detectable); a responder is defined as a patient with undetectable HCV RNA at FW 24 after achieving EVR at TW 12 and undetectable status at TW 24

Arm/Group Title	Taribavirin 20 mg/kg/Day	Taribavirin 25 mg/kg/Day	Taribavirin 30 mg/kg/Day	Ribavirin 800 mg/Day
Arm/Group Description	Oral taribavirin 20 mg/kg/day (actual doses were 20-24 mg/kg/day) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk)	Oral taribavirin tablet 25 mg/kg/day actual doses were 25-29 mg/kg/day) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk)	Oral taribavirin 30 mg/kg/day actual doses were 30-34 mg/kg/day) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk)	Oral ribavirin 800 mg/day (body weight <65 kg), 1000 mg/day (body weight 65-84 kg), 1200 mg/day (body weight 85-104 kg) or 1400 mg/day (body weight greater than or equal to 105 kg) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk)
Measure Participants	67	70	68	70
Responder Follow-Up Week 24	19 28.4%	19 27.1%	19 27.9%	19 27.1%
Non-Responder Follow-Up Week 24	48 71.6%	51 72.9%	49 72.1%	51 72.9%
Detectable HCV RNA Follow-Up Week 24	14 20.9%	15 21.4%	16 23.5%	14 20%
Discontinued Week Follow-Up Week 24	34 50.7%	36 51.4%	33 48.5%	37 52.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Taribavirin 20 mg/kg/Day, Ribavirin 800 mg/Day
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9999
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.22
	Confidence Interval	(2-Sided) 95%; -13.78 to 16.22
	Parameter Dispersion	Type: Standard Deviation; Value: 5
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Taribavirin 25 mg/kg/Day, Ribavirin 800 mg/Day
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9999
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0
	Confidence Interval	(2-Sided) 95%; -14.73 to 14.73
	Parameter Dispersion	Type: Standard Deviation; Value: 5
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Taribavirin 30 mg/kg/Day, Ribavirin 800 mg/Day
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9999
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.8
	Confidence Interval	(2-Sided) 95%; -14.11 to 15.71
	Parameter Dispersion	Type: Standard Deviation; Value: 5
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Taribavirin 20 mg/kg/Day, Taribavirin 25 mg/kg/Day
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9999
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.22
	Confidence Interval	(2-Sided) 95%; -13.78 to 16.22
	Parameter Dispersion	Type: Standard Deviation; Value: 5
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Taribavirin 20 mg/kg/Day, Taribavirin 30 mg/kg/Day
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9999
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.42
	Confidence Interval	(2-Sided) 95%; -14.76 to 15.59
	Parameter Dispersion	Type: Standard Deviation; Value: 5
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Taribavirin 25 mg/kg/Day, Taribavirin 30 mg/kg/Day
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9999
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.8
	Confidence Interval	(2-Sided) 95%; -15.71 to 14.11
	Parameter Dispersion	Type: Standard Deviation; Value: 5
	Estimation Comments

4. Secondary Outcome

Title	Relapsers at Follow-Up Visit 24
Description	Includes patients who had undetectable Hepatitis Virus C (HVC) Ribonucleic Acid (RNA) at their last visit on drug.
Time Frame	Follow-Up Week 24

Outcome Measure Data

Analysis Population Description

The analysis was performed using patients who had undetectable HVC RNA at their last visit on drug.

Arm/Group Title	Taribavirin 20 mg/kg/Day	Taribavirin 25 mg/kg/Day	Taribavirin 30 mg/kg/Day	Ribavirin 800 mg/Day
Arm/Group Description	Oral taribavirin 20 mg/kg/day (actual doses were 20-24 mg/kg/day) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk)	Oral taribavirin tablet 25 mg/kg/day actual doses were 25-29 mg/kg/day) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk)	Oral taribavirin 30 mg/kg/day actual doses were 30-34 mg/kg/day) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk)	Oral ribavirin 800 mg/day (body weight <65 kg), 1000 mg/day (body weight 65-84 kg), 1200 mg/day (body weight 85-104 kg) or 1400 mg/day (body weight greater than or equal to 105 kg) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk)
Measure Participants	29	24	22	24
Number [Participants]	10 14.9%	5 7.1%	3 4.4%	5 7.1%

Adverse Events

Time Frame	Treatment Week Follow-Up 24
Adverse Event Reporting Description	A treatment-emergent adverse event (AE) was defined as any AE that began after the first dose of double-blind study study, or began earlier yet worsened after the first dose, to 30 days after the last dose. The AEs were reported by at least 5% of patients in any treatment group and the Safety Population of 275 was used in the analysis.
Arm/Group Title	Taribavirin 20 mg/kg/Day		Taribavirin 25 mg/kg/Day		Taribavirin 30 mg/kg/Day		Ribavirin 800 mg/Day
Arm/Group Description	Oral taribavirin 20 mg/kg/day (actual doses were 20-24 mg/kg/day) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk)		Oral taribavirin tablet 25 mg/kg/day actual doses were 25-29 mg/kg/day) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk)		Oral taribavirin 30 mg/kg/day actual doses were 30-34 mg/kg/day) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk)		Oral ribavirin 800 mg/day (body weight <65 kg), 1000 mg/day (body weight 65-84 kg), 1200 mg/day (body weight 85-104 kg) or 1400 mg/day (body weight greater than or equal to 105 kg) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk)
All Cause Mortality
	Taribavirin 20 mg/kg/Day		Taribavirin 25 mg/kg/Day		Taribavirin 30 mg/kg/Day		Ribavirin 800 mg/Day
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Taribavirin 20 mg/kg/Day		Taribavirin 25 mg/kg/Day		Taribavirin 30 mg/kg/Day		Ribavirin 800 mg/Day
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/67 (10.4%)		6/70 (8.6%)		6/68 (8.8%)		9/70 (12.9%)
Cardiac disorders
Angina Pectoris	1/67 (1.5%)	1	0/70 (0%)	0	1/68 (1.5%)	1	0/70 (0%)	0
Atrial Fibrillation	0/67 (0%)	0	0/70 (0%)	0	1/68 (1.5%)	1	0/70 (0%)	0
Gastrointestinal disorders
Diarrhoea	1/67 (1.5%)	1	0/70 (0%)	0	1/68 (1.5%)	1	0/70 (0%)	0
Upper Gastrointestinal Haemorrhage	0/67 (0%)	0	0/70 (0%)	0	1/68 (1.5%)	1	0/70 (0%)	0
Colitis	1/67 (1.5%)	1	0/70 (0%)	0	0/68 (0%)	0	0/70 (0%)	0
General disorders
Chest Pain	1/67 (1.5%)	1	0/70 (0%)	0	0/68 (0%)	0	0/70 (0%)	0
Asthenia	0/67 (0%)	0	0/70 (0%)	0	0/68 (0%)	0	1/70 (1.4%)	1
Hepatobiliary disorders
Cholecystitis	0/67 (0%)	0	1/70 (1.4%)	1	0/68 (0%)	0	0/70 (0%)	0
Infections and infestations
Pneumonia	0/67 (0%)	0	1/70 (1.4%)	1	2/68 (2.9%)	2	1/70 (1.4%)	1
Appendicitis	0/67 (0%)	0	0/70 (0%)	0	1/68 (1.5%)	1	0/70 (0%)	0
Sepsis	0/67 (0%)	0	0/70 (0%)	0	1/68 (1.5%)	1	0/70 (0%)	0
Abscess Jaw	1/67 (1.5%)	1	0/70 (0%)	0	0/68 (0%)	0	0/70 (0%)	0
Injection Site Cellulitis	1/67 (1.5%)	1	0/70 (0%)	0	0/68 (0%)	0	0/70 (0%)	0
Empyema	0/67 (0%)	0	0/70 (0%)	0	0/68 (0%)	0	1/70 (1.4%)	1
Injury, poisoning and procedural complications
Accidental Overdose	1/67 (1.5%)	1	0/70 (0%)	0	0/68 (0%)	0	0/70 (0%)	0
Fibula Fracture	1/67 (1.5%)	1	0/70 (0%)	0	0/68 (0%)	0	0/70 (0%)	0
Tibia Fracture	1/67 (1.5%)	1	0/70 (0%)	0	0/68 (0%)	0	0/70 (0%)	0
Metabolism and nutrition disorders
Dehydration	0/67 (0%)	0	0/70 (0%)	0	1/68 (1.5%)	1	1/70 (1.4%)	1
Hyponatraemia	0/67 (0%)	0	0/70 (0%)	0	0/68 (0%)	0	1/70 (1.4%)	1
Musculoskeletal and connective tissue disorders
Musculoskeletal Chest Pain	0/67 (0%)	0	0/70 (0%)	0	1/68 (1.5%)	1	0/70 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gastric Cancer	0/67 (0%)	0	1/70 (1.4%)	1	0/68 (0%)	0	0/70 (0%)	0
Oesophageal Adenocarcinoma	0/67 (0%)	0	0/70 (0%)	0	0/68 (0%)	0	1/70 (1.4%)	1
Oesophageal Squamous Cell Carcinoma	0/67 (0%)	0	1/70 (1.4%)	1	0/68 (0%)	0	0/70 (0%)	0
Nervous system disorders
Metabolic Encaphalopathy	0/67 (0%)	0	0/70 (0%)	0	1/68 (1.5%)	1	0/70 (0%)	0
Status Epilepticus	0/67 (0%)	0	0/70 (0%)	0	1/68 (1.5%)	1	0/70 (0%)	0
Cerebrovascular Accident	0/67 (0%)	0	1/70 (1.4%)	1	0/68 (0%)	0	1/70 (1.4%)	1
Convulsion	0/67 (0%)	0	0/70 (0%)	0	0/68 (0%)	0	1/70 (1.4%)	1
Migraine	0/67 (0%)	0	0/70 (0%)	0	0/68 (0%)	0	1/70 (1.4%)	1
Syncope	0/67 (0%)	0	0/70 (0%)	0	0/68 (0%)	0	1/70 (1.4%)	1
Psychiatric disorders
Delirium	0/67 (0%)	0	0/70 (0%)	0	1/68 (1.5%)	1	0/70 (0%)	0
Intentional Self-injury	0/67 (0%)	0	0/70 (0%)	0	1/68 (1.5%)	1	0/70 (0%)	0
Suicidal Ideation	0/67 (0%)	0	1/70 (1.4%)	1	1/68 (1.5%)	1	3/70 (4.3%)	3
Depression	0/67 (0%)	0	0/70 (0%)	0	0/68 (0%)	0	1/70 (1.4%)	1
Anxiety	1/67 (1.5%)	1	0/70 (0%)	0	0/68 (0%)	0	0/70 (0%)	0
Mental Status Changes	0/67 (0%)	0	1/70 (1.4%)	1	0/68 (0%)	0	0/70 (0%)	0
Suicide Attempt	0/67 (0%)	0	1/70 (1.4%)	1	0/68 (0%)	0	0/70 (0%)	0
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Distress Disorder	0/67 (0%)	0	0/70 (0%)	0	1/68 (1.5%)	1	0/70 (0%)	0
Dyspnoea	0/67 (0%)	0	0/70 (0%)	0	0/68 (0%)	0	1/70 (1.4%)	1
Vascular disorders
Deep Vein Thrombosis	0/67 (0%)	0	0/70 (0%)	0	0/68 (0%)	0	1/70 (1.4%)	1
Other (Not Including Serious) Adverse Events
	Taribavirin 20 mg/kg/Day		Taribavirin 25 mg/kg/Day		Taribavirin 30 mg/kg/Day		Ribavirin 800 mg/Day
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	66/67 (98.5%)		68/70 (97.1%)		68/68 (100%)		69/70 (98.6%)
Blood and lymphatic system disorders
Anaemia	8/67 (11.9%)	8	14/70 (20%)	14	15/68 (22.1%)	15	23/70 (32.9%)	23
Neutropenia	10/67 (14.9%)	10	6/70 (8.6%)	6	11/68 (16.2%)	11	6/70 (8.6%)	6
Ear and labyrinth disorders
Vertigo	3/67 (4.5%)	3	0/70 (0%)	0	0/68 (0%)	0	4/70 (5.7%)	4
Eye disorders
Vision Blurred	3/67 (4.5%)	3	5/70 (7.1%)	5	5/68 (7.4%)	5	3/70 (4.3%)	3
Eye Pain	0/67 (0%)	0	1/70 (1.4%)	1	3/68 (4.4%)	3	5/70 (7.1%)	5
Gastrointestinal disorders
Nausea	30/67 (44.8%)	30	24/70 (34.3%)	24	29/68 (42.6%)	29	29/70 (41.4%)	29
Diarrhoea	27/67 (40.3%)	27	27/70 (38.6%)	27	25/68 (36.8%)	25	16/70 (22.9%)	16
Abdominal Pain	7/67 (10.4%)	7	10/70 (14.3%)	10	10/68 (14.7%)	10	5/70 (7.1%)	5
Vomiting	11/67 (16.4%)	11	12/70 (17.1%)	12	9/68 (13.2%)	9	5/70 (7.1%)	5
Loose Stools	7/67 (10.4%)	7	3/70 (4.3%)	3	6/68 (8.8%)	6	0/70 (0%)	0
Constipation	7/67 (10.4%)	7	6/70 (8.6%)	6	2/68 (2.9%)	2	5/70 (7.1%)	5
Dyspepsia	3/67 (4.5%)	3	4/70 (5.7%)	4	5/68 (7.4%)	5	3/70 (4.3%)	3
Haemorrhoids	3/67 (4.5%)	3	3/70 (4.3%)	3	5/68 (7.4%)	5	1/70 (1.4%)	1
Gastrooesophageal Reflux Disease	4/67 (6%)	4	3/70 (4.3%)	3	2/68 (2.9%)	2	1/70 (1.4%)	1
Abdominal Pain Upper	2/67 (3%)	2	4/70 (5.7%)	4	2/68 (2.9%)	2	5/70 (7.1%)	5
Flatulence	4/67 (6%)	4	0/70 (0%)	0	1/68 (1.5%)	1	0/70 (0%)	0
Dysphagia	2/67 (3%)	2	2/70 (2.9%)	2	0/68 (0%)	0	5/70 (7.1%)	5
General disorders
Fatigue	44/67 (65.7%)	44	37/70 (52.9%)	37	43/68 (63.2%)	43	36/70 (51.4%)	36
Influenza-like Illness	20/67 (29.9%)	20	21/70 (30%)	21	27/68 (39.7%)	27	24/70 (34.3%)	24
Chills	17/67 (25.4%)	17	16/70 (22.9%)	16	21/68 (30.9%)	21	14/70 (20%)	14
Injection Site Erythema	20/67 (29.9%)	20	9/70 (12.9%)	9	15/68 (22.1%)	15	17/70 (24.3%)	17
Pyrexia	11/67 (16.4%)	11	11/70 (15.7%)	11	12/68 (17.6%)	12	18/70 (25.7%)	18
Pain	6/67 (9%)	6	9/70 (12.9%)	9	10/68 (14.7%)	10	8/70 (11.4%)	8
Injection Site Reaction	6/67 (9%)	6	6/70 (8.6%)	6	3/68 (4.4%)	3	8/70 (11.4%)	8
Asthenia	5/67 (7.5%)	5	3/70 (4.3%)	3	4/68 (5.9%)	4	3/70 (4.3%)	3
Injection Site Rash	1/67 (1.5%)	1	4/70 (5.7%)	4	3/68 (4.4%)	3	0/70 (0%)	0
Injection Site Pruritus	4/67 (6%)	4	0/70 (0%)	0	1/68 (1.5%)	1	0/70 (0%)	0
Non-cardiac Chest Pain	1/67 (1.5%)	1	1/70 (1.4%)	1	2/68 (2.9%)	2	6/70 (8.6%)	6
Infections and infestations
Sinusitis	9/67 (13.4%)	9	1/70 (1.4%)	1	1/68 (1.5%)	1	6/70 (8.6%)	6
Urinary Tract Infection	4/67 (6%)	4	2/70 (2.9%)	2	3/68 (4.4%)	3	5/70 (7.1%)	5
Tooth Abscess	1/67 (1.5%)	1	0/70 (0%)	0	1/68 (1.5%)	1	4/70 (5.7%)	4
Investigations
Weight Decreased	6/67 (9%)	6	4/70 (5.7%)	4	5/68 (7.4%)	5	3/70 (4.3%)	3
Metabolism and nutrition disorders
Decreased Appetite	11/67 (16.4%)	11	5/70 (7.1%)	5	17/68 (25%)	17	10/70 (14.3%)	10
Anorexia	5/67 (7.5%)	5	4/70 (5.7%)	4	5/68 (7.4%)	5	8/70 (11.4%)	8
Dehydration	2/67 (3%)	2	1/70 (1.4%)	1	4/68 (5.9%)	4	1/70 (1.4%)	1
Musculoskeletal and connective tissue disorders
Myalgia	21/67 (31.3%)	21	11/70 (15.7%)	11	17/68 (25%)	17	14/70 (20%)	14
Arthralgia	14/67 (20.9%)	14	11/70 (15.7%)	11	15/68 (22.1%)	15	17/70 (24.3%)	17
Back Pain	5/67 (7.5%)	5	8/70 (11.4%)	8	5/68 (7.4%)	5	4/70 (5.7%)	4
Pain in Extremity	1/67 (1.5%)	1	1/70 (1.4%)	1	4/68 (5.9%)	4	4/70 (5.7%)	4
Nervous system disorders
Headache	30/67 (44.8%)	30	35/70 (50%)	35	22/68 (32.4%)	22	28/70 (40%)	28
Dizziness	10/67 (14.9%)	10	18/70 (25.7%)	18	13/68 (19.1%)	13	15/70 (21.4%)	15
Dysgeusia	9/67 (13.4%)	9	4/70 (5.7%)	4	5/68 (7.4%)	5	4/70 (5.7%)	4
Disturbance in Attention	6/67 (9%)	6	2/70 (2.9%)	2	6/68 (8.8%)	6	2/70 (2.9%)	2
Memory Impairment	4/67 (6%)	4	1/70 (1.4%)	1	2/68 (2.9%)	2	0/70 (0%)	0
Paraesthesia	4/67 (6%)	4	1/70 (1.4%)	1	1/68 (1.5%)	1	0/70 (0%)	0
Psychiatric disorders
Insomnia	23/67 (34.3%)	23	26/70 (37.1%)	26	23/68 (33.8%)	23	17/70 (24.3%)	17
Irritability	16/67 (23.9%)	16	12/70 (17.1%)	12	18/68 (26.5%)	18	16/70 (22.9%)	16
Depression	13/67 (19.4%)	13	24/70 (34.3%)	24	16/68 (23.5%)	16	10/70 (14.3%)	10
Anxiety	8/67 (11.9%)	8	7/70 (10%)	7	8/68 (11.8%)	8	7/70 (10%)	7
Libido Decreased	3/67 (4.5%)	3	4/70 (5.7%)	4	1/68 (1.5%)	1	0/70 (0%)	0
Mood Swings	2/67 (3%)	2	4/70 (5.7%)	4	1/68 (1.5%)	1	3/70 (4.3%)	3
Anger	4/67 (6%)	4	1/70 (1.4%)	1	0/68 (0%)	0	0/70 (0%)	0
Respiratory, thoracic and mediastinal disorders
Dyspnoea	10/67 (14.9%)	10	4/70 (5.7%)	4	9/68 (13.2%)	9	10/70 (14.3%)	10
Cough	11/67 (16.4%)	11	10/70 (14.3%)	10	8/68 (11.8%)	8	12/70 (17.1%)	12
Pharyngolaryngeal Pain	6/67 (9%)	6	4/70 (5.7%)	4	3/68 (4.4%)	3	2/70 (2.9%)	2
Upper Respiratory Tract Infection	4/67 (6%)	4	6/70 (8.6%)	6	1/68 (1.5%)	1	5/70 (7.1%)	5
Herpes Simplex	4/67 (6%)	4	2/70 (2.9%)	2	3/68 (4.4%)	3	2/70 (2.9%)	2
Epistaxis	2/67 (3%)	2	4/70 (5.7%)	4	1/68 (1.5%)	1	3/70 (4.3%)	3
Respiratory Tract Congestion	4/67 (6%)	4	0/70 (0%)	0	1/68 (1.5%)	1	0/70 (0%)	0
Dyspnoea Exertional	1/67 (1.5%)	1	1/70 (1.4%)	1	2/68 (2.9%)	2	4/70 (5.7%)	4
Skin and subcutaneous tissue disorders
Alopecia	8/67 (11.9%)	8	11/70 (15.7%)	11	12/68 (17.6%)	12	18/70 (25.7%)	18
Rash	11/67 (16.4%)	11	13/70 (18.6%)	13	12/68 (17.6%)	12	12/70 (17.1%)	12
Dry Skin	7/67 (10.4%)	7	14/70 (20%)	14	11/68 (16.2%)	11	8/70 (11.4%)	8
Pruritis	11/67 (16.4%)	11	8/70 (11.4%)	8	8/68 (11.8%)	8	13/70 (18.6%)	13
Hypotrichosis	7/67 (10.4%)	7	2/70 (2.9%)	2	3/68 (4.4%)	3	5/70 (7.1%)	5
Dermatitis	2/67 (3%)	2	4/70 (5.7%)	4	1/68 (1.5%)	1	4/70 (5.7%)	4
Hyperhidrosis	4/67 (6%)	4	0/70 (0%)	0	1/68 (1.5%)	1	2/70 (2.9%)	2
Vascular disorders
Hypertension	5/67 (7.5%)	5	1/70 (1.4%)	1	3/68 (4.4%)	3	3/70 (4.3%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Agreements may vary with individual investigators, but will not prohibit any investigator from publishing. Valeant supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.