Study of Efficacy and Safety of Grazoprevir (MK-5172) + Elbasvir (MK-8742) With or Without Ribavirin for Participants With Hepatitis C Genotype 1, 4, or 6 Infections Who Have Failed Prior Treatment With Pegylated Interferon + Ribavirin (MK-5172-068)

• Sponsor: Merck Sharp & Dohme LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02105701
• Collaborator: (none)
• Enrollment: 420
• Arms: 4
• Actual Duration (Months): 12.5

Study Details

Study Description

Brief Summary

This is an efficacy and safety study of grazoprevir (MK-5172) in combination with elbasvir (MK-8742) with or without ribavirin (RBV) in participants with chronic hepatitis C virus (HCV) genotype (GT) 1, 4, or 6 infections who have failed prior therapy with pegylated interferon and RBV. The primary study hypothesis is that in at least one of the study arms, the percentage of participants achieving sustained viral response 12 weeks after the end of all study treatment (SVR12) will be superior to 58%.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis C Infection	Drug: Grazoprevir + Elbasvir; Drug: Ribavirin	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 420 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase III Randomized Clinical Trial to Study the Efficacy and Safety of the Combination Regimen of MK-5172/MK-8742 in Subjects Who Have Failed Prior Treatment With Pegylated Interferon and Ribavirin (P/R) With Chronic HCV GT1, GT4, and GT6 Infection
• Actual Study Start Date: Jun 5, 2014
• Actual Primary Completion Date: Mar 24, 2015
• Actual Study Completion Date: Jun 19, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Grazoprevir + Elbasvir 12 weeks Participants receive grazoprevir 100 mg/elbasvir 50 mg fixed-dose combination (FDC) tablets once daily (q.d.) by mouth for 12 weeks.	Drug: Grazoprevir + Elbasvir; FDC tablet containing grazoprevir 100 mg and elbasvir 50 mg.; Other Names: MK-5172A
Experimental: Grazoprevir + Elbasvir + RBV 12 weeks Participants receive grazoprevir 100 mg/elbasvir 50 mg FDC tablets q.d. by mouth, along with RBV capsules twice daily (b.i.d.) by mouth (weight-based dosing; 800 to 1400 mg total daily dose), for 12 weeks.	Drug: Grazoprevir + Elbasvir; FDC tablet containing grazoprevir 100 mg and elbasvir 50 mg.; Other Names: MK-5172A ; Drug: Ribavirin; 200 mg capsule; Other Names: Rebetol®
Experimental: Grazoprevir + Elbasvir 16 weeks Participants receive grazoprevir 100 mg/elbasvir 50 mg FDC tablets q.d. by mouth for 16 weeks.	Drug: Grazoprevir + Elbasvir; FDC tablet containing grazoprevir 100 mg and elbasvir 50 mg.; Other Names: MK-5172A
Experimental: Grazoprevir + Elbasvir + RBV 16 weeks Participants receive grazoprevir 100 mg/elbasvir 50 mg FDC tablets q.d. by mouth, along with RBV capsules b.i.d. by mouth (weight-based dosing; 800 to 1400 mg total daily dose), for 16 weeks.	Drug: Grazoprevir + Elbasvir; FDC tablet containing grazoprevir 100 mg and elbasvir 50 mg.; Other Names: MK-5172A ; Drug: Ribavirin; 200 mg capsule; Other Names: Rebetol®

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Achieving Undetectable HCV RNA 12 Weeks After Completing Study Therapy (SVR12) [12 weeks after the end of all study treatment (up to 28 weeks)]

   HCV RNA was measured using the Roche COBAS® Taqman® HCV Test, v2.0 assay.

2. Number of Participants Experiencing Adverse Events (AE) [Up to 18 weeks]

   An AE is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.

3. Number of Participants Discontinuing Study Treatment Due to an AE [Up to 16 weeks]

   An AE is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.

Secondary Outcome Measures

1. Percentage of Participants Achieving Undetectable HCV RNA 24 Weeks After the End of All Treatment (SVR24) [24 weeks after the end of all study treatment (up to 40 weeks)]

   HCV RNA was measured using the Roche COBAS® Taqman® HCV Test, v2.0 assay.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Documented chronic HCV GT1, GT4, or GT6 with no evidence of non-typable or mixed genotype infection (positive for anti-HCV antibody, HCV ribonucleic acid [RNA], or any of the listed GTs at least 6 months prior to screening must be confirmed by screening lab results)

• Cirrhosis defined as liver biopsy showing METAVIR F4; or Fibroscan showing result

12.5 kilopascals (kPa); or FibroSure® (Fibrotest®) score of >0.75 and an aspartate aminotransferase (AST):platelet ratio index (APRI) of >2

• Absence of cirrhosis defined as liver biopsy showing absence of cirrhosis; or Fibroscan result of ≤ 12.5 kPa; or Fibrosure® (Fibrotest®) score of ≤ 0.48 and APRI ≤ 1

• Previous HCV treatment status of peginterferon/RBV Null responder; or peginterferon/RBV Partial responder; or peginterferon/RBV Treatment Relapse

• For human immunodeficiency virus (HIV) co-infected participants: documented HIV-1 infection; currently naïve to treatment with any antiretroviral therapy (ART) and have no plans to initiate ART treatment while participating in this study; or be on HIV ART for at least 8 weeks prior to study entry (dual nucleoside reverse transcriptase inhibitor [NRTI] backbone of tenofovir or abacavir and either emtricitabine or lamivudine plus raltegravir (or dolutegravir or rilpivirine) (no changes in HIV regimen allowed within 4 weeks of randomization); cluster of differentiation 4 (CD4)+ T-cell count >200 cells/mm^3 at screening; documented undetectable plasma HIV-1 RNA at least 8 weeks prior to screening; participants not on ART, HIV RNA must be <50,000 copies/mL; must have at least one viable antiretroviral regimen alternative beyond their current regimen in the event of HIV virologic failure and the development of antiretroviral drug resistance

• Agree to use two acceptable methods of birth control from at least 2 weeks prior to Day 1 and continue until at least 6 months after last dose of study drug, or longer if dictated by local regulations; a male participant who is not (or whose partner is not) of reproductive potential is eligible without requiring the use of contraception

Exclusion Criteria:

• Evidence of decompensated liver disease manifested by the presence of or history of ascites, esophageal or gastric variceal bleeding, hepatic encephalopathy or other signs or symptoms of advanced liver disease

• For participants with cirrhosis, participants who are Child-Pugh Class B or C or who have a Pugh-Turcotte (CPT) score >6, must be excluded

• Co-infected with hepatitis B virus

• Has had previous direct-acting antiviral treatment

• History of malignancy <=5 years prior except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer or carcinoma in situ; or is under evaluation for other active or suspected malignancy

• Has cirrhosis and liver imaging showing evidence of hepatocellular carcinoma (HCC) or is under evaluation for HCC

• Taking or plans to take any HIV therapy that includes a ritonavir-boosted or unboosted protease inhibitor, efavirenz or etravirine

• Currently participating or has participated in a study with an investigational compound within 30 days of signing informed consent and is not willing to refrain from participating in another such study during the course of this study

• Clinically-relevant drug or alcohol abuse within 12 months

• Pregnant, breast-feeding, or expecting to conceive or donate eggs or sperm from Day 1 and continue until at least 6 months after last dose of study drug, or longer if dictated by local regulations; or is a male whose female partner(s) is/are pregnant

• History of organ transplant (including hematopoietic stem cell transplants) other than cornea and hair

• Poor venous access

• History of gastric surgery (e.g., stapling, bypass) or history of malabsorption disorders (e.g., celiac sprue disease)

• Hemoglobinopathy, including, but not limited to, thalassemia major

• Any medical condition requiring, or likely to require, chronic systemic corticosteroids, tumor necrosis factor (TNF) antagonists, or other immunosuppressant drugs during the course of the trial

• For participants with HIV, history of opportunistic infection in the preceding 6 months

• For participants with HIV, use of HIV drugs other than a dual NRTI backbone of tenofovir or abacavir and either emtricitabine or lamivudine plus raltegravir (or dolutegravir or rilpivirine)

• Evidence or history of chronic hepatitis not caused by HCV, including but not limited to nonalcoholic steatohepatitis (NASH), drug-induced hepatitis, and autoimmune hepatitis

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Merck Sharp & Dohme LLC

Investigators

• Study Director: Medical Director, Merck Sharp & Dohme LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT02105701
• Other Study ID Numbers: 5172-068; 2014-000824-12
• First Posted: Apr 7, 2014
• Last Update Posted: Feb 5, 2021
• Last Verified: Jan 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Infections; Communicable Diseases; Hepatitis A; Hepatitis C; Hepatitis; Ribavirin; Grazoprevir

Study Results

Participant Flow

Arm/Group Title	Grazoprevir + Elbasvir 12 Weeks	Grazoprevir + Elbasvir + RBV 12 Weeks	Grazoprevir + Elbasvir 16 Weeks	Grazoprevir + Elbasvir + RBV 16 Weeks
Arm/Group Description	Participants received grazoprevir 100 mg/elbasvir 50 mg FDC tablets q.d. by mouth for 12 weeks.	Participants received grazoprevir 100 mg/elbasvir 50 mg FDC tablets q.d. by mouth, along with RBV capsules b.i.d. by mouth (weight-based dosing; 800 to 1400 mg total daily dose), for 12 weeks.	Participants received grazoprevir 100 mg/elbasvir 50 mg FDC tablets q.d. by mouth for 16 weeks.	Participants received grazoprevir 100 mg/elbasvir 50 mg FDC tablets q.d. by mouth, along with RBV capsules b.i.d. by mouth (weight-based dosing; 800 to 1400 mg total daily dose), for 16 weeks.
Period Title: Overall Study
STARTED	105	104	105	106
COMPLETED	101	103	102	104
NOT COMPLETED	4	1	3	2

Baseline Characteristics

Arm/Group Title	Grazoprevir + Elbasvir 12 Weeks	Grazoprevir + Elbasvir + RBV 12 Weeks	Grazoprevir + Elbasvir 16 Weeks	Grazoprevir + Elbasvir + RBV 16 Weeks	Total
Arm/Group Description	Participants received grazoprevir 100 mg/elbasvir 50 mg FDC tablets q.d. by mouth for 12 weeks.	Participants received grazoprevir 100 mg/elbasvir 50 mg FDC tablets q.d. by mouth, along with RBV capsules b.i.d. by mouth (weight-based dosing; 800 to 1400 mg total daily dose), for 12 weeks.	Participants received grazoprevir 100 mg/elbasvir 50 mg FDC tablets q.d. by mouth for 16 weeks.	Participants received grazoprevir 100 mg/elbasvir 50 mg FDC tablets q.d. by mouth, along with RBV capsules b.i.d. by mouth (weight-based dosing; 800 to 1400 mg total daily dose), for 16 weeks.	Total of all reporting groups
Overall Participants	105	104	105	106	420
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	55.71 (9.81)	55.46 (8.26)	54.91 (9.79)	54.98 (9.61)	55.27 (9.37)
Sex: Female, Male (Count of Participants)
Female	39 37.1%	32 30.8%	36 34.3%	42 39.6%	149 35.5%
Male	66 62.9%	72 69.2%	69 65.7%	64 60.4%	271 64.5%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Achieving Undetectable HCV RNA 12 Weeks After Completing Study Therapy (SVR12)
Description	HCV RNA was measured using the Roche COBAS® Taqman® HCV Test, v2.0 assay.
Time Frame	12 weeks after the end of all study treatment (up to 28 weeks)

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) population consists of all randomized subjects who receive at least one dose of study treatment.

Arm/Group Title	Grazoprevir + Elbasvir 12 Weeks	Grazoprevir + Elbasvir + RBV 12 Weeks	Grazoprevir + Elbasvir 16 Weeks	Grazoprevir + Elbasvir + RBV 16 Weeks
Arm/Group Description	Participants received grazoprevir 100 mg/elbasvir 50 mg FDC tablets q.d. by mouth for 12 weeks.	Participants received grazoprevir 100 mg/elbasvir 50 mg FDC tablets q.d. by mouth, along with RBV capsules b.i.d. by mouth (weight-based dosing; 800 to 1400 mg total daily dose), for 12 weeks.	Participants received grazoprevir 100 mg/elbasvir 50 mg FDC tablets q.d. by mouth for 16 weeks.	Participants received grazoprevir 100 mg/elbasvir 50 mg FDC tablets q.d. by mouth, along with RBV capsules b.i.d. by mouth (weight-based dosing; 800 to 1400 mg total daily dose), for 16 weeks.
Measure Participants	105	104	105	106
Number (95% Confidence Interval) [Percentage of participants]	92.4 88%	94.2 90.6%	92.4 88%	98.1 92.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Grazoprevir + Elbasvir 12 Weeks
	Comments	The hypothesis was that at least 1 treatment arm would have a SVR12 rate >58%.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	One-sided Exact Test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Grazoprevir + Elbasvir + RBV 12 Weeks
	Comments	The hypothesis was that at least 1 treatment arm would have a SVR12 rate >58%.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	One-sided Exact Test
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Grazoprevir + Elbasvir 16 Weeks
	Comments	The hypothesis was that at least 1 treatment arm would have a SVR12 rate >58%.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	One-sided Exact Test
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Grazoprevir + Elbasvir + RBV 16 Weeks
	Comments	The hypothesis was that at least 1 treatment arm would have a SVR12 rate >58%.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	One-sided Exact Test
	Comments

2. Primary Outcome

Title	Number of Participants Experiencing Adverse Events (AE)
Description	An AE is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Time Frame	Up to 18 weeks

Outcome Measure Data

Analysis Population Description

The All Participants as Treated (APaT) population consists of all participants who received at least one dose of study treatment.

Arm/Group Title	Grazoprevir + Elbasvir 12 Weeks	Grazoprevir + Elbasvir + RBV 12 Weeks	Grazoprevir + Elbasvir 16 Weeks	Grazoprevir + Elbasvir + RBV 16 Weeks
Arm/Group Description	Participants received grazoprevir 100 mg/elbasvir 50 mg FDC tablets q.d. by mouth for 12 weeks.	Participants received grazoprevir 100 mg/elbasvir 50 mg FDC tablets q.d. by mouth, along with RBV capsules b.i.d. by mouth (weight-based dosing; 800 to 1400 mg total daily dose), for 12 weeks.	Participants received grazoprevir 100 mg/elbasvir 50 mg FDC tablets q.d. by mouth for 16 weeks.	Participants received grazoprevir 100 mg/elbasvir 50 mg FDC tablets q.d. by mouth, along with RBV capsules b.i.d. by mouth (weight-based dosing; 800 to 1400 mg total daily dose), for 16 weeks.
Measure Participants	105	104	105	106
Number [Number of participants]	74 70.5%	85 81.7%	77 73.3%	95 89.6%

3. Primary Outcome

Title	Number of Participants Discontinuing Study Treatment Due to an AE
Description	An AE is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Time Frame	Up to 16 weeks

Outcome Measure Data

Analysis Population Description

The All Participants as Treated (APaT) population consists of all participants who received at least one dose of study treatment.

Arm/Group Title	Grazoprevir + Elbasvir 12 Weeks	Grazoprevir + Elbasvir + RBV 12 Weeks	Grazoprevir + Elbasvir 16 Weeks	Grazoprevir + Elbasvir + RBV 16 Weeks
Arm/Group Description	Participants received grazoprevir 100 mg/elbasvir 50 mg FDC tablets q.d. by mouth for 12 weeks.	Participants received grazoprevir 100 mg/elbasvir 50 mg FDC tablets q.d. by mouth, along with RBV capsules b.i.d. by mouth (weight-based dosing; 800 to 1400 mg total daily dose), for 12 weeks.	Participants received grazoprevir 100 mg/elbasvir 50 mg FDC tablets q.d. by mouth for 16 weeks.	Participants received grazoprevir 100 mg/elbasvir 50 mg FDC tablets q.d. by mouth, along with RBV capsules b.i.d. by mouth (weight-based dosing; 800 to 1400 mg total daily dose), for 16 weeks.
Measure Participants	105	104	105	106
Number [Number of participants]	1 1%	1 1%	0 0%	5 4.7%

4. Secondary Outcome

Title	Percentage of Participants Achieving Undetectable HCV RNA 24 Weeks After the End of All Treatment (SVR24)
Description	HCV RNA was measured using the Roche COBAS® Taqman® HCV Test, v2.0 assay.
Time Frame	24 weeks after the end of all study treatment (up to 40 weeks)

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) population consists of all randomized subjects who receive at least one dose of study treatment.

Arm/Group Title	Grazoprevir + Elbasvir 12 Weeks	Grazoprevir + Elbasvir + RBV 12 Weeks	Grazoprevir + Elbasvir 16 Weeks	Grazoprevir + Elbasvir + RBV 16 Weeks
Arm/Group Description	Participants received grazoprevir 100 mg/elbasvir 50 mg FDC tablets q.d. by mouth for 12 weeks.	Participants received grazoprevir 100 mg/elbasvir 50 mg FDC tablets q.d. by mouth, along with RBV capsules b.i.d. by mouth (weight-based dosing; 800 to 1400 mg total daily dose), for 12 weeks.	Participants received grazoprevir 100 mg/elbasvir 50 mg FDC tablets q.d. by mouth for 16 weeks.	Participants received grazoprevir 100 mg/elbasvir 50 mg FDC tablets q.d. by mouth, along with RBV capsules b.i.d. by mouth (weight-based dosing; 800 to 1400 mg total daily dose), for 16 weeks.
Measure Participants	105	104	105	106
Number (95% Confidence Interval) [Percentage of participants]	91.4 87%	94.2 90.6%	89.5 85.2%	95.3 89.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Grazoprevir + Elbasvir 12 Weeks
	Comments	The hypothesis was that at least 1 treatment arm would have a SVR24 rate >58%.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	One-sided Exact Test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Grazoprevir + Elbasvir + RBV 12 Weeks
	Comments	The hypothesis was that at least 1 treatment arm would have a SVR24 rate >58%.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	One-sided Exact Test
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Grazoprevir + Elbasvir 16 Weeks
	Comments	The hypothesis was that at least 1 treatment arm would have a SVR24 rate >58%.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	One-sided Exact Test
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Grazoprevir + Elbasvir + RBV 16 Weeks
	Comments	The hypothesis was that at least 1 treatment arm would have a SVR24 rate >58%.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	One-sided Exact Test
	Comments

Adverse Events

Time Frame	Up to Week 40.
Adverse Event Reporting Description	An AE is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Arm/Group Title	GZR/EBR 12 Weeks		GZR/EBR + RBV 12 Weeks		GZR/EBR 16 Weeks		GZR/EBR + RBV for 16 Weeks
Arm/Group Description	Participants received grazoprevir 100 mg/elbasvir 50 mg FDC tablets q.d. by mouth for 12 weeks.		Participants received grazoprevir 100 mg/elbasvir 50 mg FDC tablets q.d. by mouth, along with RBV capsules b.i.d. by mouth (weight-based dosing; 800 to 1400 mg total daily dose), for 12 weeks.		Participants received grazoprevir 100 mg/elbasvir 50 mg FDC tablets q.d. by mouth for 16 weeks.		Participants received grazoprevir 100 mg/elbasvir 50 mg FDC tablets q.d. by mouth, along with RBV capsules b.i.d. by mouth (weight-based dosing; 800 to 1400 mg total daily dose), for 16 weeks.
All Cause Mortality
	GZR/EBR 12 Weeks		GZR/EBR + RBV 12 Weeks		GZR/EBR 16 Weeks		GZR/EBR + RBV for 16 Weeks
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	GZR/EBR 12 Weeks		GZR/EBR + RBV 12 Weeks		GZR/EBR 16 Weeks		GZR/EBR + RBV for 16 Weeks
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/105 (5.7%)		8/104 (7.7%)		4/105 (3.8%)		6/106 (5.7%)
Blood and lymphatic system disorders
Anaemia	0/105 (0%)	0	0/104 (0%)	0	0/105 (0%)	0	1/106 (0.9%)	1
Cardiac disorders
Angina unstable	1/105 (1%)	1	0/104 (0%)	0	0/105 (0%)	0	0/106 (0%)	0
Coronary artery disease	1/105 (1%)	1	0/104 (0%)	0	0/105 (0%)	0	0/106 (0%)	0
Ear and labyrinth disorders
Sudden hearing loss	1/105 (1%)	1	0/104 (0%)	0	0/105 (0%)	0	0/106 (0%)	0
Gastrointestinal disorders
Abdominal pain	0/105 (0%)	0	1/104 (1%)	1	0/105 (0%)	0	0/106 (0%)	0
Ascites	1/105 (1%)	1	0/104 (0%)	0	0/105 (0%)	0	0/106 (0%)	0
Colitis	0/105 (0%)	0	0/104 (0%)	0	0/105 (0%)	0	1/106 (0.9%)	1
Diarrhoea	0/105 (0%)	0	1/104 (1%)	1	0/105 (0%)	0	0/106 (0%)	0
Intestinal angioedema	0/105 (0%)	0	0/104 (0%)	0	0/105 (0%)	0	1/106 (0.9%)	1
Varices oesophageal	0/105 (0%)	0	1/104 (1%)	1	0/105 (0%)	0	0/106 (0%)	0
General disorders
Non-cardiac chest pain	0/105 (0%)	0	1/104 (1%)	1	0/105 (0%)	0	0/106 (0%)	0
Infections and infestations
Herpes simplex oesophagitis	0/105 (0%)	0	0/104 (0%)	0	0/105 (0%)	0	1/106 (0.9%)	1
Infectious colitis	0/105 (0%)	0	1/104 (1%)	1	0/105 (0%)	0	0/106 (0%)	0
Parotitis	0/105 (0%)	0	1/104 (1%)	1	0/105 (0%)	0	0/106 (0%)	0
Pneumonia	1/105 (1%)	1	0/104 (0%)	0	0/105 (0%)	0	0/106 (0%)	0
Post procedural infection	0/105 (0%)	0	0/104 (0%)	0	1/105 (1%)	1	0/106 (0%)	0
Injury, poisoning and procedural complications
Hip fracture	1/105 (1%)	1	0/104 (0%)	0	0/105 (0%)	0	0/106 (0%)	0
Overdose	0/105 (0%)	0	0/104 (0%)	0	1/105 (1%)	1	0/106 (0%)	0
Rib fracture	0/105 (0%)	0	0/104 (0%)	0	0/105 (0%)	0	1/106 (0.9%)	1
Tibia fracture	0/105 (0%)	0	0/104 (0%)	0	0/105 (0%)	0	1/106 (0.9%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hepatocellular carcinoma	0/105 (0%)	0	1/104 (1%)	1	0/105 (0%)	0	0/106 (0%)	0
Splenic marginal zone lymphoma	0/105 (0%)	0	0/104 (0%)	0	1/105 (1%)	1	0/106 (0%)	0
Nervous system disorders
Loss of consciousness	0/105 (0%)	0	0/104 (0%)	0	1/105 (1%)	1	0/106 (0%)	0
Transient ischaemic attack	0/105 (0%)	0	1/104 (1%)	1	0/105 (0%)	0	0/106 (0%)	0
Psychiatric disorders
Schizophrenia	0/105 (0%)	0	1/104 (1%)	1	0/105 (0%)	0	0/106 (0%)	0
Renal and urinary disorders
Nephrolithiasis	0/105 (0%)	0	0/104 (0%)	0	0/105 (0%)	0	1/106 (0.9%)	1
Reproductive system and breast disorders
Uterine polyp	0/105 (0%)	0	1/104 (1%)	1	0/105 (0%)	0	0/106 (0%)	0
Vascular disorders
Femoral artery occlusion	1/105 (1%)	1	0/104 (0%)	0	0/105 (0%)	0	0/106 (0%)	0
Other (Not Including Serious) Adverse Events
	GZR/EBR 12 Weeks		GZR/EBR + RBV 12 Weeks		GZR/EBR 16 Weeks		GZR/EBR + RBV for 16 Weeks
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	55/105 (52.4%)		72/104 (69.2%)		58/105 (55.2%)		84/106 (79.2%)
Blood and lymphatic system disorders
Anaemia	0/105 (0%)	0	12/104 (11.5%)	13	0/105 (0%)	0	17/106 (16%)	19
Gastrointestinal disorders
Abdominal pain	6/105 (5.7%)	6	3/104 (2.9%)	3	1/105 (1%)	1	3/106 (2.8%)	3
Constipation	1/105 (1%)	1	3/104 (2.9%)	3	7/105 (6.7%)	8	5/106 (4.7%)	5
Diarrhoea	5/105 (4.8%)	5	4/104 (3.8%)	4	8/105 (7.6%)	9	9/106 (8.5%)	9
Dyspepsia	3/105 (2.9%)	3	4/104 (3.8%)	4	0/105 (0%)	0	7/106 (6.6%)	9
Nausea	9/105 (8.6%)	10	15/104 (14.4%)	19	4/105 (3.8%)	4	18/106 (17%)	20
Vomiting	2/105 (1.9%)	2	7/104 (6.7%)	8	1/105 (1%)	1	9/106 (8.5%)	10
General disorders
Asthenia	8/105 (7.6%)	9	11/104 (10.6%)	13	9/105 (8.6%)	10	10/106 (9.4%)	10
Fatigue	20/105 (19%)	21	28/104 (26.9%)	32	17/105 (16.2%)	18	32/106 (30.2%)	33
Infections and infestations
Upper respiratory tract infection	3/105 (2.9%)	3	2/104 (1.9%)	2	6/105 (5.7%)	9	5/106 (4.7%)	6
Injury, poisoning and procedural complications
Accidental overdose	3/105 (2.9%)	3	15/104 (14.4%)	22	1/105 (1%)	1	14/106 (13.2%)	23
Investigations
Haemoglobin decreased	0/105 (0%)	0	1/104 (1%)	1	0/105 (0%)	0	7/106 (6.6%)	7
Metabolism and nutrition disorders
Decreased appetite	2/105 (1.9%)	2	6/104 (5.8%)	6	1/105 (1%)	1	6/106 (5.7%)	6
Musculoskeletal and connective tissue disorders
Arthralgia	4/105 (3.8%)	4	3/104 (2.9%)	4	7/105 (6.7%)	8	4/106 (3.8%)	5
Myalgia	2/105 (1.9%)	2	6/104 (5.8%)	7	8/105 (7.6%)	8	7/106 (6.6%)	7
Nervous system disorders
Dizziness	7/105 (6.7%)	7	8/104 (7.7%)	8	5/105 (4.8%)	10	6/106 (5.7%)	8
Headache	21/105 (20%)	23	21/104 (20.2%)	23	21/105 (20%)	23	20/106 (18.9%)	22
Psychiatric disorders
Insomnia	5/105 (4.8%)	5	11/104 (10.6%)	12	7/105 (6.7%)	7	10/106 (9.4%)	10
Irritability	4/105 (3.8%)	6	5/104 (4.8%)	5	2/105 (1.9%)	2	8/106 (7.5%)	8
Respiratory, thoracic and mediastinal disorders
Cough	6/105 (5.7%)	6	10/104 (9.6%)	10	4/105 (3.8%)	4	10/106 (9.4%)	10
Dyspnoea	1/105 (1%)	1	9/104 (8.7%)	11	1/105 (1%)	1	10/106 (9.4%)	10
Dyspnoea exertional	1/105 (1%)	1	3/104 (2.9%)	4	0/105 (0%)	0	8/106 (7.5%)	8
Skin and subcutaneous tissue disorders
Pruritus	1/105 (1%)	1	11/104 (10.6%)	13	6/105 (5.7%)	6	11/106 (10.4%)	11
Rash	3/105 (2.9%)	3	4/104 (3.8%)	4	1/105 (1%)	1	8/106 (7.5%)	10

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation.