Study of Efficacy and Safety of Grazoprevir (MK-5172) + Elbasvir (MK-8742) in Chronic Hepatitis C Participants With Child-Pugh (CP)-B Hepatic Insufficiency (MK-5172-059)

• Sponsor: Merck Sharp & Dohme LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02115321
• Collaborator: (none)
• Enrollment: 40
• Arms: 4
• Actual Duration (Months): 13.2

Study Details

Study Description

Brief Summary

This study is being done to evaluate the efficacy and safety of the drug combination grazoprevir (GZR; MK-5172) + elbasvir (EBR; MK-8742) in participants with chronic hepatitis C virus (HCV) genotype (GT) 1, 4, or 6 infection and who have cirrhosis and Child-Pugh (CP) score 7-9 moderate hepatic insufficiency (CP-B). The primary hypothesis is that the percentage of HCV-infected participants with hepatic insufficiency (the CP-B population) achieving sustained viral response (SVR) 12 weeks after the end of all treatment (SVR12) will be greater than 60%. Additionally, ten non-cirrhotic (NC) HCV-infected GT1 participants will also be given GZR + EBR at the beginning of the study; this will be done for the purpose of collecting plasma pharmacokinetic (PK) data in HCV GT1-infected participants who do not have hepatic insufficiency.

Condition or Disease	Intervention/Treatment	Phase
Chronic Hepatitis C	Drug: Grazoprevir; Drug: Elbasvir; Drug: MK-5172A	Phase 2/Phase 3

Detailed Description

The study will be conducted sequentially in 3 Parts. Each participant will participate in only one Part.

Participants will be enrolled in either Part A, Part B, or Part C:

• Part A: CP-B participants will receive GZR 50 mg+ EBR 50 mg; NC participants will receive GZR 100 mg/EBR 50 mg.

• Part B: CP-B participants will receive GZR 100 mg + EBR 50 mg.

• Part C: CP-B participants will receive either GZR 50 mg or 100 mg + EBR 50 mg. Study progression from Part A to Part B and from Part B to Part C will be based upon a review of safety and efficacy in Parts A and B, respectively. Depending upon safety and efficacy in Part A, the study may progress directly from Part A to Part C using GZR 50 mg + EBR 50 mg, without performing Part B.

Study Design

• Study Type: Interventional
• Actual Enrollment: 40 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II/III Clinical Trial to Study the Efficacy and Safety of the Combination Regimen of MK-5172 and MK-8742 in Subjects With Chronic Hepatitis C Virus Infection With Advanced Cirrhosis and Child-Pugh (CP)-B Hepatic Insufficiency
• Actual Study Start Date: May 9, 2014
• Actual Primary Completion Date: Mar 5, 2015
• Actual Study Completion Date: Jun 16, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part A: CP-B GZR 50 mg + EBR 50 mg CP-B participants take GZR 50 mg + EBR 50 mg once daily (q.d.) by mouth for 12 weeks.	Drug: Grazoprevir; GZR was supplied as two 25 mg tablets in the Part A CP-B arm, or as either one GZR 100 mg tablet or one fixed-dose combination (FDC) tablet containing GZR 100 mg + EBR 50 mg in a single tablet (MK-5172A) in the Part A NC arm. GZR was taken q.d. by mouth.; Other Names: MK-5172 ; Drug: Elbasvir; EBR was supplied as 50 mg tablets and was taken q.d. by mouth.; Other Names: MK-8742
Experimental: Part A: NC GZR 100 mg + EBR 50 mg NC participants take GZR 100 mg + EBR 50 mg q.d. by mouth for 12 weeks.	Drug: Grazoprevir; GZR was supplied as two 25 mg tablets in the Part A CP-B arm, or as either one GZR 100 mg tablet or one fixed-dose combination (FDC) tablet containing GZR 100 mg + EBR 50 mg in a single tablet (MK-5172A) in the Part A NC arm. GZR was taken q.d. by mouth.; Other Names: MK-5172 ; Drug: Elbasvir; EBR was supplied as 50 mg tablets and was taken q.d. by mouth.; Other Names: MK-8742 ; Drug: MK-5172A; MK-5172A FDC tablet containing GZR 100 mg + EBR 50 mg taken q.d. by mouth.
Experimental: Part B: CP-B GZR 100 mg + EBR 50 mg CP-B participants take GZR 100 mg + EBR 50 mg q.d. by mouth for 12 weeks.	Drug: Grazoprevir; GZR was supplied as two 25 mg tablets in the Part A CP-B arm, or as either one GZR 100 mg tablet or one fixed-dose combination (FDC) tablet containing GZR 100 mg + EBR 50 mg in a single tablet (MK-5172A) in the Part A NC arm. GZR was taken q.d. by mouth.; Other Names: MK-5172 ; Drug: Elbasvir; EBR was supplied as 50 mg tablets and was taken q.d. by mouth.; Other Names: MK-8742 ; Drug: MK-5172A; MK-5172A FDC tablet containing GZR 100 mg + EBR 50 mg taken q.d. by mouth.
Experimental: Part C: CP-B GZR 50 mg or 100 mg + EBR 50 mg CP-B participants take GZR 50 mg or GZR 100 mg + EBR 50 mg q.d. by mouth for 12 weeks (GZR dose chosen based on results of Part A CP-B arm).	Drug: Grazoprevir; GZR was supplied as two 25 mg tablets in the Part A CP-B arm, or as either one GZR 100 mg tablet or one fixed-dose combination (FDC) tablet containing GZR 100 mg + EBR 50 mg in a single tablet (MK-5172A) in the Part A NC arm. GZR was taken q.d. by mouth.; Other Names: MK-5172 ; Drug: Elbasvir; EBR was supplied as 50 mg tablets and was taken q.d. by mouth.; Other Names: MK-8742 ; Drug: MK-5172A; MK-5172A FDC tablet containing GZR 100 mg + EBR 50 mg taken q.d. by mouth.

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Achieving Sustained Viral Response 12 Weeks After Completing Study Therapy (SVR12) [Week 24]

   SVR12 was defined as hepatitis C virus (HCV) ribonucleic acid (RNA) levels below the lower limit of quantification (LLoQ) 12 weeks after completing study therapy. HCV RNA was measured with the COBAS™ AmpliPrep/COBAS™ Taqman™ HCV Test, v2.0 ® assay which has a LLoQ of 15 IU/mL and a limit of detection of 15 IU/mL.

2. Number of Participants Experiencing an Adverse Event (AE) During Treatment and First 14 Follow-up Days [Up to 14 weeks]

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

3. Number of Participants Discontinuing Study Drug Due to an AE [Up to 12 weeks]

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

Secondary Outcome Measures

1. Mean Change From Baseline in Model for End-Stage Liver Disease (MELD) Scores in CP-B Participants [Baseline and Weeks 12, 24, and 36]

   The MELD score provides an objective and granular assessment of liver improvement as a continuous variable. The calculation of MELD score is based on three biochemical variables (serum bilirubin, creatinine and international normalized ratio [INR] of prothrombin time). The MELD equation is as follows: 9.57 x ln(creatinine mg/dL) +3.78 x ln(bilirubin mg/dL) +11.2 x ln (INR) + 6.43. Scores are multiplied by 10 and rounded to the nearest whole number and range from 6 (less ill) to 40 (gravely ill). MELD scores were determined at Baseline (Day 1) and again at Week 12, Follow-up (FU) Week 12 (Week 24), and FU Week 24 (Week 36). Change from baseline in MELD score = Post-baseline MELD score - baseline MELD score.

2. Percentage of Participants With HCV RNA Undetectable at Weeks 2, 4, and 12 [Week 2, 4, and 12]

   HCV RNA was measured with the COBAS™ AmpliPrep/COBAS™ Taqman™ HCV Test, v2.0 ® assay which has a LLoQ of 15 IU/mL and a limit of detection of 15 IU/mL.

3. Percentage of Participants With HCV RNA <LLoQ at Weeks 2, 4, and 12 [Weeks 2, 4, and 12]

   HCV RNA was measured with the COBAS™ AmpliPrep/COBAS™ Taqman™ HCV Test, v2.0 ® assay which has a LLoQ of 15 IU/mL and a limit of detection of 15 IU/mL.

4. Percentage of Participants Achieving Sustained Viral Response 4 Weeks After Completing Study Therapy (SVR4) [Week 16]

   SVR4 was defined as HCV RNA levels <LLoQ 4 weeks after completing study therapy. HCV RNA was measured with the COBAS™ AmpliPrep/COBAS™ Taqman™ HCV Test, v2.0 ® assay which has a LLoQ of 15 IU/mL and a limit of detection of 15 IU/mL.

5. Percentage of Participants Achieving Sustained Viral Response 24 Weeks After Completing Study Therapy (SVR24) [Week 36]

   SVR24 was defined as HCV RNA levels <LLoQ 24 weeks after completing study therapy. HCV RNA was measured with the COBAS™ AmpliPrep/COBAS™ Taqman™ HCV Test, v2.0 ® assay which has a LLoQ of 15 IU/mL and a limit of detection of 15 IU/mL.

Eligibility Criteria

Criteria

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

Inclusion criteria:

• Has documented chronic HCV GT1 infection (for Arm 4 participants may have GT4 or GT6 infection) with no evidence of non-typable or mixed genotype infection

• Has clinical evidence of hepatic cirrhosis with a score on the Child-Pugh scale from 7 to 9 and not anticipated to receive a liver transplant within the next 36 weeks (for Arm 1, Arm 3, and Arm 4)

• Has no evidence of cirrhosis (only for Arm 2 )

• Agrees to remain truly abstinent or use (or have their partner use) an acceptable method of birth control from at least 2 weeks prior to Day 1 and continue until at least 14 days after last dose of study drug, or longer if dictated by local regulations

Exclusion criteria:

• Is co-infected with hepatitis B virus or human immunodeficiency virus (HIV)

• Has previously received direct-acting antiviral therapy for HCV

• Has a history of malignancy <=5 years prior to signing informed consent except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer or carcinoma in situ; or under evaluation for other active or suspected malignancy

• Has cirrhosis and liver imaging results within 4 weeks prior to screening showing evidence of hepatocellular carcinoma (HCC), or is under evaluation for HCC

• Is 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

• Has clinically-relevant drug or alcohol abuse within 12 months of screening

• Is pregnant or breast-feeding, or expecting to conceive or donate eggs or sperm from at least 2 weeks prior to Day 1 and continue throughout treatment and follow up, or longer if dictated by local regulations

• Has received organ transplants (including hematopoietic stem cell transplants) other than cornea and hair

• Has poor venous access

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

• Requires, or likely to require, chronic systemic administration of corticosteroids during the course of the trial

• Has 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: NCT02115321
• Other Study ID Numbers: 5172-059; 2014-000672-25
• First Posted: Apr 16, 2014
• Last Update Posted: Jun 26, 2019
• Last Verified: Jun 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis; Hepatitis, Chronic; Hepatic Insufficiency; Liver Failure; Grazoprevir

Study Results

Participant Flow

Recruitment Details	The screening period lasted for 60 days. Recruitment was halted after enrolling participants in the two Part A arms, as the current clinical development plan is focused on a fixed-dose combination (FDC) product containing grazoprevir (GZR) 100 mg and elbasvir (EBR) 50 mg. No participants were enrolled in Parts B or C.

Arm/Group Title	Part A: CP-B GZR 50 mg + EBR 50 mg	Part A: NC GZR 100 mg + EBR 50 mg
Arm/Group Description	Child-Pugh score 7 to 9 (CP-B) participants take GZR 50 mg + EBR 50 mg once daily (q.d.) by mouth for 12 weeks.	Non-cirrhotic (NC) participants take GZR 100 mg + EBR 50 mg q.d. by mouth for 12 weeks.
Period Title: Overall Study
STARTED	30	10
COMPLETED	29	10
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	Part A: CP-B GZR 50 mg + EBR 50 mg	Part A: NC GZR 100 mg + ER 50 mg	Total
Arm/Group Description	CP-B participants take GZR 50 mg + EBR 50 mg q.d. by mouth for 12 weeks.	NC participants take GZR 100 mg + EBR 50 mg q.d. by mouth for 12 weeks.	Total of all reporting groups
Overall Participants	30	10	40
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	58.3 (7.0)	60.4 (5.3)	58.8 (6.6)
Sex: Female, Male (Count of Participants)
Female	13 43.3%	5 50%	18 45%
Male	17 56.7%	5 50%	22 55%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Achieving Sustained Viral Response 12 Weeks After Completing Study Therapy (SVR12)
Description	SVR12 was defined as hepatitis C virus (HCV) ribonucleic acid (RNA) levels below the lower limit of quantification (LLoQ) 12 weeks after completing study therapy. HCV RNA was measured with the COBAS™ AmpliPrep/COBAS™ Taqman™ HCV Test, v2.0 ® assay which has a LLoQ of 15 IU/mL and a limit of detection of 15 IU/mL.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) consists of all randomized participants who received at least one dose of study medication.

Arm/Group Title	Part A: CP-B GZR 50 mg + EBR 50 mg	Part A: NC GZR 100 mg + ER 50 mg
Arm/Group Description	CP-B participants take GZR 50 mg + EBR 50 mg q.d. by mouth for 12 weeks.	NC participants take GZR 100 mg + EBR 50 mg q.d. by mouth for 12 weeks.
Measure Participants	30	10
Number (95% Confidence Interval) [Percentage of participants]	90.0 300%	100.0 1000%

2. Primary Outcome

Title	Number of Participants Experiencing an Adverse Event (AE) During Treatment and First 14 Follow-up Days
Description	An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Time Frame	Up to 14 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part A: CP-B GZR 50 mg + EBR 50 mg	Part A: NC GZR 100 mg + ER 50 mg
Arm/Group Description	CP-B participants take GZR 50 mg + EBR 50 mg q.d. by mouth for 12 weeks.	NC participants take GZR 100 mg + EBR 50 mg q.d. by mouth for 12 weeks.
Measure Participants	30	10
Number [Number of participants]	25 83.3%	8 80%

3. Primary Outcome

Title	Number of Participants Discontinuing Study Drug Due to an AE
Description	An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Time Frame	Up to 12 weeks

Outcome Measure Data

Analysis Population Description

The APaT population consisted of all randomized participants who received at least one dose of study medication.

Arm/Group Title	Part A: CP-B GZR 50 mg + EBR 50 mg	Part A: NC GZR 100 mg + ER 50 mg
Arm/Group Description	CP-B participants take GZR 50 mg + EBR 50 mg q.d. by mouth for 12 weeks.	NC participants take GZR 100 mg + EBR 50 mg q.d. by mouth for 12 weeks.
Measure Participants	30	10
Number [Number of participants]	0 0%	0 0%

4. Secondary Outcome

Title	Mean Change From Baseline in Model for End-Stage Liver Disease (MELD) Scores in CP-B Participants
Description	The MELD score provides an objective and granular assessment of liver improvement as a continuous variable. The calculation of MELD score is based on three biochemical variables (serum bilirubin, creatinine and international normalized ratio [INR] of prothrombin time). The MELD equation is as follows: 9.57 x ln(creatinine mg/dL) +3.78 x ln(bilirubin mg/dL) +11.2 x ln (INR) + 6.43. Scores are multiplied by 10 and rounded to the nearest whole number and range from 6 (less ill) to 40 (gravely ill). MELD scores were determined at Baseline (Day 1) and again at Week 12, Follow-up (FU) Week 12 (Week 24), and FU Week 24 (Week 36). Change from baseline in MELD score = Post-baseline MELD score - baseline MELD score.
Time Frame	Baseline and Weeks 12, 24, and 36

Outcome Measure Data

Analysis Population Description

All CP-B participants in the FAS (all randomized participants who received at least one dose of study medication) with available data.

Arm/Group Title	Part A: CP-B GZR 50 mg + EBR 50 mg	Part A: NC GZR 100 mg + ER 50 mg
Arm/Group Description	CP-B participants take GZR 50 mg + EBR 50 mg q.d. by mouth for 12 weeks.	NC participants take GZR 100 mg + EBR 50 mg q.d. by mouth for 12 weeks.
Measure Participants	30	0
Week 12 (n=30)	-0.67 (1.35)
FU Week 12 (Week 24) [n=29]	-0.38 (1.74)
FU Week 24 (Week 36) [n=29]	-0.34 (3.15)

5. Secondary Outcome

Title	Percentage of Participants With HCV RNA Undetectable at Weeks 2, 4, and 12
Description	HCV RNA was measured with the COBAS™ AmpliPrep/COBAS™ Taqman™ HCV Test, v2.0 ® assay which has a LLoQ of 15 IU/mL and a limit of detection of 15 IU/mL.
Time Frame	Week 2, 4, and 12

Outcome Measure Data

Analysis Population Description

Per protocol, this measure was to be determined in Arm 4 (Part C); however, enrollment was halted after Part A and thus no data are available.

Arm/Group Title	Part A: CP-B GZR 50 mg + EBR 50 mg	Part A: NC GZR 100 mg + ER 50 mg
Arm/Group Description	CP-B participants take GZR 50 mg + EBR 50 mg q.d. by mouth for 12 weeks.	NC participants take GZR 100 mg + EBR 50 mg q.d. by mouth for 12 weeks.
Measure Participants	0	0

6. Secondary Outcome

Title	Percentage of Participants With HCV RNA <LLoQ at Weeks 2, 4, and 12
Description	HCV RNA was measured with the COBAS™ AmpliPrep/COBAS™ Taqman™ HCV Test, v2.0 ® assay which has a LLoQ of 15 IU/mL and a limit of detection of 15 IU/mL.
Time Frame	Weeks 2, 4, and 12

Outcome Measure Data

Analysis Population Description

Per protocol, this measure was to be determined in Arm 4 (Part C); however, enrollment was halted after Part A and thus no data are available.

Arm/Group Title	Part A: CP-B GZR 50 mg + EBR 50 mg	Part A: NC GZR 100 mg + ER 50 mg
Arm/Group Description	CP-B participants take GZR 50 mg + EBR 50 mg q.d. by mouth for 12 weeks.	NC participants take GZR 100 mg + EBR 50 mg q.d. by mouth for 12 weeks.
Measure Participants	0	0

7. Secondary Outcome

Title	Percentage of Participants Achieving Sustained Viral Response 4 Weeks After Completing Study Therapy (SVR4)
Description	SVR4 was defined as HCV RNA levels <LLoQ 4 weeks after completing study therapy. HCV RNA was measured with the COBAS™ AmpliPrep/COBAS™ Taqman™ HCV Test, v2.0 ® assay which has a LLoQ of 15 IU/mL and a limit of detection of 15 IU/mL.
Time Frame	Week 16

Outcome Measure Data

Analysis Population Description

The FAS consists of all randomized participants who received at least one dose of study medication.

Arm/Group Title	Part A: CP-B GZR 50 mg + EBR 50 mg	Part A: NC GZR 100 mg + ER 50 mg
Arm/Group Description	CP-B participants take GZR 50 mg + EBR 50 mg q.d. by mouth for 12 weeks.	NC participants take GZR 100 mg + EBR 50 mg q.d. by mouth for 12 weeks.
Measure Participants	30	10
Number (95% Confidence Interval) [Percentage of participants]	93.3 311%	100.0 1000%

8. Secondary Outcome

Title	Percentage of Participants Achieving Sustained Viral Response 24 Weeks After Completing Study Therapy (SVR24)
Description	SVR24 was defined as HCV RNA levels <LLoQ 24 weeks after completing study therapy. HCV RNA was measured with the COBAS™ AmpliPrep/COBAS™ Taqman™ HCV Test, v2.0 ® assay which has a LLoQ of 15 IU/mL and a limit of detection of 15 IU/mL.
Time Frame	Week 36

Outcome Measure Data

Analysis Population Description

The FAS consists of all randomized participants who received at least one dose of study medication.

Arm/Group Title	Part A: CP-B GZR 50 mg + EBR 50 mg	Part A: NC GZR 100 mg + ER 50 mg
Arm/Group Description	CP-B participants take GZR 50 mg + EBR 50 mg q.d. by mouth for 12 weeks.	NC participants take GZR 100 mg + EBR 50 mg q.d. by mouth for 12 weeks.
Measure Participants	30	10
Number (95% Confidence Interval) [Percentage of participants]	90.0 300%	100.0 1000%

Adverse Events

Time Frame	Up to 36 weeks.
Adverse Event Reporting Description	An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Arm/Group Title	CP-B: GZR 50 mg + EBR 50 mg for 12 Weeks		Non-cirrhotic: GZR 100 mg + EBR 50 mg for 12 Weeks
Arm/Group Description	CP-B participants take GZR 50 mg + EBR 50 mg q.d. by mouth for 12 weeks.		NC participants take GZR 100 mg + EBR 50 mg q.d. by mouth for 12 weeks.
All Cause Mortality
	CP-B: GZR 50 mg + EBR 50 mg for 12 Weeks		Non-cirrhotic: GZR 100 mg + EBR 50 mg for 12 Weeks
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	CP-B: GZR 50 mg + EBR 50 mg for 12 Weeks		Non-cirrhotic: GZR 100 mg + EBR 50 mg for 12 Weeks
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/30 (16.7%)		0/10 (0%)
Blood and lymphatic system disorders
Anaemia	1/30 (3.3%)	1	0/10 (0%)	0
Gastrointestinal disorders
Ascites	1/30 (3.3%)	1	0/10 (0%)	0
Varices oesophageal	1/30 (3.3%)	1	0/10 (0%)	0
Hepatobiliary disorders
Hepatic failure	1/30 (3.3%)	1	0/10 (0%)	0
Infections and infestations
Peritonitis bacterial	1/30 (3.3%)	2	0/10 (0%)	0
Metabolism and nutrition disorders
Malnutrition	1/30 (3.3%)	1	0/10 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hepatocellular carcinoma	1/30 (3.3%)	1	0/10 (0%)	0
Nervous system disorders
Cerebral infarction	1/30 (3.3%)	1	0/10 (0%)	0
Encephalopathy	1/30 (3.3%)	1	0/10 (0%)	0
Other (Not Including Serious) Adverse Events
	CP-B: GZR 50 mg + EBR 50 mg for 12 Weeks		Non-cirrhotic: GZR 100 mg + EBR 50 mg for 12 Weeks
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	20/30 (66.7%)		8/10 (80%)
Blood and lymphatic system disorders
Increased tendency to bruise	0/30 (0%)	0	1/10 (10%)	1
Ear and labyrinth disorders
Ear discomfort	0/30 (0%)	0	1/10 (10%)	1
Eye disorders
Retinal detachment	0/30 (0%)	0	1/10 (10%)	1
Gastrointestinal disorders
Abdominal discomfort	1/30 (3.3%)	1	1/10 (10%)	1
Abdominal pain	2/30 (6.7%)	2	1/10 (10%)	1
Abdominal pain upper	0/30 (0%)	0	1/10 (10%)	1
Diarrhoea	2/30 (6.7%)	2	0/10 (0%)	0
Nausea	3/30 (10%)	3	2/10 (20%)	2
Vomiting	2/30 (6.7%)	2	0/10 (0%)	0
Constipation	0/30 (0%)	0	1/10 (10%)	1
General disorders
Chills	2/30 (6.7%)	2	0/10 (0%)	0
Fatigue	9/30 (30%)	11	3/10 (30%)	3
Feeling abnormal	0/30 (0%)	0	1/10 (10%)	1
Pyrexia	3/30 (10%)	3	0/10 (0%)	0
Infections and infestations
Influenza	3/30 (10%)	3	0/10 (0%)	0
Tooth infection	0/30 (0%)	0	1/10 (10%)	1
Urinary tract infection	3/30 (10%)	3	0/10 (0%)	0
Pneumonia	0/30 (0%)	0	1/10 (10%)	1
Injury, poisoning and procedural complications
Ligament sprain	0/30 (0%)	0	1/10 (10%)	1
Muscle strain	0/30 (0%)	0	1/10 (10%)	1
Investigations
Blood creatine phosphokinase increased	0/30 (0%)	0	1/10 (10%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	5/30 (16.7%)	5	2/10 (20%)	3
Myalgia	2/30 (6.7%)	2	0/10 (0%)	0
Nervous system disorders
Dizziness	2/30 (6.7%)	2	0/10 (0%)	0
Headache	3/30 (10%)	3	5/10 (50%)	6
Sinus headache	0/30 (0%)	0	1/10 (10%)	1
Psychiatric disorders
Affect lability	0/30 (0%)	0	1/10 (10%)	1
Insomnia	2/30 (6.7%)	2	1/10 (10%)	1
Respiratory, thoracic and mediastinal disorders
Cough	2/30 (6.7%)	2	1/10 (10%)	1
Oropharyngeal pain	0/30 (0%)	0	1/10 (10%)	1
Sinus congestion	0/30 (0%)	0	1/10 (10%)	1
Skin and subcutaneous tissue disorders
Acne	0/30 (0%)	0	1/10 (10%)	1

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.