An Efficacy and Safety Study of Grazoprevir (MK-5172) + E... | NCT02105688

ID	Type	Description	Link
2014-000343-32	EudraCT Number
MK-5172-062	Other Identifier	Merck

Label	Type	Description	Intervention Names
Immediate Treatment Arm: Grazoprevir/Elbasvir	Experimental	In Part A, participants receive grazoprevir 100 mg plus elbasvir 50 mg FDC (MK-5172A) once daily for 12 weeks (blinded) and were followed-up for 24 weeks. In Part B, participants could enroll in a 3-year follow-up period where they were followed every 6 months for 3 years in an observational cohort (no treatment was administered during Part B).	Drug: Grazoprevir 100 mg/Elbasvir 50 mg FDC tablet (MK-5172A)
Deferred Treatment Arm: Placebo > Grazoprevir/Elbasvir	Placebo Comparator	In Part A, participants receive placebo to MK-5172A once daily for 12 weeks (blinded), followed by 4 weeks of follow-up. Afterwards, participants received 12 weeks of open-label treatment with the MK-5172A FDC and were followed-up for 24 weeks. In Part B, participants could enroll in a 3-year follow-up period where they were followed every 6 months for 3 years in an observational cohort (no treatment was administered during Part B).	Drug: Grazoprevir 100 mg/Elbasvir 50 mg FDC tablet (MK-5172A) Drug: Placebo to Grazoprevir 100 mg/Elbasvir 50 mg FDC tablet

Name	Type	Description	Arm Group Labels	Other Names
Grazoprevir 100 mg/Elbasvir 50 mg FDC tablet (MK-5172A)	Drug	Grazoprevir 100 mg/Elbasvir 50 mg FDC tablet, taken once daily by mouth for 12 weeks.	Deferred Treatment Arm: Placebo > Grazoprevir/Elbasvir

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After the End of All Study Therapy (SVR12)	Blood was drawn from each participant to assess Hepatitis C Virus ribonucleic acid (HCV RNA) plasma levels using the Roche COBAS® AmpliPrep/COBAS® Taqman HCV Test, v2.0, which had a lower limit of quantification of 15 IU/mL. SVR12 was defined as HCV RNA below the lower limit of detection (\	12 weeks after end of all therapy (Study Week 24 for Immediate Treatment Arm and Study Week 40 for Deferred Treatment Arm)
Percentage of Participants Experiencing at Least One Adverse Event (AE) During the Double-Blind (DB) Treatment Period and First 14 Follow-up Days	An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the Sponsor's product, was also an AE. For this outcome measure, the primary safety analysis compared the percentage of participants experiencing an AE in the Immediate Treatment Arm during the double-blinded active treatment period to that of the Deferred Treatment Arm during the double-blinded placebo treatment period.	DB Treatment period plus first 14 follow-up days (up to Study Week 14)
Percentage of Participants Discontinued From Study Therapy Due to AEs During the DB Treatment Period	An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the Sponsor's product, was also an AE. For this outcome measure, the primary safety analysis compared the percentage of participants discontinuing study therapy due to an AE in the Immediate Treatment Arm during the double-blinded active treatment period to that of the Deferred Treatment Arm during the double-blinded placebo treatment period.

Secondary Outcomes

Measure	Description	Time Frame
Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After the End of All Study Therapy (SVR24)	Blood was drawn from each participant to assess HCV RNA plasma levels using the Roche COBAS® AmpliPrep/COBAS® Taqman HCV Test, v2.0, which has an LLOQ of 15 IU/mL. SVR24 was defined as HCV RNA \

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Part A

Documented chronic HCV GT1, GT4, or GT6 infection with no evidence of GT2, GT3, GT5 or non-typeable genotypes and HCV ribonucleic acid (RNA) confirmed by screening lab results prior to randomization
On opiate substitution therapy (OST; methadone, levamethadone, buprenorphine, naloxone, naltrexone) for at least 3 months prior to screening
Treatment naïve to all HCV therapies
Human Immunodeficiency Virus (HIV)-infected participants enrolled in this study must meet following criteria:
Documented HIV infection
Naïve to treatment with any antiretroviral therapy (ART) OR on HIV ART for at least 8 weeks prior to study entry using a dual nucleoside reverse transcriptase inhibitor (NRTI) backbone of tenofovir or abacavir and either emtricitabine or lamivudine PLUS raltegravir (or dolutegravir or rilpivirine). Dose modifications or changes in ART during the 4 weeks prior to study entry (Day 1) are not permitted
Cluster of differentiation 4 (CD4+) T-cell count >200 cells/mm^3 if on ART or >500 cell/mm^3 if ART treatment naïve
Undetectable plasma HIV-1 RNA at least 8 weeks prior to screening if on ART or <50,000 copies/mL if ART treatment naïve
Participants with HIV-1 infection and on ART must have at least one viable antiretroviral regimen alternative beyond their current regimen in the event of HIV virologic failure or the development of anti-retroviral drug resistance
Females who are of reproductive potential must agree to avoid becoming pregnant while receiving study drug and for 14 days after the last dose of study drug by complying with one of the following: (1) practice abstinence from heterosexual activity OR (2) use (or have her partner use) acceptable contraception during heterosexual activity

Part B

Received at least one dose of grazoprevir in combination with elbasvir in Part A. Receiving OST and keeping >80% of scheduled appointments while on OST were not required for Part B.

Exclusion Criteria:

Part A

Evidence of decompensated liver disease
For participants with cirrhosis, participants who are Child-Pugh Class B or C or who have a Pugh-Turcotte (CPT) score >6
Is co-infected with hepatitis B virus
Has cirrhosis and liver imaging within 6 months of Day 1 showing evidence of hepatocellular carcinoma (HCC) or is under evaluation for HCC
Currently using or intends to use barbiturates during the treatment period of this study
Is a female and is pregnant or breast-feeding, or expecting to conceive or donate eggs from Day 1 or anytime during treatment, and 14 days after the last dose of study medication, or longer if dictated by local regulations
Any medical condition requiring or likely to require chronic systemic administration of corticosteroids, Tumor Necrosis Factor (TNF) antagonists, or other immunosuppressant drugs during the course of the trial
Evidence or history of chronic hepatitis not caused by HCV

Part B

Mentally or legally incapacitated, has significant emotional problems at the time of pre-study screening visit or expected during the conduct of the study or has a history of a clinically significant psychiatric disorder which, in the opinion of the investigator, would interfere with the study procedures
Has a medical condition or personal circumstance which, in the opinion of the investigator and/or Sponsor, places the participant at unnecessary risk through continued participation in the trial or does not allow the participant to adhere to the requirements of the protocol

Name	Affiliation	Role
Medical Director	Merck Sharp & Dohme LLC	Study Director

PubMed Identifier	Type	Citation	Retractions
27537841	Result	Dore GJ, Altice F, Litwin AH, Dalgard O, Gane EJ, Shibolet O, Luetkemeyer A, Nahass R, Peng CY, Conway B, Grebely J, Howe AY, Gendrano IN, Chen E, Huang HC, Dutko FJ, Nickle DC, Nguyen BY, Wahl J, Barr E, Robertson MN, Platt HL; C-EDGE CO-STAR Study Group. Elbasvir-Grazoprevir to Treat Hepatitis C Virus Infection in Persons Receiving Opioid Agonist Therapy: A Randomized Trial. Ann Intern Med. 2016 Nov 1;165(9):625-634. doi: 10.7326/M16-0816. Epub 2016 Aug 9.
35939812

ID	Title	Description
FG000	Immediate Treatment Arm: Grazoprevir/Elbasvir	In Part A, participants received grazoprevir 100 mg plus elbasvir 50 mg FDC (MK-5172A) once daily for 12 weeks (blinded) and were followed-up for 24 weeks. In Part B, participants could enroll in a 3-year follow-up period where they were followed every 6 months for 3 years in an observational cohort (no treatment was administered during Part B).

ID	Title	Description
BG000	Immediate Treatment Arm: Grazoprevir/Elbasvir	In Part A, participants received grazoprevir 100 mg plus elbasvir 50 mg FDC (MK-5172A) once daily for 12 weeks (blinded) and were followed-up for 24 weeks. In Part B, participants could enroll in a 3-year follow-up period where they were followed every 6 months for 3 years in an observational cohort (no treatment was administered during Part B).
BG001	Deferred Treatment Arm: Placebo > Grazoprevir/Elbasvir	In Part A, participants received placebo to MK-5172A once daily for 12 weeks (blinded), followed by 4 weeks of follow-up. Afterwards, participants received 12 weeks of open-label treatment with the MK-5172A FDC and were followed-up for 24 weeks. In Part B, participants could enroll in a 3-year follow-up period where they were followed every 6 months for 3 years in an observational cohort (no treatment was administered during Part B).
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG000201 BG001100 BG002301

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After the End of All Study Therapy (SVR12)

Blood was drawn from each participant to assess Hepatitis C Virus ribonucleic acid (HCV RNA) plasma levels using the Roche COBAS® AmpliPrep/COBAS® Taqman HCV Test, v2.0, which had a lower limit of quantification of 15 IU/mL. SVR12 was defined as HCV RNA below the lower limit of detection (\

Modified FAS (mFAS): All randomized participants receiving ≥1 dose of active study treatment and excluding participants for study discontinuation for reasons unrelated to treatment regimen, response to HCV treatment, or BL genotype (GT)2, GT3, or GT5. The primary efficacy hypothesis was evaluated within participants of the Immediate Treatment Arm.

Posted

Number

95% Confidence Interval

Percentage of Participants

12 weeks after end of all therapy (Study Week 24 for Immediate Treatment Arm and Study Week 40 for Deferred Treatment Arm)

ID	Title	Description
OG000	Immediate Treatment Arm: Grazoprevir/Elbasvir	In Part A, participants received grazoprevir 100 mg plus elbasvir 50 mg FDC (MK-5172A) once daily for 12 weeks (blinded) and were followed-up for 24 weeks. In Part B, participants could enroll in a 3-year follow-up period where they were followed every 6 months for 3 years in an observational cohort (no treatment was administered during Part B).
OG001	Deferred Treatment Arm: Placebo > Grazoprevir/Elbasvir	In Part A, participants received placebo to MK-5172A once daily for 12 weeks (blinded), followed by 4 weeks of follow-up. Afterwards, participants received 12 weeks of open-label treatment with the MK-5172A FDC and were followed-up for 24 weeks. In Part B, participants could enroll in a 3-year follow-up period where they were followed every 6 months for 3 years in an observational cohort (no treatment was administered during Part B).

Units	Counts
Participants	OG000198 OG00188

Title

Denominators

Categories

Title	Measurements
	OG00095.5(91.5 to 97.9) OG00196.6(90.4 to 99.3)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000	A one-sided exact test was used to test the null hypothesis, which was that the SVR12 rate for the ITA was less than 67% (historical reference rate derived from NCT01667731). The p-value was based on a one-sided exact test for a binomial proportion. A one-sided p-value <0.025 supports a conclusion that the true SVR12 is >67%.	One-sided exact test		<0.001														Superiority or Other (legacy)

Primary

Percentage of Participants Experiencing at Least One Adverse Event (AE) During the Double-Blind (DB) Treatment Period and First 14 Follow-up Days

An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the Sponsor's product, was also an AE. For this outcome measure, the primary safety analysis compared the percentage of participants experiencing an AE in the Immediate Treatment Arm during the double-blinded active treatment period to that of the Deferred Treatment Arm during the double-blinded placebo treatment period.

All randomized participants who received at least one dose of study treatment during the Part A DB period.

Posted

Number

Percentage of Participants

DB Treatment period plus first 14 follow-up days (up to Study Week 14)

ID	Title	Description
OG000	Immediate Treatment Arm: Grazoprevir/Elbasvir	In Part A, participants received grazoprevir 100 mg plus elbasvir 50 mg FDC (MK-5172A) once daily for 12 weeks (blinded) and were followed-up for 24 weeks. In Part B, participants could enroll in a 3-year follow-up period where they were followed every 6 months for 3 years in an observational cohort (no treatment was administered during Part B).

Primary

Percentage of Participants Discontinued From Study Therapy Due to AEs During the DB Treatment Period

An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the Sponsor's product, was also an AE. For this outcome measure, the primary safety analysis compared the percentage of participants discontinuing study therapy due to an AE in the Immediate Treatment Arm during the double-blinded active treatment period to that of the Deferred Treatment Arm during the double-blinded placebo treatment period.

All randomized participants who received at least one dose of study treatment during the Part A DB period.

Posted

Number

Percentage of Participants

DB Treatment period (up to Study Week 12)

ID	Title	Description
OG000	Immediate Treatment Arm: Grazoprevir/Elbasvir	In Part A, participants received grazoprevir 100 mg plus elbasvir 50 mg FDC (MK-5172A) once daily for 12 weeks (blinded) and were followed-up for 24 weeks. In Part B, participants could enroll in a 3-year follow-up period where they were followed every 6 months for 3 years in an observational cohort (no treatment was administered during Part B).
OG001

Secondary

Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After the End of All Study Therapy (SVR24)

Blood was drawn from each participant to assess HCV RNA plasma levels using the Roche COBAS® AmpliPrep/COBAS® Taqman HCV Test, v2.0, which has an LLOQ of 15 IU/mL. SVR24 was defined as HCV RNA \

Modified FAS (mFAS): All randomized participants receiving ≥1 dose of active study treatment and excluding participants for study discontinuation for reasons unrelated to treatment regimen, response to HCV treatment, or BL genotype (GT)2, GT3, or GT5. The secondary efficacy analysis was evaluated within participants of the Immediate Treatment Arm.

Posted

Number

95% Confidence Interval

Percentage of Participants

24 weeks after end of all therapy (Study Week 36 for Immediate Treatment Arm and Study Week 52 for Deferred Treatment Arm)

ID	Title	Description
OG000	Immediate Treatment Arm: Grazoprevir/Elbasvir	In Part A, participants received grazoprevir 100 mg plus elbasvir 50 mg FDC (MK-5172A) once daily for 12 weeks (blinded) and were followed-up for 24 weeks. In Part B, participants could enroll in a 3-year follow-up period where they were followed every 6 months for 3 years in an observational cohort (no treatment was administered during Part B).

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Immediate Treatment Arm: Grazoprevir/Elbasvir	In Part A, participants received grazoprevir 100 mg plus elbasvir 50 mg FDC (MK-5172A) once daily for 12 weeks (blinded) and were followed-up for 24 weeks. In Part B, participants could enroll in a 3-year follow-up period where they were followed every 6 months for 3 years in an observational cohort (no treatment was administered during Part B).	3	201	16	201	108	201
EG001	Deferred Treatment Arm: Placebo	In Part A, participants received placebo to MK-5172A once daily for 12 weeks (blinded), followed by 4 weeks of follow-up.	1	100	4	100	46	100
EG002	Deferred Treatment Arm: Grazoprevir/Elbasvir	In Part A, participants received placebo to MK-5172A once daily for 12 weeks (blinded), followed by 4 weeks of follow-up. Afterwards, participants received 12 weeks of open-label treatment with the MK-5172A FDC and were followed-up for 24 weeks. In Part B, participants could enroll in a 3-year follow-up period where they were followed every 6 months for 3 years in an observational cohort (no treatment was administered during Part B).	1	95	7	95	36	95

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Left ventricular failure	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected201 at risk EG0010 events0 affected100 at risk EG0020 events0 affected95 at risk
Bacteraemia	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected201 at risk EG0011 events1 affected100 at risk EG0020 events0 affected95 at risk
Cellulitis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected201 at risk EG0010 events0 affected100 at risk EG0021 events1 affected95 at risk
Pneumonia	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected201 at risk EG0011 events1 affected100 at risk EG0020 events0 affected95 at risk
Sepsis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0002 events2 affected201 at risk EG0010 events0 affected100 at risk EG0020 events0 affected95 at risk
Subcutaneous abscess	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected201 at risk EG0011 events1 affected100 at risk EG0020 events0 affected95 at risk
Systemic candida	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected201 at risk EG0011 events1 affected100 at risk EG0020 events0 affected95 at risk
Accidental overdose	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected201 at risk EG0010 events0 affected100 at risk EG0021 events1 affected95 at risk
Clavicle fracture	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected201 at risk EG0011 events1 affected100 at risk EG0020 events0 affected95 at risk
Overdose	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected201 at risk EG0010 events0 affected100 at risk EG0021 events1 affected95 at risk
Road traffic accident	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected201 at risk EG0010 events0 affected100 at risk EG0021 events1 affected95 at risk
Skin laceration	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected201 at risk EG0010 events0 affected100 at risk EG0021 events1 affected95 at risk
Spinal compression fracture	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected201 at risk EG0010 events0 affected100 at risk EG0020 events0 affected95 at risk
Bladder cancer stage II	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected201 at risk EG0010 events0 affected100 at risk EG0020 events0 affected95 at risk
Squamous cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected201 at risk EG0010 events0 affected100 at risk EG0020 events0 affected95 at risk
Squamous cell carcinoma of the oral cavity	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected201 at risk EG0010 events0 affected100 at risk EG0021 events1 affected95 at risk
Ruptured cerebral aneurysm	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected201 at risk EG0010 events0 affected100 at risk EG0020 events0 affected95 at risk
Bipolar disorder	Psychiatric disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected201 at risk EG0010 events0 affected100 at risk EG0020 events0 affected95 at risk
Completed suicide	Psychiatric disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected201 at risk EG0010 events0 affected100 at risk EG0020 events0 affected95 at risk
Depression	Psychiatric disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected201 at risk EG0010 events0 affected100 at risk EG0021 events1 affected95 at risk
Drug abuse	Psychiatric disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected201 at risk EG0010 events0 affected100 at risk EG0021 events1 affected95 at risk
Hallucination, auditory	Psychiatric disorders	MedDRA 21.0	Systematic Assessment	EG0003 events1 affected201 at risk EG0010 events0 affected100 at risk EG0020 events0 affected95 at risk
Personality disorder	Psychiatric disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected201 at risk EG0010 events0 affected100 at risk EG0020 events0 affected95 at risk
Schizophrenia	Psychiatric disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected201 at risk EG0010 events0 affected100 at risk EG0020 events0 affected95 at risk
Suicidal ideation	Psychiatric disorders	MedDRA 21.0	Systematic Assessment	EG0002 events1 affected201 at risk EG0010 events0 affected100 at risk EG0020 events0 affected95 at risk
Suicide attempt	Psychiatric disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected201 at risk EG0010 events0 affected100 at risk EG0020 events0 affected95 at risk
Acute respiratory distress syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected201 at risk EG0012 events1 affected100 at risk EG0020 events0 affected95 at risk
Emphysema	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected201 at risk EG0011 events1 affected100 at risk EG0020 events0 affected95 at risk
Pleural fibrosis	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected201 at risk EG0011 events1 affected100 at risk EG0020 events0 affected95 at risk
Skin ulcer	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected201 at risk EG0011 events1 affected100 at risk EG0021 events1 affected95 at risk
Deep vein thrombosis	Vascular disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected201 at risk EG0010 events0 affected100 at risk EG0020 events0 affected95 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal pain	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG00012 events11 affected201 at risk EG0014 events4 affected100 at risk EG0023 events3 affected95 at risk
Constipation	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG00017 events17 affected201 at risk EG0015 events4 affected100 at risk EG0022 events2 affected95 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG00022 events20 affected201 at risk EG00111 events9 affected100 at risk EG0028 events8 affected95 at risk
Nausea	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG00023 events23 affected201 at risk EG0019 events9 affected100 at risk EG0028 events8 affected95 at risk
Vomiting	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0008 events8 affected201 at risk EG0017 events7 affected100 at risk EG0025 events4 affected95 at risk
Fatigue	General disorders	MedDRA 21.0	Systematic Assessment	EG00032 events32 affected201 at risk EG00122 events20 affected100 at risk EG00214 events13 affected95 at risk
Accidental overdose	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment	EG0007 events7 affected201 at risk EG0015 events4 affected100 at risk EG0025 events5 affected95 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 21.0	Systematic Assessment	EG0008 events8 affected201 at risk EG0016 events6 affected100 at risk EG0023 events3 affected95 at risk
Headache	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG00031 events26 affected201 at risk EG00120 events14 affected100 at risk EG00215 events12 affected95 at risk
Insomnia	Psychiatric disorders	MedDRA 21.0	Systematic Assessment	EG00013 events13 affected201 at risk EG0016 events6 affected100 at risk EG0020 events0 affected95 at risk

ID	Term
D006526	Hepatitis C
D000086982	Blood-Borne Infections
D003141	Communicable Diseases
D007239	Infections
D006525	Hepatitis, Viral, Human
D014777	Virus Diseases
D018178	Flaviviridae Infections
D012327	RNA Virus Infections
D006521	Hepatitis, Chronic
D006505	Hepatitis
D008107	Liver Diseases
D004066	Digestive System Diseases
D002908	Chronic Disease
D020969	Disease Attributes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms