Safety and Efficacy of Grazoprevir (MK-5172) + Elbasvir (MK-8742) in Participants With Chronic Hepatitis C and Chronic Kidney Disease (MK-5172-052) (C-SURFER)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.

ClinicalTrials.gov Identifier: NCT02092350

Recruitment Status : Completed

First Posted : March 20, 2014

Results First Posted : April 12, 2016

Last Update Posted : September 24, 2018

Sponsor:

Information provided by (Responsible Party):

Merck Sharp & Dohme LLC

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
Condition	Hepatitis C Virus
Interventions	Drug: Grazoprevir Drug: Elbasvir Drug: Placebo to Grazoprevir Drug: Placebo to Elbasvir
Enrollment	237

Participant Flow

Recruitment Details	This multi-site study enrolled adult, male and female participants with hepatitis C virus (HCV) genotype (GT) 1 with chronic kidney disease (CKD).
Pre-assignment Details	The screening period lasted for up to 60 days.


Arm/Group Title	Immediate Treatment + Intensive PK	Deferred Treatment
Arm/Group Description	Participants received grazoprevir (...	Participants received placebo to GZ...
Arm/Group Description	Participants received grazoprevir (GZR) 100 mg tablet + elbasvir (EBR) 50 mg tablet once daily (q.d.) by mouth for 12 weeks, followed by a 24-week follow-up period. A subset of participants also underwent intensive pharmacokinetics (PK) testing.	Participants received placebo to GZR and EBR q.d. by mouth for 12 weeks. Then, after a 4-week drug-free period, participants received a fixed dose combination (FDC) tablet containing GZR 100 mg + EBR 50 mg tablet q.d. by mouth for 12 weeks, followed by a 24-week follow-up period.
Period Title: Overall Study
Started	123	114
Completed	113	102
Not Completed	10	12
Reason Not Completed
Adverse Event	0	3
Death	2	5
Lost to Follow-up	3	1
Protocol Violation	1	0
Physician Decision	1	1
Screen Failure	1	0
Withdrawal by Subject	2	2

Baseline Characteristics

Arm/Group Title		Immediate Treatment + Intensive PK	Deferred Treatment	Total
Arm/Group Description		Participants received GZR 100 mg ta...	Participants received placebo to GZ...	Total of all reporting groups
Arm/Group Description		Participants received GZR 100 mg tablet + EBR 50 mg tablet q.d. by mouth for 12 weeks, followed by a 24-week follow-up period. A subset of participants also underwent intensive PK testing.	Participants received placebo to GZR and EBR q.d. by mouth for 12 weeks. Then, after a 4-week drug-free period, participants received a FDC tablet containing GZR 100 mg + EBR 50 mg tablet q.d. by mouth for 12 weeks, followed by a 24-week follow-up period.	Total of all reporting groups
Overall Number of Baseline Participants		123	114	237
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	123 participants	114 participants	237 participants
		56.6 (9.0)	55.2 (10.0)	55.9 (9.5)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	123 participants	114 participants	237 participants
	Female	30 24.4%	33 28.9%	63 26.6%
	Male	93 75.6%	81 71.1%	174 73.4%

Outcome Measures

1.Primary Outcome


Title	Percentage of Participants With Sustained Virologic Response 12 Weeks After Completing Study Therapy (SVR12)
Description	SVR12 was defined as hepatitis C virus (HCV) ribonucleic acid (RNA) lo...
Description	SVR12 was defined as hepatitis C virus (HCV) ribonucleic acid (RNA) lower than the limit of quantification (LLoQ) 12 weeks after completing study therapy. HCV RNA was measured using the COBAS™ AmpliPrep/COBAS™ Taqman™ HCV Test, v2.0®, which has a LLoQ of 15 IU/mL.
Time Frame	Week 24 (Immediate Treatment + Intensive PK) or Week 40 (Deferred Treatment)

Outcome Measure Data

Analysis Population Description

The modified Full Analysis set (mFAS) includes all participants receiving ≥1 dose of drug and without missing data due to death or early discontinuation from study therapy for reasons unrelated to response to HCV treatment.


Arm/Group Title	Immediate Treatment + Intensive PK	Deferred Treatment
Arm/Group Description:	Participants received GZR 100 mg ta...	Participants received placebo to GZ...
Arm/Group Description:	Participants received GZR 100 mg tablet + EBR 50 mg tablet q.d. by mouth for 12 weeks, followed by a 24-week follow-up period. A subset of participants also underwent intensive PK testing.	Participants received placebo to GZR and EBR q.d. by mouth for 12 weeks. Then, after a 4-week drug-free period, participants received a FDC tablet containing GZR 100 mg + EBR 50 mg tablet q.d. by mouth for 12 weeks, followed by a 24-week follow-up period.
Overall Number of Participants Analyzed	116	99
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: Percentage of participants
	99.1 (95.3 to 100.0)	98.0 (92.9 to 99.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Immediate Treatment + Intensive PK
	Comments	The primary hypothesis was that the SVR12 rate in the Immediate Treatment plus Intensive PK arm would be >45%.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.001
	Comments	[Not Specified]
	Method	One-sided exact test
	Comments	[Not Specified]

2.Primary Outcome


Title	Number of Participants Experiencing an Adverse Event (AE) During the Initial Treatment and 14-day Follow-up Periods
Description	An AE is defined as any untoward medical occurrence in a participant a...
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. This analysis includes the Immediate Treatment + Intensive PK group and the placebo treatment period for the Deferred Treatment group.
Time Frame	Up to Week 14

Outcome Measure Data

Analysis Population Description

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


Arm/Group Title	Immediate Treatment + Intensive PK	Deferred Treatment
Arm/Group Description:	Participants received GZR 100 mg ta...	Participants received placebo to GZ...
Arm/Group Description:	Participants received GZR 100 mg tablet + EBR 50 mg tablet q.d. by mouth for 12 weeks, followed by a 24-week follow-up period. A subset of participants also underwent intensive PK testing.	Participants received placebo to GZR and EBR q.d. by mouth for 12 weeks. Then, after a 4-week drug-free period, participants received a FDC tablet containing GZR 100 mg + EBR 50 mg tablet q.d. by mouth for 12 weeks, followed by a 24-week follow-up period.
Overall Number of Participants Analyzed	122	113
Measure Type: Number Unit of Measure: Participants
	93	96

3.Primary Outcome


Title	Number of Participants Discontinuing Study Drug Due to AEs During the Initial Treatment Period
Description	An AE is defined as any untoward medical occurrence in a participant a...
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. This analysis includes the Immediate Treatment + Intensive PK group and the placebo treatment period for the Deferred Treatment group.
Time Frame	Up to Week 12

Outcome Measure Data

Analysis Population Description

The APaT population includes all enrolled participants who received at least one dose of study drug.


Arm/Group Title	Immediate Treatment + Intensive PK	Deferred Treatment
Arm/Group Description:	Participants received GZR 100 mg ta...	Participants received placebo to GZ...
Arm/Group Description:	Participants received GZR 100 mg tablet + EBR 50 mg tablet q.d. by mouth for 12 weeks, followed by a 24-week follow-up period. A subset of participants also underwent intensive PK testing.	Participants received placebo to GZR and EBR q.d. by mouth for 12 weeks. Then, after a 4-week drug-free period, participants received a FDC tablet containing GZR 100 mg + EBR 50 mg tablet q.d. by mouth for 12 weeks, followed by a 24-week follow-up period.
Overall Number of Participants Analyzed	122	113
Measure Type: Number Unit of Measure: Participants
	0	5

4.Secondary Outcome


Title	Percentage of Participants With Sustained Virologic Response 24 Weeks After Completing Study Therapy (SVR24)
Description	SVR24 was defined as HCV RNA <LLoQ 24 weeks after completing study ...
Description	SVR24 was defined as HCV RNA <LLoQ 24 weeks after completing study therapy. HCV RNA was measured using the COBAS™ AmpliPrep/COBAS™ Taqman™ HCV Test, v2.0®, which has a LLoQ of 15 IU/mL.
Time Frame	Week 36 (Immediate Treatment + Intensive PK) or Week 52 (Deferred Treatment)

Outcome Measure Data

Analysis Population Description

The mFAS includes all participants receiving ≥1 dose of drug and without missing data due to death or early discontinuation from study therapy for reasons unrelated to response to HCV treatment.


Arm/Group Title	Immediate Treatment + Intensive PK	Deferred Treatment Group
Arm/Group Description:	Participants received GZR 100 mg ta...	Participants received placebo to GZ...
Arm/Group Description:	Participants received GZR 100 mg tablet + EBR 50 mg tablet q.d. by mouth for 12 weeks, followed by a 24-week follow-up period. A subset of participants also underwent intensive PK testing.	Participants received placebo to GZR and EBR q.d. by mouth for 12 weeks. Then, after a 4-week drug-free period, participants received a FDC tablet containing GZR 100 mg + EBR 50 mg tablet q.d. by mouth for 12 weeks, followed by a 24-week follow-up period.
Overall Number of Participants Analyzed	114	99
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: Percentage of participants
	97.4 (92.5 to 99.5)	98.0 (92.9 to 99.8)

5.Secondary Outcome


Title	Percentage of Participants With Sustained Virologic Response 4 Weeks After Completing Study Therapy (SVR4)
Description	SVR4 was defined as HCV RNA <LLoQ 4 weeks after completing study th...
Description	SVR4 was defined as HCV RNA <LLoQ 4 weeks after completing study therapy. HCV RNA was measured using the COBAS™ AmpliPrep/COBAS™ Taqman™ HCV Test, v2.0®, which has a LLoQ of 15 IU/mL.
Time Frame	Week 16 (Immediate Treatment + Intensive PK) or Week 32 (Deferred Treatment)

Outcome Measure Data

Analysis Population Description

The mFAS includes all participants receiving ≥1 dose of drug and without missing data due to death or early discontinuation from study therapy for reasons unrelated to response to HCV treatment.


Arm/Group Title	Immediate Treatment + Intensive PK	Deferred Treatment Group
Arm/Group Description:	Participants received GZR 100 mg ta...	Participants received placebo to GZ...
Arm/Group Description:	Participants received GZR 100 mg tablet + EBR 50 mg tablet q.d. by mouth for 12 weeks, followed by a 24-week follow-up period. A subset of participants also underwent intensive PK testing.	Participants received placebo to GZR and EBR q.d. by mouth for 12 weeks. Then, after a 4-week drug-free period, participants received a FDC tablet containing GZR 100 mg + EBR 50 mg tablet q.d. by mouth for 12 weeks, followed by a 24-week follow-up period.
Overall Number of Participants Analyzed	118	101
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: Percentage of participants
	100.00 (96.9 to 100.0)	99.0 (94.6 to 100.0)

Adverse Events

Time Frame	Immediate Treatment + Intensive PK: up to Week 36; Deferred Treatment GZR Placebo + EBR Placebo: up to Week 16; Deferred Treatment GZR 100 mg + EBR 50 mg: Week 16 to up to Week 52.
Adverse Event Reporting Description	AE data is presented for APaT (all participants receiving ≥1 dose of study drug).

Arm/Group Title	Immediate Treatment + Intensive PK		Deferred Treatment: GZR Placebo + EBR Placebo 12 Weeks		Deferred Treatment: GZR 100 mg + EBR 50 mg 12 Weeks
Arm/Group Description	Participants received GZR 100 mg ta...		Participants received placebo to GZ...		Participants received a FDC tablet ...
Arm/Group Description	Participants received GZR 100 mg tablet + EBR 50 mg tablet q.d. by mouth for 12 weeks, followed by a 24-week follow-up period. A subset of participants also underwent intensive PK testing.		Participants received placebo to GZR and EBR q.d. by mouth for 12 weeks, followed by a 4-week drug-free period.		Participants received a FDC tablet containing GZR 100 mg + EBR 50 mg q.d. by mouth for 12 weeks, followed by a 24-week follow-up period.
All-Cause Mortality
	Immediate Treatment + Intensive PK		Deferred Treatment: GZR Placebo + EBR Placebo 12 Weeks		Deferred Treatment: GZR 100 mg + EBR 50 mg 12 Weeks
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--		--/--
Serious Adverse Events Serious Adverse Events
	Immediate Treatment + Intensive PK		Deferred Treatment: GZR Placebo + EBR Placebo 12 Weeks		Deferred Treatment: GZR 100 mg + EBR 50 mg 12 Weeks
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	30/122 (24.59%)		22/113 (19.47%)		25/102 (24.51%)
Blood and lymphatic system disorders
Anaemia ^† 2	0/122 (0.00%)	0	0/113 (0.00%)	0	3/102 (2.94%)	3
Iron deficiency anaemia ^† 2	0/122 (0.00%)	0	0/113 (0.00%)	0	1/102 (0.98%)	1
Cardiac disorders
Acute myocardial infarction ^† 1	0/122 (0.00%)	0	1/113 (0.88%)	1	0/102 (0.00%)	0
Angina unstable ^† 1	0/122 (0.00%)	0	1/113 (0.88%)	1	0/102 (0.00%)	0
Atrial fibrillation ^† 1	0/122 (0.00%)	0	1/113 (0.88%)	1	2/102 (1.96%)	3
Cardiac arrest ^† 1	1/122 (0.82%)	1	0/113 (0.00%)	0	0/102 (0.00%)	0
Cardiac failure congestive ^† 1	2/122 (1.64%)	2	0/113 (0.00%)	0	0/102 (0.00%)	0
Cardiomyopathy ^† 1	0/122 (0.00%)	0	1/113 (0.88%)	1	0/102 (0.00%)	0
Myocardial infarction ^† 1	1/122 (0.82%)	1	1/113 (0.88%)	1	0/102 (0.00%)	0
Coronary artery occlusion ^† 2	0/122 (0.00%)	0	0/113 (0.00%)	0	1/102 (0.98%)	1
Pericardial effusion ^† 2	0/122 (0.00%)	0	1/113 (0.88%)	1	1/102 (0.98%)	1
Pericarditis ^† 2	0/122 (0.00%)	0	1/113 (0.88%)	1	0/102 (0.00%)	0
Tricuspid valve incompetence ^† 2	0/122 (0.00%)	0	0/113 (0.00%)	0	1/102 (0.98%)	1
Cardiac failure ^† 2	0/122 (0.00%)	0	0/113 (0.00%)	0	1/102 (0.98%)	1
Gastrointestinal disorders
Abdominal pain ^† 1	1/122 (0.82%)	1	0/113 (0.00%)	0	0/102 (0.00%)	0
Abdominal pain upper ^† 1	1/122 (0.82%)	1	0/113 (0.00%)	0	0/102 (0.00%)	0
Constipation ^† 1	1/122 (0.82%)	1	0/113 (0.00%)	0	0/102 (0.00%)	0
Diarrhoea ^† 1	1/122 (0.82%)	1	0/113 (0.00%)	0	0/102 (0.00%)	0
Gastritis ^† 1	0/122 (0.00%)	0	1/113 (0.88%)	1	0/102 (0.00%)	0
Localised intraabdominal fluid collection ^† 1	0/122 (0.00%)	0	1/113 (0.88%)	1	0/102 (0.00%)	0
Pancreatitis ^† 1	1/122 (0.82%)	1	1/113 (0.88%)	1	0/102 (0.00%)	0
Upper gastrointestinal haemorrhage ^† 1	0/122 (0.00%)	0	2/113 (1.77%)	2	0/102 (0.00%)	0
Vomiting ^† 1	1/122 (0.82%)	1	0/113 (0.00%)	0	0/102 (0.00%)	0
Gastrointestinal haemorrhage ^† 2	0/122 (0.00%)	0	0/113 (0.00%)	0	1/102 (0.98%)	1
Retroperitoneal haematoma ^† 2	1/122 (0.82%)	1	0/113 (0.00%)	0	0/102 (0.00%)	0
General disorders
Chest pain ^† 1	1/122 (0.82%)	1	0/113 (0.00%)	0	0/102 (0.00%)	0
Death ^† 1	0/122 (0.00%)	0	1/113 (0.88%)	1	0/102 (0.00%)	0
Non-cardiac chest pain ^† 1	1/122 (0.82%)	1	0/113 (0.00%)	0	1/102 (0.98%)	1
Pyrexia ^† 1	2/122 (1.64%)	2	0/113 (0.00%)	0	1/102 (0.98%)	1
Infections and infestations
Abscess limb ^† 1	1/122 (0.82%)	1	0/113 (0.00%)	0	0/102 (0.00%)	0
Appendicitis ^† 1	1/122 (0.82%)	1	0/113 (0.00%)	0	0/102 (0.00%)	0
Citrobacter sepsis ^† 1	1/122 (0.82%)	1	0/113 (0.00%)	0	0/102 (0.00%)	0
Enterobacter sepsis ^† 1	1/122 (0.82%)	2	0/113 (0.00%)	0	0/102 (0.00%)	0
Haematoma infection ^† 1	0/122 (0.00%)	0	1/113 (0.88%)	1	0/102 (0.00%)	0
Infected fistula ^† 1	0/122 (0.00%)	0	1/113 (0.88%)	1	0/102 (0.00%)	0
Lower respiratory tract infection ^† 1	1/122 (0.82%)	1	0/113 (0.00%)	0	0/102 (0.00%)	0
Osteomyelitis ^† 1	1/122 (0.82%)	1	1/113 (0.88%)	1	0/102 (0.00%)	0
Pneumonia ^† 1	2/122 (1.64%)	2	1/113 (0.88%)	1	3/102 (2.94%)	3
Postoperative wound infection ^† 1	1/122 (0.82%)	1	0/113 (0.00%)	0	0/102 (0.00%)	0
Sepsis ^† 1	2/122 (1.64%)	2	0/113 (0.00%)	0	0/102 (0.00%)	0
Gastroenteritis ^† 2	0/122 (0.00%)	0	0/113 (0.00%)	0	1/102 (0.98%)	1
Mediastinitis ^† 2	0/122 (0.00%)	0	1/113 (0.88%)	1	0/102 (0.00%)	0
Nocardiosis ^† 2	1/122 (0.82%)	1	0/113 (0.00%)	0	0/102 (0.00%)	0
Pneumonia bacterial ^† 2	1/122 (0.82%)	1	0/113 (0.00%)	0	0/102 (0.00%)	0
Septic shock ^† 2	1/122 (0.82%)	1	0/113 (0.00%)	0	0/102 (0.00%)	0
Urinary tract infection ^† 2	1/122 (0.82%)	1	0/113 (0.00%)	0	0/102 (0.00%)	0
Injury, poisoning and procedural complications
Arteriovenous fistula aneurysm ^† 1	0/122 (0.00%)	0	1/113 (0.88%)	1	0/102 (0.00%)	0
Arteriovenous fistula site complication ^† 1	1/122 (0.82%)	1	1/113 (0.88%)	1	0/102 (0.00%)	0
Dialysis related complication ^† 1	1/122 (0.82%)	1	0/113 (0.00%)	0	0/102 (0.00%)	0
Foreign body ^† 1	1/122 (0.82%)	1	0/113 (0.00%)	0	0/102 (0.00%)	0
Genital injury ^† 1	0/122 (0.00%)	0	1/113 (0.88%)	1	0/102 (0.00%)	0
Postoperative fever ^† 1	0/122 (0.00%)	0	1/113 (0.88%)	1	0/102 (0.00%)	0
Procedural pain ^† 1	2/122 (1.64%)	2	0/113 (0.00%)	0	0/102 (0.00%)	0
Wound dehiscence ^† 1	1/122 (0.82%)	1	0/113 (0.00%)	0	0/102 (0.00%)	0
Facial bones fracture ^† 2	0/122 (0.00%)	0	0/113 (0.00%)	0	1/102 (0.98%)	1
Post procedural haematoma ^† 2	0/122 (0.00%)	0	0/113 (0.00%)	0	1/102 (0.98%)	1
Subdural haematoma ^† 2	0/122 (0.00%)	0	0/113 (0.00%)	0	1/102 (0.98%)	1
Investigations
Blood alkaline phosphatase increased ^† 1	0/122 (0.00%)	0	1/113 (0.88%)	1	0/102 (0.00%)	0
Electrocardiogram abnormal ^† 1	1/122 (0.82%)	1	0/113 (0.00%)	0	0/102 (0.00%)	0
Lipase increased ^† 1	0/122 (0.00%)	0	1/113 (0.88%)	1	0/102 (0.00%)	0
Metabolism and nutrition disorders
Dehydration ^† 1	1/122 (0.82%)	1	0/113 (0.00%)	0	1/102 (0.98%)	1
Fluid overload ^† 1	1/122 (0.82%)	1	1/113 (0.88%)	2	0/102 (0.00%)	0
Hyperglycaemia ^† 1	0/122 (0.00%)	0	1/113 (0.88%)	1	0/102 (0.00%)	0
Hyperkalaemia ^† 1	1/122 (0.82%)	1	1/113 (0.88%)	1	0/102 (0.00%)	0
Hyponatraemia ^† 2	0/122 (0.00%)	0	0/113 (0.00%)	0	1/102 (0.98%)	2
Musculoskeletal and connective tissue disorders
Costochondritis ^† 1	0/122 (0.00%)	0	1/113 (0.88%)	1	0/102 (0.00%)	0
Intervertebral disc protrusion ^† 1	1/122 (0.82%)	1	0/113 (0.00%)	0	0/102 (0.00%)	0
Myositis ^† 1	0/122 (0.00%)	0	1/113 (0.88%)	1	0/102 (0.00%)	0
Pain in extremity ^† 2	0/122 (0.00%)	0	0/113 (0.00%)	0	1/102 (0.98%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Papillary thyroid cancer ^† 1	1/122 (0.82%)	1	0/113 (0.00%)	0	0/102 (0.00%)	0
Prostate cancer ^† 1	1/122 (0.82%)	1	1/113 (0.88%)	1	0/102 (0.00%)	0
Nervous system disorders
Depressed level of consciousness ^† 1	0/122 (0.00%)	0	1/113 (0.88%)	1	0/102 (0.00%)	0
Dizziness ^† 1	0/122 (0.00%)	0	1/113 (0.88%)	1	1/102 (0.98%)	2
Headache ^† 1	0/122 (0.00%)	0	1/113 (0.88%)	1	0/102 (0.00%)	0
Hemiparesis ^† 1	1/122 (0.82%)	1	0/113 (0.00%)	0	0/102 (0.00%)	0
Presyncope ^† 1	1/122 (0.82%)	1	0/113 (0.00%)	0	0/102 (0.00%)	0
Encephalopathy ^† 2	0/122 (0.00%)	0	0/113 (0.00%)	0	1/102 (0.98%)	1
Hepatic encephalopathy ^† 2	0/122 (0.00%)	0	1/113 (0.88%)	1	1/102 (0.98%)	1
Hydrocephalus ^† 2	0/122 (0.00%)	0	0/113 (0.00%)	0	1/102 (0.98%)	1
Intraventricular haemorrhage ^† 2	0/122 (0.00%)	0	0/113 (0.00%)	0	1/102 (0.98%)	1
Nervous system disorder ^† 2	0/122 (0.00%)	0	0/113 (0.00%)	0	1/102 (0.98%)	1
Seizure ^† 2	0/122 (0.00%)	0	0/113 (0.00%)	0	1/102 (0.98%)	1
Psychiatric disorders
Disorientation ^† 2	0/122 (0.00%)	0	0/113 (0.00%)	0	1/102 (0.98%)	1
Renal and urinary disorders
Acute kidney injury ^† 2	0/122 (0.00%)	0	0/113 (0.00%)	0	3/102 (2.94%)	3
Chronic kidney disease ^† 2	1/122 (0.82%)	1	1/113 (0.88%)	1	1/102 (0.98%)	1
Tubulointerstitial nephritis ^† 2	0/122 (0.00%)	0	0/113 (0.00%)	0	1/102 (0.98%)	1
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure ^† 1	1/122 (0.82%)	1	0/113 (0.00%)	0	0/102 (0.00%)	0
Pleural effusion ^† 1	1/122 (0.82%)	1	1/113 (0.88%)	1	0/102 (0.00%)	0
Acute pulmonary oedema ^† 2	1/122 (0.82%)	1	0/113 (0.00%)	0	0/102 (0.00%)	0
Chronic obstructive pulmonary disease ^† 2	0/122 (0.00%)	0	0/113 (0.00%)	0	1/102 (0.98%)	1
Hypoxia ^† 2	0/122 (0.00%)	0	0/113 (0.00%)	0	1/102 (0.98%)	1
Mediastinal effusion ^† 2	0/122 (0.00%)	0	1/113 (0.88%)	1	0/102 (0.00%)	0
Pneumothorax ^† 2	0/122 (0.00%)	0	0/113 (0.00%)	0	1/102 (0.98%)	1
Pulmonary oedema ^† 2	0/122 (0.00%)	0	0/113 (0.00%)	0	1/102 (0.98%)	1
Aortic stenosis ^† 2	0/122 (0.00%)	0	0/113 (0.00%)	0	1/102 (0.98%)	1
Vascular disorders
Aortic aneurysm ^† 1	0/122 (0.00%)	0	2/113 (1.77%)	2	0/102 (0.00%)	0
Cryoglobulinaemia ^† 1	1/122 (0.82%)	1	0/113 (0.00%)	0	0/102 (0.00%)	0
Extremity necrosis ^† 1	1/122 (0.82%)	2	0/113 (0.00%)	0	0/102 (0.00%)	0
Hypertension ^† 1	2/122 (1.64%)	3	1/113 (0.88%)	1	0/102 (0.00%)	0
Hypertensive crisis ^† 1	1/122 (0.82%)	1	0/113 (0.00%)	0	0/102 (0.00%)	0
Orthostatic hypotension ^† 1	0/122 (0.00%)	0	1/113 (0.88%)	1	0/102 (0.00%)	0
Peripheral venous disease ^† 1	0/122 (0.00%)	0	1/113 (0.88%)	1	0/102 (0.00%)	0
Shock haemorrhagic ^† 1	0/122 (0.00%)	0	1/113 (0.88%)	1	0/102 (0.00%)	0
Aortic stenosis ^† 2	0/122 (0.00%)	0	0/113 (0.00%)	0	1/102 (0.98%)	1
† Indicates events were collected by systematic assessment 1 Term from vocabulary, MedDRA 16.0 2 Term from vocabulary, MedDRA v. 18.0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Immediate Treatment + Intensive PK		Deferred Treatment: GZR Placebo + EBR Placebo 12 Weeks		Deferred Treatment: GZR 100 mg + EBR 50 mg 12 Weeks
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	67/122 (54.92%)		68/113 (60.18%)		39/102 (38.24%)
Gastrointestinal disorders
Abdominal discomfort ^† 1	2/122 (1.64%)	2	6/113 (5.31%)	6	1/102 (0.98%)	1
Abdominal pain ^† 1	10/122 (8.20%)	13	3/113 (2.65%)	3	3/102 (2.94%)	3
Constipation ^† 1	8/122 (6.56%)	8	6/113 (5.31%)	7	3/102 (2.94%)	3
Diarrhoea ^† 1	6/122 (4.92%)	6	15/113 (13.27%)	22	5/102 (4.90%)	6
Nausea ^† 1	18/122 (14.75%)	24	18/113 (15.93%)	21	11/102 (10.78%)	12
Vomiting ^† 1	9/122 (7.38%)	13	9/113 (7.96%)	11	7/102 (6.86%)	10
General disorders
Asthenia ^† 1	7/122 (5.74%)	9	6/113 (5.31%)	6	4/102 (3.92%)	4
Fatigue ^† 1	13/122 (10.66%)	15	17/113 (15.04%)	17	10/102 (9.80%)	10
Pyrexia ^† 1	6/122 (4.92%)	7	6/113 (5.31%)	6	3/102 (2.94%)	4
Metabolism and nutrition disorders
Decreased appetite ^† 1	7/122 (5.74%)	8	3/113 (2.65%)	3	4/102 (3.92%)	4
Musculoskeletal and connective tissue disorders
Musculoskeletal pain ^† 1	0/122 (0.00%)	0	6/113 (5.31%)	6	1/102 (0.98%)	1
Myalgia ^† 1	0/122 (0.00%)	0	8/113 (7.08%)	9	2/102 (1.96%)	2
Nervous system disorders
Dizziness ^† 1	8/122 (6.56%)	9	18/113 (15.93%)	22	4/102 (3.92%)	4
Headache ^† 1	23/122 (18.85%)	26	18/113 (15.93%)	23	7/102 (6.86%)	8
Psychiatric disorders
Insomnia ^† 1	10/122 (8.20%)	10	12/113 (10.62%)	12	2/102 (1.96%)	2
Respiratory, thoracic and mediastinal disorders
Cough ^† 1	9/122 (7.38%)	10	2/113 (1.77%)	2	5/102 (4.90%)	6
Skin and subcutaneous tissue disorders
Pruritus ^† 1	4/122 (3.28%)	4	12/113 (10.62%)	12	1/102 (0.98%)	1
Vascular disorders
Hypertension ^† 1	7/122 (5.74%)	7	6/113 (5.31%)	6	2/102 (1.96%)	2
† Indicates events were collected by systematic assessment 1 Term from vocabulary, MedDRA 16.0

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	Senior Vice President, Global Clinical Development
Organization:	Merck Sharp & Dohme Corp.
Phone:	1-800-672-6372
EMail:	ClinicalTrialDisclosure@merck.com

Publications of Results:

Roth D, Nelson DR, Bruchfeld A, Liapakis A, Silva M, Monsour H Jr, Martin P, Pol S, Londoño MC, Hassanein T, Zamor PJ, Zuckerman E, Wan S, Jackson B, Nguyen BY, Robertson M, Barr E, Wahl J, Greaves W. Grazoprevir plus elbasvir in treatment-naive and treatment-experienced patients with hepatitis C virus genotype 1 infection and stage 4-5 chronic kidney disease (the C-SURFER study): a combination phase 3 study. Lancet. 2015 Oct 17;386(10003):1537-45. doi: 10.1016/S0140-6736(15)00349-9. Epub 2015 Oct 5. Erratum in: Lancet. 2015 Nov 7;386(10006):1824.

Bruchfeld A, Roth D, Martin P, Nelson DR, Pol S, Londoño MC, Monsour H Jr, Silva M, Hwang P, Arduino JM, Robertson M, Nguyen BY, Wahl J, Barr E, Greaves W. Elbasvir plus grazoprevir in patients with hepatitis C virus infection and stage 4-5 chronic kidney disease: clinical, virological, and health-related quality-of-life outcomes from a phase 3, multicentre, randomised, double-blind, placebo-controlled trial. Lancet Gastroenterol Hepatol. 2017 Aug;2(8):585-594. doi: 10.1016/S2468-1253(17)30116-4. Epub 2017 May 30.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Reau N, Robertson MN, Feng HP, Caro L, Yeh WW, Nguyen BT, Wahl J, Barr E, Hwang P, Klopfer SO. Concomitant proton pump inhibitor use does not reduce the efficacy of elbasvir/grazoprevir: A pooled analysis of 1,322 patients with hepatitis C infection. Hepatol Commun. 2017 Aug 22;1(8):757-764. doi: 10.1002/hep4.1081. eCollection 2017 Oct.

Jacobson IM, Lawitz E, Kwo PY, Hézode C, Peng CY, Howe AYM, Hwang P, Wahl J, Robertson M, Barr E, Haber BA. Safety and Efficacy of Elbasvir/Grazoprevir in Patients With Hepatitis C Virus Infection and Compensated Cirrhosis: An Integrated Analysis. Gastroenterology. 2017 May;152(6):1372-1382.e2. doi: 10.1053/j.gastro.2017.01.050. Epub 2017 Feb 11.

Layout table for additonal information

Responsible Party:	Merck Sharp & Dohme LLC
ClinicalTrials.gov Identifier:	NCT02092350
Other Study ID Numbers:	5172-052 2013-003858-25 ( EudraCT Number )
First Submitted:	March 17, 2014
First Posted:	March 20, 2014
Results First Submitted:	February 3, 2016
Results First Posted:	April 12, 2016
Last Update Posted:	September 24, 2018

To Top