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

Sponsor
Merck Sharp & Dohme LLC (Industry)
Overall Status
Completed
CT.gov ID
NCT02092350
Collaborator
(none)
237
Enrollment
3
Arms
17.5
Actual Duration (Months)

Study Details

Study Description

Brief Summary

This study will evaluate the safety and efficacy of combination treatment with grazoprevir (MK-5172) + elbasvir (MK-8742) for cirrhotic and non-cirrhotic participants with chronic Genotype 1 (GT1) hepatitis C virus (HCV) infection and chronic kidney disease (CKD). The primary study hypothesis is that the proportion of HCV GT1-infected CKD participants within the Immediate Treatment and Intensive Pharmacokinetics (PK) groups achieving a sustained viral response 12 weeks after the end of all study treatment (SVR12) will be >45%.

Condition or Disease Intervention/Treatment Phase
Phase 2/Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
237 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Phase II/III Randomized 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 and Chronic Kidney Disease
Actual Study Start Date :
Mar 17, 2014
Actual Primary Completion Date :
Mar 11, 2015
Actual Study Completion Date :
Sep 2, 2015

Arms and Interventions

Arm Intervention/Treatment
Experimental: Immediate Treatment

Participants receive grazoprevir 100 mg tablet, orally, once per day (QD) + elbasvir 50 mg tablet, orally, QD, for 12 weeks.

Drug: Grazoprevir
Grazoprevir 100 mg tablet
Other Names:
  • MK-5172

    • Drug: Elbasvir
    Elbasvir 50 mg tablet
    Other Names:
  • MK-8742

    		•
    Experimental: Deferred Treatment

    Participants receive placebos to both grazoprevir and elbasvir for 12 weeks, and after a 4-week break, grazoprevir 100 mg tablet, orally, QD + elbasvir 50 mg tablet, orally, QD for 12 weeks.

    Drug: Grazoprevir
    Grazoprevir 100 mg tablet
    Other Names:
  • MK-5172

    • Drug: Elbasvir
    Elbasvir 50 mg tablet
    Other Names:
  • MK-8742

    • Drug: Placebo to Grazoprevir
    Placebo tablet matched to grazoprevir

    Drug: Placebo to Elbasvir
    Placebo tablet matched to elbasvir
    Experimental: Intensive PK

    Participants receive grazoprevir 100 mg tablet, orally, QD + elbasvir 50 mg tablet, orally, QD for 12 weeks with intensive PK testing.

    Drug: Grazoprevir
    Grazoprevir 100 mg tablet
    Other Names:
  • MK-5172

    • Drug: Elbasvir
    Elbasvir 50 mg tablet
    Other Names:
  • MK-8742

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Percentage of Participants With Sustained Virologic Response 12 Weeks After Completing Study Therapy (SVR12) [Week 24 (Immediate Treatment + Intensive PK) or Week 40 (Deferred Treatment)]

      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.

    2. Number of Participants Experiencing an Adverse Event (AE) During the Initial Treatment and 14-day Follow-up Periods [Up to Week 14]

      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.

    3. Number of Participants Discontinuing Study Drug Due to AEs During the Initial Treatment Period [Up to Week 12]

      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.

    Secondary Outcome Measures

    1. Percentage of Participants With Sustained Virologic Response 24 Weeks After Completing Study Therapy (SVR24) [Week 36 (Immediate Treatment + Intensive PK) or Week 52 (Deferred Treatment)]

      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.

    2. Percentage of Participants With Sustained Virologic Response 4 Weeks After Completing Study Therapy (SVR4) [Week 16 (Immediate Treatment + Intensive PK) or Week 32 (Deferred Treatment)]

      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.

    Eligibility Criteria

    Criteria

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

    • Documented chronic (at least 6 months) HCV GT 1 infection (with no evidence of mixed genotypes or genotype that cannot be assigned a type)

    • Evidence or no evidence of liver cirrhosis based on one of the following:

    • Liver biopsy performed within 24 months of Day 1 (if participant is cirrhotic then there is no time restriction on biopsy)

    • Fibroscan performed within 12 months of Day 1 of this study

    • Fibrosure™ (Fibrotest™) plus aspartate aminotransferase to platelet Ratio Index [APRI] obtained during the screening period)

    • Has HCV status that is one of the following:

    • Treatment naïve

    • Prior interferon or pegylated interferon with or without ribavarin failures (null responder, partial responder, or relapser)

    • Intolerant to prior interferon or pegylated intereferon with or without ribavarin regimen

    • Chronic kidney disease (defined as glomerular filtration rate [eGFR] <=29) non-dialysis dependent or on hemodialysis for at least 3 months, including individuals awaiting kidney transplant and those with failed kidney transplants but no longer on immunosuppressant therapy)

    • Female participant of reproductive potential must agree to remain abstinent or use (or have their partner use) 2 acceptable methods of contraception from at least 2 weeks prior to Day 1 through 14 days after the last dose of study drugs, or longer if dictated by local regulations

    Exclusion Criteria:

    • Evidence of decompensated liver disease

    • On peritoneal dialysis for management of kidney disease

    • Co-infection with hepatitis B virus or human immunodeficiency virus (HIV)

    • History of malignancy <=5 years prior to signing informed consent

    • Clinical diagnosis of substance abuse

    • Pregnant, breast-feeding, expecting to conceive or donate eggs, or donate sperm from Day 1 through 14 days after the last study dose, or longer if dictated by local regulations

    • Organ transplant (including hematopoietic stem cell transplant) other than kidney, cornea, and hair

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

    • Uncontrolled or poorly controlled hypertension

    • Significant cardiovascular disorder (e.g. myocardial infarction or unstable angina) or cardiovascular procedure within 3 months prior to signing informed consent

    • New or worsening signs or symptoms of congestive heart failure within 3 months of signing informed consent

    • Severe active peripheral vascular disease

    • Recent (within 3 months prior to signing informed consent) episode or recurrence of stroke, transient ischemic attack (TIA) or neurological disorder, including but not limited to seizures

    • Evidence or history of chronic hepatitis not caused by HCV

    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:
    NCT02092350
    Other Study ID Numbers:
    • 5172-052
    • 2013-003858-25
    First Posted:
    Mar 20, 2014
    Last Update Posted:
    Sep 24, 2018
    Last Verified:
    Aug 1, 2018
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Additional relevant MeSH terms:
    Hepatitis A
    Hepatitis C
    Hepatitis C, Chronic
    Hepatitis
    Kidney Diseases
    Renal Insufficiency, Chronic
    Grazoprevir

    Study Results

    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 Detail The screening period lasted for up to 60 days.
    Arm/Group Title Immediate Treatment + Intensive PK Deferred Treatment
    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

    Baseline Characteristics

    Arm/Group Title Immediate Treatment + Intensive PK Deferred Treatment Total
    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 Participants 123 114 237
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    56.6
    (9.0)
    55.2
    (10.0)
    55.9
    (9.5)
    Sex: Female, Male (Count of 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) 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 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.
    Measure Participants 116 99
    Number (95% Confidence Interval) [Percentage of participants]
    99.1
    80.6%
    98.0
    86%
    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
    Statistical Test of Hypothesis p-Value 0.001
    Comments
    Method One-sided exact test
    Comments
    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 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 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.
    Measure Participants 122 113
    Number [Participants]
    93
    75.6%
    96
    84.2%
    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 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 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.
    Measure Participants 122 113
    Number [Participants]
    0
    0%
    5
    4.4%
    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 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 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.
    Measure Participants 114 99
    Number (95% Confidence Interval) [Percentage of participants]
    97.4
    79.2%
    98.0
    86%
    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 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 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.
    Measure Participants 118 101
    Number (95% Confidence Interval) [Percentage of participants]
    100.00
    81.3%
    99.0
    86.8%

    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 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 (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN)
    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 (24.6%) 22/113 (19.5%) 25/102 (24.5%)
    Blood and lymphatic system disorders
    Anaemia 0/122 (0%) 0 0/113 (0%) 0 3/102 (2.9%) 3
    Iron deficiency anaemia 0/122 (0%) 0 0/113 (0%) 0 1/102 (1%) 1
    Cardiac disorders
    Acute myocardial infarction 0/122 (0%) 0 1/113 (0.9%) 1 0/102 (0%) 0
    Angina unstable 0/122 (0%) 0 1/113 (0.9%) 1 0/102 (0%) 0
    Atrial fibrillation 0/122 (0%) 0 1/113 (0.9%) 1 2/102 (2%) 3
    Cardiac arrest 1/122 (0.8%) 1 0/113 (0%) 0 0/102 (0%) 0
    Cardiac failure congestive 2/122 (1.6%) 2 0/113 (0%) 0 0/102 (0%) 0
    Cardiomyopathy 0/122 (0%) 0 1/113 (0.9%) 1 0/102 (0%) 0
    Myocardial infarction 1/122 (0.8%) 1 1/113 (0.9%) 1 0/102 (0%) 0
    Coronary artery occlusion 0/122 (0%) 0 0/113 (0%) 0 1/102 (1%) 1
    Pericardial effusion 0/122 (0%) 0 1/113 (0.9%) 1 1/102 (1%) 1
    Pericarditis 0/122 (0%) 0 1/113 (0.9%) 1 0/102 (0%) 0
    Tricuspid valve incompetence 0/122 (0%) 0 0/113 (0%) 0 1/102 (1%) 1
    Cardiac failure 0/122 (0%) 0 0/113 (0%) 0 1/102 (1%) 1
    Gastrointestinal disorders
    Abdominal pain 1/122 (0.8%) 1 0/113 (0%) 0 0/102 (0%) 0
    Abdominal pain upper 1/122 (0.8%) 1 0/113 (0%) 0 0/102 (0%) 0
    Constipation 1/122 (0.8%) 1 0/113 (0%) 0 0/102 (0%) 0
    Diarrhoea 1/122 (0.8%) 1 0/113 (0%) 0 0/102 (0%) 0
    Gastritis 0/122 (0%) 0 1/113 (0.9%) 1 0/102 (0%) 0
    Localised intraabdominal fluid collection 0/122 (0%) 0 1/113 (0.9%) 1 0/102 (0%) 0
    Pancreatitis 1/122 (0.8%) 1 1/113 (0.9%) 1 0/102 (0%) 0
    Upper gastrointestinal haemorrhage 0/122 (0%) 0 2/113 (1.8%) 2 0/102 (0%) 0
    Vomiting 1/122 (0.8%) 1 0/113 (0%) 0 0/102 (0%) 0
    Gastrointestinal haemorrhage 0/122 (0%) 0 0/113 (0%) 0 1/102 (1%) 1
    Retroperitoneal haematoma 1/122 (0.8%) 1 0/113 (0%) 0 0/102 (0%) 0
    General disorders
    Chest pain 1/122 (0.8%) 1 0/113 (0%) 0 0/102 (0%) 0
    Death 0/122 (0%) 0 1/113 (0.9%) 1 0/102 (0%) 0
    Non-cardiac chest pain 1/122 (0.8%) 1 0/113 (0%) 0 1/102 (1%) 1
    Pyrexia 2/122 (1.6%) 2 0/113 (0%) 0 1/102 (1%) 1
    Infections and infestations
    Abscess limb 1/122 (0.8%) 1 0/113 (0%) 0 0/102 (0%) 0
    Appendicitis 1/122 (0.8%) 1 0/113 (0%) 0 0/102 (0%) 0
    Citrobacter sepsis 1/122 (0.8%) 1 0/113 (0%) 0 0/102 (0%) 0
    Enterobacter sepsis 1/122 (0.8%) 2 0/113 (0%) 0 0/102 (0%) 0
    Haematoma infection 0/122 (0%) 0 1/113 (0.9%) 1 0/102 (0%) 0
    Infected fistula 0/122 (0%) 0 1/113 (0.9%) 1 0/102 (0%) 0
    Lower respiratory tract infection 1/122 (0.8%) 1 0/113 (0%) 0 0/102 (0%) 0
    Osteomyelitis 1/122 (0.8%) 1 1/113 (0.9%) 1 0/102 (0%) 0
    Pneumonia 2/122 (1.6%) 2 1/113 (0.9%) 1 3/102 (2.9%) 3
    Postoperative wound infection 1/122 (0.8%) 1 0/113 (0%) 0 0/102 (0%) 0
    Sepsis 2/122 (1.6%) 2 0/113 (0%) 0 0/102 (0%) 0
    Gastroenteritis 0/122 (0%) 0 0/113 (0%) 0 1/102 (1%) 1
    Mediastinitis 0/122 (0%) 0 1/113 (0.9%) 1 0/102 (0%) 0
    Nocardiosis 1/122 (0.8%) 1 0/113 (0%) 0 0/102 (0%) 0
    Pneumonia bacterial 1/122 (0.8%) 1 0/113 (0%) 0 0/102 (0%) 0
    Septic shock 1/122 (0.8%) 1 0/113 (0%) 0 0/102 (0%) 0
    Urinary tract infection 1/122 (0.8%) 1 0/113 (0%) 0 0/102 (0%) 0
    Injury, poisoning and procedural complications
    Arteriovenous fistula aneurysm 0/122 (0%) 0 1/113 (0.9%) 1 0/102 (0%) 0
    Arteriovenous fistula site complication 1/122 (0.8%) 1 1/113 (0.9%) 1 0/102 (0%) 0
    Dialysis related complication 1/122 (0.8%) 1 0/113 (0%) 0 0/102 (0%) 0
    Foreign body 1/122 (0.8%) 1 0/113 (0%) 0 0/102 (0%) 0
    Genital injury 0/122 (0%) 0 1/113 (0.9%) 1 0/102 (0%) 0
    Postoperative fever 0/122 (0%) 0 1/113 (0.9%) 1 0/102 (0%) 0
    Procedural pain 2/122 (1.6%) 2 0/113 (0%) 0 0/102 (0%) 0
    Wound dehiscence 1/122 (0.8%) 1 0/113 (0%) 0 0/102 (0%) 0
    Facial bones fracture 0/122 (0%) 0 0/113 (0%) 0 1/102 (1%) 1
    Post procedural haematoma 0/122 (0%) 0 0/113 (0%) 0 1/102 (1%) 1
    Subdural haematoma 0/122 (0%) 0 0/113 (0%) 0 1/102 (1%) 1
    Investigations
    Blood alkaline phosphatase increased 0/122 (0%) 0 1/113 (0.9%) 1 0/102 (0%) 0
    Electrocardiogram abnormal 1/122 (0.8%) 1 0/113 (0%) 0 0/102 (0%) 0
    Lipase increased 0/122 (0%) 0 1/113 (0.9%) 1 0/102 (0%) 0
    Metabolism and nutrition disorders
    Dehydration 1/122 (0.8%) 1 0/113 (0%) 0 1/102 (1%) 1
    Fluid overload 1/122 (0.8%) 1 1/113 (0.9%) 2 0/102 (0%) 0
    Hyperglycaemia 0/122 (0%) 0 1/113 (0.9%) 1 0/102 (0%) 0
    Hyperkalaemia 1/122 (0.8%) 1 1/113 (0.9%) 1 0/102 (0%) 0
    Hyponatraemia 0/122 (0%) 0 0/113 (0%) 0 1/102 (1%) 2
    Musculoskeletal and connective tissue disorders
    Costochondritis 0/122 (0%) 0 1/113 (0.9%) 1 0/102 (0%) 0
    Intervertebral disc protrusion 1/122 (0.8%) 1 0/113 (0%) 0 0/102 (0%) 0
    Myositis 0/122 (0%) 0 1/113 (0.9%) 1 0/102 (0%) 0
    Pain in extremity 0/122 (0%) 0 0/113 (0%) 0 1/102 (1%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Papillary thyroid cancer 1/122 (0.8%) 1 0/113 (0%) 0 0/102 (0%) 0
    Prostate cancer 1/122 (0.8%) 1 1/113 (0.9%) 1 0/102 (0%) 0
    Nervous system disorders
    Depressed level of consciousness 0/122 (0%) 0 1/113 (0.9%) 1 0/102 (0%) 0
    Dizziness 0/122 (0%) 0 1/113 (0.9%) 1 1/102 (1%) 2
    Headache 0/122 (0%) 0 1/113 (0.9%) 1 0/102 (0%) 0
    Hemiparesis 1/122 (0.8%) 1 0/113 (0%) 0 0/102 (0%) 0
    Presyncope 1/122 (0.8%) 1 0/113 (0%) 0 0/102 (0%) 0
    Encephalopathy 0/122 (0%) 0 0/113 (0%) 0 1/102 (1%) 1
    Hepatic encephalopathy 0/122 (0%) 0 1/113 (0.9%) 1 1/102 (1%) 1
    Hydrocephalus 0/122 (0%) 0 0/113 (0%) 0 1/102 (1%) 1
    Intraventricular haemorrhage 0/122 (0%) 0 0/113 (0%) 0 1/102 (1%) 1
    Nervous system disorder 0/122 (0%) 0 0/113 (0%) 0 1/102 (1%) 1
    Seizure 0/122 (0%) 0 0/113 (0%) 0 1/102 (1%) 1
    Psychiatric disorders
    Disorientation 0/122 (0%) 0 0/113 (0%) 0 1/102 (1%) 1
    Renal and urinary disorders
    Acute kidney injury 0/122 (0%) 0 0/113 (0%) 0 3/102 (2.9%) 3
    Chronic kidney disease 1/122 (0.8%) 1 1/113 (0.9%) 1 1/102 (1%) 1
    Tubulointerstitial nephritis 0/122 (0%) 0 0/113 (0%) 0 1/102 (1%) 1
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure 1/122 (0.8%) 1 0/113 (0%) 0 0/102 (0%) 0
    Pleural effusion 1/122 (0.8%) 1 1/113 (0.9%) 1 0/102 (0%) 0
    Acute pulmonary oedema 1/122 (0.8%) 1 0/113 (0%) 0 0/102 (0%) 0
    Chronic obstructive pulmonary disease 0/122 (0%) 0 0/113 (0%) 0 1/102 (1%) 1
    Hypoxia 0/122 (0%) 0 0/113 (0%) 0 1/102 (1%) 1
    Mediastinal effusion 0/122 (0%) 0 1/113 (0.9%) 1 0/102 (0%) 0
    Pneumothorax 0/122 (0%) 0 0/113 (0%) 0 1/102 (1%) 1
    Pulmonary oedema 0/122 (0%) 0 0/113 (0%) 0 1/102 (1%) 1
    Aortic stenosis 0/122 (0%) 0 0/113 (0%) 0 1/102 (1%) 1
    Vascular disorders
    Aortic aneurysm 0/122 (0%) 0 2/113 (1.8%) 2 0/102 (0%) 0
    Cryoglobulinaemia 1/122 (0.8%) 1 0/113 (0%) 0 0/102 (0%) 0
    Extremity necrosis 1/122 (0.8%) 2 0/113 (0%) 0 0/102 (0%) 0
    Hypertension 2/122 (1.6%) 3 1/113 (0.9%) 1 0/102 (0%) 0
    Hypertensive crisis 1/122 (0.8%) 1 0/113 (0%) 0 0/102 (0%) 0
    Orthostatic hypotension 0/122 (0%) 0 1/113 (0.9%) 1 0/102 (0%) 0
    Peripheral venous disease 0/122 (0%) 0 1/113 (0.9%) 1 0/102 (0%) 0
    Shock haemorrhagic 0/122 (0%) 0 1/113 (0.9%) 1 0/102 (0%) 0
    Aortic stenosis 0/122 (0%) 0 0/113 (0%) 0 1/102 (1%) 1
    Other (Not Including 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 67/122 (54.9%) 68/113 (60.2%) 39/102 (38.2%)
    Gastrointestinal disorders
    Abdominal discomfort 2/122 (1.6%) 2 6/113 (5.3%) 6 1/102 (1%) 1
    Abdominal pain 10/122 (8.2%) 13 3/113 (2.7%) 3 3/102 (2.9%) 3
    Constipation 8/122 (6.6%) 8 6/113 (5.3%) 7 3/102 (2.9%) 3
    Diarrhoea 6/122 (4.9%) 6 15/113 (13.3%) 22 5/102 (4.9%) 6
    Nausea 18/122 (14.8%) 24 18/113 (15.9%) 21 11/102 (10.8%) 12
    Vomiting 9/122 (7.4%) 13 9/113 (8%) 11 7/102 (6.9%) 10
    General disorders
    Asthenia 7/122 (5.7%) 9 6/113 (5.3%) 6 4/102 (3.9%) 4
    Fatigue 13/122 (10.7%) 15 17/113 (15%) 17 10/102 (9.8%) 10
    Pyrexia 6/122 (4.9%) 7 6/113 (5.3%) 6 3/102 (2.9%) 4
    Metabolism and nutrition disorders
    Decreased appetite 7/122 (5.7%) 8 3/113 (2.7%) 3 4/102 (3.9%) 4
    Musculoskeletal and connective tissue disorders
    Musculoskeletal pain 0/122 (0%) 0 6/113 (5.3%) 6 1/102 (1%) 1
    Myalgia 0/122 (0%) 0 8/113 (7.1%) 9 2/102 (2%) 2
    Nervous system disorders
    Dizziness 8/122 (6.6%) 9 18/113 (15.9%) 22 4/102 (3.9%) 4
    Headache 23/122 (18.9%) 26 18/113 (15.9%) 23 7/102 (6.9%) 8
    Psychiatric disorders
    Insomnia 10/122 (8.2%) 10 12/113 (10.6%) 12 2/102 (2%) 2
    Respiratory, thoracic and mediastinal disorders
    Cough 9/122 (7.4%) 10 2/113 (1.8%) 2 5/102 (4.9%) 6
    Skin and subcutaneous tissue disorders
    Pruritus 4/122 (3.3%) 4 12/113 (10.6%) 12 1/102 (1%) 1
    Vascular disorders
    Hypertension 7/122 (5.7%) 7 6/113 (5.3%) 6 2/102 (2%) 2

    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.

    Results Point of Contact

    Name/Title Senior Vice President, Global Clinical Development
    Organization Merck Sharp & Dohme Corp.
    Phone 1-800-672-6372
    Email ClinicalTrialDisclosure@merck.com
    Responsible Party:
    Merck Sharp & Dohme LLC
    ClinicalTrials.gov Identifier:
    NCT02092350
    Other Study ID Numbers:
    • 5172-052
    • 2013-003858-25
    First Posted:
    Mar 20, 2014
    Last Update Posted:
    Sep 24, 2018
    Last Verified:
    Aug 1, 2018