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Trial record 40 of 82 for:    GRAZOPREVIR ANHYDROUS AND ELBASVIR

Study of Grazoprevir (MK-5172) and Elbasvir (MK-8742) in Japanese Participants With Chronic Hepatitis C (MK-5172-058)

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: NCT02203149
Recruitment Status : Completed
First Posted : July 29, 2014
Results First Posted : October 11, 2016
Last Update Posted : September 24, 2018
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Hepatitis C
Interventions Drug: Grazoprevir
Drug: Elbasvir
Drug: Placebo to Grazoprevir
Drug: Placebo to Elbasvir
Enrollment 399
Recruitment Details  
Pre-assignment Details Of 432 screened, 63 were enrolled and randomized to Part 1 and 336 were enrolled and randomized to Part 2, for a total of 399 randomized.
Arm/Group Title Part 1 Grazoprevir 50 mg + Elbasvir Part 1 Grazoprevir 100 mg + Elbasvir Part 2 Non-cirrhotic Immediate: Grazoprevir + Elbasvir Part 2 Non-cirrhotic Deferred: Placebo► Grazoprevir + Elbasvir Part 2 Cirrhotic: Grazoprevir + Elbasvir
Hide Arm/Group Description Non-cirrhotic participants take 50 mg grazoprevir in combination with 50 mg elbasvir orally (p.o.) once daily (q.d.) for 12 weeks during the blinded period of Part 1 and are followed-up for 24 weeks during the open-label period of Part 1. Non-cirrhotic participants take 100 mg grazoprevir in combination with 50 mg elbasvir p.o. q.d. for 12 weeks during the blinded period of Part 1 and are followed-up for 24 weeks during the open-label period of Part 1. Non-cirrhotic participants take 100 mg grazoprevir and 50 mg elbasvir p.o. q.d. for 12 weeks during the blinded period of Part 2, and are followed-up for 24 weeks during the open-label period of Part 2. Non-cirrhotic participants take dose-matched placebo p.o. q.d. for 12 weeks during the blinded period of Part 2 followed by a 4-week follow-up. Afterwards, participants take 100 mg grazoprevir and 50 mg elbasvir p.o. q.d. for 12 weeks and are followed-up for 24 weeks during the open-label period of Part 2. Cirrhotic participants take 100 mg grazoprevir and 50 mg elbasvir p.o. q.d. for 12 weeks during the blinded period of Part 2, and are followed-up for 24 weeks during the open-label period of Part 2.
Period Title: Part 1
Started 31 32 0 0 0
Completed 31 31 0 0 0
Not Completed 0 1 0 0 0
Reason Not Completed
Adverse Event             0             1             0             0             0
Period Title: Part 2
Started 0 [1] 0 [1] 227 74 35
Started Deferred Active Treatment 0 0 0 73 [2] 0
Completed 0 0 226 71 34
Not Completed 0 0 1 3 1
Reason Not Completed
Death             0             0             1             1             0
Withdrawal by Subject             0             0             0             1             0
Adverse Event             0             0             0             1             1
[1]
Participants of Part 1 did not enter Part 2
[2]
1 participant in Deferred Treatment Arm receiving Placebo did not receive Deferred Active Treatment.
Arm/Group Title Part 1 Grazoprevir 50 mg + Elbasvir Part 1 Grazoprevir 100 mg + Elbasvir Part 2 Non-cirrhotic Immediate: Grazoprevir + Elbasvir Part 2 Non-cirrhotic Deferred: Placebo► Grazoprevir + Elbasvir Part 2 Cirrhotic: Grazoprevir + Elbasvir Total
Hide Arm/Group Description Non-cirrhotic participants take 50 mg grazoprevir in combination with 50 mg elbasvir orally (p.o.) once daily (q.d.) for 12 weeks during the blinded period of Part 1 and are followed-up for 24 weeks during the open-label period of Part 1. Non-cirrhotic participants take 100 mg grazoprevir in combination with 50 mg elbasvir p.o. q.d. for 12 weeks during the blinded period of Part 1 and are followed-up for 24 weeks during the open-label period of Part 1. Non-cirrhotic participants take 100 mg grazoprevir and 50 mg elbasvir p.o. q.d. for 12 weeks during the blinded period of Part 2, and are followed-up for 24 weeks during the open-label period of Part 2. Non-cirrhotic participants take dose-matched placebo p.o. q.d. for 12 weeks during the blinded period of Part 2 followed by a 4-week follow-up. Afterwards, participants take 100 mg grazoprevir and 50 mg elbasvir p.o. q.d. for 12 weeks and are followed-up for 24 weeks during the open-label period of Part 2. Cirrhotic participants take 100 mg grazoprevir and 50 mg elbasvir p.o. q.d. for 12 weeks during the blinded period of Part 2, and are followed-up for 24 weeks during the open-label period of Part 2. Total of all reporting groups
Overall Number of Baseline Participants 31 32 227 74 35 399
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 31 participants 32 participants 227 participants 74 participants 35 participants 399 participants
61.1  (9.7) 58.0  (12.5) 61.1  (12.5) 60.9  (10.8) 64.8  (9.2) 61.1  (11.7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 31 participants 32 participants 227 participants 74 participants 35 participants 399 participants
Female
19
  61.3%
17
  53.1%
140
  61.7%
53
  71.6%
17
  48.6%
246
  61.7%
Male
12
  38.7%
15
  46.9%
87
  38.3%
21
  28.4%
18
  51.4%
153
  38.3%
1.Primary Outcome
Title Part 2: Percentage of Treatment-naïve Participants in the Immediate Treatment Arm Achieving Sustained Viral Response at 12 Weeks After The End of All Treatment (SVR12)
Hide Description Blood was drawn from each participant to assess Hepatitis C Virus ribonucleic acid (HCV RNA) plasma levels using the Roche COBAS® Taqman quantitative reverse transcription-polymerase chain reaction (RT-PCR) assay, v2.0, which had a lower limit of quantification (LLoQ) of 1.2 Log IU/mL (15 IU/mL) and a lower limit of detection (LLoD) below 15 IU/ml (no specific value). SVR12 was defined as undetectable HCV RNA (target not detected) at 12 weeks after the end of all study therapy. The Clopper-Pearson method was used to construct 95% confidence intervals (CIs) for the SVR12 rate. The lower limit of the 95% CI was compared to the reference rate of 75%; a lower CI limit that was higher than the reference rate would confirm the primary hypothesis and indicate that that the treatment combination was efficacious. As pre-specified in the protocol, only the Immediate Treatment Arm of Part 2 (treatment naïve participants) was included in the primary efficacy analysis.
Time Frame 12 weeks after end of all therapy in Part 2 (Study Week 24 of Part 2)
Hide Outcome Measure Data
Hide Analysis Population Description
The primary efficacy analysis was assessed in all treatment-naïve participants randomized to the Part 2 Immediate Treatment Arm who received ≥1 dose of study treatment and had any follow-up efficacy measurement. No other arms were analyzed for this outcome measure.
Arm/Group Title Part 1 Grazoprevir 50 mg + Elbasvir Part 1 Grazoprevir 100 mg + Elbasvir Part 2 Non-cirrhotic Immediate: Grazoprevir + Elbasvir Part 2 Non-cirrhotic Deferred: Placebo Part 2 Cirrhotic: Grazoprevir + Elbasvir
Hide Arm/Group Description:
Non-cirrhotic participants take 50 mg grazoprevir in combination with 50 mg elbasvir orally (p.o.) once daily (q.d.) for 12 weeks during the blinded period of Part 1 and are followed-up for 24 weeks during the open-label period of Part 1.
Non-cirrhotic participants take 100 mg grazoprevir in combination with 50 mg elbasvir p.o. q.d. for 12 weeks during the blinded period of Part 1 and are followed-up for 24 weeks during the open-label period of Part 1.
Non-cirrhotic treatment-naïve participants take 100 mg grazoprevir and 50 mg elbasvir p.o. q.d. for 12 weeks during the blinded period of Part 2, and are followed-up for 24 weeks during the open-label period of Part 2.
Non-cirrhotic participants take dose-matched placebo p.o. q.d. for 12 weeks during the blinded period of Part 2 followed by a 4-week follow-up.
Cirrhotic participants take 100 mg grazoprevir and 50 mg elbasvir p.o. q.d. for 12 weeks during the blinded period of Part 2, and are followed-up for 24 weeks during the open-label period of Part 2.
Overall Number of Participants Analyzed 0 0 149 0 0
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
96.6
(92.3 to 98.9)
2.Primary Outcome
Title Part 1: Percentage of Participants Experiencing an Adverse Event (AE) During Treatment and First 4 Follow-Up Weeks
Hide Description 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 (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, was also an AE. The primary safety evaluation was limited to the initial treatment period through Follow-up Week 4 (FUWK4).
Time Frame Up to 4 weeks post last dose in Part 1 (Up to total of 16 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants in Part 1 who received ≥1 dose of study treatment and had any safety follow-up data. Data for participants in Part 2 were analyzed and reported separately.
Arm/Group Title Part 1 Grazoprevir 50 mg + Elbasvir Part 1 Grazoprevir 100 mg + Elbasvir
Hide Arm/Group Description:
Non-cirrhotic participants take 50 mg grazoprevir in combination with 50 mg elbasvir orally (p.o.) once daily (q.d.) for 12 weeks during the blinded period of Part 1.
Non-cirrhotic participants take 100 mg grazoprevir in combination with 50 mg elbasvir p.o. q.d. for 12 weeks during the blinded period of Part 1.
Overall Number of Participants Analyzed 31 31
Measure Type: Number
Unit of Measure: percentage of participants
67.7 74.2
3.Primary Outcome
Title Part 1: Percentage of Participants That Discontinued Treatment Due to an AE
Hide Description 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 (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, was also an AE. The primary safety evaluation was limited to the initial treatment period through FUWK4.
Time Frame Up to Study Week 12 in Part 1
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants in Part 1 who received ≥1 dose of study treatment and had any safety follow-up data. Data for participants in Part 2 were analyzed and reported separately.
Arm/Group Title Part 1 Grazoprevir 50 mg + Elbasvir Part 1 Grazoprevir 100 mg + Elbasvir
Hide Arm/Group Description:
Non-cirrhotic participants take 50 mg grazoprevir in combination with 50 mg elbasvir orally (p.o.) once daily (q.d.) for 12 weeks during the blinded period of Part 1.
Non-cirrhotic participants take 100 mg grazoprevir in combination with 50 mg elbasvir p.o. q.d. for 12 weeks during the blinded period of Part 1.
Overall Number of Participants Analyzed 31 31
Measure Type: Number
Unit of Measure: percentage of participants
0.0 0.0
4.Primary Outcome
Title Part 2: Percentage of Participants Experiencing an AE During Initial Treatment and First 4 Follow-Up Weeks
Hide Description 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 preexisting condition that is temporally associated with the use of the Sponsor's product, was also an AE. The primary safety evaluation was limited to the initial treatment period and first 4 follow-up weeks, and the primary safety statistical analysis compared the percentage of participants with events between the Part 2 Immediate Treatment Arm and the Part 2 Deferred Treatment Arm while receiving placebo.
Time Frame Up to 4 weeks following initial treatment in Part 2 (Up to total of 16 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants in Part 2 who received ≥1 dose of study treatment and had any safety follow-up data. Participants in the Deferred Arm would have received only placebo treatment up to Study Week 16. Data for participants in Part 1 were analyzed and reported separately.
Arm/Group Title Part 2 Non-cirrhotic Immediate: Grazoprevir + Elbasvir Part 2 Non-cirrhotic Deferred: Placebo Part 2 Cirrhotic: Grazoprevir + Elbasvir
Hide Arm/Group Description:
Non-cirrhotic participants take 100 mg grazoprevir and 50 mg elbasvir p.o. q.d. for 12 weeks during the blinded period of Part 2.
Non-cirrhotic participants take dose-matched placebo p.o. q.d. for 12 weeks during the blinded period of Part 2 followed by a 4-week follow-up.
Cirrhotic participants take 100 mg grazoprevir and 50 mg elbasvir p.o. q.d. for 12 weeks during the blinded period of Part 2.
Overall Number of Participants Analyzed 227 74 35
Measure Type: Number
Unit of Measure: percentage of participants
64.8 67.6 80.0
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 2 Non-cirrhotic Immediate: Grazoprevir + Elbasvir, Part 2 Non-cirrhotic Deferred: Placebo
Comments 95% confidence intervals were provided for between-treatment differences in the percentage of participants with events, comparing participants in the Part 2 Immediate Treatment (Grazoprevir + Elbasvir) Arm with the Part 2 Deferred Treatment (Placebo) Arm during the double blinded period through FUWK4. These analyses were performed using the Miettinen and Nurminen method, an unconditional, asymptotic method.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Miettinen and Nurminen Method
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percentage
Estimated Value -2.8
Confidence Interval (2-Sided) 95%
-14.5 to 10.0
Estimation Comments [Not Specified]
5.Primary Outcome
Title Part 2: Percentage of Participants That Discontinued Initial Treatment Due to an AE
Hide Description 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 preexisting condition that is temporally associated with the use of the Sponsor's product, was also an AE. The primary safety evaluation was limited to the initial treatment period and first 4 follow-up weeks, and the primary safety statistical analysis compared the percentage of participants with events between the Part 2 Immediate Treatment Arm and the Part 2 Deferred Treatment Arm while receiving placebo.
Time Frame Up to Study Week 12 in Part 2
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants in Part 2 who received ≥1 dose of study treatment and had any safety follow-up data. Participants in the Deferred Arm would have received only placebo treatment up to Study Week 12. Data for participants in Part 1 were analyzed and reported separately.
Arm/Group Title Part 2 Non-cirrhotic Immediate: Grazoprevir + Elbasvir Part 2 Non-cirrhotic Deferred: Placebo Part 2 Cirrhotic: Grazoprevir + Elbasvir
Hide Arm/Group Description:
Non-cirrhotic participants take 100 mg grazoprevir and 50 mg elbasvir p.o. q.d. for 12 weeks during the blinded period of Part 2.
Non-cirrhotic participants take dose-matched placebo p.o. q.d. for 12 weeks during the blinded period of Part 2.
Cirrhotic participants take 100 mg grazoprevir and 50 mg elbasvir p.o. q.d. for 12 weeks during the blinded period of Part 2.
Overall Number of Participants Analyzed 227 74 35
Measure Type: Number
Unit of Measure: percentage of participants
1.3 1.4 0.0
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 2 Non-cirrhotic Immediate: Grazoprevir + Elbasvir, Part 2 Non-cirrhotic Deferred: Placebo
Comments 95% confidence intervals were provided for between-treatment differences in the percentage of participants with events, comparing participants in the Part 2 Immediate Treatment (Grazoprevir + Elbasvir) Arm with the Part 2 Deferred Treatment (Placebo) Arm during the double blinded period through FUWK4. These analyses were performed using the Miettinen and Nurminen method, an unconditional, asymptotic method.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Miettinen and Nurminen Method
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percentage
Estimated Value -0.0
Confidence Interval (2-Sided) 95%
-6.0 to 2.8
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Part 1: Percentage of Participants Achieving Undetectable HCV RNA Over Time
Hide Description Blood was drawn from each participant to assess HCV RNA plasma levels using the Roche COBAS® Taqman quantitative RT-PCR assay, v2.0, which had a LLoQ of 1.2 Log IU/mL (15 IU/mL) and a LLoD below 15 IU/ml (no specific value). Undetectable HCV RNA was defined as HCV RNA target not detected. The percentage of participants with undetectable HCV RNA at TW2, TW4, TW12, EOT, FUWK4, FUWK12, and FUWK24 is summarized for each arm. The Clopper-Pearson method was used to construct 95% CIs for SVR rates.
Time Frame Part 1 Treatment Weeks (TW)2, TW4, TW12, End of Treatment (EOT), FUWK4, FUWK12, FUWK24
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants in Part 1 who have received ≥1 dose of study treatment and who have any follow-up efficacy measurement. Data for participants in Part 2 were analyzed and reported separately.
Arm/Group Title Part 1 Grazoprevir 50 mg + Elbasvir Part 1 Grazoprevir 100 mg + Elbasvir
Hide Arm/Group Description:
Non-cirrhotic participants take 50 mg grazoprevir in combination with 50 mg elbasvir orally (p.o.) once daily (q.d.) for 12 weeks during the blinded period of Part 1 and are followed-up for 24 weeks during the open-label period of Part 1.
Non-cirrhotic participants take 100 mg grazoprevir in combination with 50 mg elbasvir p.o. q.d. for 12 weeks during the blinded period of Part 1 and are followed-up for 24 weeks during the open-label period of Part 1.
Overall Number of Participants Analyzed 31 31
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
TW2
22.6
(9.6 to 41.1)
35.5
(19.2 to 54.6)
TW4
77.4
(58.9 to 90.4)
83.9
(66.3 to 94.5)
TW12
100.0
(88.8 to 100.0)
100.0
(88.8 to 100.0)
EOT
100.0
(88.8 to 100.0)
100.0
(88.8 to 100.0)
FUWK4
100.0
(88.8 to 100.0)
100.0
(88.8 to 100.0)
FUWK12
100.0
(88.8 to 100.0)
96.8
(83.3 to 99.9)
FUWK24
96.8
(83.3 to 99.9)
96.8
(83.3 to 99.9)
7.Secondary Outcome
Title Part 1: Percentage of Participants Achieving HCV RNA Below the Lower Limit of Quantitation (<LLoQ) Over Time
Hide Description Blood was drawn from each participant to assess HCV RNA plasma levels using the Roche COBAS® Taqman quantitative RT-PCR assay, v2.0, which had a LLoQ of 1.2 Log IU/mL (15 IU/mL) and a LLoD below 15 IU/ml (no specific value). Undetectable HCV RNA was defined as HCV RNA target not detected. The percentage of participants with HCV RNA <LLoQ at TW2, TW4, TW12, EOT, FUWK4, FUWK12, and FUWK24 is summarized for each arm. The Clopper-Pearson method was used to construct 95% CIs for SVR rates.
Time Frame Part 1 TW2, TW4, TW12, EOT, FUWK4, FUWK12, FUWK24
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants in Part 1 who have received ≥1 dose of study treatment and who have any follow-up efficacy measurement. Data for participants in Part 2 were analyzed and reported separately.
Arm/Group Title Part 1 Grazoprevir 50 mg + Elbasvir Part 1 Grazoprevir 100 mg + Elbasvir
Hide Arm/Group Description:
Non-cirrhotic participants take 50 mg grazoprevir in combination with 50 mg elbasvir orally (p.o.) once daily (q.d.) for 12 weeks during the blinded period of Part 1 and are followed-up for 24 weeks during the open-label period of Part 1.
Non-cirrhotic participants take 100 mg grazoprevir in combination with 50 mg elbasvir p.o. q.d. for 12 weeks during the blinded period of Part 1 and are followed-up for 24 weeks during the open-label period of Part 1.
Overall Number of Participants Analyzed 31 31
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
TW2
61.3
(42.2 to 78.2)
71.0
(52.0 to 85.8)
TW4
100.0
(88.8 to 100.0)
100.0
(88.8 to 100.0)
TW12
100.0
(88.8 to 100.0)
100.0
(88.8 to 100.0)
EOT
100.0
(88.8 to 100.0)
100.0
(88.8 to 100.0)
FUWK4
100.0
(88.8 to 100.0)
100.0
(88.8 to 100.0)
FUWK12
100.0
(88.8 to 100.0)
96.8
(83.3 to 99.9)
FUWK24
100.0
(88.8 to 100.0)
96.8
(83.3 to 99.9)
8.Secondary Outcome
Title Part 2: Percentage of Participants Achieving Undetectable HCV RNA Over Time After Active Treatment
Hide Description Blood was drawn from each participant to assess HCV RNA plasma levels using the Roche COBAS® Taqman quantitative RT-PCR assay, v2.0, which had a LLoQ of 1.2 Log IU/mL (15 IU/mL) and a LLoD below 15 IU/ml (no specific value). Undetectable HCV RNA was defined as HCV RNA target not detected. The percentage of participants with undetectable HCV RNA at TW2, TW4, TW12, EOT, FUWK4, FUWK12, and FUWK24 is summarized for each arm. Data reported for the Part 2 Deferred Treatment Arm corresponds to the deferred active treatment weeks and subsequent follow-up. The Clopper-Pearson method was used to construct 95% CIs for SVR rates.
Time Frame Part 2: Active TW2, TW4, TW12, End of Treatment (EOT), FUWK4, FUWK12, FUWK24
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants in Part 2 who have received ≥1 dose of active study treatment and who have any follow-up efficacy measurement. Data for participants in Part 1 were analyzed and reported separately.
Arm/Group Title Part 2 Non-cirrhotic Immediate: Grazoprevir + Elbasvir Part 2 Non-cirrhotic Deferred: Grazoprevir + Elbasvir Part 2 Cirrhotic: Grazoprevir + Elbasvir
Hide Arm/Group Description:
Non-cirrhotic participants take 100 mg grazoprevir and 50 mg elbasvir p.o. q.d. for 12 weeks during the blinded period of Part 2, and are followed-up for 24 weeks during the open-label period of Part 2.
During the open-label period of Part 2, non-cirrhotic participants in the Deferred Treatment Arm take 100 mg grazoprevir and 50 mg elbasvir p.o. q.d. for 12 weeks and are followed-up for 24 weeks.
Cirrhotic participants take 100 mg grazoprevir and 50 mg elbasvir p.o. q.d. for 12 weeks during the blinded period of Part 2, and are followed-up for 24 weeks during the open-label period of Part 2.
Overall Number of Participants Analyzed 227 73 35
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
TW2
25.1
(19.6 to 31.3)
39.7
(28.5 to 51.9)
11.4
(3.2 to 26.7)
TW4
70.5
(64.1 to 76.3)
86.3
(76.2 to 93.2)
65.7
(47.8 to 80.9)
TW12
97.8
(94.9 to 99.3)
100.0
(95.1 to 100.0)
100.0
(90.0 to 100.0)
EOT
98.7
(96.2 to 99.7)
100.0
(95.1 to 100.0)
100.0
(90.0 to 100.0)
FUWK4
98.2
(95.5 to 99.5)
100.0
(95.1 to 100.0)
97.1
(85.1 to 99.9)
FUWK12
96.5
(93.2 to 98.5)
95.9
(88.5 to 99.1)
97.1
(85.1 to 99.9)
FUWK24
96.5
(93.2 to 98.5)
95.9
(88.5 to 99.1)
94.3
(80.8 to 99.3)
9.Secondary Outcome
Title Part 2: Percentage of Participants Achieving HCV RNA <LLoQ Over Time After Active Treatment
Hide Description Blood was drawn from each participant to assess HCV RNA plasma levels using the Roche COBAS® Taqman quantitative RT-PCR assay, v2.0, which had a LLoQ of 1.2 Log IU/mL (15 IU/mL) and a LLoD below 15 IU/ml (no specific value). Undetectable HCV RNA was defined as HCV RNA target not detected. The percentage of participants with HCV RNA <LLoQ at TW2, TW4, TW12, EOT, FUWK4, FUWK12, and FUWK24 is summarized for each arm. Data reported for the Part 2 Deferred Treatment Arm corresponds to the deferred active treatment weeks and subsequent follow-up. The Clopper-Pearson method was used to construct 95% CIs for SVR rates.
Time Frame Part 2: Active TW2, TW4, TW12, End of Treatment (EOT), FUWK4, FUWK12, FUWK24
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants in Part 2 who have received ≥1 dose of active study treatment and who have any follow-up efficacy measurement. Data for participants in Part 1 were analyzed and reported separately.
Arm/Group Title Part 2 Non-cirrhotic Immediate: Grazoprevir + Elbasvir Part 2 Non-cirrhotic Deferred: Grazoprevir + Elbasvir Part 2 Cirrhotic: Grazoprevir + Elbasvir
Hide Arm/Group Description:
Non-cirrhotic participants take 100 mg grazoprevir and 50 mg elbasvir p.o. q.d. for 12 weeks during the blinded period of Part 2, and are followed-up for 24 weeks during the open-label period of Part 2.
During the open-label period of Part 2, non-cirrhotic participants in the Deferred Treatment Arm take 100 mg grazoprevir and 50 mg elbasvir p.o. q.d. for 12 weeks and are followed-up for 24 weeks.
Cirrhotic participants take 100 mg grazoprevir and 50 mg elbasvir p.o. q.d. for 12 weeks during the blinded period of Part 2, and are followed-up for 24 weeks during the open-label period of Part 2.
Overall Number of Participants Analyzed 227 73 35
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
TW2
60.8
(54.1 to 67.2)
69.9
(58.0 to 80.1)
60.0
(42.1 to 76.1)
TW4
96.0
(92.6 to 98.2)
98.6
(92.6 to 100.0)
94.3
(80.8 to 99.3)
TW12
98.7
(96.2 to 99.7)
100.0
(95.1 to 100.0)
100.0
(90.0 to 100.0)
EOT
99.6
(97.6 to 100.0)
100.0
(95.1 to 100.0)
100.0
(90.0 to 100.0)
FUWK4
98.2
(95.5 to 99.5)
100.0
(95.1 to 100.0)
97.1
(85.1 to 99.9)
FUWK12
96.5
(93.2 to 98.5)
97.3
(90.5 to 99.7)
97.1
(85.1 to 99.9)
FUWK24
96.5
(93.2 to 98.5)
95.9
(88.5 to 99.1)
97.1
(85.1 to 99.9)
Time Frame Part 1: Up to a total of 36 weeks Part 2: Up to a total of 52 weeks
Adverse Event Reporting Description All randomized participants who received ≥1 dose of study treatment and had any safety follow-up data. AEs were reported by the treatment that participants were receiving at the time of the event; AEs for Deferred Arm reported separately for placebo and active treatment. Part 1 database=MedDRA 18.1, Part 2 database=MedDRA 19.0
 
Arm/Group Title Part 1 Grazoprevir 50 mg + Elbasvir Part 1 Grazoprevir 100 mg + Elbasvir Part 2 Non-cirrhotic Immediate: Grazoprevir + Elbasvir Part 2 Non-cirrhotic Deferred: Placebo Part 2 Non-cirrhotic Deferred: Grazoprevir + Elbasvir Part 2 Cirrhotic: Grazoprevir + Elbasvir
Hide Arm/Group Description Non-cirrhotic participants take 50 mg grazoprevir in combination with 50 mg elbasvir orally (p.o.) once daily (q.d.) for 12 weeks during the blinded period of Part 1 and are followed-up for 24 weeks during the open-label period of Part 1. Non-cirrhotic participants take 100 mg grazoprevir in combination with 50 mg elbasvir p.o. q.d. for 12 weeks during the blinded period of Part 1 and are followed-up for 24 weeks during the open-label period of Part 1. Non-cirrhotic participants take 100 mg grazoprevir and 50 mg elbasvir p.o. q.d. for 12 weeks during the blinded period of Part 2, and are followed-up for 24 weeks during the open-label period of Part 2. Non-cirrhotic participants in the Deferred Treatment Arm take dose-matched placebo p.o. q.d. for 12 weeks during the blinded period of Part 2 followed by a 4-week follow-up. During the open-label period, non-cirrhotic participants in the Deferred Treatment Arm take 100 mg grazoprevir and 50 mg elbasvir p.o. q.d. for 12 weeks and are followed-up for 24 weeks. One participant who received placebo during the blinded period did not receive active treatment during the open-label period. Cirrhotic participants take 100 mg grazoprevir and 50 mg elbasvir p.o. q.d. for 12 weeks during the blinded period of Part 2, and are followed-up for 24 weeks during the open-label period of Part 2.
All-Cause Mortality
Part 1 Grazoprevir 50 mg + Elbasvir Part 1 Grazoprevir 100 mg + Elbasvir Part 2 Non-cirrhotic Immediate: Grazoprevir + Elbasvir Part 2 Non-cirrhotic Deferred: Placebo Part 2 Non-cirrhotic Deferred: Grazoprevir + Elbasvir Part 2 Cirrhotic: Grazoprevir + Elbasvir
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--      --/--      --/--    
Hide Serious Adverse Events
Part 1 Grazoprevir 50 mg + Elbasvir Part 1 Grazoprevir 100 mg + Elbasvir Part 2 Non-cirrhotic Immediate: Grazoprevir + Elbasvir Part 2 Non-cirrhotic Deferred: Placebo Part 2 Non-cirrhotic Deferred: Grazoprevir + Elbasvir Part 2 Cirrhotic: Grazoprevir + Elbasvir
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/31 (6.45%)      1/31 (3.23%)      19/227 (8.37%)      1/74 (1.35%)      2/73 (2.74%)      3/35 (8.57%)    
Cardiac disorders             
Acute coronary syndrome  1  1/31 (3.23%)  1 0/31 (0.00%)  0 0/227 (0.00%)  0 0/74 (0.00%)  0 0/73 (0.00%)  0 0/35 (0.00%)  0
Cardiac sarcoidosis  1  0/31 (0.00%)  0 0/31 (0.00%)  0 1/227 (0.44%)  1 0/74 (0.00%)  0 0/73 (0.00%)  0 0/35 (0.00%)  0
Angina pectoris  1  0/31 (0.00%)  0 0/31 (0.00%)  0 1/227 (0.44%)  1 0/74 (0.00%)  0 0/73 (0.00%)  0 0/35 (0.00%)  0
Eye disorders             
Cataract  1  0/31 (0.00%)  0 0/31 (0.00%)  0 3/227 (1.32%)  3 0/74 (0.00%)  0 0/73 (0.00%)  0 0/35 (0.00%)  0
Gastrointestinal disorders             
Colitis ischaemic  1  0/31 (0.00%)  0 0/31 (0.00%)  0 0/227 (0.00%)  0 0/74 (0.00%)  0 1/73 (1.37%)  1 0/35 (0.00%)  0
Haematochezia  1  0/31 (0.00%)  0 1/31 (3.23%)  1 0/227 (0.00%)  0 0/74 (0.00%)  0 0/73 (0.00%)  0 0/35 (0.00%)  0
Haemorrhagic erosive gastritis  1  0/31 (0.00%)  0 0/31 (0.00%)  0 1/227 (0.44%)  1 0/74 (0.00%)  0 0/73 (0.00%)  0 0/35 (0.00%)  0
Ileus  1  0/31 (0.00%)  0 0/31 (0.00%)  0 1/227 (0.44%)  1 0/74 (0.00%)  0 0/73 (0.00%)  0 0/35 (0.00%)  0
Inguinal hernia  1  0/31 (0.00%)  0 0/31 (0.00%)  0 1/227 (0.44%)  1 0/74 (0.00%)  0 0/73 (0.00%)  0 0/35 (0.00%)  0
Large intestine polyp  1  0/31 (0.00%)  0 1/31 (3.23%)  1 1/227 (0.44%)  1 0/74 (0.00%)  0 1/73 (1.37%)  1 0/35 (0.00%)  0
General disorders             
Lead dislodgement  1 [1]  0/31 (0.00%)  0 0/31 (0.00%)  0 1/227 (0.44%)  1 0/74 (0.00%)  0 0/73 (0.00%)  0 0/35 (0.00%)  0
Infections and infestations             
Appendicitis  1  0/31 (0.00%)  0 0/31 (0.00%)  0 1/227 (0.44%)  1 0/74 (0.00%)  0 0/73 (0.00%)  0 0/35 (0.00%)  0
Sinusitis  1  0/31 (0.00%)  0 0/31 (0.00%)  0 1/227 (0.44%)  1 0/74 (0.00%)  0 0/73 (0.00%)  0 0/35 (0.00%)  0
Injury, poisoning and procedural complications             
Tibia fracture  1  0/31 (0.00%)  0 0/31 (0.00%)  0 1/227 (0.44%)  1 0/74 (0.00%)  0 0/73 (0.00%)  0 0/35 (0.00%)  0
Investigations             
Alanine aminotransferase increased  1  0/31 (0.00%)  0 0/31 (0.00%)  0 1/227 (0.44%)  1 0/74 (0.00%)  0 0/73 (0.00%)  0 0/35 (0.00%)  0
Aspartate aminotransferase increased  1  0/31 (0.00%)  0 0/31 (0.00%)  0 1/227 (0.44%)  1 0/74 (0.00%)  0 0/73 (0.00%)  0 0/35 (0.00%)  0
Musculoskeletal and connective tissue disorders             
Arthritis  1  0/31 (0.00%)  0 0/31 (0.00%)  0 1/227 (0.44%)  1 0/74 (0.00%)  0 0/73 (0.00%)  0 0/35 (0.00%)  0
Osteoarthritis  1  0/31 (0.00%)  0 0/31 (0.00%)  0 1/227 (0.44%)  1 0/74 (0.00%)  0 0/73 (0.00%)  0 0/35 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)             
Adenocarcinoma of colon  1  1/31 (3.23%)  1 0/31 (0.00%)  0 0/227 (0.00%)  0 0/74 (0.00%)  0 0/73 (0.00%)  0 0/35 (0.00%)  0
Benign anorectal neoplasm  1  0/31 (0.00%)  0 0/31 (0.00%)  0 1/227 (0.44%)  1 0/74 (0.00%)  0 0/73 (0.00%)  0 0/35 (0.00%)  0
Colon cancer  1  0/31 (0.00%)  0 0/31 (0.00%)  0 0/227 (0.00%)  0 0/74 (0.00%)  0 0/73 (0.00%)  0 1/35 (2.86%)  1
Gastrointestinal tract adenoma  1  0/31 (0.00%)  0 0/31 (0.00%)  0 0/227 (0.00%)  0 0/74 (0.00%)  0 0/73 (0.00%)  0 1/35 (2.86%)  1
Hepatocellular carcinoma  1  0/31 (0.00%)  0 0/31 (0.00%)  0 1/227 (0.44%)  1 1/74 (1.35%)  2 0/73 (0.00%)  0 1/35 (2.86%)  1
Renal cell carcinoma  1  0/31 (0.00%)  0 0/31 (0.00%)  0 1/227 (0.44%)  1 0/74 (0.00%)  0 0/73 (0.00%)  0 0/35 (0.00%)  0
Nervous system disorders             
Cerebral infarction  1  0/31 (0.00%)  0 0/31 (0.00%)  0 1/227 (0.44%)  1 0/74 (0.00%)  0 0/73 (0.00%)  0 0/35 (0.00%)  0
Sciatica  1  0/31 (0.00%)  0 0/31 (0.00%)  0 1/227 (0.44%)  1 0/74 (0.00%)  0 0/73 (0.00%)  0 0/35 (0.00%)  0
Renal and urinary disorders             
Ureterolithiasis  1  0/31 (0.00%)  0 0/31 (0.00%)  0 1/227 (0.44%)  1 0/74 (0.00%)  0 0/73 (0.00%)  0 0/35 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.1 & 19.0
[1]
appears under "Product Issues" in MedDRA v. 19.0
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Part 1 Grazoprevir 50 mg + Elbasvir Part 1 Grazoprevir 100 mg + Elbasvir Part 2 Non-cirrhotic Immediate: Grazoprevir + Elbasvir Part 2 Non-cirrhotic Deferred: Placebo Part 2 Non-cirrhotic Deferred: Grazoprevir + Elbasvir Part 2 Cirrhotic: Grazoprevir + Elbasvir
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   16/31 (51.61%)      17/31 (54.84%)      109/227 (48.02%)      27/74 (36.49%)      42/73 (57.53%)      27/35 (77.14%)    
Blood and lymphatic system disorders             
Anaemia  1  0/31 (0.00%)  0 0/31 (0.00%)  0 1/227 (0.44%)  1 0/74 (0.00%)  0 1/73 (1.37%)  1 2/35 (5.71%)  2
Eye disorders             
Conjunctival haemorrhage  1  2/31 (6.45%)  2 0/31 (0.00%)  0 3/227 (1.32%)  3 0/74 (0.00%)  0 0/73 (0.00%)  0 1/35 (2.86%)  1
Dry eye  1  2/31 (6.45%)  2 0/31 (0.00%)  0 2/227 (0.88%)  2 0/74 (0.00%)  0 0/73 (0.00%)  0 0/35 (0.00%)  0
Gastrointestinal disorders             
Abdominal pain upper  1  2/31 (6.45%)  2 1/31 (3.23%)  1 6/227 (2.64%)  6 1/74 (1.35%)  1 2/73 (2.74%)  2 0/35 (0.00%)  0
Constipation  1  0/31 (0.00%)  0 1/31 (3.23%)  1 11/227 (4.85%)  11 3/74 (4.05%)  3 4/73 (5.48%)  4 3/35 (8.57%)  3
Diarrhoea  1  2/31 (6.45%)  2 1/31 (3.23%)  2 12/227 (5.29%)  14 2/74 (2.70%)  3 6/73 (8.22%)  6 3/35 (8.57%)  3
Stomatitis  1  1/31 (3.23%)  1 0/31 (0.00%)  0 2/227 (0.88%)  2 1/74 (1.35%)  1 2/73 (2.74%)  2 2/35 (5.71%)  2
General disorders             
Malaise  1  1/31 (3.23%)  1 0/31 (0.00%)  0 7/227 (3.08%)  7 3/74 (4.05%)  5 5/73 (6.85%)  6 2/35 (5.71%)  2
Pyrexia  1  3/31 (9.68%)  3 1/31 (3.23%)  2 3/227 (1.32%)  3 1/74 (1.35%)  1 3/73 (4.11%)  3 1/35 (2.86%)  1
Infections and infestations             
Cystitis  1  0/31 (0.00%)  0 1/31 (3.23%)  1 8/227 (3.52%)  9 1/74 (1.35%)  1 6/73 (8.22%)  6 1/35 (2.86%)  1
Nasopharyngitis  1  8/31 (25.81%)  12 11/31 (35.48%)  12 47/227 (20.70%)  56 12/74 (16.22%)  18 20/73 (27.40%)  25 8/35 (22.86%)  11
Periodontitis  1  0/31 (0.00%)  0 1/31 (3.23%)  1 1/227 (0.44%)  1 1/74 (1.35%)  1 1/73 (1.37%)  1 2/35 (5.71%)  2
Injury, poisoning and procedural complications             
Accidental overdose  1  1/31 (3.23%)  1 2/31 (6.45%)  2 5/227 (2.20%)  5 1/74 (1.35%)  1 2/73 (2.74%)  2 0/35 (0.00%)  0
Ligament sprain  1  2/31 (6.45%)  2 0/31 (0.00%)  0 1/227 (0.44%)  1 0/74 (0.00%)  0 0/73 (0.00%)  0 1/35 (2.86%)  1
Tooth fracture  1  0/31 (0.00%)  0 0/31 (0.00%)  0 0/227 (0.00%)  0 0/74 (0.00%)  0 0/73 (0.00%)  0 2/35 (5.71%)  2
Investigations             
Alanine aminotransferase increased  1  1/31 (3.23%)  1 0/31 (0.00%)  0 12/227 (5.29%)  12 1/74 (1.35%)  1 3/73 (4.11%)  3 5/35 (14.29%)  5
Aspartate aminotransferase increased  1  0/31 (0.00%)  0 0/31 (0.00%)  0 10/227 (4.41%)  10 2/74 (2.70%)  3 3/73 (4.11%)  3 6/35 (17.14%)  6
Blood creatine phosphokinase increased  1  1/31 (3.23%)  1 0/31 (0.00%)  0 7/227 (3.08%)  7 4/74 (5.41%)  4 3/73 (4.11%)  4 1/35 (2.86%)  1
Protein urine present  1  0/31 (0.00%)  0 0/31 (0.00%)  0 0/227 (0.00%)  0 0/74 (0.00%)  0 0/73 (0.00%)  0 2/35 (5.71%)  2
Musculoskeletal and connective tissue disorders             
Arthralgia  1  1/31 (3.23%)  1 0/31 (0.00%)  0 8/227 (3.52%)  8 0/74 (0.00%)  0 1/73 (1.37%)  1 2/35 (5.71%)  2
Nervous system disorders             
Headache  1  5/31 (16.13%)  6 3/31 (9.68%)  3 11/227 (4.85%)  13 2/74 (2.70%)  2 2/73 (2.74%)  2 2/35 (5.71%)  2
Respiratory, thoracic and mediastinal disorders             
Epistaxis  1  0/31 (0.00%)  0 0/31 (0.00%)  0 2/227 (0.88%)  2 0/74 (0.00%)  0 0/73 (0.00%)  0 2/35 (5.71%)  3
Skin and subcutaneous tissue disorders             
Rash  1  1/31 (3.23%)  2 0/31 (0.00%)  0 9/227 (3.96%)  10 1/74 (1.35%)  1 0/73 (0.00%)  0 3/35 (8.57%)  3
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.1 & 19.0
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 investigator or sub-investigators may publicly present the academic accomplishment acquired from the Study at a specialized academic meeting or research conference. The Sponsor may freely use the information acquired from the Study for the purpose of marketing authorization application of the test drug.
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: ClinicalTrialsDisclosure@merck.com
Layout table for additonal information
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT02203149    
Other Study ID Numbers: 5172-058
142638 ( Registry Identifier: JAPIC-CTI )
First Submitted: July 25, 2014
First Posted: July 29, 2014
Results First Submitted: August 18, 2016
Results First Posted: October 11, 2016
Last Update Posted: September 24, 2018