C-WORTHy: A Study of the Combination Regimen Grazoprevir (MK-5172) and Elbasvir (MK-8742) ± Ribavirin in Participants With Chronic Hepatitis C (MK-5172-035)
Study Details
Study Description
Brief Summary
This is a study of the safety and efficacy of grazoprevir (MK-5172) in combination with elbasvir (MK-8742) ± ribavirin (RBV). The primary efficacy endpoint will be Sustained Virologic Response 12 weeks after the end of all study therapy (SVR12) in each of the treatment arms.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 2 |
Detailed Description
Part A is being done in treatment-naïve (TN), genotype 1 (GT1), interferon eligible, non-cirrhotic (N-C) participants with chronic hepatitis C (CHC). Participants will be assigned randomly to 1 of 2 treatment arms in which they will receive grazoprevir 100 mg once daily (QD) + elbasvir 20 mg or 50 mg QD and twice daily (BID) RBV, or to a treatment arm in which they will receive grazoprevir 100 mg QD + elbasvir 50 mg QD without RBV. Treatment will last 12 weeks.
In Part B, participants with hepatitis C virus (HCV) GT1 and HCV ribonucleic acid (RNA) levels of ≥10,000 IU/mL will be randomly assigned to a study arm, based on absence or presence of cirrhosis (C), whether they are TN or had poor response to previous antiviral therapy (null responders [NR]), or whether co-infected with human immunodeficiency virus (HIV); these participants will receive open-label grazoprevir (100 mg) in combination with elbasvir (50 mg) ± RBV. Treatment will last 8 to 18 weeks dependent on arm assignment.
In Part C, TN, N-C participants with HCV GT1b and HCV RNA levels of ≥10,000 IU/mL will be randomly assigned to receive open-label grazoprevir (100 mg) in combination with elbasvir (50 mg) ± RBV. Treatment will last 8 weeks.
In Part D, TN N-C participants with HCV GT3 and HCV RNA levels of ≥10,000 IU/mL will be randomly assigned to receive open-label grazoprevir (100 mg) in combination with elbasvir (50 mg) + RBV for 12 or 18 weeks.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: A1: TN NC Grazoprevir 100 mg + Elbasvir 20 mg + RBV-12 wk GT1a and GT1b participants receive Grazoprevir 100 mg tablet orally once daily (QD) for 12 weeks, Elbasvir 20 mg capsule and Placebo capsule orally QD for 12 weeks, RBV capsules orally twice daily (BID) for 24 weeks at a total daily dose from 800 to 1400 mg based on participant weight |
Drug: Grazoprevir
100 mg tablet orally QD
Other Names:
Drug: Elbasvir
Part A: 20 or 50 mg capsule orally QD Parts B, C, and D: 50 mg capsule orally QD
Other Names:
Drug: Placebo to Elbasvir
Placebo to Elbasvir 20 or 50 mg capsule, orally, once daily for 12 weeks to maintain blind (Part A only)
Drug: Ribavirin
Oral capsules BID at a total daily dose from 800 to 1400 mg based on participant weight
Other Names:
|
Experimental: A2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk GT1a and GT1b participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule and Placebo capsule orally QD for 12 weeks, RBV capsules orally BID for 24 weeks at a total daily dose from 800 to 1400 mg based on participant weight |
Drug: Grazoprevir
100 mg tablet orally QD
Other Names:
Drug: Elbasvir
Part A: 20 or 50 mg capsule orally QD Parts B, C, and D: 50 mg capsule orally QD
Other Names:
Drug: Placebo to Elbasvir
Placebo to Elbasvir 20 or 50 mg capsule, orally, once daily for 12 weeks to maintain blind (Part A only)
Drug: Ribavirin
Oral capsules BID at a total daily dose from 800 to 1400 mg based on participant weight
Other Names:
|
Experimental: A3: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 mg-12 wk GT1b only participants receive Grazoprevr 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks |
Drug: Grazoprevir
100 mg tablet orally QD
Other Names:
Drug: Elbasvir
Part A: 20 or 50 mg capsule orally QD Parts B, C, and D: 50 mg capsule orally QD
Other Names:
|
Experimental: B1: TN NC/GT1a Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk GT1a only participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks, Elbasvir 50 mg capsule orally QD for 8 weeks, RBV capsules orally BID for 8 weeks at a total daily dose from 800 to 1400 mg based on participant weight |
Drug: Grazoprevir
100 mg tablet orally QD
Other Names:
Drug: Elbasvir
Part A: 20 or 50 mg capsule orally QD Parts B, C, and D: 50 mg capsule orally QD
Other Names:
Drug: Ribavirin
Oral capsules BID at a total daily dose from 800 to 1400 mg based on participant weight
Other Names:
|
Experimental: B2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight |
Drug: Grazoprevir
100 mg tablet orally QD
Other Names:
Drug: Elbasvir
Part A: 20 or 50 mg capsule orally QD Parts B, C, and D: 50 mg capsule orally QD
Other Names:
Drug: Ribavirin
Oral capsules BID at a total daily dose from 800 to 1400 mg based on participant weight
Other Names:
|
Experimental: B3: TN NC/GT1a Grazoprevir 100 mg + Elbasvir 50 mg-12 wk GT1a only participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks |
Drug: Grazoprevir
100 mg tablet orally QD
Other Names:
Drug: Elbasvir
Part A: 20 or 50 mg capsule orally QD Parts B, C, and D: 50 mg capsule orally QD
Other Names:
|
Experimental: B4: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant |
Drug: Grazoprevir
100 mg tablet orally QD
Other Names:
Drug: Elbasvir
Part A: 20 or 50 mg capsule orally QD Parts B, C, and D: 50 mg capsule orally QD
Other Names:
Drug: Ribavirin
Oral capsules BID at a total daily dose from 800 to 1400 mg based on participant weight
Other Names:
|
Experimental: B5: TN C Grazoprevir 100 mg + Elbasvir 50 mg for 12 wk GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks |
Drug: Grazoprevir
100 mg tablet orally QD
Other Names:
Drug: Elbasvir
Part A: 20 or 50 mg capsule orally QD Parts B, C, and D: 50 mg capsule orally QD
Other Names:
|
Experimental: B6: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks, RBV capsules orally BID for 18 weeks at a total daily dose from 800 to 1400 mg based on participant weight |
Drug: Grazoprevir
100 mg tablet orally QD
Other Names:
Drug: Elbasvir
Part A: 20 or 50 mg capsule orally QD Parts B, C, and D: 50 mg capsule orally QD
Other Names:
Drug: Ribavirin
Oral capsules BID at a total daily dose from 800 to 1400 mg based on participant weight
Other Names:
|
Experimental: B7: TN C Grazoprevir 100 mg + Elbasvir 50 mg-18 wk GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks |
Drug: Grazoprevir
100 mg tablet orally QD
Other Names:
Drug: Elbasvir
Part A: 20 or 50 mg capsule orally QD Parts B, C, and D: 50 mg capsule orally QD
Other Names:
|
Experimental: B8: NR Grazoprevir 100 mg + Elbasvir 50 mg +RBV-12 wk GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight |
Drug: Grazoprevir
100 mg tablet orally QD
Other Names:
Drug: Elbasvir
Part A: 20 or 50 mg capsule orally QD Parts B, C, and D: 50 mg capsule orally QD
Other Names:
Drug: Ribavirin
Oral capsules BID at a total daily dose from 800 to 1400 mg based on participant weight
Other Names:
|
Experimental: B9: NR Grazoprevir 100 mg + Elbasvir 50 mg-12 wk GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks |
Drug: Grazoprevir
100 mg tablet orally QD
Other Names:
Drug: Elbasvir
Part A: 20 or 50 mg capsule orally QD Parts B, C, and D: 50 mg capsule orally QD
Other Names:
|
Experimental: B10: NR Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks, RBV capsules orally BID for 18 weeks at a total daily dose from 800 to 1400 mg based on participant weight |
Drug: Grazoprevir
100 mg tablet orally QD
Other Names:
Drug: Elbasvir
Part A: 20 or 50 mg capsule orally QD Parts B, C, and D: 50 mg capsule orally QD
Other Names:
Drug: Ribavirin
Oral capsules BID at a total daily dose from 800 to 1400 mg based on participant weight
Other Names:
|
Experimental: B11: NR Grazoprevir 100 mg + Elbasvir 50 mg-18 wk GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks |
Drug: Grazoprevir
100 mg tablet orally QD
Other Names:
Drug: Elbasvir
Part A: 20 or 50 mg capsule orally QD Parts B, C, and D: 50 mg capsule orally QD
Other Names:
|
Experimental: B12: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight |
Drug: Grazoprevir
100 mg tablet orally QD
Other Names:
Drug: Elbasvir
Part A: 20 or 50 mg capsule orally QD Parts B, C, and D: 50 mg capsule orally QD
Other Names:
Drug: Ribavirin
Oral capsules BID at a total daily dose from 800 to 1400 mg based on participant weight
Other Names:
|
Experimental: B13: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 mg-12 wk GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks |
Drug: Grazoprevir
100 mg tablet orally QD
Other Names:
Drug: Elbasvir
Part A: 20 or 50 mg capsule orally QD Parts B, C, and D: 50 mg capsule orally QD
Other Names:
|
Experimental: C1: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk GT1b participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks, Elbasvir 50 mg capsule orally QD for 8 weeks, and RBV capsules orally BID for 8 weeks at a total daily dose from 800 to 1400 mg based on participant weight. |
Drug: Grazoprevir
100 mg tablet orally QD
Other Names:
Drug: Elbasvir
Part A: 20 or 50 mg capsule orally QD Parts B, C, and D: 50 mg capsule orally QD
Other Names:
Drug: Ribavirin
Oral capsules BID at a total daily dose from 800 to 1400 mg based on participant weight
Other Names:
|
Experimental: C2: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 mg-8 wk GT1b participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks and Elbasvir 50 mg capsule orally QD for 8 weeks |
Drug: Grazoprevir
100 mg tablet orally QD
Other Names:
Drug: Elbasvir
Part A: 20 or 50 mg capsule orally QD Parts B, C, and D: 50 mg capsule orally QD
Other Names:
|
Experimental: D1: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk GT3 participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, and RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight |
Drug: Grazoprevir
100 mg tablet orally QD
Other Names:
Drug: Elbasvir
Part A: 20 or 50 mg capsule orally QD Parts B, C, and D: 50 mg capsule orally QD
Other Names:
Drug: Ribavirin
Oral capsules BID at a total daily dose from 800 to 1400 mg based on participant weight
Other Names:
|
Experimental: D2: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk GT3 participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks, and RBV capsules orally BID for 18 weeks at a total daily dose from 800 to 1400 mg based on participant weight |
Drug: Grazoprevir
100 mg tablet orally QD
Other Names:
Drug: Elbasvir
Part A: 20 or 50 mg capsule orally QD Parts B, C, and D: 50 mg capsule orally QD
Other Names:
Drug: Ribavirin
Oral capsules BID at a total daily dose from 800 to 1400 mg based on participant weight
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After the End of All Study Therapy (SVR12) [12 weeks after end of therapy (up to 30 weeks)]
Blood was drawn from each participant to assess Hepatitis C Virus ribonucleic acid (HCV RNA) plasma levels using the Roche COBAS™ Taqman™ HCV Test, v2.0 at various time points prior to, during, and after dosing. The Roche COBAS Taqman HCV Test, v2.0 assay (High Pure System) had a lower limit of quantification of 25 IU/mL and a limit of detection of 15.1 IU/mL (in plasma). SVR12 was defined as HCV RNA <25 IU/ml at 12 weeks after the end of all study therapy. 95% confidence intervals provided based on the Clopper-Pearson method.
- Percentage of Participants Experiencing at Least One Adverse Event (AE) During the Treatment Period and First 14 Follow-up Days [From Day 1 [post-dose] through 14 days following last dose of study drug (up to 20 weeks)]
An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding, for example), 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 which is temporally associated with the use of the SPONSOR's product, was also an AE.
- Percentage of Participants Discontinuing Study Therapy Due to an AE During the Treatment Period and First 14 Follow-up Days [From Day 1 [post-dose] through 14 days following last dose of study drug (up to 20 weeks)]
An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding, for example), 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 which is temporally associated with the use of the SPONSOR's product, was also an AE.
Secondary Outcome Measures
- Mean Time to First Achievement of Undetectable Hepatitis C Virus Ribonucleic Acid (HCV RNA) [From first dose of study medication until first achievement of undetectable HCV RNA (up to 18 weeks of treatment)]
Blood was drawn from each participant to assess HCV RNA plasma levels using the Roche COBAS™ Taqman™ HCV Test, v2.0 at various time points prior to, during, and after dosing. Kaplan Meier summary statistics were used to characterize the time to first achievement of undetectable HCV RNA.
- Percentage of Participants Achieving Undetectable HCV RNA at Week 2 [Week 2]
HCV-RNA levels in plasma were measured using the Roche COBAS™ Taqman™ HCV Test (v.2.0) on blood samples drawn from each participant during treatment at various time points prior to, during, and after dosing. Undetectable HCV RNA was defined as below the 15.1 IU/ml limit of detection. The percentage of participants achieving undetectable HCV RNA and accompanying 95% CIs were reported at TW2 for each treatment arm of the PP Population. 95% confidence intervals provided based on the Clopper-Pearson method.
- Percentage of Participants Achieving Undetectable HCV RNA at Week 4 [Week 4]
HCV-RNA levels in plasma were measured using the Roche COBAS™ Taqman™ HCV Test (v.2.0) on blood samples drawn from each participant during treatment at various time points prior to, during, and after dosing. Undetectable HCV RNA was defined as below the 15.1 IU/ml limit of detection. The percentage of participants achieving undetectable HCV RNA and accompanying 95% CIs were reported at TW4 for each treatment arm of the PP Population. 95% confidence intervals provided based on the Clopper-Pearson method.
- Percentage of Participants Achieving Undetectable HCV RNA at Week 12 [Week 12]
HCV-RNA levels in plasma were measured using the Roche COBAS™ Taqman™ HCV Test (v.2.0) on blood samples drawn from each participant during treatment at various time points prior to, during, and after dosing. Undetectable HCV RNA was defined as below the 15.1 IU/ml limit of detection. The percentage of participants achieving undetectable HCV RNA and accompanying 95% CIs were reported at TW12 for each treatment arm of the PP Population (as applicable). 95% confidence intervals provided based on the Clopper-Pearson method.
- Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 2 [Week 2]
HCV-RNA levels in plasma were measured using the Roche COBAS™ Taqman™ HCV Test (v.2.0) on blood samples drawn from each participant during treatment at various time points prior to, during, and after dosing. The Roche COBAS Taqman HCV Test, v2.0 assay (High Pure System) had a LLoQ of 25 IU/mL and a limit of detection of 15.1 IU/mL (in plasma). The percentage of participants achieving HCV RNA levels <25 IU/ml and accompanying 95% CIs were reported at TW2 for each treatment arm of the PP Population. 95% confidence intervals provided based on the Clopper-Pearson method.
- Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 4 [Week 4]
HCV-RNA levels in plasma were measured using the Roche COBAS™ Taqman™ HCV Test (v.2.0) on blood samples drawn from each participant during treatment at various time points prior to, during, and after dosing. The Roche COBAS Taqman HCV Test, v2.0 assay (High Pure System) had a LLoQ of 25 IU/mL and a limit of detection of 15.1 IU/mL (in plasma). The percentage of participants achieving HCV RNA levels <25 IU/ml and accompanying 95% CIs were reported at TW4 for each treatment arm of the PP Population. 95% confidence intervals provided based on the Clopper-Pearson method.
- Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 12 [Week 12]
HCV-RNA levels in plasma were measured using the Roche COBAS™ Taqman™ HCV Test (v.2.0) on blood samples drawn from each participant during treatment at various time points prior to, during, and after dosing. The Roche COBAS Taqman HCV Test, v2.0 assay (High Pure System) had a LLoQ of 25 IU/mL and a limit of detection of 15.1 IU/mL (in plasma). The percentage of participants achieving HCV RNA levels <25 IU/ml and accompanying 95% CIs were reported at TW12 for each treatment arm of the PP Population (as applicable). 95% confidence intervals provided based on the Clopper-Pearson method.
- Percentage of Participants Achieving Sustained Virologic Response 4 Weeks After the End of All Therapy (SVR4) [4 weeks after end of therapy (up to 22 weeks)]
Blood was drawn from each participant to assess Hepatitis C Virus ribonucleic acid (HCV RNA) plasma levels using the Roche COBAS™ Taqman™ HCV Test, v2.0 at various time points prior to, during, and after dosing. The Roche COBAS Taqman HCV Test, v2.0 assay (High Pure System) had a LLoQ of 25 IU/mL and a limit of detection of 15.1 IU/mL (in plasma). SVR4 was defined as HCV RNA <25 IU/ml at 4 weeks after the end of all study therapy. 95% confidence intervals provided based on the Clopper-Pearson method.
- Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After the End of All Study Therapy (SVR24) [24 weeks after end of therapy (up to 42 weeks)]
Blood was drawn from each participant to assess Hepatitis C Virus ribonucleic acid (HCV RNA) plasma levels using the Roche COBAS™ Taqman™ HCV Test, v2.0 at various time points prior to, during, and after dosing. The Roche COBAS Taqman HCV Test, v2.0 assay (High Pure System) had a LLoQ of 25 IU/mL and a limit of detection of 15.1 IU/mL (in plasma). SVR24 was defined as HCV RNA <25 IU/ml at 24 weeks after the end of all study therapy. 95% confidence intervals provided based on the Clopper-Pearson method.
Eligibility Criteria
Criteria
Inclusion criteria:
All participants
- CHC genotype 1 (GT1) virus infection (Parts A, B, and C) or GT3 virus infection (Part
- Female participants of childbearing potential or male participant with female partners of childbearing potential, must use two acceptable methods of birth control from ≥2 weeks prior to Day 1 until ≥6 months after last dose of study drug, or longer if dictated by local regulations
Part A - Absence (no medical history or physical findings) of ascites, bleeding esophageal varices, hepatic encephalopathy, or other signs or symptoms of advanced liver disease, or cirrhosis - No evidence of advanced fibrosis, cirrhosis and/or hepatocellular carcinoma by biopsy or noninvasive testing (FibroScan and/or FibroTest)
Parts B, C, and D
-
Treatment naïve with or without cirrhosis, or
-
Prior treatment failure to Peg-IFN/Ribavirin with or without cirrhosis, or
-
Co-infected with human immunodeficiency virus (HIV) without cirrhosis
-
Absence (no medical history or physical findings) of ascites, bleeding esophageal varices, hepatic encephalopathy, or other signs or symptoms of advanced liver disease
-
Liver disease staging assessment by liver biopsy or noninvasive testing (FibroScan and/or FibroTest)
Exclusion criteria:
All participants
-
Non-GT1 HCV infection (Part A, Part B, and Part C) or a non-GT3 HCV infection (Part D) including a mixed GT infection (with a non-GT1 [Part A, Part B, and Part C] or non-GT3 [Part D]) or a non-typeable genotype
-
Evidence of hepatocellular carcinoma (HCC) or is under evaluation for HCC
-
Currently participating or participated in a study with an investigational compound within 30 days of signing informed consent and is not willing to refrain from participating in another study
-
Diabetic and/or hypertensive with clinically significant ocular examination findings
-
History of depression associated with hospitalization for depression, electroconvulsive therapy, or resulting in prolonged absence from work and/or significant disruption of daily functions
-
Suicidal or homicidal ideations and/or attempt, or history of severe psychiatric disorders
-
Clinical diagnosis of substance abuse
-
Current history of seizure disorder, stroke, or transient ischemic attack
-
Immunologically mediated disease
-
Chronic pulmonary disease
-
Clinically significant cardiac abnormalities/dysfunction
-
Active clinical gout within the last year
-
Hemoglobinopathy or myelodysplastic syndromes
-
History of organ transplants including hematopoietic stem cell transplants
-
Poor venous access
-
Indwelling venous catheter
-
History of gastric surgery or malabsorption disorders
-
Severe concurrent disease
-
Evidence of active or suspected malignancy, or a history of malignancy, ≤5 years before
-
Pregnant, lactating, expecting to conceive or donate eggs
-
Male participant with pregnant female partner
-
Member/family member of the investigational study or sponsor staff directly involved with this study
-
Evidence or history of chronic hepatitis not caused by HCV
Part A
-
Not treatment-naïve
-
Documented to be HIV positive
-
Taking or planning to take significant inducers or inhibitors of CYP3A4 substrates or herbal supplements 2 weeks prior to start of study medications
Parts B, C, and D
-
Previously received any HCV direct-acting antivirals
-
Requiring, or likely to require, chronic systemic administration of corticosteroids during the course of the trial
-
For participants diagnosed with diabetes mellitus, documented HbA1c >8.5%
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Merck Sharp & Dohme LLC
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
- Lawitz E, Gane E, Pearlman B, Tam E, Ghesquiere W, Guyader D, Alric L, Bronowicki JP, Lester L, Sievert W, Ghalib R, Balart L, Sund F, Lagging M, Dutko F, Shaughnessy M, Hwang P, Howe AY, Wahl J, Robertson M, Barr E, Haber B. Efficacy and safety of 12 weeks versus 18 weeks of treatment with grazoprevir (MK-5172) and elbasvir (MK-8742) with or without ribavirin for hepatitis C virus genotype 1 infection in previously untreated patients with cirrhosis and patients with previous null response with or without cirrhosis (C-WORTHY): a randomised, open-label phase 2 trial. Lancet. 2015 Mar 21;385(9973):1075-86. doi: 10.1016/S0140-6736(14)61795-5. Epub 2014 Nov 11. Erratum in: Lancet. 2015 Mar 21;385(9973):1074.
- Sulkowski M, Hezode C, Gerstoft J, Vierling JM, Mallolas J, Pol S, Kugelmas M, Murillo A, Weis N, Nahass R, Shibolet O, Serfaty L, Bourliere M, DeJesus E, Zuckerman E, Dutko F, Shaughnessy M, Hwang P, Howe AY, Wahl J, Robertson M, Barr E, Haber B. Efficacy and safety of 8 weeks versus 12 weeks of treatment with grazoprevir (MK-5172) and elbasvir (MK-8742) with or without ribavirin in patients with hepatitis C virus genotype 1 mono-infection and HIV/hepatitis C virus co-infection (C-WORTHY): a randomised, open-label phase 2 trial. Lancet. 2015 Mar 21;385(9973):1087-97. doi: 10.1016/S0140-6736(14)61793-1. Epub 2014 Nov 11.
- 5172-035
- 2012-003354-89
Study Results
Participant Flow
Recruitment Details | Male/female participants with Hepatitis C Virus (HCV) genotype 1 (GT1) or GT3 who were either treatment-naïve (TN) or prior null responder (NR), cirrhotic (C) or noncirrhotic (NC), and monoinfected with HCV or coinfected with HCV and human immunodeficiency virus (HIV) were recruited based on entry requirements for Parts A, B, C, or D. |
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Pre-assignment Detail | 573 participants were randomized on study. 65 TN NC GT1 participants were randomized in Part A. Part B randomized 94 TN NC participants, 123 TN C participants, 130 NR participants (C and NC), and 59 TN HIV coinfected participants. Part C randomized 61 TN NC GT1b participants, and Part D randomized 41 TN NC GT3 participants. |
Arm/Group Title | A1: TN NC Grazoprevir 100 mg + Elbasvir 20 mg + RBV-12 wk | A2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | A3: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | B1: TN NC/GT1a Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | B2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | B3: TN NC/GT1a Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | B4: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | B5: TN C Grazoprevir 100 mg + Elbasvir 50 mg for 12 wk | B6: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk | B7: TN C Grazoprevir 100 mg + Elbasvir 50 Mg-18 wk | B8: NR Grazoprevir 100 mg + Elbasvir 50 mg +RBV-12 wk | B9: NR Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | B10: NR Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | B11: NR Grazoprevir 100 mg + Elbasvir 50 Mg-18 wk | B12: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | B13: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | C1: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | C2: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 Mg-8 wk | D1: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | D2: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Arm/Group Description | GT1a and GT1b participants receive Grazoprevir 100 mg tablet orally once daily (QD) for 12 weeks, Elbasvir 20 mg capsule and Placebo capsule orally QD for 12 weeks, RBV capsules orally twice daily (BID) for 24 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a and GT1b participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule and Placebo capsule orally QD for 12 weeks, RBV capsules orally BID for 24 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1b only participants receive Grazoprevr 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1a only participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks, Elbasvir 50 mg capsule orally QD for 8 weeks, RBV capsules orally BID for 8 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a only participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks, RBV capsules orally BID for 18 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks, Elbasvir 50 mg capsule orally QD for 8 weeks, RBV capsules orally BID for 8 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1b participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks, Elbasvir 50 mg capsule orally QD for 8 weeks, and RBV capsules orally BID for 8 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1b participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks and Elbasvir 50 mg capsule orally QD for 8 weeks. | GT3 participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, and RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT3 participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks, and RBV capsules orally BID for 18 weeks at a total daily dose from 800 to 1400 mg based on participant weight. |
Period Title: Overall Study | ||||||||||||||||||||
STARTED | 25 | 27 | 13 | 30 | 33 | 31 | 31 | 29 | 32 | 31 | 32 | 33 | 33 | 32 | 29 | 30 | 30 | 31 | 20 | 21 |
Treated | 25 | 28 | 12 | 30 | 33 | 31 | 31 | 29 | 32 | 31 | 32 | 33 | 33 | 32 | 29 | 30 | 30 | 31 | 20 | 21 |
COMPLETED | 22 | 26 | 13 | 28 | 31 | 31 | 30 | 29 | 32 | 29 | 30 | 33 | 32 | 32 | 29 | 27 | 29 | 31 | 16 | 15 |
NOT COMPLETED | 3 | 1 | 0 | 2 | 2 | 0 | 1 | 0 | 0 | 2 | 2 | 0 | 1 | 0 | 0 | 3 | 1 | 0 | 4 | 6 |
Baseline Characteristics
Arm/Group Title | A1: TN NC Grazoprevir 100 mg + Elbasvir 20 mg + RBV-12 wk | A2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | A3: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | B1: TN NC/GT1a Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | B2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | B3: TN NC/GT1a Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | B4: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | B5: TN C Grazoprevir 100 mg + Elbasvir 50 mg for 12 wk | B6: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk | B7: TN C Grazoprevir 100 mg + Elbasvir 50 Mg-18 wk | B8: NR Grazoprevir 100 mg + Elbasvir 50 mg +RBV-12 wk | B9: NR Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | B10: NR Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | B11: NR Grazoprevir 100 mg + Elbasvir 50 Mg-18 wk | B12: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | B13: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | C1: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | C2: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 Mg-8 wk | D1: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | D2: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk | Total |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Arm/Group Description | GT1a and GT1b participants receive Grazoprevir 100 mg tablet orally once daily (QD) for 12 weeks, Elbasvir 20 mg capsule and Placebo capsule orally QD for 12 weeks, RBV capsules orally twice daily (BID) for 24 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a and GT1b participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule and Placebo capsule orally QD for 12 weeks, RBV capsules orally BID for 24 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1b only participants receive Grazoprevr 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1a only participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks, Elbasvir 50 mg capsule orally QD for 8 weeks, RBV capsules orally BID for 8 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a only participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks, RBV capsules orally BID for 18 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks, Elbasvir 50 mg capsule orally QD for 8 weeks, RBV capsules orally BID for 8 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1b participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks, Elbasvir 50 mg capsule orally QD for 8 weeks, and RBV capsules orally BID for 8 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1b participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks and Elbasvir 50 mg capsule orally QD for 8 weeks. | GT3 participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, and RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT3 participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks, and RBV capsules orally BID for 18 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | Total of all reporting groups |
Overall Participants | 25 | 27 | 13 | 30 | 33 | 31 | 31 | 29 | 32 | 31 | 32 | 33 | 33 | 32 | 29 | 30 | 30 | 31 | 20 | 21 | 573 |
Age (years) [Mean (Standard Deviation) ] | |||||||||||||||||||||
Mean (Standard Deviation) [years] |
48.7
(12.5)
|
43.9
(12.6)
|
43.3
(13.5)
|
48.4
(11.9)
|
49.7
(11.5)
|
53.6
(8.4)
|
57.0
(7.0)
|
59.0
(7.8)
|
58.8
(8.2)
|
58.9
(8.0)
|
52.2
(8.8)
|
54.4
(9.1)
|
56.2
(10.9)
|
54.3
(12.3)
|
46.2
(8.4)
|
43.5
(10.4)
|
50.6
(10.9)
|
55.3
(10.3)
|
49.0
(11.5)
|
42.4
(10.8)
|
51.9
(11.3)
|
Sex: Female, Male (Count of Participants) | |||||||||||||||||||||
Female |
13
52%
|
17
63%
|
6
46.2%
|
12
40%
|
15
45.5%
|
15
48.4%
|
12
38.7%
|
10
34.5%
|
17
53.1%
|
10
32.3%
|
12
37.5%
|
13
39.4%
|
17
51.5%
|
14
43.8%
|
6
20.7%
|
6
20%
|
14
46.7%
|
18
58.1%
|
12
60%
|
13
61.9%
|
252
44%
|
Male |
12
48%
|
10
37%
|
7
53.8%
|
18
60%
|
18
54.5%
|
16
51.6%
|
19
61.3%
|
19
65.5%
|
15
46.9%
|
21
67.7%
|
20
62.5%
|
20
60.6%
|
16
48.5%
|
18
56.3%
|
23
79.3%
|
24
80%
|
16
53.3%
|
13
41.9%
|
8
40%
|
8
38.1%
|
321
56%
|
Outcome Measures
Title | Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After the End of All Study Therapy (SVR12) |
---|---|
Description | Blood was drawn from each participant to assess Hepatitis C Virus ribonucleic acid (HCV RNA) plasma levels using the Roche COBAS™ Taqman™ HCV Test, v2.0 at various time points prior to, during, and after dosing. The Roche COBAS Taqman HCV Test, v2.0 assay (High Pure System) had a lower limit of quantification of 25 IU/mL and a limit of detection of 15.1 IU/mL (in plasma). SVR12 was defined as HCV RNA <25 IU/ml at 12 weeks after the end of all study therapy. 95% confidence intervals provided based on the Clopper-Pearson method. |
Time Frame | 12 weeks after end of therapy (up to 30 weeks) |
Outcome Measure Data
Analysis Population Description |
---|
The Per-Protocol (PP) population; all randomized participants who received ≥1 dose of study treatment and without important protocol deviations who had data available at the respective time point. |
Arm/Group Title | A1: TN NC Grazoprevir 100 mg + Elbasvir 20 mg + RBV-12 wk | A2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | A3: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | B1: TN NC/GT1a Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | B2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | B3: TN NC/GT1a Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | B4: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | B5: TN C Grazoprevir 100 mg + Elbasvir 50 mg for 12 wk | B6: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk | B7: TN C Grazoprevir 100 mg + Elbasvir 50 Mg-18 wk | B8: NR Grazoprevir 100 mg + Elbasvir 50 mg +RBV-12 wk | B9: NR Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | B10: NR Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | B11: NR Grazoprevir 100 mg + Elbasvir 50 Mg-18 wk | B12: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | B13: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | C1: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | C2: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 Mg-8 wk | D1: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | D2: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Arm/Group Description | GT1a and GT1b participants receive Grazoprevir 100 mg tablet orally once daily (QD) for 12 weeks, Elbasvir 20 mg capsule and Placebo capsule orally QD for 12 weeks, RBV capsules orally twice daily (BID) for 24 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a and GT1b participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule and Placebo capsule orally QD for 12 weeks, RBV capsules orally BID for 24 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1b only participants receive Grazoprevr 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1a only participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks, Elbasvir 50 mg capsule orally QD for 8 weeks, RBV capsules orally BID for 8 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a only participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks, RBV capsules orally BID for 18 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks, Elbasvir 50 mg capsule orally QD for 8 weeks, RBV capsules orally BID for 8 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1b participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks, Elbasvir 50 mg capsule orally QD for 8 weeks, and RBV capsules orally BID for 8 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1b participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks and Elbasvir 50 mg capsule orally QD for 8 weeks. | GT3 participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, and RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT3 participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks, and RBV capsules orally BID for 18 weeks at a total daily dose from 800 to 1400 mg based on participant weight. |
Measure Participants | 22 | 24 | 12 | 29 | 29 | 31 | 30 | 29 | 31 | 31 | 30 | 33 | 33 | 32 | 29 | 28 | 29 | 31 | 19 | 18 |
Number (95% Confidence Interval) [percentage of participants] |
100.0
400%
|
95.8
354.8%
|
100.0
769.2%
|
82.8
276%
|
100.0
303%
|
96.8
312.3%
|
90.0
290.3%
|
96.6
333.1%
|
100.0
312.5%
|
93.5
301.6%
|
100.0
312.5%
|
90.9
275.5%
|
100.0
303%
|
96.9
302.8%
|
96.6
333.1%
|
92.9
309.7%
|
93.1
310.3%
|
93.5
301.6%
|
47.4
237%
|
61.1
291%
|
Title | Percentage of Participants Experiencing at Least One Adverse Event (AE) During the Treatment Period and First 14 Follow-up Days |
---|---|
Description | An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding, for example), 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 which is temporally associated with the use of the SPONSOR's product, was also an AE. |
Time Frame | From Day 1 [post-dose] through 14 days following last dose of study drug (up to 20 weeks) |
Outcome Measure Data
Analysis Population Description |
---|
All Participants as Treated (APaT) population; all randomized who received ≥1 dose of study treatment according to treatment actually received. One participant randomized to A3 arm was treated on A2 arm and thus was counted under the A2 arm (n=28). |
Arm/Group Title | A1: TN NC Grazoprevir 100 mg + Elbasvir 20 mg + RBV-12 wk | A2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | A3: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | B1: TN NC/GT1a Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | B2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | B3: TN NC/GT1a Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | B4: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | B5: TN C Grazoprevir 100 mg + Elbasvir 50 mg for 12 wk | B6: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk | B7: TN C Grazoprevir 100 mg + Elbasvir 50 Mg-18 wk | B8: NR Grazoprevir 100 mg + Elbasvir 50 mg +RBV-12 wk | B9: NR Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | B10: NR Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | B11: NR Grazoprevir 100 mg + Elbasvir 50 Mg-18 wk | B12: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | B13: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | C1: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | C2: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 Mg-8 wk | D1: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | D2: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Arm/Group Description | GT1a and GT1b participants receive Grazoprevir 100 mg tablet orally once daily (QD) for 12 weeks, Elbasvir 20 mg capsule and Placebo capsule orally QD for 12 weeks, RBV capsules orally twice daily (BID) for 24 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a and GT1b participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule and Placebo capsule orally QD for 12 weeks, RBV capsules orally BID for 24 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1b only participants receive Grazoprevr 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1a only participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks, Elbasvir 50 mg capsule orally QD for 8 weeks, RBV capsules orally BID for 8 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a only participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks, RBV capsules orally BID for 18 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks, Elbasvir 50 mg capsule orally QD for 8 weeks, RBV capsules orally BID for 8 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1b participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks, Elbasvir 50 mg capsule orally QD for 8 weeks, and RBV capsules orally BID for 8 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1b participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks and Elbasvir 50 mg capsule orally QD for 8 weeks. | GT3 participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, and RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT3 participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks, and RBV capsules orally BID for 18 weeks at a total daily dose from 800 to 1400 mg based on participant weight. |
Measure Participants | 25 | 28 | 12 | 30 | 33 | 31 | 31 | 29 | 32 | 31 | 32 | 33 | 33 | 32 | 29 | 30 | 30 | 31 | 20 | 21 |
Number (95% Confidence Interval) [percentage of participants] |
88.0
352%
|
85.7
317.4%
|
91.7
705.4%
|
90.0
300%
|
72.7
220.3%
|
87.1
281%
|
77.4
249.7%
|
65.5
225.9%
|
87.5
273.4%
|
83.9
270.6%
|
81.3
254.1%
|
78.8
238.8%
|
97.0
293.9%
|
81.3
254.1%
|
65.5
225.9%
|
53.3
177.7%
|
73.3
244.3%
|
54.8
176.8%
|
85.0
425%
|
90.5
431%
|
Title | Percentage of Participants Discontinuing Study Therapy Due to an AE During the Treatment Period and First 14 Follow-up Days |
---|---|
Description | An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding, for example), 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 which is temporally associated with the use of the SPONSOR's product, was also an AE. |
Time Frame | From Day 1 [post-dose] through 14 days following last dose of study drug (up to 20 weeks) |
Outcome Measure Data
Analysis Population Description |
---|
APaT population; all randomized who received ≥1 dose of study treatment according to treatment actually received. One participant randomized to A3 arm was treated on A2 arm and thus was counted under the A2 arm (n=28). |
Arm/Group Title | A1: TN NC Grazoprevir 100 mg + Elbasvir 20 mg + RBV-12 wk | A2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | A3: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | B1: TN NC/GT1a Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | B2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | B3: TN NC/GT1a Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | B4: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | B5: TN C Grazoprevir 100 mg + Elbasvir 50 mg for 12 wk | B6: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk | B7: TN C Grazoprevir 100 mg + Elbasvir 50 Mg-18 wk | B8: NR Grazoprevir 100 mg + Elbasvir 50 mg +RBV-12 wk | B9: NR Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | B10: NR Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | B11: NR Grazoprevir 100 mg + Elbasvir 50 Mg-18 wk | B12: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | B13: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | C1: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | C2: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 Mg-8 wk | D1: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | D2: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Arm/Group Description | GT1a and GT1b participants receive Grazoprevir 100 mg tablet orally once daily (QD) for 12 weeks, Elbasvir 20 mg capsule and Placebo capsule orally QD for 12 weeks, RBV capsules orally twice daily (BID) for 24 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a and GT1b participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule and Placebo capsule orally QD for 12 weeks, RBV capsules orally BID for 24 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1b only participants receive Grazoprevr 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1a only participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks, Elbasvir 50 mg capsule orally QD for 8 weeks, RBV capsules orally BID for 8 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a only participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks, RBV capsules orally BID for 18 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks, Elbasvir 50 mg capsule orally QD for 8 weeks, RBV capsules orally BID for 8 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1b participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks, Elbasvir 50 mg capsule orally QD for 8 weeks, and RBV capsules orally BID for 8 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1b participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks and Elbasvir 50 mg capsule orally QD for 8 weeks. | GT3 participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, and RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT3 participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks, and RBV capsules orally BID for 18 weeks at a total daily dose from 800 to 1400 mg based on participant weight. |
Measure Participants | 25 | 28 | 12 | 30 | 33 | 31 | 31 | 29 | 32 | 31 | 32 | 33 | 33 | 32 | 29 | 30 | 30 | 31 | 20 | 21 |
Number (95% Confidence Interval) [percentage of participants] |
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
6.3
19.7%
|
0.0
0%
|
3.1
9.7%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
4.8
22.9%
|
Title | Mean Time to First Achievement of Undetectable Hepatitis C Virus Ribonucleic Acid (HCV RNA) |
---|---|
Description | Blood was drawn from each participant to assess HCV RNA plasma levels using the Roche COBAS™ Taqman™ HCV Test, v2.0 at various time points prior to, during, and after dosing. Kaplan Meier summary statistics were used to characterize the time to first achievement of undetectable HCV RNA. |
Time Frame | From first dose of study medication until first achievement of undetectable HCV RNA (up to 18 weeks of treatment) |
Outcome Measure Data
Analysis Population Description |
---|
FAS; all randomized participants who received ≥1 dose of study treatment. |
Arm/Group Title | A1: TN NC Grazoprevir 100 mg + Elbasvir 20 mg + RBV-12 wk | A2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | A3: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | B1: TN NC/GT1a Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | B2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | B3: TN NC/GT1a Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | B4: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | B5: TN C Grazoprevir 100 mg + Elbasvir 50 mg for 12 wk | B6: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk | B7: TN C Grazoprevir 100 mg + Elbasvir 50 Mg-18 wk | B8: NR Grazoprevir 100 mg + Elbasvir 50 mg +RBV-12 wk | B9: NR Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | B10: NR Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | B11: NR Grazoprevir 100 mg + Elbasvir 50 Mg-18 wk | B12: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | B13: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | C1: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | C2: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 Mg-8 wk | D1: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | D2: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Arm/Group Description | GT1a and GT1b participants receive Grazoprevir 100 mg tablet orally once daily (QD) for 12 weeks, Elbasvir 20 mg capsule and Placebo capsule orally QD for 12 weeks, RBV capsules orally twice daily (BID) for 24 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a and GT1b participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule and Placebo capsule orally QD for 12 weeks, RBV capsules orally BID for 24 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1b only participants receive Grazoprevr 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1a only participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks, Elbasvir 50 mg capsule orally QD for 8 weeks, RBV capsules orally BID for 8 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a only participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks, RBV capsules orally BID for 18 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks, Elbasvir 50 mg capsule orally QD for 8 weeks, RBV capsules orally BID for 8 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1b participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks, Elbasvir 50 mg capsule orally QD for 8 weeks, and RBV capsules orally BID for 8 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1b participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks and Elbasvir 50 mg capsule orally QD for 8 weeks. | GT3 participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, and RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT3 participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks, and RBV capsules orally BID for 18 weeks at a total daily dose from 800 to 1400 mg based on participant weight. |
Measure Participants | 25 | 27 | 13 | 30 | 33 | 31 | 31 | 29 | 32 | 31 | 32 | 33 | 33 | 32 | 29 | 30 | 30 | 31 | 20 | 21 |
Mean (Standard Error) [days] |
21.7
(2.2)
|
19.2
(1.8)
|
23.4
(2.9)
|
27.9
(3.0)
|
30.7
(2.3)
|
32.0
(3.0)
|
37.0
(2.8)
|
33.2
(2.4)
|
33.1
(2.8)
|
33.7
(2.6)
|
31.9
(2.2)
|
37.4
(2.5)
|
37.4
(2.7)
|
42.7
(3.3)
|
27.6
(3.0)
|
29.0
(2.9)
|
23.7
(2.1)
|
34.5
(2.6)
|
30.1
(3.7)
|
19.8
(2.3)
|
Title | Percentage of Participants Achieving Undetectable HCV RNA at Week 2 |
---|---|
Description | HCV-RNA levels in plasma were measured using the Roche COBAS™ Taqman™ HCV Test (v.2.0) on blood samples drawn from each participant during treatment at various time points prior to, during, and after dosing. Undetectable HCV RNA was defined as below the 15.1 IU/ml limit of detection. The percentage of participants achieving undetectable HCV RNA and accompanying 95% CIs were reported at TW2 for each treatment arm of the PP Population. 95% confidence intervals provided based on the Clopper-Pearson method. |
Time Frame | Week 2 |
Outcome Measure Data
Analysis Population Description |
---|
The PP population; all randomized participants who received ≥1 dose of study treatment and without important protocol deviations who had data available at the respective time point. |
Arm/Group Title | A1: TN NC Grazoprevir 100 mg + Elbasvir 20 mg + RBV-12 wk | A2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | A3: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | B1: TN NC/GT1a Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | B2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | B3: TN NC/GT1a Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | B4: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | B5: TN C Grazoprevir 100 mg + Elbasvir 50 mg for 12 wk | B6: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk | B7: TN C Grazoprevir 100 mg + Elbasvir 50 Mg-18 wk | B8: NR Grazoprevir 100 mg + Elbasvir 50 mg +RBV-12 wk | B9: NR Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | B10: NR Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | B11: NR Grazoprevir 100 mg + Elbasvir 50 Mg-18 wk | B12: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | B13: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | C1: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | C2: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 Mg-8 wk | D1: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | D2: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Arm/Group Description | GT1a and GT1b participants receive Grazoprevir 100 mg tablet orally once daily (QD) for 12 weeks, Elbasvir 20 mg capsule and Placebo capsule orally QD for 12 weeks, RBV capsules orally twice daily (BID) for 24 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a and GT1b participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule and Placebo capsule orally QD for 12 weeks, RBV capsules orally BID for 24 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1b only participants receive Grazoprevr 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1a only participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks, Elbasvir 50 mg capsule orally QD for 8 weeks, RBV capsules orally BID for 8 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a only participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks, RBV capsules orally BID for 18 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks, Elbasvir 50 mg capsule orally QD for 8 weeks, RBV capsules orally BID for 8 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1b participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks, Elbasvir 50 mg capsule orally QD for 8 weeks, and RBV capsules orally BID for 8 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1b participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks and Elbasvir 50 mg capsule orally QD for 8 weeks. | GT3 participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, and RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT3 participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks, and RBV capsules orally BID for 18 weeks at a total daily dose from 800 to 1400 mg based on participant weight. |
Measure Participants | 23 | 25 | 12 | 29 | 30 | 31 | 30 | 29 | 32 | 31 | 31 | 33 | 33 | 32 | 29 | 30 | 30 | 31 | 20 | 20 |
Number (95% Confidence Interval) [percentage of participants] |
52.2
208.8%
|
44.0
163%
|
41.7
320.8%
|
44.8
149.3%
|
20.0
60.6%
|
16.1
51.9%
|
6.7
21.6%
|
10.3
35.5%
|
25.0
78.1%
|
16.1
51.9%
|
12.9
40.3%
|
6.1
18.5%
|
6.1
18.5%
|
6.3
19.7%
|
37.9
130.7%
|
40.0
133.3%
|
46.7
155.7%
|
12.9
41.6%
|
40.0
200%
|
70.0
333.3%
|
Title | Percentage of Participants Achieving Undetectable HCV RNA at Week 4 |
---|---|
Description | HCV-RNA levels in plasma were measured using the Roche COBAS™ Taqman™ HCV Test (v.2.0) on blood samples drawn from each participant during treatment at various time points prior to, during, and after dosing. Undetectable HCV RNA was defined as below the 15.1 IU/ml limit of detection. The percentage of participants achieving undetectable HCV RNA and accompanying 95% CIs were reported at TW4 for each treatment arm of the PP Population. 95% confidence intervals provided based on the Clopper-Pearson method. |
Time Frame | Week 4 |
Outcome Measure Data
Analysis Population Description |
---|
The PP population; all randomized participants who received ≥1 dose of study treatment and without important protocol deviations who had data available at the respective time point. |
Arm/Group Title | A1: TN NC Grazoprevir 100 mg + Elbasvir 20 mg + RBV-12 wk | A2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | A3: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | B1: TN NC/GT1a Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | B2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | B3: TN NC/GT1a Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | B4: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | B5: TN C Grazoprevir 100 mg + Elbasvir 50 mg for 12 wk | B6: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk | B7: TN C Grazoprevir 100 mg + Elbasvir 50 Mg-18 wk | B8: NR Grazoprevir 100 mg + Elbasvir 50 mg +RBV-12 wk | B9: NR Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | B10: NR Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | B11: NR Grazoprevir 100 mg + Elbasvir 50 Mg-18 wk | B12: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | B13: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | C1: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | C2: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 Mg-8 wk | D1: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | D2: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Arm/Group Description | GT1a and GT1b participants receive Grazoprevir 100 mg tablet orally once daily (QD) for 12 weeks, Elbasvir 20 mg capsule and Placebo capsule orally QD for 12 weeks, RBV capsules orally twice daily (BID) for 24 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a and GT1b participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule and Placebo capsule orally QD for 12 weeks, RBV capsules orally BID for 24 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1b only participants receive Grazoprevr 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1a only participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks, Elbasvir 50 mg capsule orally QD for 8 weeks, RBV capsules orally BID for 8 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a only participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks, RBV capsules orally BID for 18 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks, Elbasvir 50 mg capsule orally QD for 8 weeks, RBV capsules orally BID for 8 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1b participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks, Elbasvir 50 mg capsule orally QD for 8 weeks, and RBV capsules orally BID for 8 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1b participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks and Elbasvir 50 mg capsule orally QD for 8 weeks. | GT3 participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, and RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT3 participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks, and RBV capsules orally BID for 18 weeks at a total daily dose from 800 to 1400 mg based on participant weight. |
Measure Participants | 23 | 24 | 12 | 30 | 30 | 31 | 30 | 29 | 32 | 31 | 30 | 32 | 33 | 32 | 29 | 28 | 30 | 31 | 20 | 18 |
Number (95% Confidence Interval) [percentage of participants] |
73.9
295.6%
|
91.7
339.6%
|
75.0
576.9%
|
73.3
244.3%
|
83.3
252.4%
|
77.4
249.7%
|
60.0
193.5%
|
79.3
273.4%
|
71.9
224.7%
|
71.0
229%
|
83.3
260.3%
|
68.8
208.5%
|
69.7
211.2%
|
53.1
165.9%
|
75.9
261.7%
|
78.6
262%
|
86.7
289%
|
74.2
239.4%
|
50.0
250%
|
77.8
370.5%
|
Title | Percentage of Participants Achieving Undetectable HCV RNA at Week 12 |
---|---|
Description | HCV-RNA levels in plasma were measured using the Roche COBAS™ Taqman™ HCV Test (v.2.0) on blood samples drawn from each participant during treatment at various time points prior to, during, and after dosing. Undetectable HCV RNA was defined as below the 15.1 IU/ml limit of detection. The percentage of participants achieving undetectable HCV RNA and accompanying 95% CIs were reported at TW12 for each treatment arm of the PP Population (as applicable). 95% confidence intervals provided based on the Clopper-Pearson method. |
Time Frame | Week 12 |
Outcome Measure Data
Analysis Population Description |
---|
The PP population; all randomized participants who received ≥1 dose of study treatment and without important protocol deviations who had data available at the respective time point. The B1, C1, and C2 arms only received 8 weeks of treatment and were thus excluded from this analysis. |
Arm/Group Title | A1: TN NC Grazoprevir 100 mg + Elbasvir 20 mg + RBV-12 wk | A2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | A3: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | B1: TN NC/GT1a Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | B2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | B3: TN NC/GT1a Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | B4: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | B5: TN C Grazoprevir 100 mg + Elbasvir 50 mg for 12 wk | B6: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk | B7: TN C Grazoprevir 100 mg + Elbasvir 50 Mg-18 wk | B8: NR Grazoprevir 100 mg + Elbasvir 50 mg +RBV-12 wk | B9: NR Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | B10: NR Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | B11: NR Grazoprevir 100 mg + Elbasvir 50 Mg-18 wk | B12: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | B13: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | C1: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | C2: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 Mg-8 wk | D1: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | D2: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Arm/Group Description | GT1a and GT1b participants receive Grazoprevir 100 mg tablet orally once daily (QD) for 12 weeks, Elbasvir 20 mg capsule and Placebo capsule orally QD for 12 weeks, RBV capsules orally twice daily (BID) for 24 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a and GT1b participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule and Placebo capsule orally QD for 12 weeks, RBV capsules orally BID for 24 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1b only participants receive Grazoprevr 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1a only participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks, Elbasvir 50 mg capsule orally QD for 8 weeks, RBV capsules orally BID for 8 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a only participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks, RBV capsules orally BID for 18 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks, Elbasvir 50 mg capsule orally QD for 8 weeks, RBV capsules orally BID for 8 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1b participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks, Elbasvir 50 mg capsule orally QD for 8 weeks, and RBV capsules orally BID for 8 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1b participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks and Elbasvir 50 mg capsule orally QD for 8 weeks. | GT3 participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, and RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT3 participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks, and RBV capsules orally BID for 18 weeks at a total daily dose from 800 to 1400 mg based on participant weight. |
Measure Participants | 22 | 24 | 12 | 0 | 29 | 31 | 30 | 29 | 31 | 31 | 30 | 32 | 33 | 32 | 29 | 28 | 0 | 0 | 19 | 20 |
Number (95% Confidence Interval) [percentage of participants] |
100.0
400%
|
100.0
370.4%
|
100.0
769.2%
|
100.0
333.3%
|
100.0
303%
|
93.3
301%
|
96.6
311.6%
|
100.0
344.8%
|
100.0
312.5%
|
100.0
322.6%
|
93.8
293.1%
|
100.0
303%
|
96.9
293.6%
|
93.1
290.9%
|
92.9
320.3%
|
47.7
159%
|
65.0
216.7%
|
Title | Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 2 |
---|---|
Description | HCV-RNA levels in plasma were measured using the Roche COBAS™ Taqman™ HCV Test (v.2.0) on blood samples drawn from each participant during treatment at various time points prior to, during, and after dosing. The Roche COBAS Taqman HCV Test, v2.0 assay (High Pure System) had a LLoQ of 25 IU/mL and a limit of detection of 15.1 IU/mL (in plasma). The percentage of participants achieving HCV RNA levels <25 IU/ml and accompanying 95% CIs were reported at TW2 for each treatment arm of the PP Population. 95% confidence intervals provided based on the Clopper-Pearson method. |
Time Frame | Week 2 |
Outcome Measure Data
Analysis Population Description |
---|
The PP population; all randomized participants who received ≥1 dose of study treatment and without important protocol deviations who had data available at the respective time point. |
Arm/Group Title | A1: TN NC Grazoprevir 100 mg + Elbasvir 20 mg + RBV-12 wk | A2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | A3: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | B1: TN NC/GT1a Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | B2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | B3: TN NC/GT1a Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | B4: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | B5: TN C Grazoprevir 100 mg + Elbasvir 50 mg for 12 wk | B6: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk | B7: TN C Grazoprevir 100 mg + Elbasvir 50 Mg-18 wk | B8: NR Grazoprevir 100 mg + Elbasvir 50 mg +RBV-12 wk | B9: NR Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | B10: NR Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | B11: NR Grazoprevir 100 mg + Elbasvir 50 Mg-18 wk | B12: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | B13: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | C1: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | C2: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 Mg-8 wk | D1: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | D2: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Arm/Group Description | GT1a and GT1b participants receive Grazoprevir 100 mg tablet orally once daily (QD) for 12 weeks, Elbasvir 20 mg capsule and Placebo capsule orally QD for 12 weeks, RBV capsules orally twice daily (BID) for 24 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a and GT1b participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule and Placebo capsule orally QD for 12 weeks, RBV capsules orally BID for 24 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1b only participants receive Grazoprevr 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1a only participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks, Elbasvir 50 mg capsule orally QD for 8 weeks, RBV capsules orally BID for 8 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a only participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks, RBV capsules orally BID for 18 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks, Elbasvir 50 mg capsule orally QD for 8 weeks, RBV capsules orally BID for 8 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1b participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks, Elbasvir 50 mg capsule orally QD for 8 weeks, and RBV capsules orally BID for 8 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1b participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks and Elbasvir 50 mg capsule orally QD for 8 weeks. | GT3 participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, and RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT3 participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks, and RBV capsules orally BID for 18 weeks at a total daily dose from 800 to 1400 mg based on participant weight. |
Measure Participants | 23 | 25 | 12 | 29 | 30 | 31 | 30 | 29 | 32 | 31 | 31 | 33 | 33 | 32 | 29 | 30 | 30 | 31 | 20 | 20 |
Number (95% Confidence Interval) [percentage of participants] |
91.3
365.2%
|
92.0
340.7%
|
91.7
705.4%
|
86.2
287.3%
|
73.3
222.1%
|
77.4
249.7%
|
60.0
193.5%
|
79.3
273.4%
|
78.1
244.1%
|
67.7
218.4%
|
77.4
241.9%
|
66.7
202.1%
|
57.6
174.5%
|
62.5
195.3%
|
89.7
309.3%
|
76.7
255.7%
|
76.7
255.7%
|
61.3
197.7%
|
70.0
350%
|
85.0
404.8%
|
Title | Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 4 |
---|---|
Description | HCV-RNA levels in plasma were measured using the Roche COBAS™ Taqman™ HCV Test (v.2.0) on blood samples drawn from each participant during treatment at various time points prior to, during, and after dosing. The Roche COBAS Taqman HCV Test, v2.0 assay (High Pure System) had a LLoQ of 25 IU/mL and a limit of detection of 15.1 IU/mL (in plasma). The percentage of participants achieving HCV RNA levels <25 IU/ml and accompanying 95% CIs were reported at TW4 for each treatment arm of the PP Population. 95% confidence intervals provided based on the Clopper-Pearson method. |
Time Frame | Week 4 |
Outcome Measure Data
Analysis Population Description |
---|
The PP population; all randomized participants who received ≥1 dose of study treatment and without important protocol deviations who had data available at the respective time point. |
Arm/Group Title | A1: TN NC Grazoprevir 100 mg + Elbasvir 20 mg + RBV-12 wk | A2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | A3: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | B1: TN NC/GT1a Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | B2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | B3: TN NC/GT1a Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | B4: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | B5: TN C Grazoprevir 100 mg + Elbasvir 50 mg for 12 wk | B6: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk | B7: TN C Grazoprevir 100 mg + Elbasvir 50 Mg-18 wk | B8: NR Grazoprevir 100 mg + Elbasvir 50 mg +RBV-12 wk | B9: NR Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | B10: NR Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | B11: NR Grazoprevir 100 mg + Elbasvir 50 Mg-18 wk | B12: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | B13: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | C1: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | C2: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 Mg-8 wk | D1: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | D2: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Arm/Group Description | GT1a and GT1b participants receive Grazoprevir 100 mg tablet orally once daily (QD) for 12 weeks, Elbasvir 20 mg capsule and Placebo capsule orally QD for 12 weeks, RBV capsules orally twice daily (BID) for 24 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a and GT1b participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule and Placebo capsule orally QD for 12 weeks, RBV capsules orally BID for 24 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1b only participants receive Grazoprevr 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1a only participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks, Elbasvir 50 mg capsule orally QD for 8 weeks, RBV capsules orally BID for 8 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a only participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks, RBV capsules orally BID for 18 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks, Elbasvir 50 mg capsule orally QD for 8 weeks, RBV capsules orally BID for 8 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1b participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks, Elbasvir 50 mg capsule orally QD for 8 weeks, and RBV capsules orally BID for 8 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1b participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks and Elbasvir 50 mg capsule orally QD for 8 weeks. | GT3 participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, and RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT3 participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks, and RBV capsules orally BID for 18 weeks at a total daily dose from 800 to 1400 mg based on participant weight. |
Measure Participants | 23 | 24 | 12 | 30 | 30 | 31 | 30 | 29 | 32 | 31 | 30 | 32 | 33 | 32 | 29 | 28 | 30 | 31 | 20 | 18 |
Number (95% Confidence Interval) [percentage of participants] |
100.0
400%
|
100.0
370.4%
|
100.0
769.2%
|
100.0
333.3%
|
100.0
303%
|
100.0
322.6%
|
90.0
290.3%
|
100.0
344.8%
|
100.0
312.5%
|
90.3
291.3%
|
100.0
312.5%
|
96.9
293.6%
|
97.0
293.9%
|
93.8
293.1%
|
100.0
344.8%
|
100.0
333.3%
|
100.0
333.3%
|
96.8
312.3%
|
65.0
325%
|
83.3
396.7%
|
Title | Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 12 |
---|---|
Description | HCV-RNA levels in plasma were measured using the Roche COBAS™ Taqman™ HCV Test (v.2.0) on blood samples drawn from each participant during treatment at various time points prior to, during, and after dosing. The Roche COBAS Taqman HCV Test, v2.0 assay (High Pure System) had a LLoQ of 25 IU/mL and a limit of detection of 15.1 IU/mL (in plasma). The percentage of participants achieving HCV RNA levels <25 IU/ml and accompanying 95% CIs were reported at TW12 for each treatment arm of the PP Population (as applicable). 95% confidence intervals provided based on the Clopper-Pearson method. |
Time Frame | Week 12 |
Outcome Measure Data
Analysis Population Description |
---|
The PP population; all randomized participants who received ≥1 dose of study treatment and without important protocol deviations who had data available at the respective time point. The B1, C1, and C2 arms only received 8 weeks of treatment and were thus excluded from this analysis. |
Arm/Group Title | A1: TN NC Grazoprevir 100 mg + Elbasvir 20 mg + RBV-12 wk | A2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | A3: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | B1: TN NC/GT1a Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | B2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | B3: TN NC/GT1a Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | B4: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | B5: TN C Grazoprevir 100 mg + Elbasvir 50 mg for 12 wk | B6: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk | B7: TN C Grazoprevir 100 mg + Elbasvir 50 Mg-18 wk | B8: NR Grazoprevir 100 mg + Elbasvir 50 mg +RBV-12 wk | B9: NR Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | B10: NR Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | B11: NR Grazoprevir 100 mg + Elbasvir 50 Mg-18 wk | B12: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | B13: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | C1: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | C2: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 Mg-8 wk | D1: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | D2: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Arm/Group Description | GT1a and GT1b participants receive Grazoprevir 100 mg tablet orally once daily (QD) for 12 weeks, Elbasvir 20 mg capsule and Placebo capsule orally QD for 12 weeks, RBV capsules orally twice daily (BID) for 24 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a and GT1b participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule and Placebo capsule orally QD for 12 weeks, RBV capsules orally BID for 24 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1b only participants receive Grazoprevr 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1a only participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks, Elbasvir 50 mg capsule orally QD for 8 weeks, RBV capsules orally BID for 8 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a only participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks, RBV capsules orally BID for 18 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks, Elbasvir 50 mg capsule orally QD for 8 weeks, RBV capsules orally BID for 8 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1b participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks, Elbasvir 50 mg capsule orally QD for 8 weeks, and RBV capsules orally BID for 8 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1b participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks and Elbasvir 50 mg capsule orally QD for 8 weeks. | GT3 participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, and RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT3 participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks, and RBV capsules orally BID for 18 weeks at a total daily dose from 800 to 1400 mg based on participant weight. |
Measure Participants | 22 | 24 | 12 | 0 | 29 | 31 | 30 | 29 | 31 | 31 | 30 | 32 | 33 | 32 | 29 | 28 | 0 | 0 | 19 | 20 |
Number (95% Confidence Interval) [percentage of participants] |
100.0
400%
|
100.0
370.4%
|
100.0
769.2%
|
100.0
333.3%
|
100.0
303%
|
93.3
301%
|
100.0
322.6%
|
100.0
344.8%
|
100.0
312.5%
|
100.0
322.6%
|
100.0
312.5%
|
100.0
303%
|
96.9
293.6%
|
100.0
312.5%
|
92.9
320.3%
|
47.4
158%
|
75.0
250%
|
Title | Percentage of Participants Achieving Sustained Virologic Response 4 Weeks After the End of All Therapy (SVR4) |
---|---|
Description | Blood was drawn from each participant to assess Hepatitis C Virus ribonucleic acid (HCV RNA) plasma levels using the Roche COBAS™ Taqman™ HCV Test, v2.0 at various time points prior to, during, and after dosing. The Roche COBAS Taqman HCV Test, v2.0 assay (High Pure System) had a LLoQ of 25 IU/mL and a limit of detection of 15.1 IU/mL (in plasma). SVR4 was defined as HCV RNA <25 IU/ml at 4 weeks after the end of all study therapy. 95% confidence intervals provided based on the Clopper-Pearson method. |
Time Frame | 4 weeks after end of therapy (up to 22 weeks) |
Outcome Measure Data
Analysis Population Description |
---|
The PP population; all randomized participants who received ≥1 dose of study treatment and without important protocol deviations who had data available at the respective time point. |
Arm/Group Title | A1: TN NC Grazoprevir 100 mg + Elbasvir 20 mg + RBV-12 wk | A2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | A3: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | B1: TN NC/GT1a Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | B2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | B3: TN NC/GT1a Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | B4: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | B5: TN C Grazoprevir 100 mg + Elbasvir 50 mg for 12 wk | B6: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk | B7: TN C Grazoprevir 100 mg + Elbasvir 50 Mg-18 wk | B8: NR Grazoprevir 100 mg + Elbasvir 50 mg +RBV-12 wk | B9: NR Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | B10: NR Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | B11: NR Grazoprevir 100 mg + Elbasvir 50 Mg-18 wk | B12: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | B13: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | C1: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | C2: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 Mg-8 wk | D1: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | D2: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Arm/Group Description | GT1a and GT1b participants receive Grazoprevir 100 mg tablet orally once daily (QD) for 12 weeks, Elbasvir 20 mg capsule and Placebo capsule orally QD for 12 weeks, RBV capsules orally twice daily (BID) for 24 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a and GT1b participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule and Placebo capsule orally QD for 12 weeks, RBV capsules orally BID for 24 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1b only participants receive Grazoprevr 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1a only participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks, Elbasvir 50 mg capsule orally QD for 8 weeks, RBV capsules orally BID for 8 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a only participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks, RBV capsules orally BID for 18 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks, Elbasvir 50 mg capsule orally QD for 8 weeks, RBV capsules orally BID for 8 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1b participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks, Elbasvir 50 mg capsule orally QD for 8 weeks, and RBV capsules orally BID for 8 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1b participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks and Elbasvir 50 mg capsule orally QD for 8 weeks. | GT3 participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, and RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT3 participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks, and RBV capsules orally BID for 18 weeks at a total daily dose from 800 to 1400 mg based on participant weight. |
Measure Participants | 22 | 24 | 12 | 30 | 29 | 31 | 30 | 29 | 31 | 31 | 30 | 33 | 33 | 32 | 29 | 29 | 29 | 31 | 20 | 18 |
Number (95% Confidence Interval) [percentage of participants] |
100.0
400%
|
95.8
354.8%
|
100.0
769.2%
|
93.3
311%
|
100.0
303%
|
96.8
312.3%
|
96.7
311.9%
|
96.6
333.1%
|
100.0
312.5%
|
96.8
312.3%
|
100.0
312.5%
|
93.9
284.5%
|
100.0
303%
|
96.9
302.8%
|
96.6
333.1%
|
93.1
310.3%
|
93.1
310.3%
|
96.8
312.3%
|
50.0
250%
|
61.1
291%
|
Title | Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After the End of All Study Therapy (SVR24) |
---|---|
Description | Blood was drawn from each participant to assess Hepatitis C Virus ribonucleic acid (HCV RNA) plasma levels using the Roche COBAS™ Taqman™ HCV Test, v2.0 at various time points prior to, during, and after dosing. The Roche COBAS Taqman HCV Test, v2.0 assay (High Pure System) had a LLoQ of 25 IU/mL and a limit of detection of 15.1 IU/mL (in plasma). SVR24 was defined as HCV RNA <25 IU/ml at 24 weeks after the end of all study therapy. 95% confidence intervals provided based on the Clopper-Pearson method. |
Time Frame | 24 weeks after end of therapy (up to 42 weeks) |
Outcome Measure Data
Analysis Population Description |
---|
The PP population; all randomized participants who received ≥1 dose of study treatment and without important protocol deviations who had data available at the respective time point. |
Arm/Group Title | A1: TN NC Grazoprevir 100 mg + Elbasvir 20 mg + RBV-12 wk | A2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | A3: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | B1: TN NC/GT1a Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | B2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | B3: TN NC/GT1a Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | B4: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | B5: TN C Grazoprevir 100 mg + Elbasvir 50 mg for 12 wk | B6: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk | B7: TN C Grazoprevir 100 mg + Elbasvir 50 Mg-18 wk | B8: NR Grazoprevir 100 mg + Elbasvir 50 mg +RBV-12 wk | B9: NR Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | B10: NR Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | B11: NR Grazoprevir 100 mg + Elbasvir 50 Mg-18 wk | B12: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | B13: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | C1: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | C2: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 Mg-8 wk | D1: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | D2: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Arm/Group Description | GT1a and GT1b participants receive Grazoprevir 100 mg tablet orally once daily (QD) for 12 weeks, Elbasvir 20 mg capsule and Placebo capsule orally QD for 12 weeks, RBV capsules orally twice daily (BID) for 24 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a and GT1b participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule and Placebo capsule orally QD for 12 weeks, RBV capsules orally BID for 24 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1b only participants receive Grazoprevr 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1a only participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks, Elbasvir 50 mg capsule orally QD for 8 weeks, RBV capsules orally BID for 8 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a only participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks, RBV capsules orally BID for 18 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks, Elbasvir 50 mg capsule orally QD for 8 weeks, RBV capsules orally BID for 8 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1b participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks, Elbasvir 50 mg capsule orally QD for 8 weeks, and RBV capsules orally BID for 8 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1b participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks and Elbasvir 50 mg capsule orally QD for 8 weeks. | GT3 participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, and RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT3 participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks, and RBV capsules orally BID for 18 weeks at a total daily dose from 800 to 1400 mg based on participant weight. |
Measure Participants | 20 | 24 | 12 | 28 | 29 | 31 | 30 | 29 | 31 | 29 | 29 | 33 | 32 | 32 | 29 | 27 | 29 | 31 | 19 | 17 |
Number (95% Confidence Interval) [percentage of participants] |
100.0
400%
|
95.8
354.8%
|
100.0
769.2%
|
78.6
262%
|
100.0
303%
|
96.8
312.3%
|
90.0
290.3%
|
96.6
333.1%
|
100.0
312.5%
|
93.1
300.3%
|
100.0
312.5%
|
90.9
275.5%
|
100.0
303%
|
96.9
302.8%
|
96.6
333.1%
|
88.9
296.3%
|
93.1
310.3%
|
93.5
301.6%
|
47.4
237%
|
58.8
280%
|
Adverse Events
Time Frame | Treatment and Follow-up periods (up to 42 weeks) | |||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Adverse Event Reporting Description | All Participants as Treated (APaT) population; all randomized who received ≥1 dose of study treatment according to treatment actually received. One participant randomized to A3 arm was treated on A2 arm and thus was counted under the A2 arm (n=28). | |||||||||||||||||||||||||||||||||||||||
Arm/Group Title | A1: TN NC Grazoprevir 100 mg + Elbasvir 20 mg + RBV-12 wk | A2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | A3: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | B1: TN NC/GT1a Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | B2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | B3: TN NC/GT1a Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | B4: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | B5: TN C Grazoprevir 100 mg + Elbasvir 50 mg for 12 wk | B6: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk | B7: TN C Grazoprevir 100 mg + Elbasvir 50 Mg-18 wk | B8: NR Grazoprevir 100 mg + Elbasvir 50 mg +RBV-12 wk | B9: NR Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | B10: NR Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | B11: NR Grazoprevir 100 mg + Elbasvir 50 Mg-18 wk | B12: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | B13: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | C1: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | C2: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 Mg-8 wk | D1: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | D2: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk | ||||||||||||||||||||
Arm/Group Description | GT1a and GT1b participants receive Grazoprevir 100 mg tablet orally once daily (QD) for 12 weeks, Elbasvir 20 mg capsule and Placebo capsule orally QD for 12 weeks, RBV capsules orally twice daily (BID) for 24 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a and GT1b participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule and Placebo capsule orally QD for 12 weeks, RBV capsules orally BID for 24 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1b only participants receive Grazoprevr 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1a only participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks, Elbasvir 50 mg capsule orally QD for 8 weeks, RBV capsules orally BID for 8 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a only participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks, RBV capsules orally BID for 18 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks, Elbasvir 50 mg capsule orally QD for 8 weeks, RBV capsules orally BID for 8 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks. | GT1b participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks, Elbasvir 50 mg capsule orally QD for 8 weeks, and RBV capsules orally BID for 8 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT1b participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks and Elbasvir 50 mg capsule orally QD for 8 weeks. | GT3 participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, and RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | GT3 participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks, and RBV capsules orally BID for 18 weeks at a total daily dose from 800 to 1400 mg based on participant weight. | ||||||||||||||||||||
All Cause Mortality |
||||||||||||||||||||||||||||||||||||||||
A1: TN NC Grazoprevir 100 mg + Elbasvir 20 mg + RBV-12 wk | A2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | A3: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | B1: TN NC/GT1a Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | B2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | B3: TN NC/GT1a Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | B4: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | B5: TN C Grazoprevir 100 mg + Elbasvir 50 mg for 12 wk | B6: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk | B7: TN C Grazoprevir 100 mg + Elbasvir 50 Mg-18 wk | B8: NR Grazoprevir 100 mg + Elbasvir 50 mg +RBV-12 wk | B9: NR Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | B10: NR Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | B11: NR Grazoprevir 100 mg + Elbasvir 50 Mg-18 wk | B12: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | B13: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | C1: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | C2: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 Mg-8 wk | D1: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | D2: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk | |||||||||||||||||||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | 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 | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||||||||||||||||||
Serious Adverse Events |
||||||||||||||||||||||||||||||||||||||||
A1: TN NC Grazoprevir 100 mg + Elbasvir 20 mg + RBV-12 wk | A2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | A3: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | B1: TN NC/GT1a Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | B2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | B3: TN NC/GT1a Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | B4: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | B5: TN C Grazoprevir 100 mg + Elbasvir 50 mg for 12 wk | B6: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk | B7: TN C Grazoprevir 100 mg + Elbasvir 50 Mg-18 wk | B8: NR Grazoprevir 100 mg + Elbasvir 50 mg +RBV-12 wk | B9: NR Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | B10: NR Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | B11: NR Grazoprevir 100 mg + Elbasvir 50 Mg-18 wk | B12: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | B13: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | C1: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | C2: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 Mg-8 wk | D1: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | D2: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk | |||||||||||||||||||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | 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 | 1/25 (4%) | 0/28 (0%) | 0/12 (0%) | 0/30 (0%) | 0/33 (0%) | 0/31 (0%) | 1/31 (3.2%) | 2/29 (6.9%) | 1/32 (3.1%) | 1/31 (3.2%) | 2/32 (6.3%) | 1/33 (3%) | 0/33 (0%) | 1/32 (3.1%) | 1/29 (3.4%) | 2/30 (6.7%) | 1/30 (3.3%) | 0/31 (0%) | 0/20 (0%) | 2/21 (9.5%) | ||||||||||||||||||||
Cardiac disorders | ||||||||||||||||||||||||||||||||||||||||
Atrial fibrillation | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 0/12 (0%) | 0 | 0/30 (0%) | 0 | 0/33 (0%) | 0 | 0/31 (0%) | 0 | 0/31 (0%) | 0 | 0/29 (0%) | 0 | 0/32 (0%) | 0 | 0/31 (0%) | 0 | 1/32 (3.1%) | 1 | 0/33 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 0/20 (0%) | 0 | 0/21 (0%) | 0 |
Gastrointestinal disorders | ||||||||||||||||||||||||||||||||||||||||
Abdominal pain | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 0/12 (0%) | 0 | 0/30 (0%) | 0 | 0/33 (0%) | 0 | 0/31 (0%) | 0 | 0/31 (0%) | 0 | 1/29 (3.4%) | 1 | 0/32 (0%) | 0 | 0/31 (0%) | 0 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 0/33 (0%) | 0 | 1/32 (3.1%) | 1 | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 1/30 (3.3%) | 1 | 0/31 (0%) | 0 | 0/20 (0%) | 0 | 0/21 (0%) | 0 |
Gastritis | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 0/12 (0%) | 0 | 0/30 (0%) | 0 | 0/33 (0%) | 0 | 0/31 (0%) | 0 | 0/31 (0%) | 0 | 0/29 (0%) | 0 | 1/32 (3.1%) | 1 | 0/31 (0%) | 0 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 0/20 (0%) | 0 | 0/21 (0%) | 0 |
Nausea | 1/25 (4%) | 1 | 0/28 (0%) | 0 | 0/12 (0%) | 0 | 0/30 (0%) | 0 | 0/33 (0%) | 0 | 0/31 (0%) | 0 | 0/31 (0%) | 0 | 0/29 (0%) | 0 | 0/32 (0%) | 0 | 0/31 (0%) | 0 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 0/20 (0%) | 0 | 0/21 (0%) | 0 |
General disorders | ||||||||||||||||||||||||||||||||||||||||
Asthenia | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 0/12 (0%) | 0 | 0/30 (0%) | 0 | 0/33 (0%) | 0 | 0/31 (0%) | 0 | 0/31 (0%) | 0 | 0/29 (0%) | 0 | 0/32 (0%) | 0 | 0/31 (0%) | 0 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 1/29 (3.4%) | 1 | 0/30 (0%) | 0 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 0/20 (0%) | 0 | 0/21 (0%) | 0 |
Chest pain | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 0/12 (0%) | 0 | 0/30 (0%) | 0 | 0/33 (0%) | 0 | 0/31 (0%) | 0 | 0/31 (0%) | 0 | 0/29 (0%) | 0 | 0/32 (0%) | 0 | 1/31 (3.2%) | 1 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 0/20 (0%) | 0 | 0/21 (0%) | 0 |
Hepatobiliary disorders | ||||||||||||||||||||||||||||||||||||||||
Cholangitis | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 0/12 (0%) | 0 | 0/30 (0%) | 0 | 0/33 (0%) | 0 | 0/31 (0%) | 0 | 0/31 (0%) | 0 | 0/29 (0%) | 0 | 0/32 (0%) | 0 | 0/31 (0%) | 0 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 1/30 (3.3%) | 1 | 0/31 (0%) | 0 | 0/20 (0%) | 0 | 0/21 (0%) | 0 |
Cholecystitis acute | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 0/12 (0%) | 0 | 0/30 (0%) | 0 | 0/33 (0%) | 0 | 0/31 (0%) | 0 | 0/31 (0%) | 0 | 0/29 (0%) | 0 | 0/32 (0%) | 0 | 0/31 (0%) | 0 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 0/20 (0%) | 0 | 1/21 (4.8%) | 1 |
Infections and infestations | ||||||||||||||||||||||||||||||||||||||||
Bacteraemia | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 0/12 (0%) | 0 | 0/30 (0%) | 0 | 0/33 (0%) | 0 | 0/31 (0%) | 0 | 0/31 (0%) | 0 | 0/29 (0%) | 0 | 0/32 (0%) | 0 | 0/31 (0%) | 0 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 1/30 (3.3%) | 1 | 0/31 (0%) | 0 | 0/20 (0%) | 0 | 0/21 (0%) | 0 |
Scrotal abscess | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 0/12 (0%) | 0 | 0/30 (0%) | 0 | 0/33 (0%) | 0 | 0/31 (0%) | 0 | 0/31 (0%) | 0 | 0/29 (0%) | 0 | 0/32 (0%) | 0 | 0/31 (0%) | 0 | 0/32 (0%) | 0 | 1/33 (3%) | 1 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 0/20 (0%) | 0 | 0/21 (0%) | 0 |
Staphylococcal infection | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 0/12 (0%) | 0 | 0/30 (0%) | 0 | 0/33 (0%) | 0 | 0/31 (0%) | 0 | 0/31 (0%) | 0 | 0/29 (0%) | 0 | 0/32 (0%) | 0 | 0/31 (0%) | 0 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/29 (0%) | 0 | 1/30 (3.3%) | 1 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 0/20 (0%) | 0 | 0/21 (0%) | 0 |
Injury, poisoning and procedural complications | ||||||||||||||||||||||||||||||||||||||||
Road traffic accident | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 0/12 (0%) | 0 | 0/30 (0%) | 0 | 0/33 (0%) | 0 | 0/31 (0%) | 0 | 0/31 (0%) | 0 | 0/29 (0%) | 0 | 0/32 (0%) | 0 | 0/31 (0%) | 0 | 1/32 (3.1%) | 1 | 0/33 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 0/20 (0%) | 0 | 0/21 (0%) | 0 |
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||||||||||||||||||||||||||||
Hepatic cancer | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 0/12 (0%) | 0 | 0/30 (0%) | 0 | 0/33 (0%) | 0 | 0/31 (0%) | 0 | 1/31 (3.2%) | 1 | 0/29 (0%) | 0 | 0/32 (0%) | 0 | 0/31 (0%) | 0 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 0/20 (0%) | 0 | 0/21 (0%) | 0 |
Transitional cell carcinoma | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 0/12 (0%) | 0 | 0/30 (0%) | 0 | 0/33 (0%) | 0 | 0/31 (0%) | 0 | 0/31 (0%) | 0 | 1/29 (3.4%) | 1 | 0/32 (0%) | 0 | 0/31 (0%) | 0 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 0/20 (0%) | 0 | 0/21 (0%) | 0 |
Psychiatric disorders | ||||||||||||||||||||||||||||||||||||||||
Depression | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 0/12 (0%) | 0 | 0/30 (0%) | 0 | 0/33 (0%) | 0 | 0/31 (0%) | 0 | 0/31 (0%) | 0 | 0/29 (0%) | 0 | 0/32 (0%) | 0 | 0/31 (0%) | 0 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 0/20 (0%) | 0 | 1/21 (4.8%) | 1 |
Renal and urinary disorders | ||||||||||||||||||||||||||||||||||||||||
Hydronephrosis | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 0/12 (0%) | 0 | 0/30 (0%) | 0 | 0/33 (0%) | 0 | 0/31 (0%) | 0 | 0/31 (0%) | 0 | 0/29 (0%) | 0 | 0/32 (0%) | 0 | 0/31 (0%) | 0 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/29 (0%) | 0 | 1/30 (3.3%) | 1 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 0/20 (0%) | 0 | 0/21 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||||||||||||||||||||||||||||||||||||
A1: TN NC Grazoprevir 100 mg + Elbasvir 20 mg + RBV-12 wk | A2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | A3: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | B1: TN NC/GT1a Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | B2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | B3: TN NC/GT1a Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | B4: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | B5: TN C Grazoprevir 100 mg + Elbasvir 50 mg for 12 wk | B6: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk | B7: TN C Grazoprevir 100 mg + Elbasvir 50 Mg-18 wk | B8: NR Grazoprevir 100 mg + Elbasvir 50 mg +RBV-12 wk | B9: NR Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | B10: NR Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | B11: NR Grazoprevir 100 mg + Elbasvir 50 Mg-18 wk | B12: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | B13: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 Mg-12 wk | C1: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | C2: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 Mg-8 wk | D1: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | D2: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk | |||||||||||||||||||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | 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 | 19/25 (76%) | 24/28 (85.7%) | 11/12 (91.7%) | 27/30 (90%) | 23/33 (69.7%) | 24/31 (77.4%) | 23/31 (74.2%) | 18/29 (62.1%) | 26/32 (81.3%) | 24/31 (77.4%) | 24/32 (75%) | 25/33 (75.8%) | 32/33 (97%) | 25/32 (78.1%) | 18/29 (62.1%) | 14/30 (46.7%) | 22/30 (73.3%) | 14/31 (45.2%) | 16/20 (80%) | 20/21 (95.2%) | ||||||||||||||||||||
Blood and lymphatic system disorders | ||||||||||||||||||||||||||||||||||||||||
Anaemia | 3/25 (12%) | 3 | 2/28 (7.1%) | 2 | 0/12 (0%) | 0 | 1/30 (3.3%) | 1 | 0/33 (0%) | 0 | 0/31 (0%) | 0 | 1/31 (3.2%) | 1 | 0/29 (0%) | 0 | 4/32 (12.5%) | 4 | 0/31 (0%) | 0 | 2/32 (6.3%) | 2 | 0/33 (0%) | 0 | 5/33 (15.2%) | 5 | 0/32 (0%) | 0 | 2/29 (6.9%) | 2 | 0/30 (0%) | 0 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 3/20 (15%) | 3 | 0/21 (0%) | 0 |
Cardiac disorders | ||||||||||||||||||||||||||||||||||||||||
Palpitations | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 1/12 (8.3%) | 1 | 1/30 (3.3%) | 1 | 2/33 (6.1%) | 2 | 0/31 (0%) | 0 | 0/31 (0%) | 0 | 0/29 (0%) | 0 | 0/32 (0%) | 0 | 0/31 (0%) | 0 | 1/32 (3.1%) | 1 | 0/33 (0%) | 0 | 1/33 (3%) | 1 | 1/32 (3.1%) | 1 | 0/29 (0%) | 0 | 1/30 (3.3%) | 1 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 1/20 (5%) | 1 | 1/21 (4.8%) | 1 |
Ear and labyrinth disorders | ||||||||||||||||||||||||||||||||||||||||
Ear pain | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 0/12 (0%) | 0 | 0/30 (0%) | 0 | 2/33 (6.1%) | 2 | 0/31 (0%) | 0 | 0/31 (0%) | 0 | 0/29 (0%) | 0 | 0/32 (0%) | 0 | 0/31 (0%) | 0 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 0/20 (0%) | 0 | 1/21 (4.8%) | 1 |
Gastrointestinal disorders | ||||||||||||||||||||||||||||||||||||||||
Abdominal discomfort | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 1/12 (8.3%) | 1 | 0/30 (0%) | 0 | 0/33 (0%) | 0 | 1/31 (3.2%) | 1 | 0/31 (0%) | 0 | 0/29 (0%) | 0 | 1/32 (3.1%) | 1 | 2/31 (6.5%) | 2 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 0/33 (0%) | 0 | 1/32 (3.1%) | 1 | 1/29 (3.4%) | 1 | 0/30 (0%) | 0 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 0/20 (0%) | 0 | 0/21 (0%) | 0 |
Abdominal pain | 0/25 (0%) | 0 | 2/28 (7.1%) | 2 | 0/12 (0%) | 0 | 0/30 (0%) | 0 | 2/33 (6.1%) | 2 | 1/31 (3.2%) | 1 | 0/31 (0%) | 0 | 1/29 (3.4%) | 1 | 2/32 (6.3%) | 2 | 1/31 (3.2%) | 1 | 1/32 (3.1%) | 1 | 1/33 (3%) | 1 | 2/33 (6.1%) | 4 | 1/32 (3.1%) | 3 | 1/29 (3.4%) | 1 | 0/30 (0%) | 0 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 1/20 (5%) | 1 | 3/21 (14.3%) | 3 |
Abdominal pain upper | 5/25 (20%) | 5 | 2/28 (7.1%) | 3 | 1/12 (8.3%) | 1 | 2/30 (6.7%) | 2 | 3/33 (9.1%) | 3 | 0/31 (0%) | 0 | 3/31 (9.7%) | 3 | 0/29 (0%) | 0 | 3/32 (9.4%) | 3 | 0/31 (0%) | 0 | 1/32 (3.1%) | 1 | 2/33 (6.1%) | 2 | 3/33 (9.1%) | 4 | 5/32 (15.6%) | 5 | 0/29 (0%) | 0 | 1/30 (3.3%) | 1 | 1/30 (3.3%) | 1 | 0/31 (0%) | 0 | 1/20 (5%) | 1 | 2/21 (9.5%) | 2 |
Constipation | 1/25 (4%) | 2 | 0/28 (0%) | 0 | 0/12 (0%) | 0 | 1/30 (3.3%) | 1 | 0/33 (0%) | 0 | 1/31 (3.2%) | 1 | 1/31 (3.2%) | 1 | 1/29 (3.4%) | 1 | 0/32 (0%) | 0 | 0/31 (0%) | 0 | 0/32 (0%) | 0 | 3/33 (9.1%) | 4 | 4/33 (12.1%) | 5 | 2/32 (6.3%) | 2 | 0/29 (0%) | 0 | 1/30 (3.3%) | 1 | 1/30 (3.3%) | 1 | 0/31 (0%) | 0 | 0/20 (0%) | 0 | 0/21 (0%) | 0 |
Diarrhoea | 3/25 (12%) | 3 | 5/28 (17.9%) | 5 | 1/12 (8.3%) | 1 | 5/30 (16.7%) | 5 | 2/33 (6.1%) | 2 | 4/31 (12.9%) | 5 | 1/31 (3.2%) | 1 | 2/29 (6.9%) | 2 | 4/32 (12.5%) | 4 | 1/31 (3.2%) | 1 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 3/33 (9.1%) | 3 | 7/32 (21.9%) | 7 | 1/29 (3.4%) | 1 | 0/30 (0%) | 0 | 1/30 (3.3%) | 1 | 2/31 (6.5%) | 3 | 1/20 (5%) | 1 | 0/21 (0%) | 0 |
Dry mouth | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 0/12 (0%) | 0 | 1/30 (3.3%) | 1 | 1/33 (3%) | 1 | 1/31 (3.2%) | 1 | 1/31 (3.2%) | 1 | 1/29 (3.4%) | 1 | 1/32 (3.1%) | 1 | 1/31 (3.2%) | 1 | 1/32 (3.1%) | 1 | 0/33 (0%) | 0 | 2/33 (6.1%) | 2 | 1/32 (3.1%) | 1 | 1/29 (3.4%) | 1 | 0/30 (0%) | 0 | 2/30 (6.7%) | 2 | 0/31 (0%) | 0 | 1/20 (5%) | 1 | 1/21 (4.8%) | 1 |
Dyspepsia | 3/25 (12%) | 4 | 2/28 (7.1%) | 2 | 0/12 (0%) | 0 | 1/30 (3.3%) | 1 | 1/33 (3%) | 1 | 0/31 (0%) | 0 | 0/31 (0%) | 0 | 0/29 (0%) | 0 | 0/32 (0%) | 0 | 0/31 (0%) | 0 | 1/32 (3.1%) | 1 | 1/33 (3%) | 1 | 3/33 (9.1%) | 3 | 1/32 (3.1%) | 1 | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 0/30 (0%) | 0 | 1/31 (3.2%) | 1 | 0/20 (0%) | 0 | 3/21 (14.3%) | 3 |
Flatulence | 1/25 (4%) | 1 | 1/28 (3.6%) | 1 | 0/12 (0%) | 0 | 0/30 (0%) | 0 | 2/33 (6.1%) | 2 | 0/31 (0%) | 0 | 0/31 (0%) | 0 | 0/29 (0%) | 0 | 1/32 (3.1%) | 1 | 1/31 (3.2%) | 1 | 0/32 (0%) | 0 | 1/33 (3%) | 1 | 1/33 (3%) | 1 | 1/32 (3.1%) | 1 | 1/29 (3.4%) | 1 | 0/30 (0%) | 0 | 1/30 (3.3%) | 1 | 0/31 (0%) | 0 | 0/20 (0%) | 0 | 0/21 (0%) | 0 |
Frequent bowel movements | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 0/12 (0%) | 0 | 0/30 (0%) | 0 | 0/33 (0%) | 0 | 0/31 (0%) | 0 | 1/31 (3.2%) | 1 | 0/29 (0%) | 0 | 0/32 (0%) | 0 | 0/31 (0%) | 0 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 0/33 (0%) | 0 | 2/32 (6.3%) | 2 | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 0/20 (0%) | 0 | 0/21 (0%) | 0 |
Gastrooesophageal reflux disease | 1/25 (4%) | 1 | 0/28 (0%) | 0 | 0/12 (0%) | 0 | 1/30 (3.3%) | 1 | 0/33 (0%) | 0 | 1/31 (3.2%) | 1 | 2/31 (6.5%) | 2 | 0/29 (0%) | 0 | 2/32 (6.3%) | 2 | 1/31 (3.2%) | 1 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 1/33 (3%) | 1 | 1/32 (3.1%) | 1 | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 1/30 (3.3%) | 1 | 0/31 (0%) | 0 | 1/20 (5%) | 1 | 1/21 (4.8%) | 1 |
Nausea | 5/25 (20%) | 5 | 7/28 (25%) | 7 | 2/12 (16.7%) | 2 | 8/30 (26.7%) | 8 | 6/33 (18.2%) | 6 | 5/31 (16.1%) | 5 | 4/31 (12.9%) | 4 | 0/29 (0%) | 0 | 4/32 (12.5%) | 5 | 4/31 (12.9%) | 5 | 4/32 (12.5%) | 4 | 2/33 (6.1%) | 2 | 5/33 (15.2%) | 6 | 1/32 (3.1%) | 1 | 0/29 (0%) | 0 | 1/30 (3.3%) | 1 | 6/30 (20%) | 6 | 3/31 (9.7%) | 3 | 3/20 (15%) | 3 | 6/21 (28.6%) | 7 |
Tooth impacted | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 1/12 (8.3%) | 1 | 0/30 (0%) | 0 | 0/33 (0%) | 0 | 0/31 (0%) | 0 | 0/31 (0%) | 0 | 0/29 (0%) | 0 | 0/32 (0%) | 0 | 0/31 (0%) | 0 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 0/20 (0%) | 0 | 0/21 (0%) | 0 |
Vomiting | 2/25 (8%) | 2 | 4/28 (14.3%) | 5 | 0/12 (0%) | 0 | 2/30 (6.7%) | 2 | 2/33 (6.1%) | 2 | 1/31 (3.2%) | 1 | 2/31 (6.5%) | 2 | 2/29 (6.9%) | 2 | 3/32 (9.4%) | 5 | 2/31 (6.5%) | 2 | 0/32 (0%) | 0 | 2/33 (6.1%) | 3 | 3/33 (9.1%) | 3 | 0/32 (0%) | 0 | 0/29 (0%) | 0 | 1/30 (3.3%) | 1 | 1/30 (3.3%) | 1 | 0/31 (0%) | 0 | 0/20 (0%) | 0 | 3/21 (14.3%) | 3 |
General disorders | ||||||||||||||||||||||||||||||||||||||||
Asthenia | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 0/12 (0%) | 0 | 1/30 (3.3%) | 1 | 3/33 (9.1%) | 3 | 3/31 (9.7%) | 3 | 2/31 (6.5%) | 2 | 1/29 (3.4%) | 1 | 5/32 (15.6%) | 6 | 2/31 (6.5%) | 2 | 7/32 (21.9%) | 7 | 5/33 (15.2%) | 7 | 6/33 (18.2%) | 6 | 7/32 (21.9%) | 7 | 4/29 (13.8%) | 5 | 1/30 (3.3%) | 1 | 1/30 (3.3%) | 1 | 2/31 (6.5%) | 2 | 2/20 (10%) | 2 | 3/21 (14.3%) | 3 |
Chills | 1/25 (4%) | 1 | 0/28 (0%) | 0 | 0/12 (0%) | 0 | 1/30 (3.3%) | 1 | 0/33 (0%) | 0 | 0/31 (0%) | 0 | 0/31 (0%) | 0 | 0/29 (0%) | 0 | 2/32 (6.3%) | 3 | 2/31 (6.5%) | 2 | 0/32 (0%) | 0 | 1/33 (3%) | 1 | 1/33 (3%) | 1 | 0/32 (0%) | 0 | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 0/30 (0%) | 0 | 1/31 (3.2%) | 2 | 0/20 (0%) | 0 | 0/21 (0%) | 0 |
Fatigue | 9/25 (36%) | 9 | 5/28 (17.9%) | 5 | 4/12 (33.3%) | 4 | 15/30 (50%) | 15 | 10/33 (30.3%) | 10 | 6/31 (19.4%) | 7 | 11/31 (35.5%) | 11 | 6/29 (20.7%) | 6 | 9/32 (28.1%) | 10 | 6/31 (19.4%) | 7 | 6/32 (18.8%) | 6 | 10/33 (30.3%) | 12 | 15/33 (45.5%) | 16 | 8/32 (25%) | 8 | 2/29 (6.9%) | 2 | 2/30 (6.7%) | 2 | 11/30 (36.7%) | 11 | 3/31 (9.7%) | 3 | 2/20 (10%) | 2 | 3/21 (14.3%) | 3 |
Influenza like illness | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 0/12 (0%) | 0 | 0/30 (0%) | 0 | 0/33 (0%) | 0 | 0/31 (0%) | 0 | 0/31 (0%) | 0 | 0/29 (0%) | 0 | 1/32 (3.1%) | 1 | 0/31 (0%) | 0 | 1/32 (3.1%) | 1 | 0/33 (0%) | 0 | 2/33 (6.1%) | 2 | 1/32 (3.1%) | 1 | 1/29 (3.4%) | 1 | 0/30 (0%) | 0 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 0/20 (0%) | 0 | 0/21 (0%) | 0 |
Malaise | 2/25 (8%) | 2 | 0/28 (0%) | 0 | 0/12 (0%) | 0 | 0/30 (0%) | 0 | 0/33 (0%) | 0 | 0/31 (0%) | 0 | 0/31 (0%) | 0 | 0/29 (0%) | 0 | 1/32 (3.1%) | 1 | 0/31 (0%) | 0 | 1/32 (3.1%) | 1 | 0/33 (0%) | 0 | 1/33 (3%) | 1 | 0/32 (0%) | 0 | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 1/30 (3.3%) | 1 | 0/31 (0%) | 0 | 0/20 (0%) | 0 | 0/21 (0%) | 0 |
Oedema peripheral | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 1/12 (8.3%) | 1 | 0/30 (0%) | 0 | 0/33 (0%) | 0 | 0/31 (0%) | 0 | 0/31 (0%) | 0 | 1/29 (3.4%) | 1 | 0/32 (0%) | 0 | 1/31 (3.2%) | 1 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 0/33 (0%) | 0 | 1/32 (3.1%) | 1 | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 0/20 (0%) | 0 | 0/21 (0%) | 0 |
Pain | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 0/12 (0%) | 0 | 0/30 (0%) | 0 | 0/33 (0%) | 0 | 0/31 (0%) | 0 | 1/31 (3.2%) | 1 | 0/29 (0%) | 0 | 1/32 (3.1%) | 1 | 0/31 (0%) | 0 | 1/32 (3.1%) | 1 | 1/33 (3%) | 1 | 0/33 (0%) | 0 | 2/32 (6.3%) | 2 | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 0/20 (0%) | 0 | 1/21 (4.8%) | 1 |
Peripheral swelling | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 1/12 (8.3%) | 1 | 0/30 (0%) | 0 | 0/33 (0%) | 0 | 0/31 (0%) | 0 | 0/31 (0%) | 0 | 1/29 (3.4%) | 1 | 1/32 (3.1%) | 1 | 0/31 (0%) | 0 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 0/20 (0%) | 0 | 0/21 (0%) | 0 |
Hepatobiliary disorders | ||||||||||||||||||||||||||||||||||||||||
Hyperbilirubinaemia | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 0/12 (0%) | 0 | 1/30 (3.3%) | 1 | 2/33 (6.1%) | 2 | 0/31 (0%) | 0 | 0/31 (0%) | 0 | 0/29 (0%) | 0 | 1/32 (3.1%) | 1 | 0/31 (0%) | 0 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 0/20 (0%) | 0 | 0/21 (0%) | 0 |
Infections and infestations | ||||||||||||||||||||||||||||||||||||||||
Bronchitis | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 0/12 (0%) | 0 | 2/30 (6.7%) | 2 | 0/33 (0%) | 0 | 0/31 (0%) | 0 | 1/31 (3.2%) | 1 | 0/29 (0%) | 0 | 2/32 (6.3%) | 2 | 1/31 (3.2%) | 2 | 0/32 (0%) | 0 | 1/33 (3%) | 1 | 4/33 (12.1%) | 4 | 0/32 (0%) | 0 | 1/29 (3.4%) | 1 | 0/30 (0%) | 0 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 0/20 (0%) | 0 | 0/21 (0%) | 0 |
Ear infection | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 0/12 (0%) | 0 | 0/30 (0%) | 0 | 0/33 (0%) | 0 | 0/31 (0%) | 0 | 0/31 (0%) | 0 | 0/29 (0%) | 0 | 1/32 (3.1%) | 1 | 2/31 (6.5%) | 2 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 0/20 (0%) | 0 | 0/21 (0%) | 0 |
Gastroenteritis | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 0/12 (0%) | 0 | 0/30 (0%) | 0 | 0/33 (0%) | 0 | 1/31 (3.2%) | 1 | 1/31 (3.2%) | 1 | 0/29 (0%) | 0 | 2/32 (6.3%) | 2 | 0/31 (0%) | 0 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 1/33 (3%) | 1 | 1/32 (3.1%) | 1 | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 1/30 (3.3%) | 1 | 0/31 (0%) | 0 | 0/20 (0%) | 0 | 0/21 (0%) | 0 |
Influenza | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 0/12 (0%) | 0 | 0/30 (0%) | 0 | 0/33 (0%) | 0 | 1/31 (3.2%) | 1 | 1/31 (3.2%) | 1 | 1/29 (3.4%) | 1 | 0/32 (0%) | 0 | 0/31 (0%) | 0 | 1/32 (3.1%) | 1 | 2/33 (6.1%) | 2 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 0/20 (0%) | 0 | 1/21 (4.8%) | 1 |
Nasopharyngitis | 2/25 (8%) | 2 | 0/28 (0%) | 0 | 0/12 (0%) | 0 | 1/30 (3.3%) | 1 | 3/33 (9.1%) | 3 | 1/31 (3.2%) | 1 | 2/31 (6.5%) | 2 | 0/29 (0%) | 0 | 0/32 (0%) | 0 | 4/31 (12.9%) | 5 | 3/32 (9.4%) | 3 | 1/33 (3%) | 1 | 5/33 (15.2%) | 6 | 0/32 (0%) | 0 | 1/29 (3.4%) | 1 | 0/30 (0%) | 0 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 0/20 (0%) | 0 | 0/21 (0%) | 0 |
Oral herpes | 1/25 (4%) | 1 | 0/28 (0%) | 0 | 0/12 (0%) | 0 | 0/30 (0%) | 0 | 1/33 (3%) | 1 | 0/31 (0%) | 0 | 0/31 (0%) | 0 | 0/29 (0%) | 0 | 1/32 (3.1%) | 1 | 0/31 (0%) | 0 | 1/32 (3.1%) | 1 | 0/33 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 0/20 (0%) | 0 | 2/21 (9.5%) | 2 |
Sinusitis | 0/25 (0%) | 0 | 3/28 (10.7%) | 3 | 0/12 (0%) | 0 | 1/30 (3.3%) | 1 | 0/33 (0%) | 0 | 0/31 (0%) | 0 | 0/31 (0%) | 0 | 0/29 (0%) | 0 | 0/32 (0%) | 0 | 0/31 (0%) | 0 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 2/33 (6.1%) | 2 | 0/32 (0%) | 0 | 2/29 (6.9%) | 2 | 0/30 (0%) | 0 | 0/30 (0%) | 0 | 2/31 (6.5%) | 2 | 0/20 (0%) | 0 | 0/21 (0%) | 0 |
Upper respiratory tract infection | 2/25 (8%) | 2 | 1/28 (3.6%) | 1 | 0/12 (0%) | 0 | 3/30 (10%) | 3 | 1/33 (3%) | 1 | 0/31 (0%) | 0 | 0/31 (0%) | 0 | 2/29 (6.9%) | 2 | 3/32 (9.4%) | 3 | 1/31 (3.2%) | 1 | 0/32 (0%) | 0 | 1/33 (3%) | 1 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/29 (0%) | 0 | 1/30 (3.3%) | 1 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 3/20 (15%) | 3 | 5/21 (23.8%) | 5 |
Urinary tract infection | 1/25 (4%) | 1 | 2/28 (7.1%) | 2 | 0/12 (0%) | 0 | 1/30 (3.3%) | 1 | 0/33 (0%) | 0 | 0/31 (0%) | 0 | 0/31 (0%) | 0 | 1/29 (3.4%) | 3 | 0/32 (0%) | 0 | 1/31 (3.2%) | 1 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/29 (0%) | 0 | 1/30 (3.3%) | 1 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 0/20 (0%) | 0 | 0/21 (0%) | 0 |
Injury, poisoning and procedural complications | ||||||||||||||||||||||||||||||||||||||||
Accidental overdose | 1/25 (4%) | 1 | 1/28 (3.6%) | 1 | 1/12 (8.3%) | 1 | 3/30 (10%) | 3 | 4/33 (12.1%) | 5 | 0/31 (0%) | 0 | 5/31 (16.1%) | 6 | 0/29 (0%) | 0 | 3/32 (9.4%) | 3 | 0/31 (0%) | 0 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 2/33 (6.1%) | 5 | 0/32 (0%) | 0 | 1/29 (3.4%) | 1 | 0/30 (0%) | 0 | 2/30 (6.7%) | 2 | 0/31 (0%) | 0 | 3/20 (15%) | 4 | 2/21 (9.5%) | 4 |
Arthropod sting | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 1/12 (8.3%) | 1 | 0/30 (0%) | 0 | 0/33 (0%) | 0 | 0/31 (0%) | 0 | 0/31 (0%) | 0 | 0/29 (0%) | 0 | 0/32 (0%) | 0 | 0/31 (0%) | 0 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 0/20 (0%) | 0 | 0/21 (0%) | 0 |
Contusion | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 1/12 (8.3%) | 1 | 0/30 (0%) | 0 | 0/33 (0%) | 0 | 0/31 (0%) | 0 | 0/31 (0%) | 0 | 0/29 (0%) | 0 | 0/32 (0%) | 0 | 0/31 (0%) | 0 | 1/32 (3.1%) | 1 | 0/33 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 0/20 (0%) | 0 | 0/21 (0%) | 0 |
Investigations | ||||||||||||||||||||||||||||||||||||||||
Alanine aminotransferase increased | 0/25 (0%) | 0 | 2/28 (7.1%) | 2 | 0/12 (0%) | 0 | 0/30 (0%) | 0 | 0/33 (0%) | 0 | 0/31 (0%) | 0 | 0/31 (0%) | 0 | 0/29 (0%) | 0 | 0/32 (0%) | 0 | 0/31 (0%) | 0 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 0/20 (0%) | 0 | 0/21 (0%) | 0 |
Amylase increased | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 0/12 (0%) | 0 | 0/30 (0%) | 0 | 0/33 (0%) | 0 | 0/31 (0%) | 0 | 0/31 (0%) | 0 | 2/29 (6.9%) | 2 | 0/32 (0%) | 0 | 0/31 (0%) | 0 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 0/20 (0%) | 0 | 0/21 (0%) | 0 |
Aspartate aminotransferase increased | 0/25 (0%) | 0 | 2/28 (7.1%) | 2 | 0/12 (0%) | 0 | 0/30 (0%) | 0 | 0/33 (0%) | 0 | 0/31 (0%) | 0 | 0/31 (0%) | 0 | 0/29 (0%) | 0 | 0/32 (0%) | 0 | 0/31 (0%) | 0 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 0/20 (0%) | 0 | 0/21 (0%) | 0 |
Blood creatine phosphokinase increased | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 1/12 (8.3%) | 1 | 0/30 (0%) | 0 | 0/33 (0%) | 0 | 0/31 (0%) | 0 | 0/31 (0%) | 0 | 0/29 (0%) | 0 | 0/32 (0%) | 0 | 0/31 (0%) | 0 | 1/32 (3.1%) | 1 | 0/33 (0%) | 0 | 0/33 (0%) | 0 | 1/32 (3.1%) | 1 | 1/29 (3.4%) | 1 | 0/30 (0%) | 0 | 1/30 (3.3%) | 1 | 1/31 (3.2%) | 1 | 0/20 (0%) | 0 | 1/21 (4.8%) | 1 |
International normalised ratio increased | 3/25 (12%) | 8 | 0/28 (0%) | 0 | 0/12 (0%) | 0 | 0/30 (0%) | 0 | 2/33 (6.1%) | 2 | 0/31 (0%) | 0 | 0/31 (0%) | 0 | 0/29 (0%) | 0 | 0/32 (0%) | 0 | 0/31 (0%) | 0 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 0/20 (0%) | 0 | 0/21 (0%) | 0 |
Lipase increased | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 0/12 (0%) | 0 | 0/30 (0%) | 0 | 0/33 (0%) | 0 | 0/31 (0%) | 0 | 0/31 (0%) | 0 | 2/29 (6.9%) | 2 | 0/32 (0%) | 0 | 0/31 (0%) | 0 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 0/20 (0%) | 0 | 0/21 (0%) | 0 |
Metabolism and nutrition disorders | ||||||||||||||||||||||||||||||||||||||||
Decreased appetite | 1/25 (4%) | 1 | 1/28 (3.6%) | 1 | 0/12 (0%) | 0 | 4/30 (13.3%) | 5 | 0/33 (0%) | 0 | 2/31 (6.5%) | 2 | 1/31 (3.2%) | 1 | 2/29 (6.9%) | 2 | 1/32 (3.1%) | 1 | 2/31 (6.5%) | 2 | 1/32 (3.1%) | 1 | 2/33 (6.1%) | 2 | 2/33 (6.1%) | 2 | 1/32 (3.1%) | 1 | 0/29 (0%) | 0 | 1/30 (3.3%) | 1 | 1/30 (3.3%) | 1 | 0/31 (0%) | 0 | 1/20 (5%) | 1 | 0/21 (0%) | 0 |
Musculoskeletal and connective tissue disorders | ||||||||||||||||||||||||||||||||||||||||
Arthralgia | 2/25 (8%) | 2 | 1/28 (3.6%) | 1 | 0/12 (0%) | 0 | 1/30 (3.3%) | 1 | 2/33 (6.1%) | 3 | 2/31 (6.5%) | 2 | 2/31 (6.5%) | 2 | 3/29 (10.3%) | 4 | 2/32 (6.3%) | 2 | 2/31 (6.5%) | 2 | 2/32 (6.3%) | 2 | 0/33 (0%) | 0 | 4/33 (12.1%) | 4 | 4/32 (12.5%) | 4 | 0/29 (0%) | 0 | 1/30 (3.3%) | 2 | 1/30 (3.3%) | 1 | 1/31 (3.2%) | 1 | 0/20 (0%) | 0 | 0/21 (0%) | 0 |
Back pain | 2/25 (8%) | 2 | 0/28 (0%) | 0 | 0/12 (0%) | 0 | 0/30 (0%) | 0 | 2/33 (6.1%) | 2 | 2/31 (6.5%) | 2 | 0/31 (0%) | 0 | 2/29 (6.9%) | 2 | 4/32 (12.5%) | 4 | 2/31 (6.5%) | 2 | 3/32 (9.4%) | 4 | 0/33 (0%) | 0 | 1/33 (3%) | 1 | 5/32 (15.6%) | 5 | 1/29 (3.4%) | 1 | 1/30 (3.3%) | 1 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 1/20 (5%) | 1 | 0/21 (0%) | 0 |
Joint swelling | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 0/12 (0%) | 0 | 2/30 (6.7%) | 2 | 0/33 (0%) | 0 | 0/31 (0%) | 0 | 0/31 (0%) | 0 | 0/29 (0%) | 0 | 0/32 (0%) | 0 | 0/31 (0%) | 0 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 0/20 (0%) | 0 | 0/21 (0%) | 0 |
Muscle spasms | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 0/12 (0%) | 0 | 1/30 (3.3%) | 1 | 2/33 (6.1%) | 2 | 1/31 (3.2%) | 1 | 0/31 (0%) | 0 | 1/29 (3.4%) | 1 | 1/32 (3.1%) | 1 | 0/31 (0%) | 0 | 1/32 (3.1%) | 1 | 0/33 (0%) | 0 | 2/33 (6.1%) | 2 | 2/32 (6.3%) | 2 | 0/29 (0%) | 0 | 1/30 (3.3%) | 1 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 0/20 (0%) | 0 | 0/21 (0%) | 0 |
Muscular weakness | 1/25 (4%) | 1 | 0/28 (0%) | 0 | 0/12 (0%) | 0 | 1/30 (3.3%) | 1 | 0/33 (0%) | 0 | 1/31 (3.2%) | 1 | 0/31 (0%) | 0 | 0/29 (0%) | 0 | 0/32 (0%) | 0 | 0/31 (0%) | 0 | 2/32 (6.3%) | 2 | 0/33 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 0/20 (0%) | 0 | 0/21 (0%) | 0 |
Musculoskeletal pain | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 0/12 (0%) | 0 | 0/30 (0%) | 0 | 0/33 (0%) | 0 | 1/31 (3.2%) | 1 | 0/31 (0%) | 0 | 0/29 (0%) | 0 | 0/32 (0%) | 0 | 1/31 (3.2%) | 1 | 1/32 (3.1%) | 1 | 1/33 (3%) | 1 | 1/33 (3%) | 1 | 2/32 (6.3%) | 2 | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 0/20 (0%) | 0 | 0/21 (0%) | 0 |
Myalgia | 2/25 (8%) | 2 | 1/28 (3.6%) | 1 | 2/12 (16.7%) | 2 | 0/30 (0%) | 0 | 1/33 (3%) | 1 | 1/31 (3.2%) | 1 | 1/31 (3.2%) | 1 | 1/29 (3.4%) | 1 | 0/32 (0%) | 0 | 1/31 (3.2%) | 1 | 1/32 (3.1%) | 1 | 6/33 (18.2%) | 8 | 6/33 (18.2%) | 6 | 4/32 (12.5%) | 4 | 1/29 (3.4%) | 1 | 0/30 (0%) | 0 | 1/30 (3.3%) | 1 | 3/31 (9.7%) | 4 | 0/20 (0%) | 0 | 0/21 (0%) | 0 |
Neck pain | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 0/12 (0%) | 0 | 0/30 (0%) | 0 | 1/33 (3%) | 1 | 2/31 (6.5%) | 2 | 0/31 (0%) | 0 | 0/29 (0%) | 0 | 0/32 (0%) | 0 | 0/31 (0%) | 0 | 1/32 (3.1%) | 1 | 0/33 (0%) | 0 | 2/33 (6.1%) | 2 | 0/32 (0%) | 0 | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 0/20 (0%) | 0 | 0/21 (0%) | 0 |
Nervous system disorders | ||||||||||||||||||||||||||||||||||||||||
Disturbance in attention | 1/25 (4%) | 1 | 0/28 (0%) | 0 | 0/12 (0%) | 0 | 3/30 (10%) | 3 | 1/33 (3%) | 1 | 0/31 (0%) | 0 | 0/31 (0%) | 0 | 1/29 (3.4%) | 1 | 0/32 (0%) | 0 | 0/31 (0%) | 0 | 1/32 (3.1%) | 1 | 1/33 (3%) | 1 | 1/33 (3%) | 1 | 0/32 (0%) | 0 | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 0/20 (0%) | 0 | 0/21 (0%) | 0 |
Dizziness | 4/25 (16%) | 4 | 2/28 (7.1%) | 2 | 1/12 (8.3%) | 1 | 3/30 (10%) | 3 | 1/33 (3%) | 1 | 3/31 (9.7%) | 3 | 2/31 (6.5%) | 2 | 2/29 (6.9%) | 2 | 2/32 (6.3%) | 2 | 4/31 (12.9%) | 4 | 2/32 (6.3%) | 2 | 1/33 (3%) | 1 | 2/33 (6.1%) | 2 | 0/32 (0%) | 0 | 1/29 (3.4%) | 1 | 0/30 (0%) | 0 | 2/30 (6.7%) | 2 | 0/31 (0%) | 0 | 1/20 (5%) | 1 | 1/21 (4.8%) | 1 |
Dysgeusia | 1/25 (4%) | 1 | 0/28 (0%) | 0 | 0/12 (0%) | 0 | 1/30 (3.3%) | 1 | 0/33 (0%) | 0 | 0/31 (0%) | 0 | 1/31 (3.2%) | 1 | 0/29 (0%) | 0 | 2/32 (6.3%) | 2 | 0/31 (0%) | 0 | 1/32 (3.1%) | 1 | 0/33 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 1/30 (3.3%) | 1 | 0/31 (0%) | 0 | 0/20 (0%) | 0 | 1/21 (4.8%) | 1 |
Headache | 4/25 (16%) | 4 | 6/28 (21.4%) | 6 | 5/12 (41.7%) | 5 | 7/30 (23.3%) | 7 | 7/33 (21.2%) | 9 | 10/31 (32.3%) | 11 | 2/31 (6.5%) | 3 | 4/29 (13.8%) | 5 | 11/32 (34.4%) | 13 | 10/31 (32.3%) | 12 | 10/32 (31.3%) | 12 | 6/33 (18.2%) | 6 | 6/33 (18.2%) | 7 | 10/32 (31.3%) | 10 | 4/29 (13.8%) | 5 | 2/30 (6.7%) | 2 | 6/30 (20%) | 6 | 5/31 (16.1%) | 6 | 5/20 (25%) | 5 | 5/21 (23.8%) | 5 |
Somnolence | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 1/12 (8.3%) | 1 | 1/30 (3.3%) | 1 | 0/33 (0%) | 0 | 0/31 (0%) | 0 | 0/31 (0%) | 0 | 0/29 (0%) | 0 | 0/32 (0%) | 0 | 0/31 (0%) | 0 | 1/32 (3.1%) | 1 | 2/33 (6.1%) | 2 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/29 (0%) | 0 | 1/30 (3.3%) | 1 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 0/20 (0%) | 0 | 0/21 (0%) | 0 |
Tremor | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 0/12 (0%) | 0 | 0/30 (0%) | 0 | 0/33 (0%) | 0 | 0/31 (0%) | 0 | 0/31 (0%) | 0 | 0/29 (0%) | 0 | 0/32 (0%) | 0 | 0/31 (0%) | 0 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 2/33 (6.1%) | 2 | 0/32 (0%) | 0 | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 1/30 (3.3%) | 1 | 0/31 (0%) | 0 | 0/20 (0%) | 0 | 0/21 (0%) | 0 |
Psychiatric disorders | ||||||||||||||||||||||||||||||||||||||||
Affect lability | 1/25 (4%) | 1 | 0/28 (0%) | 0 | 0/12 (0%) | 0 | 2/30 (6.7%) | 2 | 0/33 (0%) | 0 | 0/31 (0%) | 0 | 1/31 (3.2%) | 1 | 1/29 (3.4%) | 1 | 0/32 (0%) | 0 | 0/31 (0%) | 0 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 2/33 (6.1%) | 3 | 0/32 (0%) | 0 | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 0/20 (0%) | 0 | 1/21 (4.8%) | 1 |
Agitation | 2/25 (8%) | 2 | 0/28 (0%) | 0 | 0/12 (0%) | 0 | 0/30 (0%) | 0 | 0/33 (0%) | 0 | 0/31 (0%) | 0 | 0/31 (0%) | 0 | 0/29 (0%) | 0 | 0/32 (0%) | 0 | 0/31 (0%) | 0 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 1/30 (3.3%) | 1 | 0/31 (0%) | 0 | 0/20 (0%) | 0 | 0/21 (0%) | 0 |
Anxiety | 0/25 (0%) | 0 | 1/28 (3.6%) | 1 | 1/12 (8.3%) | 1 | 0/30 (0%) | 0 | 3/33 (9.1%) | 3 | 2/31 (6.5%) | 2 | 0/31 (0%) | 0 | 0/29 (0%) | 0 | 0/32 (0%) | 0 | 0/31 (0%) | 0 | 1/32 (3.1%) | 1 | 1/33 (3%) | 1 | 3/33 (9.1%) | 3 | 0/32 (0%) | 0 | 0/29 (0%) | 0 | 1/30 (3.3%) | 1 | 1/30 (3.3%) | 1 | 0/31 (0%) | 0 | 1/20 (5%) | 1 | 1/21 (4.8%) | 1 |
Depression | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 2/12 (16.7%) | 2 | 0/30 (0%) | 0 | 2/33 (6.1%) | 2 | 1/31 (3.2%) | 1 | 2/31 (6.5%) | 2 | 0/29 (0%) | 0 | 1/32 (3.1%) | 1 | 1/31 (3.2%) | 2 | 2/32 (6.3%) | 2 | 0/33 (0%) | 0 | 1/33 (3%) | 1 | 0/32 (0%) | 0 | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 3/30 (10%) | 3 | 0/31 (0%) | 0 | 0/20 (0%) | 0 | 1/21 (4.8%) | 1 |
Insomnia | 3/25 (12%) | 3 | 2/28 (7.1%) | 2 | 1/12 (8.3%) | 1 | 3/30 (10%) | 3 | 7/33 (21.2%) | 8 | 2/31 (6.5%) | 2 | 5/31 (16.1%) | 5 | 2/29 (6.9%) | 2 | 4/32 (12.5%) | 4 | 0/31 (0%) | 0 | 2/32 (6.3%) | 3 | 3/33 (9.1%) | 3 | 6/33 (18.2%) | 6 | 1/32 (3.1%) | 1 | 2/29 (6.9%) | 3 | 0/30 (0%) | 0 | 1/30 (3.3%) | 1 | 0/31 (0%) | 0 | 3/20 (15%) | 3 | 3/21 (14.3%) | 3 |
Irritability | 2/25 (8%) | 2 | 1/28 (3.6%) | 1 | 1/12 (8.3%) | 1 | 2/30 (6.7%) | 2 | 2/33 (6.1%) | 2 | 0/31 (0%) | 0 | 0/31 (0%) | 0 | 0/29 (0%) | 0 | 0/32 (0%) | 0 | 2/31 (6.5%) | 2 | 2/32 (6.3%) | 2 | 1/33 (3%) | 1 | 2/33 (6.1%) | 2 | 1/32 (3.1%) | 1 | 1/29 (3.4%) | 1 | 0/30 (0%) | 0 | 2/30 (6.7%) | 2 | 0/31 (0%) | 0 | 0/20 (0%) | 0 | 0/21 (0%) | 0 |
Mood swings | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 0/12 (0%) | 0 | 3/30 (10%) | 3 | 0/33 (0%) | 0 | 1/31 (3.2%) | 1 | 1/31 (3.2%) | 1 | 0/29 (0%) | 0 | 0/32 (0%) | 0 | 1/31 (3.2%) | 1 | 1/32 (3.1%) | 1 | 0/33 (0%) | 0 | 1/33 (3%) | 1 | 0/32 (0%) | 0 | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 0/20 (0%) | 0 | 0/21 (0%) | 0 |
Nightmare | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 0/12 (0%) | 0 | 0/30 (0%) | 0 | 0/33 (0%) | 0 | 1/31 (3.2%) | 1 | 0/31 (0%) | 0 | 0/29 (0%) | 0 | 0/32 (0%) | 0 | 0/31 (0%) | 0 | 2/32 (6.3%) | 2 | 0/33 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 0/20 (0%) | 0 | 0/21 (0%) | 0 |
Sleep disorder | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 0/12 (0%) | 0 | 1/30 (3.3%) | 1 | 2/33 (6.1%) | 2 | 3/31 (9.7%) | 3 | 4/31 (12.9%) | 4 | 0/29 (0%) | 0 | 0/32 (0%) | 0 | 1/31 (3.2%) | 1 | 0/32 (0%) | 0 | 1/33 (3%) | 1 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 4/29 (13.8%) | 4 | 0/30 (0%) | 0 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 0/20 (0%) | 0 | 1/21 (4.8%) | 1 |
Renal and urinary disorders | ||||||||||||||||||||||||||||||||||||||||
Chromaturia | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 0/12 (0%) | 0 | 1/30 (3.3%) | 1 | 0/33 (0%) | 0 | 0/31 (0%) | 0 | 2/31 (6.5%) | 2 | 0/29 (0%) | 0 | 0/32 (0%) | 0 | 0/31 (0%) | 0 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 0/20 (0%) | 0 | 0/21 (0%) | 0 |
Respiratory, thoracic and mediastinal disorders | ||||||||||||||||||||||||||||||||||||||||
Cough | 1/25 (4%) | 1 | 2/28 (7.1%) | 2 | 0/12 (0%) | 0 | 1/30 (3.3%) | 1 | 1/33 (3%) | 1 | 1/31 (3.2%) | 1 | 1/31 (3.2%) | 1 | 2/29 (6.9%) | 2 | 6/32 (18.8%) | 6 | 1/31 (3.2%) | 1 | 5/32 (15.6%) | 5 | 1/33 (3%) | 1 | 5/33 (15.2%) | 6 | 1/32 (3.1%) | 1 | 2/29 (6.9%) | 3 | 1/30 (3.3%) | 1 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 1/20 (5%) | 1 | 1/21 (4.8%) | 1 |
Dyspnoea | 5/25 (20%) | 5 | 1/28 (3.6%) | 1 | 0/12 (0%) | 0 | 4/30 (13.3%) | 4 | 0/33 (0%) | 0 | 1/31 (3.2%) | 1 | 1/31 (3.2%) | 1 | 0/29 (0%) | 0 | 5/32 (15.6%) | 5 | 1/31 (3.2%) | 1 | 1/32 (3.1%) | 1 | 2/33 (6.1%) | 2 | 6/33 (18.2%) | 7 | 0/32 (0%) | 0 | 1/29 (3.4%) | 1 | 0/30 (0%) | 0 | 2/30 (6.7%) | 2 | 0/31 (0%) | 0 | 0/20 (0%) | 0 | 3/21 (14.3%) | 3 |
Dyspnoea exertional | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 0/12 (0%) | 0 | 2/30 (6.7%) | 2 | 0/33 (0%) | 0 | 0/31 (0%) | 0 | 1/31 (3.2%) | 1 | 0/29 (0%) | 0 | 1/32 (3.1%) | 1 | 0/31 (0%) | 0 | 1/32 (3.1%) | 1 | 0/33 (0%) | 0 | 3/33 (9.1%) | 3 | 0/32 (0%) | 0 | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 1/30 (3.3%) | 1 | 0/31 (0%) | 0 | 0/20 (0%) | 0 | 1/21 (4.8%) | 1 |
Epistaxis | 1/25 (4%) | 1 | 0/28 (0%) | 0 | 0/12 (0%) | 0 | 0/30 (0%) | 0 | 0/33 (0%) | 0 | 0/31 (0%) | 0 | 1/31 (3.2%) | 1 | 0/29 (0%) | 0 | 3/32 (9.4%) | 3 | 0/31 (0%) | 0 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 0/20 (0%) | 0 | 0/21 (0%) | 0 |
Oropharyngeal pain | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 0/12 (0%) | 0 | 1/30 (3.3%) | 2 | 1/33 (3%) | 1 | 2/31 (6.5%) | 2 | 0/31 (0%) | 0 | 0/29 (0%) | 0 | 0/32 (0%) | 0 | 0/31 (0%) | 0 | 1/32 (3.1%) | 1 | 1/33 (3%) | 1 | 2/33 (6.1%) | 2 | 2/32 (6.3%) | 2 | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 1/30 (3.3%) | 1 | 0/31 (0%) | 0 | 0/20 (0%) | 0 | 1/21 (4.8%) | 1 |
Productive cough | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 0/12 (0%) | 0 | 1/30 (3.3%) | 1 | 0/33 (0%) | 0 | 0/31 (0%) | 0 | 0/31 (0%) | 0 | 0/29 (0%) | 0 | 0/32 (0%) | 0 | 0/31 (0%) | 0 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 2/33 (6.1%) | 2 | 0/32 (0%) | 0 | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 0/20 (0%) | 0 | 2/21 (9.5%) | 2 |
Rhinorrhoea | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 0/12 (0%) | 0 | 2/30 (6.7%) | 2 | 0/33 (0%) | 0 | 1/31 (3.2%) | 1 | 0/31 (0%) | 0 | 0/29 (0%) | 0 | 0/32 (0%) | 0 | 0/31 (0%) | 0 | 1/32 (3.1%) | 1 | 0/33 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 0/20 (0%) | 0 | 0/21 (0%) | 0 |
Skin and subcutaneous tissue disorders | ||||||||||||||||||||||||||||||||||||||||
Alopecia | 2/25 (8%) | 2 | 1/28 (3.6%) | 1 | 0/12 (0%) | 0 | 0/30 (0%) | 0 | 0/33 (0%) | 0 | 1/31 (3.2%) | 1 | 0/31 (0%) | 0 | 0/29 (0%) | 0 | 0/32 (0%) | 0 | 0/31 (0%) | 0 | 2/32 (6.3%) | 2 | 0/33 (0%) | 0 | 1/33 (3%) | 1 | 0/32 (0%) | 0 | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 0/20 (0%) | 0 | 1/21 (4.8%) | 1 |
Dermatitis contact | 2/25 (8%) | 2 | 0/28 (0%) | 0 | 1/12 (8.3%) | 1 | 1/30 (3.3%) | 1 | 0/33 (0%) | 0 | 0/31 (0%) | 0 | 0/31 (0%) | 0 | 0/29 (0%) | 0 | 0/32 (0%) | 0 | 0/31 (0%) | 0 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 0/20 (0%) | 0 | 1/21 (4.8%) | 1 |
Dry skin | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 0/12 (0%) | 0 | 2/30 (6.7%) | 2 | 0/33 (0%) | 0 | 0/31 (0%) | 0 | 2/31 (6.5%) | 2 | 0/29 (0%) | 0 | 4/32 (12.5%) | 4 | 1/31 (3.2%) | 1 | 1/32 (3.1%) | 1 | 0/33 (0%) | 0 | 4/33 (12.1%) | 4 | 0/32 (0%) | 0 | 1/29 (3.4%) | 1 | 1/30 (3.3%) | 1 | 1/30 (3.3%) | 1 | 1/31 (3.2%) | 1 | 0/20 (0%) | 0 | 1/21 (4.8%) | 1 |
Eczema | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 0/12 (0%) | 0 | 0/30 (0%) | 0 | 0/33 (0%) | 0 | 0/31 (0%) | 0 | 0/31 (0%) | 0 | 0/29 (0%) | 0 | 2/32 (6.3%) | 2 | 0/31 (0%) | 0 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 1/33 (3%) | 1 | 1/32 (3.1%) | 1 | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 1/20 (5%) | 1 | 2/21 (9.5%) | 3 |
Pruritus | 1/25 (4%) | 1 | 2/28 (7.1%) | 2 | 0/12 (0%) | 0 | 6/30 (20%) | 6 | 4/33 (12.1%) | 4 | 0/31 (0%) | 0 | 2/31 (6.5%) | 2 | 1/29 (3.4%) | 1 | 5/32 (15.6%) | 5 | 2/31 (6.5%) | 2 | 1/32 (3.1%) | 1 | 2/33 (6.1%) | 2 | 10/33 (30.3%) | 10 | 1/32 (3.1%) | 1 | 3/29 (10.3%) | 3 | 0/30 (0%) | 0 | 4/30 (13.3%) | 4 | 0/31 (0%) | 0 | 1/20 (5%) | 1 | 3/21 (14.3%) | 3 |
Rash | 1/25 (4%) | 1 | 5/28 (17.9%) | 5 | 1/12 (8.3%) | 1 | 0/30 (0%) | 0 | 3/33 (9.1%) | 4 | 1/31 (3.2%) | 1 | 3/31 (9.7%) | 4 | 0/29 (0%) | 0 | 7/32 (21.9%) | 8 | 0/31 (0%) | 0 | 3/32 (9.4%) | 4 | 3/33 (9.1%) | 3 | 3/33 (9.1%) | 3 | 0/32 (0%) | 0 | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 3/30 (10%) | 3 | 1/31 (3.2%) | 1 | 3/20 (15%) | 6 | 2/21 (9.5%) | 2 |
Rash pruritic | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 0/12 (0%) | 0 | 2/30 (6.7%) | 2 | 0/33 (0%) | 0 | 0/31 (0%) | 0 | 0/31 (0%) | 0 | 0/29 (0%) | 0 | 0/32 (0%) | 0 | 0/31 (0%) | 0 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 0/20 (0%) | 0 | 0/21 (0%) | 0 |
Vascular disorders | ||||||||||||||||||||||||||||||||||||||||
Flushing | 1/25 (4%) | 1 | 0/28 (0%) | 0 | 0/12 (0%) | 0 | 1/30 (3.3%) | 1 | 0/33 (0%) | 0 | 2/31 (6.5%) | 3 | 1/31 (3.2%) | 1 | 0/29 (0%) | 0 | 0/32 (0%) | 0 | 0/31 (0%) | 0 | 0/32 (0%) | 0 | 0/33 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/29 (0%) | 0 | 0/30 (0%) | 0 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 0/20 (0%) | 0 | 0/21 (0%) | 0 |
Hypertension | 1/25 (4%) | 1 | 0/28 (0%) | 0 | 0/12 (0%) | 0 | 0/30 (0%) | 0 | 2/33 (6.1%) | 2 | 1/31 (3.2%) | 1 | 0/31 (0%) | 0 | 1/29 (3.4%) | 1 | 1/32 (3.1%) | 1 | 0/31 (0%) | 0 | 1/32 (3.1%) | 1 | 0/33 (0%) | 0 | 0/33 (0%) | 0 | 1/32 (3.1%) | 1 | 0/29 (0%) | 0 | 1/30 (3.3%) | 1 | 0/30 (0%) | 0 | 0/31 (0%) | 0 | 0/20 (0%) | 0 | 0/21 (0%) | 0 |
Limitations/Caveats
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. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results. Sponsor review can be expedited to meet publication timelines.
Results Point of Contact
Name/Title | Results Point of Contact* Name or Official Title Senior Vice President, Global Clinical Development |
---|---|
Organization | Merck Sharp & Dohme Corp. |
Phone | 1-800-672-6372 |
ClinicalTrialsDisclosure@merck.com |
- 5172-035
- 2012-003354-89