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NCT00998985

A Study of Grazoprevir (MK-5172) in Hepatitis C-Infected Male Participants (MK-5172-004)

Completed Phase 1 Results posted Last updated 17 July 2018
What this trial tests

Phase 1 trial testing Grazoprevir in Hepatitis C in 91 participants. Completed in 8 November 2012.

Timeline
23 February 2010
Primary endpoint
8 November 2012
8 November 2012

Quick facts

Lead sponsorMerck Sharp & Dohme LLC
PhasePhase 1
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposetreatment
Enrollment91
Start date23 February 2010
Primary completion8 November 2012
Estimated completion8 November 2012

Drugs / interventions tested

Conditions studied

Sponsor

Merck Sharp & Dohme LLC — full company profile →

Who can join

Adults 18 to 65, male only, with Hepatitis C. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With Clinical and Laboratory Adverse Events (AEs) Primary · All AEs: 15 Days after last dose; Serious AEs (SAEs) up to 2 months after last dose (Up to 67 days)

An AE is any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's product, whether or not considered related to the use of the product. 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, is also an AE.

GroupValue95% CI
400 mg Grazoprevir - GT1 and GT36
600 mg Grazoprevir - GT1 and GT33
800 mg Grazoprevir - GT1 and GT313
200 mg Grazoprevir - GT1 and GT34
100 mg Grazoprevir - GT1 and GT31
50 mg Grazoprevir - GT10
30 mg Grazoprevir - GT13
10 mg Grazoprevir - GT14
Placebo for Grazoprevir - GT1 and GT32
Area Under the Curve for 0 to 24 Hours Post-dose (AUC[0-24hr]) of Grazoprevir on Day 7 Secondary · Day 7 at the following time points: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, and 24 hours post-dose

Blood samples were collected on Day 7 at pre-dose up to 24 hours post-dose in order to determine the AUC 0-24hrs of Grazoprevir. It is hypothesized that the Geometric Mean of Day 7 Grazoprevir AUC0-24hr. exceeds 3.2 uM.hr.

GroupValue95% CI
400 mg Grazoprevir - GT1 and GT318.212.2 – 27.2
600 mg Grazoprevir - GT1 and GT341.928.0 – 62.6
800 mg Grazoprevir - GT1 and GT372.554.1 – 97.2
200 mg Grazoprevir - GT1 and GT33.212.14 – 4.80
100 mg Grazoprevir - GT1 and GT31.160.774 – 1.73
50 mg Grazoprevir - GT10.4190.237 – 0.740
30 mg Grazoprevir - GT10.2600.147 – 0.459
10 mg Grazoprevir - GT10.06280.0355 – 0.111
24 Hour Plasma Concentration (C[24hr]) of Grazoprevir on Day 7 Secondary · Day 7 at 24 hours post-dose

Blood samples were collected on Day 7 at 24 hours post-dose in order to determine the C24hr of Grazoprevir. It is hypothesized that the Geometric Mean of Day 7 Grazoprevir C24hr exceeds 28 nM.

GroupValue95% CI
400 mg Grazoprevir - GT1 and GT370.246.9 – 105
600 mg Grazoprevir - GT1 and GT393.262.3 – 140
800 mg Grazoprevir - GT1 and GT3174130 – 233
200 mg Grazoprevir - GT1 and GT322.214.8 – 33.2
100 mg Grazoprevir - GT1 and GT320.113.4 – 30.1
50 mg Grazoprevir - GT112.77.16 – 22.4
30 mg Grazoprevir - GT17.204.07 – 12.7
10 mg Grazoprevir - GT12.411.36 – 4.27
Maximum log10 HCV RNA Reduction From Baseline Following Administration of Grazoprevir in Participants With GT1 HCV or Pooled GT1 and GT3 HCV Participants Treated With Placebo Secondary · Baseline and up to approximately 2 months

Blood samples were collected at baseline and at intervals up to 2 months post-dose in order to determine the maximum log10 reduction from baseline in plasma HCV RNA, expressed in international units (IU)/mL.

GroupValue95% CI
400 mg Grazoprevir - GT15.144.55 – 5.73
600 mg Grazoprevir - GT15.324.73 – 5.91
800 mg Grazoprevir - GT15.725.38 – 6.07
200 mg Grazoprevir - GT15.534.94 – 6.12
100 mg Grazoprevir - GT14.744.15 – 5.33
50 mg Grazoprevir - GT15.264.67 – 5.85
30 mg Grazoprevir - GT15.064.47 – 5.66
10 mg Grazoprevir - GT13.843.25 – 4.43
Placebo for Grazoprevir - GT1 and GT30.390.04 – 0.73
Maximum log10 HCV RNA Reduction From Baseline Following Administration of Grazoprevir in Participants With GT3 HCV or Pooled GT1 and GT3 HCV Participants Treated With Placebo Secondary · Baseline and up to approximately 2 months

Blood samples were collected at baseline and at intervals up to 2 months post-dose in order to determine the maximum log10 reduction from baseline in plasma HCV RNA.

GroupValue95% CI
400 mg Grazoprevir - GT34.233.65 – 4.81
600 mg Grazoprevir - GT35.364.79 – 5.94
800 mg Grazoprevir - GT34.603.95 – 5.24
200 mg Grazoprevir - GT33.322.75 – 3.90
100 mg Grazoprevir - GT32.642.06 – 3.22
Placebo for Grazoprevir - GT1 and GT30.390.05 – 0.72

Adverse events — posted to ClinicalTrials.gov

Time frame: All AEs: 15 Days after last dose; Serious AEs (SAEs) up to 2 months after last dose (Up to 67 days). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

400 mg Grazoprevir - GT1 and GT3
Serious: 0/10 (0%)
Deaths:
600 mg Grazoprevir - GT1 and GT3
Serious: 0/10 (0%)
Deaths:
800 mg Grazoprevir - GT1 and GT3
Serious: 0/20 (0%)
Deaths:
200 mg Grazoprevir - GT1 and GT3
Serious: 0/10 (0%)
Deaths:
100 mg Grazoprevir - GT1 and GT3
Serious: 0/10 (0%)
Deaths:
50 mg Grazoprevir - GT1
Serious: 0/6 (0%)
Deaths:
30 mg Grazoprevir - GT1
Serious: 0/5 (0%)
Deaths:
10 mg Grazoprevir - GT1
Serious: 0/5 (0%)
Deaths:
Placebo for Grazoprevir - GT1 and GT3
Serious: 0/15 (0%)
Deaths:
Other adverse events (23 terms — click to expand)

ReactionSystem400 mg Grazoprevir - GT1 a…600 mg Grazoprevir - GT1 a…800 mg Grazoprevir - GT1 a…200 mg Grazoprevir - GT1 a…100 mg Grazoprevir - GT1 a…50 mg Grazoprevir - GT130 mg Grazoprevir - GT110 mg Grazoprevir - GT1Placebo for Grazoprevir - …
HeadacheNervous system disorders
DiarrhoeaGastrointestinal disorders
FatigueGeneral disorders
NasopharyngitisInfections and infestations
FlatulenceGastrointestinal disorders
Abdominal painGastrointestinal disorders
Abdominal pain upperGastrointestinal disorders
Aphthous stomatitisGastrointestinal disorders
NauseaGastrointestinal disorders
ToothacheGastrointestinal disorders
VomitingGastrointestinal disorders
Vessel puncture site haematomaGeneral disorders
ContusionInjury, poisoning and procedural complications
Back painMusculoskeletal and connective tissue disorders
Pain in extremityMusculoskeletal and connective tissue disorders
DysgeusiaNervous system disorders
MigraineNervous system disorders
InsomniaPsychiatric disorders
Erectile dysfunctionReproductive system and breast disorders
Oropharyngeal painRespiratory, thoracic and mediastinal disorders
MaculeSkin and subcutaneous tissue disorders
Night sweatsSkin and subcutaneous tissue disorders
PruritusSkin and subcutaneous tissue disorders

Data from ClinicalTrials.gov NCT00998985 adverse events section.

Sponsor's own description

This multiple dose study will assess the safety, tolerability, pharmacokinetics and pharmacodynamics of grazoprevir (MK-5172) in Genotype (GT) 1 and GT3 Hepatitis C virus (HCV)- infected participants. The primary hypothesis is that administration of grazoprevir for 7 days is sufficiently safe and well tolerated in HCV-infected males.

Publications & conference data

4 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Direct-acting antivirals for chronic hepatitis C.
    Jakobsen JC, Nielsen EE, Feinberg J, Katakam KK, et al · · 2017 · cited 61× · PMID 28922704 · DOI 10.1002/14651858.cd012143.pub3
  2. Direct-acting antivirals for chronic hepatitis C.
    Jakobsen JC, Nielsen EE, Feinberg J, Katakam KK, et al · · 2017 · cited 37× · PMID 28585310 · DOI 10.1002/14651858.cd012143.pub2
  3. Superinfection and cure of infected cells as mechanisms for hepatitis C virus adaptation and persistence.
    Ke R, Li H, Wang S, Ding W, et al · · 2018 · cited 17× · PMID 29987026 · DOI 10.1073/pnas.1805267115
  4. Antiviral Activity, Safety, and Tolerability of Multiple Ascending Doses of Elbasvir or Grazoprevir in Participants Infected With Hepatitis C Virus Genotype-1 or -3.
    Yeh WW, Fraser IP, Jumes P, Petry A, et al · · 2018 · cited 3× · PMID 29703432 · DOI 10.1016/j.clinthera.2018.03.002

Verify or expand the search:

Other trials of Grazoprevir

Trials testing the same drug.

Other recruiting trials for Hepatitis C

Currently open trials in the same condition.

Other Merck Sharp & Dohme LLC trials

Trials by the same sponsor.

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing