Trial Outcomes & Findings for A Study of Grazoprevir (MK-5172) in Hepatitis C-Infected Male Participants (MK-5172-004) (NCT NCT00998985)

Last Updated: 2018-07-17

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

91 participants

Primary outcome timeframe

All AEs: 15 Days after last dose; Serious AEs (SAEs) up to 2 months after last dose (Up to 67 days)

Results posted on

2018-07-17

Participant Flow

One of the originally planned treatment groups (50 mg Grazoprevir - GT3) was not conducted because other results indicated that further evaluation of 50 mg Grazoprevir in GT3 participants was not necessary. It is therefore not included in the Participant Flow.

Participant milestones

Participant milestones
Measure	400 mg Grazoprevir - GT1 GT1 HCV-infected Participants: 400 mg Grazoprevir orally, once daily for 7 consecutive days	600 mg Grazoprevir - GT1 GT1 HCV-infected Participants: 600 mg Grazoprevir orally, once daily for 7 consecutive days	800 mg Grazoprevir - GT1 GT1 HCV-infected Participants: 800 mg Grazoprevir orally, once daily for 7 consecutive days	400 mg Grazoprevir - GT3 GT3 HCV-infected Participants: 400 mg Grazoprevir orally, once daily for 7 consecutive days	600 mg Grazoprevir - GT3 GT3 HCV-infected Participants: 600 mg Grazoprevir orally, once daily for 7 consecutive days	800 mg Grazoprevir - GT3 GT3 HCV-infected Participants: 800 mg Grazoprevir orally, once daily for 7 consecutive days	200 mg Grazoprevir - GT1 GT1 HCV-infected Participants: 200 mg Grazoprevir orally, once daily for 7 consecutive days	100 mg Grazoprevir - GT1 GT1 HCV-infected Participants: 100 mg Grazoprevir orally, once daily for 7 consecutive days	50 mg Grazoprevir - GT1 GT1 HCV-infected Participants: 50 mg Grazoprevir orally, once daily for 7 consecutive days	200 mg Grazoprevir - GT3 GT3 HCV-infected Participants: 200 mg Grazoprevir orally, once daily for 7 consecutive days	100 mg Grazoprevir - GT3 GT3 HCV-infected Participants: 100 mg Grazoprevir orally, once daily for 7 consecutive days	30 mg Grazoprevir - GT1 GT1 HCV-infected Participants: 30 mg Grazoprevir orally, once daily for 7 consecutive days	10 mg Grazoprevir - GT1 GT1 HCV-infected Participants: 10 mg Grazoprevir orally, once daily for 7 consecutive days	Placebo for Grazoprevir - GT1 and GT3 GT1 and GT3 HCV-infected Participants: Placebo for Grazoprevir orally, once daily for 7 consecutive days
Overall Study STARTED	5	5	15	5	5	5	5	5	6	5	5	5	5	15
Overall Study COMPLETED	5	5	15	5	5	4	5	5	5	5	5	5	5	15
Overall Study NOT COMPLETED	0	0	0	0	0	1	0	0	1	0	0	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	400 mg Grazoprevir - GT1 GT1 HCV-infected Participants: 400 mg Grazoprevir orally, once daily for 7 consecutive days	600 mg Grazoprevir - GT1 GT1 HCV-infected Participants: 600 mg Grazoprevir orally, once daily for 7 consecutive days	800 mg Grazoprevir - GT1 GT1 HCV-infected Participants: 800 mg Grazoprevir orally, once daily for 7 consecutive days	400 mg Grazoprevir - GT3 GT3 HCV-infected Participants: 400 mg Grazoprevir orally, once daily for 7 consecutive days	600 mg Grazoprevir - GT3 GT3 HCV-infected Participants: 600 mg Grazoprevir orally, once daily for 7 consecutive days	800 mg Grazoprevir - GT3 GT3 HCV-infected Participants: 800 mg Grazoprevir orally, once daily for 7 consecutive days	200 mg Grazoprevir - GT1 GT1 HCV-infected Participants: 200 mg Grazoprevir orally, once daily for 7 consecutive days	100 mg Grazoprevir - GT1 GT1 HCV-infected Participants: 100 mg Grazoprevir orally, once daily for 7 consecutive days	50 mg Grazoprevir - GT1 GT1 HCV-infected Participants: 50 mg Grazoprevir orally, once daily for 7 consecutive days	200 mg Grazoprevir - GT3 GT3 HCV-infected Participants: 200 mg Grazoprevir orally, once daily for 7 consecutive days	100 mg Grazoprevir - GT3 GT3 HCV-infected Participants: 100 mg Grazoprevir orally, once daily for 7 consecutive days	30 mg Grazoprevir - GT1 GT1 HCV-infected Participants: 30 mg Grazoprevir orally, once daily for 7 consecutive days	10 mg Grazoprevir - GT1 GT1 HCV-infected Participants: 10 mg Grazoprevir orally, once daily for 7 consecutive days	Placebo for Grazoprevir - GT1 and GT3 GT1 and GT3 HCV-infected Participants: Placebo for Grazoprevir orally, once daily for 7 consecutive days
Overall Study Withdrawal by Subject	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Overall Study Protocol Violation	0	0	0	0	0	1	0	0	0	0	0	0	0	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	400 mg Grazoprevir - GT1 n=5 Participants GT1 HCV-infected Participants: 400 mg Grazoprevir orally, once daily for 7 consecutive days	600 mg Grazoprevir - GT1 n=5 Participants GT1 HCV-infected Participants: 600 mg Grazoprevir orally, once daily for 7 consecutive days	800 mg Grazoprevir - GT1 n=15 Participants GT1 HCV-infected Participants: 800 mg Grazoprevir orally, once daily for 7 consecutive days	400 mg Grazoprevir - GT3 n=5 Participants GT3 HCV-infected Participants: 400 mg Grazoprevir orally, once daily for 7 consecutive days	600 mg Grazoprevir - GT3 n=5 Participants GT3 HCV-infected Participants: 600 mg Grazoprevir orally, once daily for 7 consecutive days	800 mg Grazoprevir - GT3 n=5 Participants GT3 HCV-infected Participants: 800 mg Grazoprevir orally, once daily for 7 consecutive days	200 mg Grazoprevir - GT1 n=5 Participants GT1 HCV-infected Participants: 200 mg Grazoprevir orally, once daily for 7 consecutive days	100 mg Grazoprevir - GT1 n=5 Participants GT1 HCV-infected Participants: 100 mg Grazoprevir orally, once daily for 7 consecutive days	50 mg Grazoprevir - GT1 n=6 Participants GT1 HCV-infected Participants: 50 mg Grazoprevir orally, once daily for 7 consecutive days	200 mg Grazoprevir - GT3 n=5 Participants GT3 HCV-infected Participants: 200 mg Grazoprevir orally, once daily for 7 consecutive days	100 mg Grazoprevir - GT3 n=5 Participants GT3 HCV-infected Participants: 100 mg Grazoprevir orally, once daily for 7 consecutive days	30 mg Grazoprevir - GT1 n=5 Participants GT1 HCV-infected Participants: 30 mg Grazoprevir orally, once daily for 7 consecutive days	10 mg Grazoprevir - GT1 n=5 Participants GT1 HCV-infected Participants: 10 mg Grazoprevir orally, once daily for 7 consecutive days	Placebo for Grazoprevir - GT1 and GT3 n=15 Participants GT1 and GT3 HCV-infected Participants: Placebo for Grazoprevir orally, once daily for 7 consecutive days	Total n=91 Participants Total of all reporting groups
Age, Continuous	42.4 Years STANDARD_DEVIATION 12.8 • n=5 Participants	47.2 Years STANDARD_DEVIATION 12.2 • n=7 Participants	46.7 Years STANDARD_DEVIATION 9.7 • n=5 Participants	42.8 Years STANDARD_DEVIATION 14.4 • n=4 Participants	38.0 Years STANDARD_DEVIATION 13.1 • n=21 Participants	46.2 Years STANDARD_DEVIATION 10.8 • n=10 Participants	51.0 Years STANDARD_DEVIATION 16.2 • n=115 Participants	48.4 Years STANDARD_DEVIATION 5.9 • n=6 Participants	36.8 Years STANDARD_DEVIATION 6.0 • n=6 Participants	40.0 Years STANDARD_DEVIATION 10.2 • n=64 Participants	31.4 Years STANDARD_DEVIATION 6.3 • n=17 Participants	55.8 Years STANDARD_DEVIATION 5.4 • n=21 Participants	48.4 Years STANDARD_DEVIATION 13.1 • n=22 Participants	45.6 Years STANDARD_DEVIATION 11.5 • n=8 Participants	44.7 Years STANDARD_DEVIATION 11.5 • n=16 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=6 Participants	0 Participants n=6 Participants	0 Participants n=64 Participants	0 Participants n=17 Participants	0 Participants n=21 Participants	0 Participants n=22 Participants	0 Participants n=8 Participants	0 Participants n=16 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	5 Participants n=7 Participants	15 Participants n=5 Participants	5 Participants n=4 Participants	5 Participants n=21 Participants	5 Participants n=10 Participants	5 Participants n=115 Participants	5 Participants n=6 Participants	6 Participants n=6 Participants	5 Participants n=64 Participants	5 Participants n=17 Participants	5 Participants n=21 Participants	5 Participants n=22 Participants	15 Participants n=8 Participants	91 Participants n=16 Participants

PRIMARY outcome

Timeframe: All AEs: 15 Days after last dose; Serious AEs (SAEs) up to 2 months after last dose (Up to 67 days)

Population: All participants who received at least one dose of the investigational drug according to the treatment(s) they actually received. Participants with either GT1 or GT3 who received the same treatment were combined for the summary into a single GT1 and GT3 arm.

Outcome measures

Outcome measures
Measure	400 mg Grazoprevir - GT1 and GT3 n=10 Participants GT1 and GT3 HCV-infected Participants: 400 mg Grazoprevir orally, once daily for 7 consecutive days	600 mg Grazoprevir - GT1 and GT3 n=10 Participants GT1 and GT3 HCV-infected Participants: 600 mg Grazoprevir orally, once daily for 7 consecutive days	800 mg Grazoprevir - GT1 and GT3 n=20 Participants GT1 and GT3 HCV-infected Participants: 800 mg Grazoprevir orally, once daily for 7 consecutive days	200 mg Grazoprevir - GT1 and GT3 n=10 Participants GT1 and GT3 HCV-infected Participants: 200 mg Grazoprevir orally, once daily for 7 consecutive days	100 mg Grazoprevir - GT1 and GT3 n=10 Participants GT1 and GT3 HCV-infected Participants: 100 mg Grazoprevir orally, once daily for 7 consecutive days	50 mg Grazoprevir - GT1 n=6 Participants GT1 HCV-infected Participants: 50 mg Grazoprevir orally, once daily for 7 consecutive days	30 mg Grazoprevir - GT1 n=5 Participants GT1 HCV-infected Participants: 30 mg Grazoprevir orally, once daily for 7 consecutive days	10 mg Grazoprevir - GT1 n=5 Participants GT1 HCV-infected Participants: 10 mg Grazoprevir orally, once daily for 7 consecutive days	Placebo for Grazoprevir - GT1 and GT3 n=15 Participants GT1 and GT3 HCV-infected Participants: Placebo for Grazoprevir orally, once daily for 7 consecutive days	400 mg Grazoprevir - GT3 GT3 HCV-infected Participants: 400 mg Grazoprevir orally, once daily for 7 consecutive days	600 mg Grazoprevir - GT3 GT3 HCV-infected Participants: 600 mg Grazoprevir orally, once daily for 7 consecutive days	800 mg Grazoprevir - GT3 GT3 HCV-infected Participants: 800 mg Grazoprevir orally, once daily for 7 consecutive days	200 mg Grazoprevir - GT3 GT3 HCV-infected Participants: 200 mg Grazoprevir orally, once daily for 7 consecutive days	100 mg Grazoprevir - GT3 GT3 HCV-infected Participants: 100 mg Grazoprevir orally, once daily for 7 consecutive days
Number of Participants With Clinical and Laboratory Adverse Events (AEs)	6 Participants	3 Participants	13 Participants	4 Participants	1 Participants	0 Participants	3 Participants	4 Participants	2 Participants	—	—	—	—	—

SECONDARY outcome

Timeframe: Day 7 at the following time points: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, and 24 hours post-dose

Population: Participants who complied with the protocol sufficiently to ensure that these data will exhibit the effects of treatment, according to the underlying scientific model. GT1 or GT3 participants who received the same treatment were combined into a single arm. Participants with placebo were not analyzed as they did not receive grazoprevir.

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.

Outcome measures

Outcome measures
Measure	400 mg Grazoprevir - GT1 and GT3 n=10 Participants GT1 and GT3 HCV-infected Participants: 400 mg Grazoprevir orally, once daily for 7 consecutive days	600 mg Grazoprevir - GT1 and GT3 n=10 Participants GT1 and GT3 HCV-infected Participants: 600 mg Grazoprevir orally, once daily for 7 consecutive days	800 mg Grazoprevir - GT1 and GT3 n=18 Participants GT1 and GT3 HCV-infected Participants: 800 mg Grazoprevir orally, once daily for 7 consecutive days	200 mg Grazoprevir - GT1 and GT3 n=10 Participants GT1 and GT3 HCV-infected Participants: 200 mg Grazoprevir orally, once daily for 7 consecutive days	100 mg Grazoprevir - GT1 and GT3 n=10 Participants GT1 and GT3 HCV-infected Participants: 100 mg Grazoprevir orally, once daily for 7 consecutive days	50 mg Grazoprevir - GT1 n=5 Participants GT1 HCV-infected Participants: 50 mg Grazoprevir orally, once daily for 7 consecutive days	30 mg Grazoprevir - GT1 n=5 Participants GT1 HCV-infected Participants: 30 mg Grazoprevir orally, once daily for 7 consecutive days	10 mg Grazoprevir - GT1 n=5 Participants GT1 HCV-infected Participants: 10 mg Grazoprevir orally, once daily for 7 consecutive days	Placebo for Grazoprevir - GT1 and GT3 GT1 and GT3 HCV-infected Participants: Placebo for Grazoprevir orally, once daily for 7 consecutive days	400 mg Grazoprevir - GT3 GT3 HCV-infected Participants: 400 mg Grazoprevir orally, once daily for 7 consecutive days	600 mg Grazoprevir - GT3 GT3 HCV-infected Participants: 600 mg Grazoprevir orally, once daily for 7 consecutive days	800 mg Grazoprevir - GT3 GT3 HCV-infected Participants: 800 mg Grazoprevir orally, once daily for 7 consecutive days	200 mg Grazoprevir - GT3 GT3 HCV-infected Participants: 200 mg Grazoprevir orally, once daily for 7 consecutive days	100 mg Grazoprevir - GT3 GT3 HCV-infected Participants: 100 mg Grazoprevir orally, once daily for 7 consecutive days
Area Under the Curve for 0 to 24 Hours Post-dose (AUC[0-24hr]) of Grazoprevir on Day 7	18.2 uM.hr Interval 12.2 to 27.2	41.9 uM.hr Interval 28.0 to 62.6	72.5 uM.hr Interval 54.1 to 97.2	3.21 uM.hr Interval 2.14 to 4.8	1.16 uM.hr Interval 0.774 to 1.73	0.419 uM.hr Interval 0.237 to 0.74	0.260 uM.hr Interval 0.147 to 0.459	0.0628 uM.hr Interval 0.0355 to 0.111	—	—	—	—	—	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	400 mg Grazoprevir - GT1 and GT3 n=10 Participants GT1 and GT3 HCV-infected Participants: 400 mg Grazoprevir orally, once daily for 7 consecutive days	600 mg Grazoprevir - GT1 and GT3 n=10 Participants GT1 and GT3 HCV-infected Participants: 600 mg Grazoprevir orally, once daily for 7 consecutive days	800 mg Grazoprevir - GT1 and GT3 n=18 Participants GT1 and GT3 HCV-infected Participants: 800 mg Grazoprevir orally, once daily for 7 consecutive days	200 mg Grazoprevir - GT1 and GT3 n=10 Participants GT1 and GT3 HCV-infected Participants: 200 mg Grazoprevir orally, once daily for 7 consecutive days	100 mg Grazoprevir - GT1 and GT3 n=10 Participants GT1 and GT3 HCV-infected Participants: 100 mg Grazoprevir orally, once daily for 7 consecutive days	50 mg Grazoprevir - GT1 n=5 Participants GT1 HCV-infected Participants: 50 mg Grazoprevir orally, once daily for 7 consecutive days	30 mg Grazoprevir - GT1 n=5 Participants GT1 HCV-infected Participants: 30 mg Grazoprevir orally, once daily for 7 consecutive days	10 mg Grazoprevir - GT1 n=5 Participants GT1 HCV-infected Participants: 10 mg Grazoprevir orally, once daily for 7 consecutive days	Placebo for Grazoprevir - GT1 and GT3 GT1 and GT3 HCV-infected Participants: Placebo for Grazoprevir orally, once daily for 7 consecutive days	400 mg Grazoprevir - GT3 GT3 HCV-infected Participants: 400 mg Grazoprevir orally, once daily for 7 consecutive days	600 mg Grazoprevir - GT3 GT3 HCV-infected Participants: 600 mg Grazoprevir orally, once daily for 7 consecutive days	800 mg Grazoprevir - GT3 GT3 HCV-infected Participants: 800 mg Grazoprevir orally, once daily for 7 consecutive days	200 mg Grazoprevir - GT3 GT3 HCV-infected Participants: 200 mg Grazoprevir orally, once daily for 7 consecutive days	100 mg Grazoprevir - GT3 GT3 HCV-infected Participants: 100 mg Grazoprevir orally, once daily for 7 consecutive days
24 Hour Plasma Concentration (C[24hr]) of Grazoprevir on Day 7	70.2 nM Interval 46.9 to 105.0	93.2 nM Interval 62.3 to 140.0	174 nM Interval 130.0 to 233.0	22.2 nM Interval 14.8 to 33.2	20.1 nM Interval 13.4 to 30.1	12.7 nM Interval 7.16 to 22.4	7.20 nM Interval 4.07 to 12.7	2.41 nM Interval 1.36 to 4.27	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline and up to approximately 2 months

Population: Participants who complied with the protocol sufficiently to ensure that these data will exhibit the effects of treatment, according to the underlying scientific model. One GT1 participant treated with 50 mg grazoprevir, who discontinued, and all GT3 participants treated with grazoprevir were excluded from analysis.

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.

Outcome measures

Outcome measures
Measure	400 mg Grazoprevir - GT1 and GT3 n=5 Participants GT1 and GT3 HCV-infected Participants: 400 mg Grazoprevir orally, once daily for 7 consecutive days	600 mg Grazoprevir - GT1 and GT3 n=5 Participants GT1 and GT3 HCV-infected Participants: 600 mg Grazoprevir orally, once daily for 7 consecutive days	800 mg Grazoprevir - GT1 and GT3 n=15 Participants GT1 and GT3 HCV-infected Participants: 800 mg Grazoprevir orally, once daily for 7 consecutive days	200 mg Grazoprevir - GT1 and GT3 n=5 Participants GT1 and GT3 HCV-infected Participants: 200 mg Grazoprevir orally, once daily for 7 consecutive days	100 mg Grazoprevir - GT1 and GT3 n=5 Participants GT1 and GT3 HCV-infected Participants: 100 mg Grazoprevir orally, once daily for 7 consecutive days	50 mg Grazoprevir - GT1 n=5 Participants GT1 HCV-infected Participants: 50 mg Grazoprevir orally, once daily for 7 consecutive days	30 mg Grazoprevir - GT1 n=5 Participants GT1 HCV-infected Participants: 30 mg Grazoprevir orally, once daily for 7 consecutive days	10 mg Grazoprevir - GT1 n=5 Participants GT1 HCV-infected Participants: 10 mg Grazoprevir orally, once daily for 7 consecutive days	Placebo for Grazoprevir - GT1 and GT3 n=15 Participants GT1 and GT3 HCV-infected Participants: Placebo for Grazoprevir orally, once daily for 7 consecutive days	400 mg Grazoprevir - GT3 GT3 HCV-infected Participants: 400 mg Grazoprevir orally, once daily for 7 consecutive days	600 mg Grazoprevir - GT3 GT3 HCV-infected Participants: 600 mg Grazoprevir orally, once daily for 7 consecutive days	800 mg Grazoprevir - GT3 GT3 HCV-infected Participants: 800 mg Grazoprevir orally, once daily for 7 consecutive days	200 mg Grazoprevir - GT3 GT3 HCV-infected Participants: 200 mg Grazoprevir orally, once daily for 7 consecutive days	100 mg Grazoprevir - GT3 GT3 HCV-infected Participants: 100 mg Grazoprevir orally, once daily for 7 consecutive days
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	5.14 log10 IU/mL Interval 4.55 to 5.73	5.32 log10 IU/mL Interval 4.73 to 5.91	5.72 log10 IU/mL Interval 5.38 to 6.07	5.53 log10 IU/mL Interval 4.94 to 6.12	4.74 log10 IU/mL Interval 4.15 to 5.33	5.26 log10 IU/mL Interval 4.67 to 5.85	5.06 log10 IU/mL Interval 4.47 to 5.66	3.84 log10 IU/mL Interval 3.25 to 4.43	0.39 log10 IU/mL Interval 0.04 to 0.73	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline and up to approximately 2 months

Population: Participants who complied with the protocol sufficiently to ensure that these data will exhibit the effects of treatment, according to the underlying scientific model. One GT3 participant treated with 800 mg grazoprevir, who discontinued, and all GT1 participants were excluded from analysis.

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.