Trial Outcomes & Findings for A Multiple Dose Study of Grazoprevir (MK-5172) in Hepatitis C-Infected Participants (MK-5172-010) (NCT NCT01537900)

Results Overview

Each participant was assigned to undergo Fine Needle Aspiration (FNA) to obtain liver tissue at different time points. Specifically, one participant underwent FNA at 4 hr post-dose only, another participant underwent FNA at 8 hr post-dose only, and a third participant underwent FNA at 24 hr post-dose only. (The fourth participant underwent FNA at 72 hr post-dose and therefore was not included in the calculation of AUC0-24hr.) Therefore, in calculating AUC0-24hr, there were only 3 data points: 1 data point at 4 hr post-dose, 1 data point at 8 hr post-dose, and 1 data point at 24 hr post-dose. The model assumed that drug concentration was at steady-state, and that the concentration at 24 hr post-dose was equal to the concentration at 0 hr post-dose.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

4 participants

Primary outcome timeframe

4, 8, and 24 hours post-dose on Day 7

Results posted on

2018-09-14

Participant Flow

Participant milestones

Participant milestones
Measure	Grazoprevir 100 mg Participants received GZR 100 mg once daily (q.d.) for 7 days. Liver FNA was performed on Day 7.
Overall Study STARTED	4
Overall Study COMPLETED	4
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Multiple Dose Study of Grazoprevir (MK-5172) in Hepatitis C-Infected Participants (MK-5172-010)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Grazoprevir 100 mg n=4 Participants Participants received GZR 100 mg q.d. for 7 days. Liver FNA was performed on Day 7.
Age, Continuous	42.5 Years STANDARD_DEVIATION 12.9 • n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants

PRIMARY outcome

Timeframe: 4, 8, and 24 hours post-dose on Day 7

Population: The per protocol population (PPP) includes all participants (4, 8, and 24 hr time points) who complied with the protocol sufficiently to ensure that the data were likely to exhibit the effects of treatment. As each data point was obtained from unique participants, there is no measure of variability.

Each participant was assigned to undergo Fine Needle Aspiration (FNA) to obtain liver tissue at different time points. Specifically, one participant underwent FNA at 4 hr post-dose only, another participant underwent FNA at 8 hr post-dose only, and a third participant underwent FNA at 24 hr post-dose only. (The fourth participant underwent FNA at 72 hr post-dose and therefore was not included in the calculation of AUC0-24hr.) Therefore, in calculating AUC0-24hr, there were only 3 data points: 1 data point at 4 hr post-dose, 1 data point at 8 hr post-dose, and 1 data point at 24 hr post-dose. The model assumed that drug concentration was at steady-state, and that the concentration at 24 hr post-dose was equal to the concentration at 0 hr post-dose.

Outcome measures

Outcome measures
Measure	Grazoprevir 100 mg n=3 Participants Participants received GZR 100 mg q.d. for 7 days. Liver FNA was performed on Day 7.
Estimated Area Under the Liver Concentration-time Curve for 24 Hours Post-dose (AUC[H]0-24hr) of Grazoprevir	19800 µM*hr

PRIMARY outcome

Timeframe: 4, 8, 24, and 72 hours post-dose on Day 7

Population: The PPP includes all participants who complied with the protocol sufficiently to ensure that the data were likely to exhibit the effects of treatment.

C(H)Xhr of GZR was expressed as liver concentration (μmol GZR/L liver) using the concentration of the extracted liver sample (mass of the liver biopsy/0.2 mL solvent), and assuming that liver has the specific gravity of water (1 g/mL). The arithmetic mean C(H)Xhr concentration is based on the means of 4 FNA passes per participant in all 4 participants.

Outcome measures

Outcome measures
Measure	Grazoprevir 100 mg n=4 Participants Participants received GZR 100 mg q.d. for 7 days. Liver FNA was performed on Day 7.
Hepatic Concentration of GZR (C[H]Xhr) Hepatic concentration at 4 hours (C[H]4hr)	390 µM Standard Deviation 186
Hepatic Concentration of GZR (C[H]Xhr) Hepatic concentration at 8 hours (C[H]8hr)	1340 µM Standard Deviation 1335
Hepatic Concentration of GZR (C[H]Xhr) Hepatic concentration at 24 hours (C[H]24hr)	575 µM Standard Deviation 505
Hepatic Concentration of GZR (C[H]Xhr) Hepatic concentration at 72 hours (C[H]72hr)	434 µM Standard Deviation 108

Adverse Events

Grazoprevir 100 mg

Serious events: 1 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Grazoprevir 100 mg n=4 participants at risk Participants received GZR 100 mg q.d. for 7 days. Liver FNA was performed on Day 7.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	25.0% 1/4 • Number of events 1 • From Screening up to 14 days after final dose (up to Day 21)

Other adverse events

Other adverse events
Measure	Grazoprevir 100 mg n=4 participants at risk Participants received GZR 100 mg q.d. for 7 days. Liver FNA was performed on Day 7.
Gastrointestinal disorders Diarrhoea	25.0% 1/4 • Number of events 2 • From Screening up to 14 days after final dose (up to Day 21)

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The SPONSOR must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation.
Publication restrictions are in place

Restriction type: OTHER