A Multiple Dose Study of Grazoprevir (MK-5172) in Hepatitis C-Infected Participants (MK-5172-010)
- Registration Number
- NCT01537900
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
The goal of this study was to compare hepatic pharmacokinetics (PK) derived from liver tissue to plasma PK after administration of grazoprevir (MK-5172) to participants with chronic hepatitis C virus (HCV) infection. Participants will be randomized to one of four different liver ultrasound-guided Fine Needle Aspirate (FNA) schedules (at 4-, 8-, 24-, or 72-hours after the Day 7 dose).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 4
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Grazoprevir 100 mg Grazoprevir Participants received GZR 100 mg once daily (q.d.) for 7 days. Liver FNA was performed on Day 7.
- Primary Outcome Measures
Name Time Method Estimated Area Under the Liver Concentration-time Curve for 24 Hours Post-dose (AUC[H]0-24hr) of Grazoprevir 4, 8, and 24 hours post-dose on Day 7 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.
Hepatic Concentration of GZR (C[H]Xhr) 4, 8, 24, and 72 hours post-dose on Day 7 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.
Apparent Terminal Hepatic Half-life (t[H]½ ) of GZR 4, 8, 24, and 72 hours post-dose on Day 7 t(H)1/2 is a measure of the time required for the maximum post-dose liver concentration of GZR to decrease by 50%.
- Secondary Outcome Measures
Name Time Method Plasma AUC[0-24 hr] of GZR Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose on Day 7 AUC0-24hr is a measure of the mean concentration of drug in plasma after dosing to 24 hours post-dose.
Lowest Plasma Concentration (Ctrough) of GZR Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose on Day 7 Ctrough is a measure of drug concentration 24 hours post-dose.
Time to Maximum Plasma Concentration (Tmax) of GZR Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose on Day 7 Tmax is a measure of time to reach maximum post-dose plasma drug concentration.
Maximum Plasma Concentration (Cmax) of GZR Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose on Day 7 Cmax is a measure of the maximum plasma concentration post-dose.
Plasma t½ of GZR Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose on Day 7 t1/2 is a measure of time for the maximum plasma concentration of GZR to decrease by 50%.