A Multiple Dose Study of Grazoprevir (MK-5172) in Hepatitis C-Infected Participants (MK-5172-010)
|ClinicalTrials.gov Identifier: NCT01537900|
Recruitment Status : Completed
First Posted : February 23, 2012
Results First Posted : March 4, 2016
Last Update Posted : March 30, 2017
|Condition or disease||Intervention/treatment||Phase|
|Hepatitis C||Drug: Grazoprevir||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||4 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Multiple Dose Study to Evaluate Pharmacokinetics and Hepatitis C Virus RNA Dynamics Following Administration of MK-5172 in Hepatitis C Infected Patients|
|Study Start Date :||October 2013|
|Actual Primary Completion Date :||July 2014|
|Actual Study Completion Date :||July 2014|
Experimental: Grazoprevir 100 mg
Participants received GZR 100 mg once daily (q.d.) for 7 days. Liver FNA was performed on Day 7.
GZR 100 mg tablet by mouth q.d. for 7 days.
Other Name: MK-5172
- Estimated Area Under the Liver Concentration-time Curve for 24 Hours Post-dose (AUC[H]0-24hr) of Grazoprevir [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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%.
- Plasma AUC[0-24 hr] of GZR [ Time Frame: 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.
- Maximum Plasma Concentration (Cmax) of GZR [ Time Frame: 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.
- Lowest Plasma Concentration (Ctrough) of GZR [ Time Frame: 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 [ Time Frame: 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.
- Plasma t½ of GZR [ Time Frame: 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%.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01537900
|Study Director:||Medical Director||Merck Sharp & Dohme Corp.|