Safety, Pharmacokinetics, and Pharmacodynamics of MK-2248 in Participants With Hepatitis C (MK-2248-002)
- Registration Number
- NCT02161510
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
The objective of this study is to identify a safe dose of MK-2248 in participants with Hepatitis C Virus (HCV) that mediates at least a 3 log10 reduction in viral load (VL) from baseline. It is anticipated that once-daily administration of a safe and well tolerated dose of MK-2248 will reduce VL by at least 3 log10 IU/mL.
- Detailed Description
In this Phase 1b study, the pharmacokinetic (PK), pharmacodynamic (PD), and safety profile of MK-2248 in HCV-infected participants will be evaluated as follows: Part I will assess sequentially ascending MK-2248 doses from 200 mg to ≤800 mg over 4 panels (A, B, C, and D). Part II will assess sequentially ascending MK-2248 doses from 200 mg to ≤800 mg over 4 panels (E, F, G, and H). Part III will assess sequentially ascending MK-2248 doses ranging up to ≤800 mg in 2 panels (I and J). The potential relationship between plasma MK-2248 levels and VL reduction will be determined.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 13
Inclusion Criteria
- clinical diagnosis of chronic HCV defined by positive serology for HCV or positive HCV RNA for at least 6 months and detectable HCV RNA in peripheral blood ≥10^5 IU/mL at screening
- Body Mass Index (BMI) ≥18 to <37 kg/m^2
- in good health other than HCV infection with normal laboratory values
Exclusion Criteria
- history of clinically significant and not stably controlled endocrine, gastrointestinal, cardiovascular, hematological, hepatic (excepting HCV infection), immunological, renal, respiratory, genitourinary, or major neurological abnormalities or disease
- history of cancer other than adequately treated non-melanomatous skin carcinoma, malignancies which have been successfully treated ≥10 years prior with no recurrence, or cancer that is unlikely to sustain a recurrence for the duration of the trial
- history of significant multiple and/or severe allergies or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food
- positive for hepatitis B surface antigen or human immunodeficiency virus
- had major surgery or lost 1 unit of blood within 4 weeks prior to screening
- QTc interval ≥470 msec (males) or ≥480 msec (females)
- received prior treatment with other HCV inhibitors
- clinical or laboratory evidence of decompensated liver disease
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Part I: MK-2248 ≤800 mg (Panel C) MK-2248 Based on safety, PK, and PD data from the preceding panel, HCV participants will take MK-2248 at approximately ≤800 mg by mouth for 7 days. Part I: MK-2248 ≤800 mg (Panel B) MK-2248 Based on safety, PK, and PD data from the preceding panel, HCV participants will take MK-2248 at approximately ≤800 mg by mouth once daily for 7 days. Part II: MK-2248 ≤800 mg (Panel H) MK-2248 Based on safety, PK, and PD data from the preceding panel, HCV participants will take MK-2248 at approximately ≤800 mg by mouth once daily for 7 days. Part II: MK-2248 ≤800 mg (Panel G) MK-2248 Based on safety, PK, and PD data from the preceding panel, HCV participants will take MK-2248 at approximately ≤800 mg by mouth once daily for 7 days. Part I: MK-2248 200 mg (Panel A) MK-2248 HCV participants will take MK-2248 200 mg by mouth once daily for 7 days. Part I: MK-2248 ≤800 mg (Panel D) MK-2248 Based on safety, PK, and PD data from the preceding panel, HCV participants will take MK-2248 at approximately ≤800 mg by mouth once daily for 7 days. Part II: MK-2248 ≤800 mg (Panel F) MK-2248 Based on safety, PK, and PD data from the preceding panel, HCV participants will take MK-2248 at approximately ≤800 mg by mouth once daily for 7 days. Part II: MK-2248 200 mg (Panel E) MK-2248 HCV participants will take MK-2248 200 mg by mouth once daily for 7 days. Part III: MK-2248 ≤800 mg (Panel J) MK-2248 Based on safety, PK, and PD data from the preceding panel, HCV participants will take MK-2248 at approximately ≤800 mg by mouth once daily for 7 days. Part III: MK-2248 ≤800 mg (Panel I) MK-2248 Based on safety, PK, and PD data from the preceding panel, HCV participants will take MK-2248 at approximately ≤800 mg by mouth once daily for 7 days.
- Primary Outcome Measures
Name Time Method Number of participants experiencing an adverse event (AE) Up to Day 42 Maximum change from baseline in VL Up to Day 42 Number of participants who discontinue from study treatment due to an AE Up to Day 7
- Secondary Outcome Measures
Name Time Method Area under the plasma-concentration curve at zero to 24 hours post-dose (AUC[0-24hr]) of MK-2248 and circulating metabolite(s) Up to Day 10 Apparent volume of distribution (V/F) of MK-2248 in plasma Up to Day 10 Total clearance (amount of drug cleared relative to the total systemically available amount per unit time [CL/F]) of MK-2248 in plasma Up to Day 10 Plasma concentration at 24 hours post-dose (C24hr) of MK-2248 and circulating metabolite(s) Up to Day 10 Maximum observed post-dose plasma concentration (Cmax) of MK-2248 and circulating metabolite(s) Up to Day 10 Time post-dose at which the maximum observed plasma concentraton (Tmax) of MK-2248 and circulating metabolite(s) occurs Up to Day 10 Time required for Cmax to decrease by half (apparent t1/2) of MK-2248 and circulating metabolite(s) in plasma Up to Day 10 Accumulation ratio of MK-2248 and circulating metabolite(s) in plasma Up to Day 10