Hepatitis C
Conditions
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.
Interventions
DRUGMK-2248
MK-2248 in once-daily oral doses of 200-≤800 mg for 7 days
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum change from baseline in VL | Up to Day 42 |
| Number of participants experiencing an adverse event (AE) | Up to Day 42 |
| Number of participants who discontinue from study treatment due to an AE | Up to Day 7 |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| Plasma concentration at 24 hours post-dose (C24hr) of MK-2248 and circulating metabolite(s) | 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 |
| Apparent volume of distribution (V/F) of MK-2248 in plasma | Up to Day 10 |
| Accumulation ratio of MK-2248 and circulating metabolite(s) in plasma | Up to Day 10 |
| 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 |
| Maximum observed post-dose plasma concentration (Cmax) of MK-2248 and circulating metabolite(s) | Up to Day 10 |
Outcome results
None listed