Clinical trial NCT02161510: Safety, Pharmacokinetics, and Pharmacodynamics of MK-2248 in Participants With Hepatitis C (MK-2248-002)
Official title: A Multiple Dose Study to Evaluate Safety, Pharmacokinetics, and Pharmacodynamics of MK-2248 in Subjects With Hepatitis C Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatitis C
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2014-06-11
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Maximum change from baseline in VL
timeFrame: Up to Day 42
measure: Number of participants experiencing an adverse event (AE)
timeFrame: Up to Day 42
measure: Number of participants who discontinue from study treatment due to an AE
timeFrame: Up to Day 7
Secondary outcomes:
measure: Plasma concentration at 24 hours post-dose (C24hr) of MK-2248 and circulating metabolite(s)
timeFrame: Up to Day 10
measure: Area under the plasma-concentration curve at zero to 24 hours post-dose (AUC[0-24hr]) of MK-2248 and circulating metabolite(s)
timeFrame: Up to Day 10
measure: Maximum observed post-dose plasma concentration (Cmax) of MK-2248 and circulating metabolite(s)
timeFrame: Up to Day 10
measure: Time post-dose at which the maximum observed plasma concentraton (Tmax) of MK-2248 and circulating metabolite(s) occurs
timeFrame: Up to Day 10
measure: Time required for Cmax to decrease by half (apparent t1/2) of MK-2248 and circulating metabolite(s) in plasma
timeFrame: Up to Day 10
measure: Accumulation ratio of MK-2248 and circulating metabolite(s) in plasma
timeFrame: Up to Day 10
measure: Total clearance (amount of drug cleared relative to the total systemically available amount per unit time [CL/F]) of MK-2248 in plasma
timeFrame: Up to Day 10
measure: Apparent volume of distribution (V/F) of MK-2248 in plasma
timeFrame: Up to Day 10
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: