Safety, Pharmacokinetics, and Pharmacodynamics of MK-2248 in Participants With Hepatitis C (MK-2248-002)

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 1

Conditions: Hepatitis C

Treatments: Drug: MK-2248

Study type: Interventional

Funder types: Industry

Identifiers

NCT02161510

2248-002

2014-001494-14 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 13 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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13 participants in 10 patient groups

Part I: MK-2248 200 mg (Panel A)

Experimental group

Description:

HCV participants will take MK-2248 200 mg by mouth once daily for 7 days.

Treatment:

Drug: MK-2248

Part I: MK-2248 ≤800 mg (Panel B)

Experimental group

Description:

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.

Treatment:

Drug: MK-2248

Part I: MK-2248 ≤800 mg (Panel C)

Experimental group

Description:

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.

Treatment:

Drug: MK-2248

Part I: MK-2248 ≤800 mg (Panel D)

Experimental group

Description:

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.

Treatment:

Drug: MK-2248

Part II: MK-2248 200 mg (Panel E)

Experimental group

Description:

HCV participants will take MK-2248 200 mg by mouth once daily for 7 days.

Treatment:

Drug: MK-2248

Part II: MK-2248 ≤800 mg (Panel F)

Experimental group

Description:

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.

Treatment:

Drug: MK-2248

Part II: MK-2248 ≤800 mg (Panel G)

Experimental group

Description:

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.

Treatment:

Drug: MK-2248

Part II: MK-2248 ≤800 mg (Panel H)

Experimental group

Description:

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.

Treatment:

Drug: MK-2248

Part III: MK-2248 ≤800 mg (Panel I)

Experimental group

Description:

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.

Treatment:

Drug: MK-2248

Part III: MK-2248 ≤800 mg (Panel J)

Experimental group

Description:

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.

Treatment:

Drug: MK-2248