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

Hepatitis C Clinical Trial

Official title:

A Multiple Dose Study to Evaluate Safety, Pharmacokinetics, and Pharmacodynamics of MK-2248 in Subjects With Hepatitis C Infection

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02161510
• Other study ID #: 2248-002
• Secondary ID: 2014-001494-14
• Status: Completed
• Phase: Phase 1
• First received: June 10, 2014
• Last updated: June 5, 2015
• Start date: July 2014
• Est. completion date: April 2015

Study information

• Verified date: June 2015
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 13
• Est. completion date: April 2015
• Est. primary completion date: November 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis C

Intervention

Drug:
• MK-2248
MK-2248 in once-daily oral doses of 200-=800 mg for 7 days

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum change from baseline in VL		Up to Day 42	No
Primary	Number of participants experiencing an adverse event (AE)		Up to Day 42	Yes
Primary	Number of participants who discontinue from study treatment due to an AE		Up to Day 7	Yes
Secondary	Plasma concentration at 24 hours post-dose (C24hr) of MK-2248 and circulating metabolite(s)		Up to Day 10	No
Secondary	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	No
Secondary	Maximum observed post-dose plasma concentration (Cmax) of MK-2248 and circulating metabolite(s)		Up to Day 10	No
Secondary	Time post-dose at which the maximum observed plasma concentraton (Tmax) of MK-2248 and circulating metabolite(s) occurs		Up to Day 10	No
Secondary	Time required for Cmax to decrease by half (apparent t1/2) of MK-2248 and circulating metabolite(s) in plasma		Up to Day 10	No
Secondary	Accumulation ratio of MK-2248 and circulating metabolite(s) in plasma		Up to Day 10	No
Secondary	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	No
Secondary	Apparent volume of distribution (V/F) of MK-2248 in plasma		Up to Day 10	No