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

NCT02161510 | Completed Phase 1

• 2 other identifiers: 2248-0022014-001494-14
• Study Type: interventional
• Target: 13
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Hepatitis C

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (8)

• Plasma concentration at 24 hours post-dose (C24hr) of MK-2248 and circulating metabolite(s)

  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

• 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

Study Arms (10)

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

EXPERIMENTAL

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

Drug: MK-2248

Part I: MK-2248 ≤800 mg (Panel B)

EXPERIMENTAL

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.

Drug: MK-2248

Part I: MK-2248 ≤800 mg (Panel C)

EXPERIMENTAL

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.

Drug: MK-2248

Part I: MK-2248 ≤800 mg (Panel D)

EXPERIMENTAL

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.

Drug: MK-2248

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

EXPERIMENTAL

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

Drug: MK-2248

Part II: MK-2248 ≤800 mg (Panel F)

EXPERIMENTAL

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.

Drug: MK-2248

Part II: MK-2248 ≤800 mg (Panel G)

EXPERIMENTAL

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.

Drug: MK-2248

Part II: MK-2248 ≤800 mg (Panel H)

EXPERIMENTAL

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.

Drug: MK-2248

Part III: MK-2248 ≤800 mg (Panel I)

EXPERIMENTAL

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.

Drug: MK-2248

Part III: MK-2248 ≤800 mg (Panel J)

EXPERIMENTAL

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.

Drug: MK-2248

Interventions

MK-2248 DRUG

MK-2248 in once-daily oral doses of 200-≤800 mg for 7 days

Part I: MK-2248 200 mg (Panel A); Part I: MK-2248 ≤800 mg (Panel B); Part I: MK-2248 ≤800 mg (Panel C); Part I: MK-2248 ≤800 mg (Panel D); Part II: MK-2248 200 mg (Panel E); Part II: MK-2248 ≤800 mg (Panel F); Part II: MK-2248 ≤800 mg (Panel G); Part II: MK-2248 ≤800 mg (Panel H); Part III: MK-2248 ≤800 mg (Panel I); Part III: MK-2248 ≤800 mg (Panel J)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

MeSH Terms

Conditions

Hepatitis C

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 10, 2014
• First Posted: June 11, 2014
• Study Start: July 1, 2014
• Primary Completion: November 1, 2014
• Study Completion: April 1, 2015
• Last Updated: June 8, 2015

Record last verified: 2015-06