Back to results

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

Primary Purpose

Hepatitis C

Status

Completed

Phase

Phase 1

Locations

Study Type

Interventional

Intervention

MK-2248

About this trial

This is an interventional treatment trial for Hepatitis C

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm Type

Experimental

Arm Label

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)

Arm Description

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

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.

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.

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.

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

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.

Outcomes

Primary Outcome Measures

Maximum change from baseline in VL

Number of participants experiencing an adverse event (AE)

Number of participants who discontinue from study treatment due to an AE

Secondary Outcome Measures

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

Area under the plasma-concentration curve at zero to 24 hours post-dose (AUC[0-24hr]) of MK-2248 and circulating metabolite(s)

Maximum observed post-dose plasma concentration (Cmax) of MK-2248 and circulating metabolite(s)

Time post-dose at which the maximum observed plasma concentraton (Tmax) of MK-2248 and circulating metabolite(s) occurs

Time required for Cmax to decrease by half (apparent t1/2) of MK-2248 and circulating metabolite(s) in plasma

Accumulation ratio of MK-2248 and circulating metabolite(s) in plasma

Total clearance (amount of drug cleared relative to the total systemically available amount per unit time [CL/F]) of MK-2248 in plasma

Apparent volume of distribution (V/F) of MK-2248 in plasma

Full Information

NCT ID

NCT02161510

First Posted

June 10, 2014

Last Updated

June 5, 2015

Sponsor

Merck Sharp & Dohme LLC

1. Study Identification

Unique Protocol Identification Number

NCT02161510

Brief Title

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

2. Study Status

Record Verification Date

June 2015

Overall Recruitment Status

Completed

Study Start Date

July 2014 (undefined)

Primary Completion Date

November 2014 (Actual)

Study Completion Date

April 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Merck Sharp & Dohme LLC

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hepatitis C

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

13 (Actual)

8. Arms, Groups, and Interventions

Arm Title

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

Arm Type

Experimental

Arm Description

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

Arm Title

Part I: MK-2248 ≤800 mg (Panel B)

Arm Type

Experimental

Arm 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.

Arm Title

Part I: MK-2248 ≤800 mg (Panel C)

Arm Type

Experimental

Arm 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.

Arm Title

Part I: MK-2248 ≤800 mg (Panel D)

Arm Type

Experimental

Arm 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.

Arm Title

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

Arm Type

Experimental

Arm Description

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

Arm Title

Part II: MK-2248 ≤800 mg (Panel F)

Arm Type

Experimental

Arm 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.

Arm Title

Part II: MK-2248 ≤800 mg (Panel G)

Arm Type

Experimental

Arm 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.

Arm Title

Part II: MK-2248 ≤800 mg (Panel H)

Arm Type

Experimental

Arm 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.

Arm Title

Part III: MK-2248 ≤800 mg (Panel I)

Arm Type

Experimental

Arm 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.

Arm Title

Part III: MK-2248 ≤800 mg (Panel J)

Arm Type

Experimental

Arm 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.

Intervention Type

Drug

Intervention Name(s)

MK-2248

Intervention Description

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

Primary Outcome Measure Information:

Title

Maximum change from baseline in VL

Time Frame

Up to Day 42

Title

Number of participants experiencing an adverse event (AE)

Time Frame

Up to Day 42

Title

Number of participants who discontinue from study treatment due to an AE

Time Frame

Up to Day 7

Secondary Outcome Measure Information:

Title

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

Time Frame

Up to Day 10

Title

Area under the plasma-concentration curve at zero to 24 hours post-dose (AUC[0-24hr]) of MK-2248 and circulating metabolite(s)

Time Frame

Up to Day 10

Title

Maximum observed post-dose plasma concentration (Cmax) of MK-2248 and circulating metabolite(s)

Time Frame

Up to Day 10

Title

Time post-dose at which the maximum observed plasma concentraton (Tmax) of MK-2248 and circulating metabolite(s) occurs

Time Frame

Up to Day 10

Title

Time required for Cmax to decrease by half (apparent t1/2) of MK-2248 and circulating metabolite(s) in plasma

Time Frame

Up to Day 10

Title

Accumulation ratio of MK-2248 and circulating metabolite(s) in plasma

Time Frame

Up to Day 10

Title

Total clearance (amount of drug cleared relative to the total systemically available amount per unit time [CL/F]) of MK-2248 in plasma

Time Frame

Up to Day 10

Title

Apparent volume of distribution (V/F) of MK-2248 in plasma

Time Frame

Up to Day 10

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Medical Director

Organizational Affiliation

Merck Sharp & Dohme LLC

Official's Role

Study Director

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs