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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Hepatitis C

Intervention / Treatment
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* Drug: MK-2248


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part I: MK-2248 200 mg (Panel A)<br>HCV participants will take MK-2248 200 mg by mouth once daily for 7 days. | Drug: MK-2248<br>* MK-2248 in once-daily oral doses of 200-≤800 mg for 7 days<br>|
| Experimental: Part I: MK-2248 ≤800 mg (Panel B)<br>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<br>* MK-2248 in once-daily oral doses of 200-≤800 mg for 7 days<br>|
| Experimental: Part I: MK-2248 ≤800 mg (Panel C)<br>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<br>* MK-2248 in once-daily oral doses of 200-≤800 mg for 7 days<br>|
| Experimental: Part I: MK-2248 ≤800 mg (Panel D)<br>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<br>* MK-2248 in once-daily oral doses of 200-≤800 mg for 7 days<br>|
| Experimental: Part II: MK-2248 200 mg (Panel E)<br>HCV participants will take MK-2248 200 mg by mouth once daily for 7 days. | Drug: MK-2248<br>* MK-2248 in once-daily oral doses of 200-≤800 mg for 7 days<br>|
| Experimental: Part II: MK-2248 ≤800 mg (Panel F)<br>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<br>* MK-2248 in once-daily oral doses of 200-≤800 mg for 7 days<br>|
| Experimental: Part II: MK-2248 ≤800 mg (Panel G)<br>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<br>* MK-2248 in once-daily oral doses of 200-≤800 mg for 7 days<br>|
| Experimental: Part II: MK-2248 ≤800 mg (Panel H)<br>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<br>* MK-2248 in once-daily oral doses of 200-≤800 mg for 7 days<br>|
| Experimental: Part III: MK-2248 ≤800 mg (Panel I)<br>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<br>* MK-2248 in once-daily oral doses of 200-≤800 mg for 7 days<br>|
| Experimental: Part III: MK-2248 ≤800 mg (Panel J)<br>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<br>* MK-2248 in once-daily oral doses of 200-≤800 mg for 7 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Accumulation ratio of MK-2248 and circulating metabolite(s) in plasma |  | Up to Day 10 | 
| 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 | 
| Apparent volume of distribution (V/F) of MK-2248 in plasma |  | Up to Day 10 |