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| ID | Type | Description | Link |
|---|---|---|---|
| 2014-001494-14 | EudraCT Number |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part I: MK-2248 200 mg (Panel A) | Experimental | HCV participants will take MK-2248 200 mg by mouth once daily for 7 days. |
|
| 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. |
|
| 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. |
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| 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. |
|
| Part II: MK-2248 200 mg (Panel E) | Experimental | HCV participants will take MK-2248 200 mg by mouth once daily for 7 days. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MK-2248 | Drug | MK-2248 in once-daily oral doses of 200-≤800 mg for 7 days |
|
| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Merck Sharp & Dohme LLC | Study Director |
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| ID | Term |
|---|---|
| D006526 | Hepatitis C |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D006525 | Hepatitis, Viral, Human |
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| 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. |
|
| 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. |
|
| 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. |
|
| 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. |
|
| 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. |
|
| 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 |
| D014777 |
| Virus Diseases |
| D018178 | Flaviviridae Infections |
| D012327 | RNA Virus Infections |
| D006505 | Hepatitis |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |