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

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ClinicalTrials.gov Identifier: NCT02161510
Recruitment Status : Completed
First Posted : June 11, 2014
Last Update Posted : June 8, 2015
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

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.

Condition or disease Intervention/treatment Phase
Hepatitis C Drug: MK-2248 Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 13 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multiple Dose Study to Evaluate Safety, Pharmacokinetics, and Pharmacodynamics of MK-2248 in Subjects With Hepatitis C Infection
Study Start Date : July 2014
Actual Primary Completion Date : November 2014
Actual Study Completion Date : April 2015

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Part I: MK-2248 200 mg (Panel A)
HCV participants will take MK-2248 200 mg by mouth once daily for 7 days.
Drug: MK-2248
MK-2248 in once-daily oral doses of 200-≤800 mg for 7 days

Experimental: Part I: MK-2248 ≤800 mg (Panel B)
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
MK-2248 in once-daily oral doses of 200-≤800 mg for 7 days

Experimental: Part I: MK-2248 ≤800 mg (Panel C)
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
MK-2248 in once-daily oral doses of 200-≤800 mg for 7 days

Experimental: Part I: MK-2248 ≤800 mg (Panel D)
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
MK-2248 in once-daily oral doses of 200-≤800 mg for 7 days

Experimental: Part II: MK-2248 200 mg (Panel E)
HCV participants will take MK-2248 200 mg by mouth once daily for 7 days.
Drug: MK-2248
MK-2248 in once-daily oral doses of 200-≤800 mg for 7 days

Experimental: Part II: MK-2248 ≤800 mg (Panel F)
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
MK-2248 in once-daily oral doses of 200-≤800 mg for 7 days

Experimental: Part II: MK-2248 ≤800 mg (Panel G)
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
MK-2248 in once-daily oral doses of 200-≤800 mg for 7 days

Experimental: Part II: MK-2248 ≤800 mg (Panel H)
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
MK-2248 in once-daily oral doses of 200-≤800 mg for 7 days

Experimental: Part III: MK-2248 ≤800 mg (Panel I)
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
MK-2248 in once-daily oral doses of 200-≤800 mg for 7 days

Experimental: Part III: MK-2248 ≤800 mg (Panel J)
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
MK-2248 in once-daily oral doses of 200-≤800 mg for 7 days




Primary Outcome Measures :
  1. Maximum change from baseline in VL [ Time Frame: Up to Day 42 ]
  2. Number of participants experiencing an adverse event (AE) [ Time Frame: Up to Day 42 ]
  3. Number of participants who discontinue from study treatment due to an AE [ Time Frame: Up to Day 7 ]

Secondary Outcome Measures :
  1. Plasma concentration at 24 hours post-dose (C24hr) of MK-2248 and circulating metabolite(s) [ Time Frame: Up to Day 10 ]
  2. 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 ]
  3. Maximum observed post-dose plasma concentration (Cmax) of MK-2248 and circulating metabolite(s) [ Time Frame: Up to Day 10 ]
  4. 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 ]
  5. 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 ]
  6. Accumulation ratio of MK-2248 and circulating metabolite(s) in plasma [ Time Frame: Up to Day 10 ]
  7. 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 ]
  8. Apparent volume of distribution (V/F) of MK-2248 in plasma [ Time Frame: Up to Day 10 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02161510


Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
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Study Director: Medical Director Merck Sharp & Dohme Corp.
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Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT02161510    
Other Study ID Numbers: 2248-002
2014-001494-14 ( EudraCT Number )
First Posted: June 11, 2014    Key Record Dates
Last Update Posted: June 8, 2015
Last Verified: June 2015
Additional relevant MeSH terms:
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Hepatitis A
Hepatitis C
Hepatitis
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections