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A Multiple Dose Study to Evaluate the Safety and Efficacy of MK-2748 in Hepatitis C-Infected Participants (MK-2748-002 AM1)

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ClinicalTrials.gov Identifier: NCT01593735
Recruitment Status : Completed
First Posted : May 8, 2012
Last Update Posted : January 22, 2015
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Brief Summary:
This is a multiple dose study of the safety and efficacy of MK-2748 to be done in 2 Parts. Part I will enroll genotype 1 (GT1) hepatitis C virus (HCV)-infected participants and Part II will enroll genotype 3 (GT3) HCV-infected participants. Both Parts may run concurrently or may be staggered.

Condition or disease Intervention/treatment Phase
Hepatitis C Drug: MK-2748 Drug: Placebo Phase 1

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Multiple Dose Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of MK-2748 in Hepatitis C-Infected Participants
Study Start Date : May 2012
Actual Primary Completion Date : February 2013
Actual Study Completion Date : February 2013

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Panel A: GT1, low dose
Participants with genotype 1 (GT1) Hepatitis C Virus (HCV) will receive low dose MK-2748 daily for 7 days.
Drug: MK-2748
MK-2748 tablets, orally, once daily for 7 days, dose level dependent on Panel assignment

Drug: Placebo
Placebo tablets, orally, once daily for 7 days

Experimental: Panel B: GT1, lower dose
Participants with GT1 HCV will receive lower dose MK-2748 daily for 7 days.
Drug: MK-2748
MK-2748 tablets, orally, once daily for 7 days, dose level dependent on Panel assignment

Drug: Placebo
Placebo tablets, orally, once daily for 7 days

Experimental: Panel C: GT1, dose based on Panels A+B
Participants with GT1 HCV will be dosed with MK-2748 daily for 7 days based on the safety, pharmacokinetic, and/or pharmacodynamic data from Panels A (low dose) and B (lower dose).
Drug: MK-2748
MK-2748 tablets, orally, once daily for 7 days, dose level dependent on Panel assignment

Drug: Placebo
Placebo tablets, orally, once daily for 7 days

Experimental: Panel G: GT1, dose based on Panels A+B+C
Participants with GT1 HCV will be dosed with MK-2748 daily for 7 days based on the safety, pharmacokinetic, and/or pharmacodynamic data from Panels A (low dose), B (lower dose), and C.
Drug: MK-2748
MK-2748 tablets, orally, once daily for 7 days, dose level dependent on Panel assignment

Drug: Placebo
Placebo tablets, orally, once daily for 7 days

Experimental: Panel H: GT1, dose based on Panels A+B+C+G
Participants with GT1 HCV will be dosed with MK-2748 daily for 7 days based on the safety, pharmacokinetic, and/or pharmacodynamic data from Panels A (low dose), B (lower dose), C, and G.
Drug: MK-2748
MK-2748 tablets, orally, once daily for 7 days, dose level dependent on Panel assignment

Drug: Placebo
Placebo tablets, orally, once daily for 7 days

Experimental: Panel D: GT3, low dose (Omitted)
Participants with genotype 3 (GT3) HCV were to receive low dose MK-2748 daily for 7 days. Panel D was omitted from the study design and participants were not enrolled in this panel.
Drug: MK-2748
MK-2748 tablets, orally, once daily for 7 days, dose level dependent on Panel assignment

Drug: Placebo
Placebo tablets, orally, once daily for 7 days

Experimental: Panel E: GT3, high dose
Participants with genotype 3 (GT3) HCV will receive high dose MK-2748 daily for 7 days.
Drug: MK-2748
MK-2748 tablets, orally, once daily for 7 days, dose level dependent on Panel assignment

Drug: Placebo
Placebo tablets, orally, once daily for 7 days

Experimental: Panel F: GT3, dose based on Panel E
Participants with GT3 HCV will be dosed with MK-2748 daily for 7 days based on the safety, pharmacokinetic, and/or pharmacodynamic data from Panel E (high dose).
Drug: MK-2748
MK-2748 tablets, orally, once daily for 7 days, dose level dependent on Panel assignment

Drug: Placebo
Placebo tablets, orally, once daily for 7 days

Experimental: Panel I: GT3, dose based on Panels E+F
Participants with GT3 HCV will be dosed with MK-2748 daily for 7 days based on the safety, pharmacokinetic, and/or pharmacodynamic data from Panels E (high dose) and F.
Drug: MK-2748
MK-2748 tablets, orally, once daily for 7 days, dose level dependent on Panel assignment

Drug: Placebo
Placebo tablets, orally, once daily for 7 days

Experimental: Panel J: GT3, dose based on Panels E+F+I
Participants with GT3 HCV will be dosed with MK-2748 daily for 7 days based on the safety, pharmacokinetic, and/or pharmacodynamic data from Panels E (high dose), F, and I.
Drug: MK-2748
MK-2748 tablets, orally, once daily for 7 days, dose level dependent on Panel assignment

Drug: Placebo
Placebo tablets, orally, once daily for 7 days




Primary Outcome Measures :
  1. Change from baseline in HCV RNA viral load (log 10 copies/mL) in GT1 HCV-infected participants [ Time Frame: Predose on Day 1 through Day 56 ]
  2. Change from baseline in HCV RNA viral load (log 10 copies/mL) in GT3 HCV-infected participants [ Time Frame: Predose on Day 1 through Day 56 ]
  3. Number of participants experiencing clinical or laboratory adverse events (AEs) [ Time Frame: From first dose up to 21 days ]
  4. Number of participants discontinued from study treatment due to AEs [ Time Frame: From Day 1 through Day 7 ]

Secondary Outcome Measures :
  1. Area under the plasma concentration curve from Hour 0 to Hour 24 (AUC0-24hr) for MK-2748 [ Time Frame: Day 1 and Day 7, predose through 24 hours post-dose ]
  2. Plasma concentration of MK-2748 (C24) on Day 7 of dosing [ Time Frame: 24 hours post-dose on Day 7 ]


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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 infection (GT1 or GT3) for at least 6 months and detectable HCV-RNA in peripheral blood
  • Body mass index (BMI) of 18 to 37 kg/m^2
  • No clinically significant abnormality on electrocardiogram (ECG)
  • Stable health
  • Willing to use appropriate contraception throughout the study and for 90 days after last dose of study drug

Exclusion criteria:

  • Participant is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study
  • History of stroke, chronic seizures, or major neurological disorder
  • History of clinically significant endocrine, gastrointestinal (excepting HCV infection), cardiovascular, hematological, hepatic, immunological, renal, respiratory, or genitourinary abnormalities or diseases
  • History of neoplastic disease (exceptions of adequately treated non-melanomatous skin carcinoma or carcinoma in situ of the cervix, or other malignancies which have been successfully treated ≥10 years prior and unlikely to recur
  • Positive Hepatitis B surface antigen
  • Documented human immunodeficiency virus (HIV) infection
  • Consumption of excessive amounts of alcohol, defined as greater than 2 glasses of alcoholic beverages (1 glass is approximately equivalent to: beer [284 mL/10 ounces],wine [125 mL/4 ounces], or distilled spirits [25 mL/1 ounce]) per day
  • Consumption of excessive amounts, defined as greater than 6 servings (1 serving is approximately equivalent to 120 mg of caffeine) or coffee, tea, cola, or other caffeinated beverages per day
  • Major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to study enrollment
  • History of significant multiple and/or severe allergies (including latex allergy), or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food
  • Current regular user (including "recreational use") of any illicit drugs or history of drug (including alcohol) abuse within approximately 2 months prior to enrollment
  • Evidence or history of chronic hepatitis not caused by HCV including but not limited to non-HCV viral hepatitis, non-alcoholic steatohepatitis (NASH), drug induced hepatitis, autoimmune hepatitis
  • Previous treatment with other HCV NS3/4A protease inhibitors
  • Previous exposure to interferon-alpha and/or ribavirin within 3 months prior to study enrollment
  • Clinical or laboratory evidence of advanced or decompensated liver disease; evidence of bridging fibrosis or higher grade fibrosis (Metavir score ≥3)
  • Participation in another investigational study within 4 weeks prior to enrollment

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01593735     History of Changes
Other Study ID Numbers: 2748-002
2011-006296-18 ( EudraCT Number )
First Posted: May 8, 2012    Key Record Dates
Last Update Posted: January 22, 2015
Last Verified: January 2015

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections