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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01593735
First received: May 4, 2012
Last updated: February 18, 2014
Last verified: February 2014
  Purpose

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 Intervention Phase
Hepatitis C
Drug: MK-2748
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, 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

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Number of participants experiencing clinical or laboratory adverse events (AEs) [ Time Frame: From first dose up to 21 days ] [ Designated as safety issue: Yes ]
  • Number of participants discontinued from study treatment due to AEs [ Time Frame: From Day 1 through Day 7 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • Plasma concentration of MK-2748 (C24) on Day 7 of dosing [ Time Frame: 24 hours post-dose on Day 7 ] [ Designated as safety issue: No ]

Enrollment: 30
Study Start Date: May 2012
Study Completion Date: February 2013
Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01593735     History of Changes
Other Study ID Numbers: 2748-002, 2011-006296-18
Study First Received: May 4, 2012
Last Updated: February 18, 2014
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on July 23, 2014