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:
Merck
Information provided by (Responsible Party):
Merck
ClinicalTrials.gov Identifier:
NCT01593735
First received: May 4, 2012
Last updated: March 5, 2013
Last verified: March 2013
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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:
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
No Contacts or Locations Provided
More Information
No publications provided
| Responsible Party: | Merck |
| ClinicalTrials.gov Identifier: | NCT01593735 History of Changes |
| Other Study ID Numbers: | 2748-002, 2011-006296-18 |
| Study First Received: | May 4, 2012 |
| Last Updated: | March 5, 2013 |
| 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 May 19, 2013