Hepatic Pharmacokinetic Profile for Vaniprevir (MK-7009) and Hepatitis C Virus RNA Levels After Vaniprevir Administration (Study MK-7009-029-02)

This study has been terminated.
(This study was stopped for business and program changes. There is a plan to replace this study with a similar study design, but different study number.)
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00954993
First received: August 6, 2009
Last updated: October 25, 2013
Last verified: October 2013
  Purpose

This study will evaluate the hepatic (liver) and plasma pharmacokinetics of Vaniprevir (MK-7009) by evaluation of RNA of the hepatitis C virus (HCV) in genotype 1, HCV-infected participants.


Condition Intervention Phase
Chronic Hepatitis C Infection
Drug: MK-7009 (Vaniprevir)
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multiple Dose Study to Evaluate Pharmacokinetics and Hepatitis C Virus RNA Following Administration of MK-7009 in Hepatitis C Infected Patients

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Steady-state hepatic pharmacokinetics of Vaniprevir (AUC) [ Time Frame: 0 to 24 hours postdose ] [ Designated as safety issue: No ]
    Area under the liver concentration versus time curve

  • Steady-state hepatic pharmacokinetics of Vaniprevir (concentration of drug in the liver) [ Time Frame: 6 hour, 12 hour, 24 hour postdose ] [ Designated as safety issue: No ]
    Concentration of drug in the liver at 6, 12, and 24 hours postdose.

  • Steady-state hepatic pharmacokinetics of Vaniprevir(apparent terminal half-life) [ Time Frame: 0 to 24 hours postdose ] [ Designated as safety issue: No ]
    Half-life of drug in plasma


Enrollment: 3
Study Start Date: September 2010
Study Completion Date: March 2011
Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Vaniprevir
Vaniprevir (MK-7009) treatment
Drug: MK-7009 (Vaniprevir)
Period 1: Vaniprevir 600 mg twice daily on Days 1-3 and a single dose of Vaniprevir 600 mg on Day 4. Period 2: Vaniprevir 300 mg twice daily on Days 1-3 and a single dose of Vaniprevir 300 mg on Day 4. There will be at least a 30-day washout interval between periods 1 and 2.

  Eligibility

Ages Eligible for Study:   40 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Participant is a male or female between 40 to 65 years of age at the prestudy (screening) visit
  • Participant has a Body Mass Index (BMI) ≥18.5 kg/m2 and ≤36.0 kg/m2. BMI is calculated by taking the Participant's weight in kg and dividing by the Participant's height in meters squared
  • Participant requires a diagnostic biopsy, per local treatment guidelines, to monitor progression of liver disease.
  • Participant has chronic compensated, genotype 1 HCV infection as defined by positive serology for HCV and detectable HCV RNA in peripheral blood

Participant has the following laboratory values at the screening visit:

  • Alanine aminotransferase (ALT): ≤400 U/L
  • Aspartate aminotransferase AST: ≤400 U/L
  • Total bilirubin: ≤2.4 mg/dL
  • Direct bilirubin: ≤1.0 mg/dL
  • Creatinine clearance (Clcr): ≥60 mL/min (by the Cockcroft-Gault equation*)
  • Albumin: ≥3.3 g/dL
  • Alkaline phosphatase: ≤260 U/L
  • Hemoglobin: ≥13 g/dL (men), ≥12 g/dL (women)
  • White blood cell count: 3.8 to 10.7 ×103/μL
  • Absolute neutrophil count: ≥1.5 ×103/μL
  • Platelet count: ≥120 ×103/μL
  • International normalized ratio (INR): ≤1.2
  • Thyroid stimulating hormone (TSH): 0.34 to 5.60 μIU/mL
  • Alpha fetoprotein (AFP): <100 ng/mL

    • Participant does not have cirrhosis as confirmed by FibroSure™/FibroTest®
    • Participant is treatment-experienced, with regard to prior treatment for chronic HCV infection
    • Participant has the ability to avoid use of anticoagulants, nonsteroidal anti-inflammatory agents and aspirin for at least five (5) days preceding the initial liver biopsy and continuing throughout the entire study
    • Participant understands the study procedures and agrees to participate in the study by giving written informed consent
    • Participant is willing to comply with the study restrictions

Exclusion Criteria:

  • Participant is under the age of legal consent, is mentally or legally incapacitated/ institutionalized, has significant emotional problems at the time of prestudy screening visit or expected during the conduct of the study or has a history of a clinically significant psychiatric disorder which, in the opinion of the investigator, would interfere with the study procedures. Controlled psychiatric disorders are allowable conditions if participants are well controlled at the time of enrollment and are expected to remain well controlled during the study in the opinion of the investigator
  • Participant has a history of stroke, chronic seizures, or major neurological disorder
  • Participant did not achieve a viral response to prior treatment with licensed interferon-based therapy (i.e., is a 'null responder'). Viral response is defined by a ≥2-logˆ10 decline in HCV viral RNA within the first 12 weeks of therapy
  • Participant has previously been treated with an NS3/4A protease inhibitor for chronic HCV infection
  • Evidence of high grade bridging fibrosis (eg, METAVIR score >3, Ishak score >4 or Scheuer score >3) from prior liver biopsy within 3 years of study entry
  • Participant has evidence or history of chronic hepatitis not caused by HCV including but not limited to non-HCV viral hepatitis, nonalcoholic steatohepatitis (NASH), drug-induced hepatitis or autoimmune hepatitis. Note: Participants with history of acute non- HCV-related hepatitis which resolved >6 months before study entry can be enrolled
  • Participant has clinical or laboratory evidence of cirrhosis or other advanced liver disease
  • Participant has decompensated liver disease as indicated by a history of ascites, hepatic encephalopathy, or bleeding esophageal varices
  • Participant has been diagnosed or suspected of hepatocellular carcinoma
  • Participant has clinically significant abnormality on electrocardiogram (ECG) performed at the prestudy screening visit
  • Participant has coinfection with human immunodeficiency virus (HIV)
  • Participant has positive Hepatitis B surface antigen or other evidence of active Hepatitis B infection
  • Participant has a history of gastric bypass surgery, bowel resection or other disorder that in the opinion of the investigator may interfere with the absorption of the study medication
  • Participant has a history of clinically significant uncontrolled endocrine, gastrointestinal, cardiovascular, hematological, immunological, renal, respiratory, or genitourinary abnormalities or diseases
  • Participant has a history of neoplastic disease (including leukemia, lymphoma, malignant melanoma), or myeloproliferative disease, regardless of the time since treatment
  • Participant has any condition or prestudy laboratory abnormality, or history of any illness, which, in the opinion of the investigator, might confound the results of the study or pose additional risk in administering the study drug to the Participant
  • At the time of screening, Participant consumes excessive amounts of alcohol, defined as greater than 3 glasses of alcoholic beverages (1 glass is approximately equivalent to: beer [284 mL], wine [125 mL], or distilled spirits [25 mL]) per day
  • Participant is currently a regular user (including use of any illicit drugs or has a history of drug (including alcohol) abuse within the last 3 months
  • Within 2 weeks prior to first study dose and through the study follow-up period, Participant is taking or is anticipated to require any prescription or nonprescription medications not identified as prohibited in Section 3.2.1.
  • Participant has had surgery, donated 1 unit of blood (approximately 500 mL) or participated in another investigational study within a period of 4 weeks prior to the prestudy (screening) visit
  • Participant has a history of multiple and/or severe allergies, or has had an anaphylactic reaction or intolerability to prescription or nonprescription drugs or food
  • Female participant is pregnant, lactating, expecting to conceive or donate eggs, or is of childbearing potential and unwilling to commit to two methods of birth control as outlined in inclusion criterion
  • Male Participant is planning to impregnate or provide sperm donation or has a female sexual partner of childbearing potential and is unwilling to commit to using two methods of birth control as outlined in inclusion criterion
  • There is any concern by the investigator regarding the safe participation of the participant in the study or for any other reason; the investigator considers the participant inappropriate for participation in the study
  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: NCT00954993     History of Changes
Other Study ID Numbers: 7009-029, 7009-029-02
Study First Received: August 6, 2009
Last Updated: October 25, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Merck Sharp & Dohme Corp.:
Hepatitis C Virus (HCV)
Vaniprevir
MK-7009

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis, Chronic
Hepatitis C
Hepatitis C, Chronic
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 29, 2014