Clinical trial NCT00954993: Pharmacokinetics of Vaniprevir (MK-7009) and Hepatitis C Virus RNA Levels After Vaniprevir Treatment (MK-7009-029)
Official title: A Multiple Dose Study to Evaluate Pharmacokinetics and Hepatitis C Virus RNA Following Administration of MK-7009 in Hepatitis C Infected Patients
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Chronic Hepatitis C Infection
Keywords: Hepatitis C Virus (HCV)
Vaniprevir
MK-7009
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2009-08-07
Enrollment: 3
Sex: ALL
Minimum age (years): 40
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


Eligibility 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.
* 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 met pre-specified criteria based on laboratory values at screening for the following: -- 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

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.
* 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-log\^10 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 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 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
* 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

Primary outcomes:
measure: Area Under the Curve (AUC) (0-12 Hrs) of Vaniprevir in the Liver
timeFrame: 6, 12 and 24 hours postdose on day 4 of each period (up to Day 148)
measure: Concentration of Vaniprevir in the Liver
timeFrame: 6, 12 and 24 hours postdose on day 4 of each period (up to day 148)
measure: Apparent Terminal Half-life (t-1/2) of Vaniprevir in the Liver
timeFrame: 6, 12 and 24 hours postdose on day 4 of each period (up to day 148)
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: