Pharmacokinetics of Vaniprevir (MK-7009) and Hepatitis C Virus RNA Levels After Vaniprevir Treatment (MK-7009-029)

Chronic Hepatitis C Infection Clinical Trial

Official title:

A Multiple Dose Study to Evaluate Pharmacokinetics and Hepatitis C Virus RNA Following Administration of MK-7009 in Hepatitis C Infected Patients

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00954993
• Other study ID #: 7009-029
• Secondary ID: 2009-013076-41
• Status: Terminated
• Phase: Phase 1
• Start date: January 13, 2010
• Est. completion date: March 4, 2011

Study information

• Verified date: September 2018
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: March 4, 2011
• Est. primary completion date: March 4, 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Chronic Hepatitis C Infection
• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• 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 was at least a 30-day (up to approximately 140-day) washout interval between periods 1 and 2.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area Under the Curve (AUC) (0-12 Hrs) of Vaniprevir in the Liver	Participants were treated with vaniprevir twice daily on days 1,2, and 3. On treatment Day 4 participants were treated once with vaniprevir; then core needle liver biopsies were to be collected at 6, 12 and 24 hours postdose to determine the AUC of vaniprevir. AUC is the integrated area under the curve for plasma concentration of vaniprevir over time.	6, 12 and 24 hours postdose on day 4 of each period (up to Day 148)
Primary	Concentration of Vaniprevir in the Liver	Participants were treated with vaniprevir on days, 1,2, and 3. On treatment Day 4 participants were treated once with vaniprevir; then core needle liver biopsies were collected at 6, 12, and 24 hours postdose to determine the concentration of vaniprevir in the liver.	6, 12 and 24 hours postdose on day 4 of each period (up to day 148)
Primary	Apparent Terminal Half-life (t-1/2) of Vaniprevir in the Liver	Participants were treated with vaniprevir twice daily on days 1,2, and 3. On treatment Day 4 participants were treated once with vaniprevir; then core needle liver biopsies were to be collected at 6, 12 and 24 hours postdose to determine the t-1/2 of vaniprevir. The t-1/2 is the time taken to eliminate half the amount of vaniprevir.	6, 12 and 24 hours postdose on day 4 of each period (up to day 148)