Chronic Hepatitis C InfectionPhase 1NCT00954993

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

A Phase 1 study testing Vaniprevir in people with Chronic Hepatitis C Infection, run by Merck Sharp & Dohme LLC.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

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. Read more about this study

Who is it for?: Ages 40 to 65 years
Conditions the study is for: Chronic Hepatitis C Infection
What is being tested?: Vaniprevir
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 3 participants
Where: No sites listed yet
Study dates: 13 Jan 2010to 4 Mar 2011
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 40 to 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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.

Show all 18Show fewer

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

About this study

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

Conditions: Chronic Hepatitis C Infection
Being tested: Vaniprevir
Keywords: Hepatitis C Virus (HCV), Vaniprevir, MK-7009
Medical subject headings: Hepatitis C

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

VaniprevirDrug
Also called MK-7009
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.

Study groups in NCT00954993
Study group	Role	What they receive
Vaniprevir 600 mg - 300 mg	Experimental	For each participant in period 1, 600 mg of Vaniprevir was taken twice daily on Days 1-3 and a single dose of Vaniprevir 600 mg was taken on Day 4. Period 1 was followed by a minimum 30-day, up to approximately 140 day, washout interval. In period 2, 300 mg of Vaniprevir was taken twice daily by each participant on Days 1-3 and a single dose of Vaniprevir 300 mg was taken on Day 4. Receives: Drug: Vaniprevir

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 6, 12 and 24 hours postdose on day 4 of each period (up to Day 148)
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.
Measured: 6, 12 and 24 hours postdose on day 4 of each period (up to day 148)
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.
Measured: 6, 12 and 24 hours postdose on day 4 of each period (up to day 148)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

13 Jan 20104 Mar 2011

First posted7 Aug 2009 (estimated)
Study start13 Jan 2010
Primary completion4 Mar 2011
Study completion4 Mar 2011

Why it stopped: This study was stopped for business and program changes. At no time was the safety of any participants at risk.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Chronic Hepatitis C InfectionStudies of the same condition, open and under way.
More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 3 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00954993
Sponsor's protocol ID: 7009-029
Other IDs: 2009-013076-41, 2009
Status last verified: Sep 2018
First submitted: 6 Aug 2009
Last updated: 18 Oct 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: Yes: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

RecruitingObservational study
Evaluation of Patients With Liver Disease
Hepatitis D, Hepatitis C
Active, not recruitingPhase 4
People With CHC Who Achieved a Sustained Virological Response Following Therapy With Direct Acting Antiviral Agents
Diabetes Mellitus, Hepatitis C, Chronic
RecruitingObservational study
"Constitution of a Biological Collection to Establish Preclinical Translational Models for the Study of Tumors and Chronic Liver Diseases".
Chronic Liver Disease and Cirrhosis, Liver Cancer
Active, not recruitingPhase 4
Sofosbuvir/Velpatasvir Treatment of Chronic Hepatitis C During Pregnancy
Hepatitis C, Chronic, Pregnancy; Infection
Enrolling by invitationObservational study
Comparative Autoantibody and Immunologic Cell Marker Study
Autoimmune Diseases, Lupus Erythematosus, Systemic

All Chronic Hepatitis C Infection trials

Study at a glance

From the registry record, last updated by the sponsor on 18 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Multiple Dose Study to Evaluate Pharmacokinetics and Hepatitis C Virus RNA Following Administration of MK-7009 in Hepatitis C Infected Patients
ClinicalTrials.gov ID: NCT00954993
Acronym / sponsor ID: 7009-029
Conditions: Chronic Hepatitis C Infection
Keywords: Hepatitis C Virus (HCV), Vaniprevir, MK-7009
Phase: Phase 1
Study type: Interventional
Recruitment status: TerminatedReason stopped: This study was stopped for business and program changes. At no time was the safety of any participants at risk.
Enrolment: 3 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: 13 Jan 2010 (actual)
Primary completion: 4 Mar 2011 (actual)
Study completion: 4 Mar 2011 (actual)
First posted: 7 Aug 2009 (estimated)
Results: Posted 29 Sep 2014

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Vaniprevir 600 mg - 300 mg	Experimental	Drug: VaniprevirFor each participant in period 1, 600 mg of Vaniprevir was taken twice daily on Days 1-3 and a single dose of Vaniprevir 600 mg was taken on Day 4. Period 1 was followed by a minimum 30-day, up to approximately 140 day, washout interval. In period 2, 300 mg of Vaniprevir was taken twice daily by each participant on Days 1-3 and a single dose of Vaniprevir 300 mg was taken on Day 4.

Who may qualify

Ages: 40 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (8 listed)

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

Key exclusion criteria (18 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
VaniprevirAlso: MK-7009Period 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.	Drug	Vaniprevir 600 mg - 300 mg

Primary outcome

Area Under the Curve (AUC) (0-12 Hrs) of Vaniprevir in the Liver
Time frame: 6, 12 and 24 hours postdose on day 4 of each period (up to Day 148)
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.
Concentration of Vaniprevir in the Liver
Time frame: 6, 12 and 24 hours postdose on day 4 of each period (up to day 148)
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.
Apparent Terminal Half-life (t-1/2) of Vaniprevir in the Liver
Time frame: 6, 12 and 24 hours postdose on day 4 of each period (up to day 148)
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.

Results and safety

Results posted to the registry on 29 Sep 2014, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Vaniprevir 600 mg - 300 mg Arm	3	3

Primary outcome: Area Under the Curve (AUC) (0-12 Hrs) of Vaniprevir in the Liver

Time frame: 6, 12 and 24 hours postdose on day 4 of each period (up to Day 148)

Population analysed: Since only a single liver sample timepoint at either 6 or 12 hours was obtained from each participant, and no 24 hour timepoint was collected from any participant due to the early termination of the study, the AUC (0-12 hrs) was not calculated

Primary outcome: Concentration of Vaniprevir in the Liver

Time frame: 6, 12 and 24 hours postdose on day 4 of each period (up to day 148). Median (Full Range). Unit: nM

Measure	600 mg Dose of Vaniprevir n = 3	300 mg Dose of Vaniprevir n = 3
6 Hours (n=2)	169000 (79100 to 258000)	84600 (67500 to 102000)
12 Hours (n=1)	53700 (53700 to 53700)	29400 (29400 to 29400)

Population analysed: Participants treated with vaniprevir who had a liver biopsy were analyzed as two separate groups that received 600 mg and 300 mg doses . No biopsies were collected at the 24 hour timepoint.

Primary outcome: Apparent Terminal Half-life (t-1/2) of Vaniprevir in the Liver

Time frame: 6, 12 and 24 hours postdose on day 4 of each period (up to day 148)

Population analysed: Since only a single liver sample timepoint was obtained from each participant at either 6 or 12 hours, and the 24 hour timepoint was not collected from any participant due to the early termination of the study, the t-1/2 could not be determined.

Adverse events

Time frame: Up to approximately Day 148. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
600 mg Dose of Vaniprevir	0 of 3 (0%)	3 of 3 (100%)	Not reported
300 mg Dose of Vaniprevir	0 of 3 (0%)	2 of 3 (66.7%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 18 Oct 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: Yes. https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Related trials for Chronic Hepatitis C Infection

RecruitingObservational study
Evaluation of Patients With Liver Disease
Hepatitis D, Hepatitis C
Active, not recruitingPhase 4
People With CHC Who Achieved a Sustained Virological Response Following Therapy With Direct Acting Antiviral Agents
Diabetes Mellitus, Hepatitis C, Chronic
RecruitingObservational study
"Constitution of a Biological Collection to Establish Preclinical Translational Models for the Study of Tumors and Chronic Liver Diseases".
Chronic Liver Disease and Cirrhosis, Liver Cancer
Active, not recruitingPhase 4
Sofosbuvir/Velpatasvir Treatment of Chronic Hepatitis C During Pregnancy
Hepatitis C, Chronic, Pregnancy; Infection
Enrolling by invitationObservational study
Comparative Autoantibody and Immunologic Cell Marker Study
Autoimmune Diseases, Lupus Erythematosus, Systemic

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Medical Director study director

Merck Sharp & Dohme LLC

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Vaniprevir in people with Chronic Hepatitis C Infection, run by Merck Sharp & Dohme LLC.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 18 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 29 Sep 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Area Under the Curve (AUC) (0-12 Hrs) of Vaniprevir in the Liver (time frame: 6, 12 and 24 hours postdose on day 4 of each period (up to Day 148)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00954993.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Oct 2018.