Simvastatin for the Treatment of Chronic Hepatitis B

Phase 1

Completed

• Conditions: Hepatitis B
• Interventions: Drug: Simvastatin; Drug: Entecavir; Drug: Tenofovir

• Registration Number: NCT00994773
• Lead Sponsor: Bader, Ted, M.D.

Brief Summary

The investigators have shown robust in vitro anti-hepatitis B activity of simvastatin alone and synergistic activity with all four FDA-approved anti-hepatitis B oral drugs tested. The investigators propose phase 1 studies in 48 chronic hepatitis B human carriers who have never been treated before. Doses of drugs will remain at or below FDA-approved dosage levels for cholesterol lowering (simvastatin) or hepatitis B (tenofovir or entecavir). Arm 1 will have simvastatin monotherapy only. Arm 2 will combine simvastatin with tenofovir. Arm 3 will combine simvastatin with entecavir. For maximum safety, the 3 arms and the dose groups in each arm will be filled consecutively and not concurrently. The definition of efficacy for simvastatin alone will be a 1 log drop of hepatitis B virus in 14 days. Efficacy for combination of drugs will require a 2 log drop of hepatitis B virus in 14 days. Numerous safety tests and stop rules are noted in the protocol.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2009-10-10
• Study First Submitted QC: 2009-10-13
• Study First Posted: 2009-10-14
• Study Start: 2009-12
• Primary Completion: 2011-10
• Study Completion: 2011-12
• Status Verified: 2012-08
• Last Update Submitted: 2012-08-15
• Last Update Posted: 2012-08-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 32

Inclusion Criteria

1. Hepatitis B positive by HBV DNA within 180 days.
2. Ages 18-70.
3. Men and non-pregnant women eligible.
4. Veteran's eligibility or appropriate health insurance.

Exclusion Criteria

1. Use of any anti-HBV medicine within 30 days.
2. Decompensated cirrhosis as evidenced by esophageal varices, ascites, or encephalopathy. (grade 1 varices without history of bleeding will be allowed, if patient meets Child's-Pugh functional classification grade A).
3. A positive urine test for marijuana or alcohol within 2 months of screening.(Allowed to repeat tests on different days, if positive first time in order to become eligible for study.
4. Severe cardiovascular disease (ejection fraction <20%)* or uncontrolled angina.
5. Severe pulmonary disease (FEV1 < 1.0).
6. Chronic renal insufficiency (creatinine clearance <50 ml/min.
7. HIV positive patients.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Simvastatin and entecavir	Simvastatin	Simvastatin combined with entecavir
Simvastatin and entecavir	Entecavir	Simvastatin combined with entecavir
Simvastatin and tenofovir	Simvastatin	Simvastatin combined with tenofovir
Simvastatin and tenofovir	Tenofovir	Simvastatin combined with tenofovir
Simvastatin	Simvastatin	Simvastatin orally

Primary Outcome Measures

Name	Time	Method
Reduction of HBV DNA by one log.	14 days	Simvastatin will be given in doses of 5,10,20,and 40mg per day

Secondary Outcome Measures

Name	Time	Method
Alanine aminotransferase (ALT) reduction	14 days	ALT changes will be noted

Trial Locations

Locations (1)

VA Medical Center; 🇺🇸 Oklahoma City, Oklahoma, United States