NCT00994773

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
32

participants targeted

Target at P50-P75 for phase_1

Timeline
Completed

Started Dec 2009

Typical duration for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 10, 2009

Completed
4 days until next milestone

First Posted

Study publicly available on registry

October 14, 2009

Completed
2 months until next milestone

Study Start

First participant enrolled

December 1, 2009

Completed
1.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2011

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2011

Completed
Last Updated

August 16, 2012

Status Verified

August 1, 2012

Enrollment Period

1.8 years

First QC Date

October 10, 2009

Last Update Submit

August 15, 2012

Conditions

Hepatitis B

Keywords

Hepatitis BsimvastatinHBV DNA

Outcome Measures

Primary Outcomes (1)

  • Reduction of HBV DNA by one log.

    Simvastatin will be given in doses of 5,10,20,and 40mg per day

    14 days

Secondary Outcomes (1)

  • Alanine aminotransferase (ALT) reduction

    14 days

Study Arms (3)

Simvastatin

EXPERIMENTAL

Simvastatin orally

Drug: Simvastatin

Simvastatin and tenofovir

EXPERIMENTAL

Simvastatin combined with tenofovir

Drug: SimvastatinDrug: Tenofovir

Simvastatin and entecavir

EXPERIMENTAL

Simvastatin combined with entecavir

Drug: SimvastatinDrug: Entecavir

Interventions

SimvastatinDRUG

daily doses for 14 days

Also known as: Zocor
SimvastatinSimvastatin and entecavirSimvastatin and tenofovir
TenofovirDRUG
Simvastatin and tenofovir
EntecavirDRUG

Entecavir

Simvastatin and entecavir

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

  • Use of any anti-HBV medicine within 30 days.
  • 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).
  • 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.
  • Severe cardiovascular disease (ejection fraction \<20%)\* or uncontrolled angina.
  • Severe pulmonary disease (FEV1 \< 1.0).
  • Chronic renal insufficiency (creatinine clearance \<50 ml/min.
  • HIV positive patients.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

VA Medical Center

Oklahoma City, Oklahoma, 74104, United States

Location

MeSH Terms

Conditions

Hepatitis B

Interventions

SimvastatinTenofovirentecavir

Condition Hierarchy (Ancestors)

Blood-Borne InfectionsCommunicable DiseasesInfectionsHepadnaviridae InfectionsDNA Virus InfectionsVirus DiseasesHepatitis, Viral, HumanHepatitisLiver DiseasesDigestive System Diseases

Intervention Hierarchy (Ancestors)

LovastatinNaphthalenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsPolycyclic CompoundsOrganophosphonatesOrganophosphorus CompoundsAdeninePurinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic Compounds

Study Officials

  • Teddy Bader, M.D.

    University of Oklahoma

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDIV
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Director of Liver Diseases, OUHSC/VAMC

Study Record Dates

First Submitted

October 10, 2009

First Posted

October 14, 2009

Study Start

December 1, 2009

Primary Completion

October 1, 2011

Study Completion

December 1, 2011

Last Updated

August 16, 2012

Record last verified: 2012-08

Locations

US(1)