A Study to Compare Tenofovir DF Versus the Combination of Emtricitabine Plus Tenofovir DF for the Treatment of Chronic Hepatitis B in Patients With Normal Alanine Aminotransferase (ALT)
| Status: | Completed |
|---|---|
| Conditions: | Hepatitis, Hepatitis |
| Therapuetic Areas: | Immunology / Infectious Diseases |
| Healthy: | No |
| Age Range: | 18 - 69 |
| Updated: | 4/21/2016 |
| Start Date: | September 2007 |
| End Date: | August 2012 |
A Randomized, Double-Blind Study Evaluating Tenofovir Disoproxil Fumarate (DF) Monotherapy Versus the Combination of Emtricitabine and Tenofovir DF for the Treatment of Chronic Hepatitis B
The main objective of the study was to evaluate the antiviral activity of tenofovir
disoproxil fumarate (tenofovir DF) monotherapy versus emtricitabine (FTC) plus tenofovir DF
combination therapy for the treatment of chronic hepatitis B (HBV) in participants in the
immune tolerant phase of HBV infection.
The efficacy of tenofovir DF monotherapy versus FTC plus tenofovir DF combination therapy
was evaluated for suppression of the virus (decrease in HBV DNA), serological response
(generation of antibodies to the virus), biochemical response (changes in liver enzymes),
and the development of drug-resistant mutations. The safety and tolerability of both
tenofovir DF monotherapy and FTC plus tenofovir DF were evaluated by routine monitoring for
adverse events and changes in laboratory parameters.
Participants were randomized in a 1:1 ratio to receive tenofovir DF monotherapy or FTC plus
tenofovir DF. All subjects were to continue on blinded study medication until the last
subject reached Week 192. Participants who permanently discontinued study drug (on or before
Week 192) were followed for a 24-week treatment-free follow-up period, or until initiation
of alternative HBV therapy, whichever occurred first. Subjects who discontinued study drug
on or after Week 48 because of hepatitis B surface antigen (HBsAg) loss or seroconversion to
antibody to hepatitis B surface antigen (anti-HBs), however, were to have returned for their
regularly scheduled through Week 192 and every 16 weeks thereafter until the last subject
reached Week 192.
disoproxil fumarate (tenofovir DF) monotherapy versus emtricitabine (FTC) plus tenofovir DF
combination therapy for the treatment of chronic hepatitis B (HBV) in participants in the
immune tolerant phase of HBV infection.
The efficacy of tenofovir DF monotherapy versus FTC plus tenofovir DF combination therapy
was evaluated for suppression of the virus (decrease in HBV DNA), serological response
(generation of antibodies to the virus), biochemical response (changes in liver enzymes),
and the development of drug-resistant mutations. The safety and tolerability of both
tenofovir DF monotherapy and FTC plus tenofovir DF were evaluated by routine monitoring for
adverse events and changes in laboratory parameters.
Participants were randomized in a 1:1 ratio to receive tenofovir DF monotherapy or FTC plus
tenofovir DF. All subjects were to continue on blinded study medication until the last
subject reached Week 192. Participants who permanently discontinued study drug (on or before
Week 192) were followed for a 24-week treatment-free follow-up period, or until initiation
of alternative HBV therapy, whichever occurred first. Subjects who discontinued study drug
on or after Week 48 because of hepatitis B surface antigen (HBsAg) loss or seroconversion to
antibody to hepatitis B surface antigen (anti-HBs), however, were to have returned for their
regularly scheduled through Week 192 and every 16 weeks thereafter until the last subject
reached Week 192.
Inclusion Criteria:
- Chronic HBV infection, defined as positive serum HBsAg for at least 6 months or HBsAg
positive > 3 months and positive for immunoglobulin G antibody against hepatitis B
core antigen
- 18 through 69 years of age, inclusive
- Hepatitis B e antigen (HBeAg) positive
- HBV DNA ≥ 10^8 copies/mL
- ALT ≤ the upper limit of the normal range (ULN)
- Willing and able to provide written informed consent
- Negative serum beta-human chorionic gonadotropin (for females of childbearing
potential only)
- Calculated creatinine clearance ≥ 70 mL/min
- Hemoglobin ≥ 10 g/dL
- Neutrophils ≥ 1,500/mm^3
- No prior oral HBV therapy (eg, nucleotide and/or nucleoside therapy or other
investigational agents for HBV infection)
Exclusion Criteria:
- Pregnant women, women who were breast feeding, or who believed they may have wished
to become pregnant during the course of the study
- Males and females of reproductive potential unwilling to use an effective method of
contraception during the study
- Decompensated liver disease defined as direct (conjugated) bilirubin > 1.2 x ULN,
prothrombin time > 1.2 x ULN, platelets < 150,000/mm^3, serum albumin < 3.5 g/dL, or
prior history of clinical hepatic decompensation (eg, ascites, jaundice,
encephalopathy, or variceal hemorrhage)
- Received interferon (pegylated or not) therapy within 6 months of the screening visit
- Alpha-fetoprotein > 50 ng/mL
- Evidence of hepatocellular carcinoma
- Coinfection with hepatitis C virus (by serology), HIV, or hepatitis D virus
- Significant renal, cardiovascular, pulmonary, or neurological disease
- Received solid organ or bone marrow transplantation
- Was currently receiving therapy with immunomodulators (eg, corticosteroids, etc.),
investigational agents, nephrotoxic agents, or agents susceptible of modifying renal
excretion
- Had proximal tubulopathy
- Known hypersensitivity to the study drugs, the metabolites, or formulation excipients
We found this trial at
10
sites
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials