Viral Kinetics Study of Telbivudine and Entecavir in Adults With Chronic Hepatitis B

Hepatitis B Clinical Trial

Official title:

A Randomized, Open-label, Controlled, Multicenter, Exploratory Trial to Characterize the Results of Daily Oral Administration of Telbivudine (LDT600) 600 mg or Entecavir (ETV) 0.5 mg Given Over 12 Weeks on the Kinetics of Hepatitis B Virus (HBV) DNA in Adults With HBeAg-positive, Compensated Chronic Hepatitis B (CHB)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00412529
• Other study ID #: CLDT600A2407
• Status: Completed
• Phase: Phase 3
• First received: December 15, 2006
• Last updated: February 23, 2015
• Start date: December 2006

Study information

• Verified date: February 2015
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: Korea: Food and Drug AdministrationUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This exploratory study is designed to determine the early viral kinetic profile during treatment with telbivudine or entecavir at multiple time points over 12 weeks.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 44
• Est. primary completion date: February 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Male or female, 18-70 years of age with documented compensated hepatitis B "e" antigen (HBeAg)-positive chronic hepatitis B

• Able to comply with study regimen and provide written informed consent

Exclusion Criteria:

• Pregnant or breastfeeding

• Unwilling to use double barrier method of contraception

• Co-infected with hepatitis C virus (HCV), hepatitis D virus (HDV) or human immunodeficiency virus (HIV)

• Received Hepatitis B therapy in the past

• Use of immunomodulatory therapy in past 12 months

• History of or symptoms of hepatic decompensation or pancreatitis

• Frequent or prolonged use of potentially hepatotoxic or nephrotoxic drugs

• Concurrent medication likely to preclude compliance with schedule of evaluations

• Use of other investigational drugs within 30 days of enrollment

• Abnormal laboratory values during screening

Other protocol-defined inclusion/exclusion criteria may apply

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Hepatitis B
• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• Entecavir
Entecavir 0.5 mg once daily for 12 weeks.
• Telbivudine
Telbivudine 600 mg once daily for 12 weeks.

Locations

Country	Name	City	State
Korea, Republic of	Holy Family Hospital_Bucheon	Bucheon,Kyunggi
Korea, Republic of	Inje University Busan Paik Hospital	Busan
Korea, Republic of	Yeungnam University Medical Center	Daegu
Korea, Republic of	Gachon Univ. Gil Medical Center Hospital	Incheon
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Kangnam Sacred Heart Hospital	Seoul
Korea, Republic of	Korea University Medical Center_Anam	Seoul
Korea, Republic of	The Catholic University of Korea	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (1)

Suh DJ, Um SH, Herrmann E, Kim JH, Lee YS, Lee HJ, Lee MS, Lee YJ, Bao W, Lopez P, Lee HC, Avila C, Zeuzem S. Early viral kinetics of telbivudine and entecavir: results of a 12-week randomized exploratory study with patients with HBeAg-positive chronic he — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Mean Hepatitis B Virus (HBV) DNA Levels	Baseline HBV DNA is defined as the last pre-dose assessment of HBV DNA.	Baseline (day 1) to Week 12 (day 85)	No
Secondary	Change in Mean HBV DNA Level	Baseline HBV DNA is defined as the last pre-dose assessment of HBV DNA.HBV DNA reductions, considered as the repeated measures, from baseline to Weeks 2, 4, 8.	Baseline (day 1) to Weeks 2, 4, 8	No
Secondary	The Area Under the Curve (AUC) of HBV DNA Change.	In AUC efficacy analyses, all the visits from baseline to Week 12 visit (including the planned and the repeated) with a non-missing HBV DNA level were included.	From Baseline to Week 12	No
Secondary	Change in Alanine Aminotransferase (ALT) Levels		From Baseline to Week 12	No
Secondary	Characterization of Very Early Viral Kinetics: Estimation of Viral Clearance	Viral kinetic parameters were estimated with a bi-phasic mathematical model: V(t) = (1-e)pI(t) - cV(t); I(t) = (1- ?)TV(t) - dI(t); V serum viral load, I productively infected cells, e efficiency factor of blocking virus production, p viral production rate, c viral clearance rate, ? efficiency factor of blocking de novo infection, ß de novo infection rate, T uninfected target cells, d rate of infected cell loss. Maximum-likelihood estimation for the viral kinetic parameters entailed fitting a nonlinear differential equation system via the least-squares approach from serum HBV DNA data.	Baseline to 12 weeks	No
Secondary	Characterization of Very Early Viral Kinetics: Estimation of the Rate of Infected Cell Loss	Viral kinetic parameters were estimated with a bi-phasic mathematical model: V(t) = (1-e)pI(t) - cV(t); I(t) = (1- ?)TV(t) - dI(t); V serum viral load, I productively infected cells, e efficiency factor of blocking virus production, p viral production rate, c viral clearance rate, ? efficiency factor of blocking de novo infection, ß de novo infection rate, T uninfected target cells, d rate of infected cell loss. Maximum-likelihood estimation for the viral kinetic parameters entailed fitting a nonlinear differential equation system via the least-squares approach from serum HBV DNA data.	Baseline to 12 weeks	No
Secondary	Characterization of Very Early Viral Kinetics: Estimation of the Efficiency Factor of Blocking Virus Production	Viral kinetic parameters were estimated with a bi-phasic mathematical model of HBV DNA by using compartments of free virus, infected cells, and uninfected target cells. The model parameter of interest was the effectiveness of the drug in blocking virus production from infected cells (efficacy, e). Blocking efficiency was within the range between 0 and 1.	Baseline to 12 weeks	No
Secondary	Number of Patients Who Are Polymerase Chain Reaction (PCR) Negative	PCR negative was considered <300 copies/mL. PCR positive was considered =>300 copies/mL.	At Week 12	No

External Links

•   Early Viral Kinetics of Telbivudine and Entecavir: Results of a 12-Week Randomized Exploratory Study with Patients with HBeAg-Positive Chronic Hepatitis B