Evaluation of the Pharmacokinetics, Safety, Tolerability and Efficacy of Entecavir (ETV) in Pediatric Subjects With Chronic Hepatitis B Virus (HBV) Infection Who Are HBeAg-Positive

Bristol-Myers Squibb10 sites in 2 countries64 target enrollmentJune 30, 2007

ConditionsHepatitis B, Chronic

InterventionsEntecavir

DrugsEntecavir

Overview

Phase: Phase 1
Intervention: Entecavir
Conditions: Hepatitis B, Chronic
Sponsor: Bristol-Myers Squibb
Enrollment: 64
Locations: 10
Primary Endpoint: Number of Participants With Serious Adverse Events (SAE) and Discontinuations Due to Adverse Events (AEs) - On Treatment
Status: Completed
Last Updated: 8 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The purpose of this clinical study is to determine the appropriate doses of entecavir to use in children and adolescents. Safety, tolerability and efficacy will also be studied

Registry

clinicaltrials.gov

Start Date

June 30, 2007

End Date

September 4, 2017

Last Updated

8 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Bristol-Myers Squibb

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•2-18 years of age
•Group A: Lamivudine naive (\<1 week of Lamivudine) and not within 24 weeks of screening; Group B: Lamivudine experienced (\> 12 weeks of Lamivudine); Group C: nucleoside/nucleotide experienced (\> 12 weeks of nucleoside/tide therapy) added as a country-specific protocol amendment (not all sites had Group C).
•HBV Deoxyribonucleic acid (DNA) ≥ 100000 copies/mL; ≥ 10000 copies for nucleoside/nucleotide experienced (Group C)
•Detectable Hepatitis B surface antigen (HBsAg) for 24 weeks prior to screening
•Hepatitis B e antigen (HBeAg) positive
•Compensated liver and renal function
•Elevated alanine aminotransferase (ALT) at screening and during the 24 weeks prior to screening (for Groups A and B)

Exclusion Criteria

•Coinfection with Human immunodeficiency virus (HIV), Hepatitis C virus (HCV), Hepatitis D Virus (HDV)
•Children who were breastfed while their mother received Lamivudine, or children whose mothers received Lamivudine during pregnancy

Arms & Interventions

Arm 1: Entecavir

Intervention: Entecavir

Outcomes

Primary Outcomes

Number of Participants With Serious Adverse Events (SAE) and Discontinuations Due to Adverse Events (AEs) - On Treatment

Time Frame: Day 1 to Week 120

AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Medical Dictionary for Regulatory Activities (MedDRA) version 16.0 was used.

Secondary Outcomes

Mean Maximum Observed Plasma Concentration (Cmax) and Mean Trough Observed Plasma Concentration (Cmin) of Entecavir in LVD-naive and LVD-experienced Participants, by Age Cohort(Day 14)
Median Time of Maximum Observed Plasma Concentration (Tmax) in LVD-naive and LVD-experienced Participants, by Age Cohort(Day 14)
Mean Area Under the Concentration-Time Curve in One Dosing Interval [AUC(TAU)] of Entecavir in LVD-naive and LVD-experienced Participants, by Age Cohort(Day 14)
Mean Apparent Total Body Clearance (CLT/F) of Entecavir in LVD-naive and LVD-experienced Participants, by Age Cohort(At 2 weeks)
Number of Participants With HBV DNA Less Than 50 IU/mL Through Week 96 in Treated Participants(Baseline to Week 96)
Number of Participants With Hepatitis B e Antigen (HBeAg) Loss Through Week 96 in Treated Participants(Baseline to Week 96)
Number of Participants With Hepatitis B s Antigen (HBsAg) Loss Through Week 96 in Treated Participants(Baseline to Week 96)
Number of Participants With Hepatitis B e Antigen Seroconversion Through Week 96 in Treated Participants(Baseline through Week 96)
Number of Participants With HBV DNA Less Than Lower Limit of Detection (LLD) for the Roche COBAS TaqMan - HPS Assay at Week 96 in Treated Participants(Baseline to Week 96)
Number of Participants With HBV DNA Less Than Lower Limit of Quantification (LLQ) for the Roche COBAS TaqMan - HPS Assay Through Week 96 in Treated Participants(Baseline through Week 96)
Number of Participants With HB s Antigen (HBsAg) Seroconversion Through Week 96 in Treated Participants(Baseline through Week 96)
Number of Participants Who Had a Protocol Defined Response (PDR) Through Week 96 in Treated Participants(Baseline to Week 96)
Mean Log10 Change From Baseline in HBV DNA Using Roche COBAS TaqMan - HPS Through Week 96 in Treated Participants(Baseline to Week 96)
Alanine Aminotransferase (ALT) Normalization From Baseline Through Week 96 in Treated Participants(Baseline to Week 96)
Number of Participants With HBV DNA by PCR Categories at Weeks 48 and 96 in Treated Participants(Baseline, Week 48, Week 96)
Number of Participants With a Combination of ALT Normalization and HBV DNA Less Than 50 IU/mL Through Week 96 in Treated Participants(Baseline to Week 96)
Number of Participants With a Combination of ALT Normalization and HBV DNA Less Than 50 IU/mL, Plus HBeAg Seroconversion Through Week 96 in Treated Participants(Baseline to Week 96)
Number of Participants With a Combination of ALT Normalization and HBV DNA Less Than 50 IU/mL, Without HBeAg Seroconversion, Through Week 96 in Treated Participants(Baseline to Week 96)
Number of Participants With Hematology Laboratory Abnormalities (Grades 1 - 4) - On Treatment - Treated Participants(Day 1 to Week 120)
Number of Participants With Chemistry Laboratory Abnormalities (Grades 1 - 4) - On Treatment - Treated Participants(Day 1 to Week 120)
Number of Participants With Electrolyte Laboratory Abnormalities (Grades 1 - 4) - On Treatment - Treated Participants(Day 1 Week 120)