Suboptimal Responders to Adefovir Switching to Entecavir

Hepatitis B, Chronic Clinical Trial

Official title:

A Comparative Study of the Week 12 Antiviral Efficacy and Safety of Switching to Entecavir vs. Continuing Adefovir Treatment in Adults With Chronic Hepatitis B and Suboptimal Response to Adefovir

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00718887
• Other study ID #: AI463-171
• Status: Completed
• Phase: Phase 4
• First received: July 17, 2008
• Last updated: January 4, 2013
• Start date: July 2008
• Est. completion date: January 2011

Study information

• Verified date: January 2013
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Switching to Entecavir will result in superior antiviral efficacy as compared to continuing with Adefovir in patients with a suboptimal response to Adefovir

Recruitment information / eligibility

• Status: Completed
• Enrollment: 228
• Est. completion date: January 2011
• Est. primary completion date: December 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 16 Years and older

Eligibility

Inclusion Criteria:

• Chronic infection with hepatitis B virus (HBV)(detectable hepatitis B surface antibody (HBsAg) at screening and at least 24 weeks prior to screening, or detectable HBsAg for <24 weeks and negative for immunoglobulin M core antibody)

• Documentation of hepatitis B e antigen (HBeAg) positive or negative status

• Naive to nucleoside/nucleotide analogues, with the exception of adefovir

• Suboptimal response to adefovir treatment

• No lamivudine/telbivudine, entecavir, or adefovir resistance-associated substitutions at screening

• Male or female gender, aged 16 years and older

• Compensated liver function

• Serum alanine aminotransferase level <10*upper limit of normal at screening

Exclusion Criteria:

• Women who are pregnant or breastfeeding

• Evidence of decompensated cirrhosis

• Coinfection with HIV, hepatitis C virus, or hepatitis D virus

• Recent history of pancreatitis (within 24 weeks prior to the first dose of study medication)

• Chronic renal insufficiency, defined as a creatinine clearance <50 mL/min

• Current abuse of illegal drugs or alcohol, sufficient in the investigator's opinion to prevent adequate compliance with study therapy or to increase the risk of hepatotoxicity or pancreatitis

• Other serious medical conditions that might preclude completion of this study or that require chronic administration of prohibited medications

• Serum creatinine level >1.5 mg/dL; hemoglobin level <10.0 g/dL; platelet count <70,000/mm^3; absolute neutrophil count <1500 cells/mm^3; serum alpha fetoprotein level >100 ng/mL

• Except adefovir, any prior therapy with nucleoside or nucleotide analogue antiviral agents with activity against hepatitis B (eg, lamivudine, entecavir), or any other experimental anti-HBV antiviral, or any China Traditional Medicine

• Therapy with interferon, thymosin alpha, or other immunostimulators within 24 weeks of randomization

• Required chronic administration of medications that cause immunosuppression, that are associated with a high risk of nephrotoxicity or hepatotoxicity, or that affect renal excretion.

Study Design

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

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis B
• Hepatitis B, Chronic

Intervention

Drug:
• Entecavir
Tablets, Oral, 0.5 mg, once daily (QD), 52 weeks
• Adefovir/Entecavir
Tablets, Oral, 10-mg adefovir QD for 12 weeks followed by 0.5-mg entecavir QD for a maximum of 52 weeks

Locations

Country	Name	City	State
China	Local Institution	Beijing	Beijing
China	Local Institution	Changchun	Jilin
China	Local Institution	Guiyang	Guizhou
China	Local Institution	Nanchang	Jiangxi
China	Local Institution	Nanjing	Jiangsu
China	Local Institution	Shanghai	Shanghai
China	Local Institution	Shanghai	Shanghai
China	Local Institution	Shenyang	Liaoning

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Who Achieved a Hepatitis B Virus (HBV) DNA Level <50 IU/mL at Week 12 by Polymerase Chain Reaction Testing	HBV DNA Level <50 IU/mL=approximately 300 copies/mL.	At Week 12 from Day 1	No
Secondary	Percentage of Participants Who Achieved an HBV DNA Level <50 IU/mL at Week 48 by Polymerase Chain Reaction Testing	HBV=hepatitis B virus. HBV DNA Level <50 IU/mL=approximately 300 copies/mL.	At Week 48 from Day 1	No
Secondary	Mean log10 Reduction From Baseline in Serum HBV DNA Level by Polymerase Chain Reaction Testing	HBV=hepatitis B virus	At Weeks 12 and 48 from Day 1	No
Secondary	Percentage of Participants Who Achieved Normalization of Alanine Aminotransferase (ALT)	ULN=upper limit of normal. ALT normalization= =1*ULN, among participants with baseline ALT >1*ULN	At Weeks 12 and 48 from Day 1	No
Secondary	Percentage of Participants With Loss of Hepatitis B e Antigen (HBeAg) and Hepatitis B e (HBe) Seroconversion		At Weeks 12 and 48 from Day 1	No
Secondary	Number of Participants With Hepatitis B s Surface Antibody (HBsAG) Loss and HBsAG Seroconversion		At Weeks 12 and 48 from Day 1	No
Secondary	Number of Participants With Genotypic Resistance to Entecavir		At Week 48 from Day 1	No
Secondary	Number of Participants With Adverse Events, Treatment-related AEs, Serious Adverse Events (SAEs), Treatment-related SAEs, Death as Outcome, Discontinuations Due to AEs, and Abnormalities in Laboratory Test Results (LTR) Leading to Discontinuation	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. Treatment-related=possibly, probably, or certainly related to and of unknown relationship to study drug.	Continually from Day 1 through Week 48, and through 24-week follow-up period	Yes
Secondary	Percentage of Participants With Grade 3 or 4 Abnormalities in Laboratory Test Results	Hematology testing assessed levels of hemoglobin, white blood cells, platelets, neutrophils, international normalized ration, red blood cells, lymphocytes, and monocytes.	Day 1 through Week 48	Yes

External Links

•   BMS Clinical Trials Disclosure
•   For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm
•   Investigator Inquiry form