Suboptimal Responders to Adefovir Switching to Entecavir
This study has been completed.
Sponsor:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00718887
First received: July 17, 2008
Last updated: January 4, 2013
Last verified: January 2013
- Full Text View
- Tabular View
- Study Results
- Disclaimer
- How to Read a Study Record
Purpose
Switching to Entecavir will result in superior antiviral efficacy as compared to continuing with Adefovir in patients with a suboptimal response to Adefovir
| Condition | Intervention | Phase |
|---|---|---|
|
Hepatitis B, Chronic |
Drug: Entecavir Drug: Adefovir/Entecavir |
Phase 4 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Crossover Assignment Masking: Open Label Primary Purpose: Treatment |
| 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 |
Resource links provided by NLM:
Further study details as provided by Bristol-Myers Squibb:
Primary Outcome Measures:
- Percentage of Participants Who Achieved a Hepatitis B Virus (HBV) DNA Level <50 IU/mL at Week 12 by Polymerase Chain Reaction Testing [ Time Frame: At Week 12 from Day 1 ] [ Designated as safety issue: No ]HBV DNA Level <50 IU/mL=approximately 300 copies/mL.
Secondary Outcome Measures:
- Percentage of Participants Who Achieved an HBV DNA Level <50 IU/mL at Week 48 by Polymerase Chain Reaction Testing [ Time Frame: At Week 48 from Day 1 ] [ Designated as safety issue: No ]HBV=hepatitis B virus. HBV DNA Level <50 IU/mL=approximately 300 copies/mL.
- Mean log10 Reduction From Baseline in Serum HBV DNA Level by Polymerase Chain Reaction Testing [ Time Frame: At Weeks 12 and 48 from Day 1 ] [ Designated as safety issue: No ]HBV=hepatitis B virus
- Percentage of Participants Who Achieved Normalization of Alanine Aminotransferase (ALT) [ Time Frame: At Weeks 12 and 48 from Day 1 ] [ Designated as safety issue: No ]ULN=upper limit of normal. ALT normalization= ≤1*ULN, among participants with baseline ALT >1*ULN
- Percentage of Participants With Loss of Hepatitis B e Antigen (HBeAg) and Hepatitis B e (HBe) Seroconversion [ Time Frame: At Weeks 12 and 48 from Day 1 ] [ Designated as safety issue: No ]
- Number of Participants With Hepatitis B s Surface Antibody (HBsAG) Loss and HBsAG Seroconversion [ Time Frame: At Weeks 12 and 48 from Day 1 ] [ Designated as safety issue: No ]
- Number of Participants With Genotypic Resistance to Entecavir [ Time Frame: At Week 48 from Day 1 ] [ Designated as safety issue: No ]
- 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 [ Time Frame: Continually from Day 1 through Week 48, and through 24-week follow-up period ] [ Designated as safety issue: Yes ]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.
- Percentage of Participants With Grade 3 or 4 Abnormalities in Laboratory Test Results [ Time Frame: Day 1 through Week 48 ] [ Designated as safety issue: Yes ]Hematology testing assessed levels of hemoglobin, white blood cells, platelets, neutrophils, international normalized ration, red blood cells, lymphocytes, and monocytes.
| Enrollment: | 228 |
| Study Start Date: | July 2008 |
| Study Completion Date: | January 2011 |
| Primary Completion Date: | December 2009 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Experimental: Entecavir, 0.5 mg QD |
Drug: Entecavir
Tablets, Oral, 0.5 mg, once daily (QD), 52 weeks
Other Names:
|
|
Adefovir, 10 mg QD/Entecavir, 0.5 mg QD
Control
|
Drug: Adefovir/Entecavir
Tablets, Oral, 10-mg adefovir QD for 12 weeks followed by 0.5-mg entecavir QD for a maximum of 52 weeks
Other Names:
|
Eligibility| Ages Eligible for Study: | 16 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
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.
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00718887
Locations
| China, Beijing | |
| Local Institution | |
| Beijing, Beijing, China, 100011 | |
| China, Guizhou | |
| Local Institution | |
| Guiyang, Guizhou, China, 550004 | |
| China, Jiangsu | |
| Local Institution | |
| Nanjing, Jiangsu, China, 210002 | |
| China, Jiangxi | |
| Local Institution | |
| Nanchang, Jiangxi, China, 330006 | |
| China, Jilin | |
| Local Institution | |
| Changchun, Jilin, China, 130021 | |
| China, Liaoning | |
| Local Institution | |
| Shenyang, Liaoning, China, 110004 | |
| China, Shanghai | |
| Local Institution | |
| Shanghai, Shanghai, China, 200235 | |
| Local Institution | |
| Shanghai, Shanghai, China | |
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
| Study Director: | Bristol-Myers Squibb | Bristol-Myers Squibb |
More Information
Additional Information:
No publications provided
| Responsible Party: | Bristol-Myers Squibb |
| ClinicalTrials.gov Identifier: | NCT00718887 History of Changes |
| Other Study ID Numbers: | AI463-171 |
| Study First Received: | July 17, 2008 |
| Results First Received: | October 17, 2012 |
| Last Updated: | January 4, 2013 |
| Health Authority: | China: Food and Drug Administration |
Additional relevant MeSH terms:
|
Hepatitis Hepatitis A Hepatitis B Hepatitis B, Chronic Liver Diseases Digestive System Diseases Hepatitis, Viral, Human Virus Diseases Enterovirus Infections Picornaviridae Infections RNA Virus Infections Hepadnaviridae Infections DNA Virus Infections |
Hepatitis, Chronic Adefovir Adefovir dipivoxil Entecavir Antiviral Agents Anti-Infective Agents Therapeutic Uses Pharmacologic Actions Reverse Transcriptase Inhibitors Nucleic Acid Synthesis Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-Retroviral Agents |
ClinicalTrials.gov processed this record on May 22, 2013