Study Comparing the Safety of Switching From Lamivudine to Adefovir Dipivoxil Versus Overlapping Lamivudine and Adefovir Before Adefovir Dipivoxil Monotherapy in Patients With Chronic Hepatitis B

NCT00307242 | Completed Phase 4 DMC

• 1 other identifier: 05U.164
• Study Type: interventional
• Target: 40
• Locations: 0 countries
• Sites: N/A

Brief Summary

In earlier clinical studies, when patients who have been on lamivudine (LAM) were switched to adefovir dipivoxil (ADV), some patients developed ALT flares with an elevation of ALT \> 10 x the upper limits of normal (ULN). There were no cases of hepatic decompensation with the flares, however. The transition methods were varied among physicians from no overlapping to overlapping for 1 to 3 months with LAM and ADV. There is still some uncertainty about the optimal approach to switching from LAM to ADV. This study will compare the safety of directly switching to ADV to a protocolled switch after a period of overlap of 12 weeks. This will facilitate pro-active switching in patients on LAM and will also highlight genotypic resistance ahead of phenotypic resistance as a reason to switch patients. Data to date have only been presented as part of a controlled study in patients with clinically evident LAM-resistance. This study will enroll patients who still have serum hepatitis B virus (HBV) DNA suppression whilst receiving LAM.

Conditions

Chronic Hepatitis B

Keywords

Adefovir Dipivoxil; Lamivudine; Hepatitis B

Outcome Measures

Primary Outcomes (5)

• Observe the proportion of patients with ALT elevations (> 10 x ULN) at any time over the course of the switch

  baseline, 3, 6, 9, and 12 months

• Study serum HBV DNA levels over time

  baseline, 3, 6, 9, and 12 months

• Study serum ALT levels over time

  baseline, 3, 6, 9, and 12 months

• Study the proportion of patients with YMDD variants at entry

  baseline, 3, 6, 9, and 12 months

• Study the safety during the switching period

  baseline, 3, 6, 9, and 12 months

Study Arms (2)

Direct switch to Adefovir Dipivoxil from Lamivudine

ACTIVE COMPARATOR

Drug: Adefovir Dipivoxil

Overlapping Lamivudine and Adefovir Dipivoxil for 3 months followed by ADV monotherapy

ACTIVE COMPARATOR

Drug: Adefovir Dipivoxil

Interventions

Adefovir Dipivoxil DRUG

Direct switch to Adefovir Dipivoxil from Lamivudine; Overlapping Lamivudine and Adefovir Dipivoxil for 3 months followed by ADV monotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and females ≥ 18 years of age with chronic hepatitis B
• Hepatitis B surface antigen (HBsAg)(+) for a minimum of 6 months prior to entry
• Hepatitis B envelope antigen (HBeAg)(+) or (-) at baseline
• Patients having previously received LAM for at least 24 weeks
• Patients with compensated liver function (Child-Pugh score ≤ 6)

You may not qualify if:

• Any serious or active medical or psychiatric illness which, in the opinion of the investigator, would interfere with patient treatment, assessment or compliance with the protocol.
• Received immunoglobulins, interferon or other immune or cytokine-based therapies with possible activity in hepatitis B disease within 6 months prior to study screening.
• Organ or bone marrow transplant recipients.
• Evidence of active liver disease due to other causes (e.g., Wilson's disease, hemochromatosis, autoimmune hepatitis, hepatitis C or hepatitis D co-infection)
• Patients taking parenteral (intravenous or intramuscular or subcutaneous) or oral steroids, immuno-suppressant therapies or chemotherapeutic agents within 2 months of study screening or expected to receive these agents during the course of the study.
• Previous participation in an investigational trial involving administration of any investigational compound within 2 months prior to the study screening or those who received anti-HBV therapy other than lamivudine within the previous 3 months (e.g. anabolic steroids, ketaconazole, itraconazole, isoniazid, rifampin, rifabutin, simvastatin, lovastatin)
• Clinically relevant alcohol or drug use or history of alcohol or drug use considered by the investigator to be sufficient to hinder compliance with treatment, follow up procedures or evaluation of adverse events
• Lactating females or females with a positive serum pregnancy test.
• Females of childbearing potential (post-puberty) unwilling or unable to have pregnancy testing at any study visit
• Therapy with nephrotoxic drugs (e.g. aminoglycosides, amphotericin B, vancomycin, cidofovir, foscarnet, cisplatin pentamidine, tacrolimus, cyclosporine) or competitors of renal excretion (e.g. probenecid) within 2 months prior to study screening or the expectation that subject will receive these during the course of the study.
• The use of antiviral therapy with agents demonstrating potential anti-HBV activity other than lamivudine within the previous 3 months (e.g. famciclovir, lobucavir, emtricitabine, DAPD, L-FMAU, entecavir, ganciclovir or others).
• History of hypersensitivity to nucleoside and/or nucleotide analogues.
• Clinical, ultrasonographic or radiologic evidence of hepatic mass suggestive of hepatocellular carcinoma.
• Serum alphafetoprotein (AFP) \> 50 ng/mL at the first screening visit. However, if the AFP level is \> 50 ng/mL at the first screening visit, but has remained stable or decreased over the 6 months preceding the first screening visit, and if there is no radiologic or ultrasonic evidence of hepatic mass(es) suggestive of hepatocellular carcinoma, the patient will be allowed to enroll.
• Inability to comply with study requirements.

Sponsors & Collaborators

• Thomas Jefferson University: lead

MeSH Terms

Conditions

Hepatitis B, Chronic; Hepatitis B

Interventions

adefovir dipivoxil

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Hie-Won Hann, M.D.

  Thomas Jefferson University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 24, 2006
• First Posted: March 27, 2006
• Study Start: June 17, 2005
• Primary Completion: February 1, 2009
• Study Completion: February 5, 2009
• Last Updated: November 12, 2021

Record last verified: 2021-11