Evaluate Efficacy, Safety and PK of Adefovir Dipivoxil Liquid Suspension in Patients With Chronic Hepatitis B

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT00071201
First received: October 15, 2003
Last updated: October 14, 2013
Last verified: October 2013
  Purpose

This is a multi-center phase 3, open-label, parallel-group study designed to evaluate the efficacy, safety and pharmacokinetics of adefovir dipivoxil liquid suspension in patients with chronic hepatitis B and varying degrees of renal impairment.


Condition Intervention Phase
Chronic Hepatitis B
Drug: Adefovir Dipivoxil for oral suspension, 2 mg/mL
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multi-Center Phase 3, Open-Label, Parallel-Group Study to Evaluate the Efficacy, Safety and Pharmacokinetics of Adefovir Dipivoxil Liquid Suspension in Patients With Chronic Hepatitis B and Varying Degrees of Renal Impairment

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Estimated Enrollment: 48
Study Start Date: June 2003
Study Completion Date: March 2006
Primary Completion Date: March 2006 (Final data collection date for primary outcome measure)
Detailed Description:

Approximately 48 patients with chronic hepatitis B will be enrolled into four groups representing varying degrees of renal function. Grouping will be achieved through estimation of creatinine clearance (CLcr) using the Cockcroft-Gault method of calculation at the time of screening:

Group 1: Mild (Clcr = greater than or equal to 50 to less than 80 mL/min)

Group 2: Moderate (Clcr = greater than or equal to 20 to less than 50 mL/min)

Group 3: Severe (Clcr = greater than or equal to 10 to less than 20 mL/min)

Group 4A-B: End stage renal disease (ESRD) including hemodialysis:

  • Group 4A (Clcr = less than 10 mL/min)
  • Group 4B (Patients undergoing hemodialysis)

At the baseline visit (day 0), blood and urine samples will be collected pre-dose (prior to 0 hour) after which patients will receive an oral dose of liquid adefovir dipivoxil according to the treatment guideline outlined in the protocol.

Pharmacokinetic parameters in plasma will be determined for the day 0 and week 12 visits for all patients and at the week 48 visit for group 1, 2, 3, and 4A patients. Pharmacokinetic parameters in urine will be determined for the day 0, week 12 and week 48 visits for group 1, 2, 3, and 4A patients.

At week 4, 8, 16, 20, 24, 28, 32, 36, 40, and 44 visits, pharmacokinetic assessments in plasma will be determined pre-dose (Ctrough levels) in groups 1, 2, 3, and 4A. For group 4B patients, pharmacokinetic assessments will be determined at weeks 4 and 8 prior to and upon completion of hemodialysis.

Evaluations of safety and efficacy will be conducted at 4 weekly intervals up to week 48 for groups 1, 2, 3, and 4A, and up to week 12 for group 4B. At these visits, patients will receive the next study medication allocation. Study medication administration will continue for up to a total of 48 weeks.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

INCLUSION CRITERIA:

  • Male or female ages 18 through 65 years
  • Able to give written informed consent and comply with the requirements of the study
  • Females of childbearing potential must have a negative serum pregnancy test at screening and must use effective methods of contraception throughout the study.
  • Positive serum HBV DNA equal to or greater than 100,000 copies/mL
  • Patients with abnormal renal function, defined as a calculated creatinine clearance less than 80 mL/min, or end stage renal disease undergoing hemodialysis
  • For non-hemodialysis patients, renal function must be "stable"
  • ALT value equal to or greater than 1.2 to equal to or less than 15 times the upper limit of normal on at least two occasions, or histological evidence of necroinflammation and/or fibrosis
  • Compensated liver disease with the following:

    • Prothrombin time equal to or less than to 1 second above normal range
    • Total bilirubin equal to or less than to 2.5 mg/dL or normal direct bilirubin
  • No history of variceal bleeding or encephalopathy
  • HIV, HCV, and HDV seronegative
  • Adequate hematological function defined as:

    • Absolute neutrophil count equal to or greater than 750/mm3
    • Platelets equal to or greater than 50,000/mm3
    • Hemoglobin equal to or greater than 7.5 g/dL

EXCLUSION CRITERIA:

  • Inability to comply with study requirements
  • Lactating or pregnant females
  • History or current manifestations of clinically significant cardiac, respiratory, endocrine (including diabetes mellitus), metabolic, gastrointestinal, dermatological, infectious, malignant, hematological, neurological, rheumatologic or psychiatric disorder, which is not related to the patient's renal insufficiency or deemed by the investigator to preclude suitability for pharmacokinetic assessment or interfere with patient treatment, assessment, or compliance with the protocol
  • Received interferon within 6 months prior to study screening
  • Bone marrow transplant recipients
  • Renal transplant less than 6 months prior to study entry, or clinical evidence of rejection
  • Patients expected to receive organ transplantation within 48 weeks
  • Evidence of active liver disease due to other causes
  • Patients taking chemotherapeutic agents within 2 months or expected to receive these agents during the study
  • Previous participation in an investigational trial involving any investigational compound within 2 months, or within 5 half-lives of the study drug if sooner
  • History of alcohol or drug abuse sufficient to hinder compliance with protocol
  • Child-Pugh-Turcotte score over 9
  • Evidence of hepatic mass suggestive of hepatocellular carcinoma
  • History of malignancy other than basal cell carcinoma or treated cervical carcinoma in situ or cervical dysplasia
  • The use of systemic drugs with potential activity against HBV for a period of more than 12 weeks in duration at any time
  • The use of adefovir dipivoxil for a period of more than 12 weeks in duration at any time. Hemodialysis patients may be enrolled regardless of prior treatment duration with adefovir dipivoxil if treatment completed greater than or equal to 16 weeks before study.
  • Hypersensitivity to nucleoside and/or nucleotide analogs
  • Received hepatotoxic drugs within 2 months or plan to receive them
  • Received nephrotoxic drugs or competitors of renal excretion within 2 months or plan to receive them, except for transplant patients
  • Current use of other pivalic acid containing medications
  • Patients undergoing continuous ambulatory peritoneal dialysis (CAPD)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00071201

Locations
United States, California
Gilead Sciences, Inc. 333 Lakeside Drive
Foster City, California, United States, 94404
Sponsors and Collaborators
Gilead Sciences
  More Information

Additional Information:
Publications:
Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT00071201     History of Changes
Other Study ID Numbers: GS-02-526
Study First Received: October 15, 2003
Last Updated: October 14, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis B
Hepatitis, Chronic
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
Adefovir
Adefovir dipivoxil
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 August 28, 2014