Chronic Hepatitis BPhase 3NCT00071201
Evaluate Efficacy, Safety and PK of Adefovir Dipivoxil Liquid Suspension in Patients With Chronic Hepatitis B
A Phase 3 study testing Adefovir Dipivoxil for oral suspension, 2 mg/mL in people with Chronic Hepatitis B, run by Gilead Sciences at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Chronic Hepatitis B
- What is being tested?
- Adefovir Dipivoxil for oral suspension, 2 mg/mL
- Type of treatment
- Pill or oral medicine
- How many people
- 48 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2003to Mar 2006
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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"
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- 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
Who cannot join
- 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
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- 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)
Trial locations and contacts
1 site in 1 country.
United States1 site
Gilead Sciences, Inc. 333 Lakeside Drive
Foster City, California, 94404
About this study
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
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.
Read the 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.
- Conditions
- Chronic Hepatitis B
- Being tested
- Adefovir Dipivoxil for oral suspension, 2 mg/mL
- Medical subject headings
- Hepatitis B, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Adefovir Dipivoxil for oral suspension, 2 mg/mLDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Oct 2003 (estimated)
- Study startJun 2003
- Primary completionMar 2006
- Study completionMar 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Chronic Hepatitis BStudies of the same condition, open and under way.
- More trials run by Gilead SciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 48 participants
Sponsor and investigators
- Lead sponsor
- Gilead Sciences
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00071201
- Sponsor's protocol ID
- GS-02-526
- Status last verified
- Oct 2013
- First submitted
- 15 Oct 2003
- Last updated
- 16 Oct 2013
- Results posted
- No
Publications
Hadziyannis SJ, Tassopoulos NC, Heathcote EJ, Chang TT, Kitis G, Rizzetto M, Marcellin P, Lim SG, Goodman Z, Wulfsohn MS, Xiong S, Fry J, Brosgart CL; Adefovir Dipivoxil 438 Study Group. Adefovir dipivoxil for the treatment of hepatitis B e antigen-negative chronic hepatitis B. N Engl J Med. 2003 Feb 27;348(9):800-7. doi: 10.1056/NEJMoa021812.
PubMed 12606734Marcellin P, Chang TT, Lim SG, Tong MJ, Sievert W, Shiffman ML, Jeffers L, Goodman Z, Wulfsohn MS, Xiong S, Fry J, Brosgart CL; Adefovir Dipivoxil 437 Study Group. Adefovir dipivoxil for the treatment of hepatitis B e antigen-positive chronic hepatitis B. N Engl J Med. 2003 Feb 27;348(9):808-16. doi: 10.1056/NEJMoa020681.
PubMed 12606735Westland CE, Yang H, Delaney WE 4th, Gibbs CS, Miller MD, Wulfsohn M, Fry J, Brosgart CL, Xiong S; 437 and 438 Study Teams. Week 48 resistance surveillance in two phase 3 clinical studies of adefovir dipivoxil for chronic hepatitis B. Hepatology. 2003 Jul;38(1):96-103. doi: 10.1053/jhep.2003.50288.
PubMed 12829991
Study at a glance
From the registry record, last updated by the sponsor on 16 Oct 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00071201
- Acronym / sponsor ID
- GS-02-526
- Conditions
- Chronic Hepatitis B
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants
- Lead sponsor
- Gilead SciencesIndustry (pharma, biotech, devices)
- Study start
- Jun 2003
- Primary completion
- Mar 2006 (actual)
- Study completion
- Mar 2006 (actual)
- First posted
- 17 Oct 2003 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 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
Key exclusion criteria (21 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Adefovir Dipivoxil for oral suspension, 2 mg/mL | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Oct 2013.
- Background: PubMed 12606734Hadziyannis SJ, Tassopoulos NC, Heathcote EJ, Chang TT, Kitis G, Rizzetto M, Marcellin P, Lim SG, Goodman Z, Wulfsohn MS, Xiong S, Fry J, Brosgart CL; Adefovir Dipivoxil 438 Study Group. Adefovir dipivoxil for the treatment of hepatitis B e antigen-negative chronic hepatitis B. N Engl J Med. 2003 Feb 27;348(9):800-7. doi: 10.1056/NEJMoa021812.
- Background: PubMed 12606735Marcellin P, Chang TT, Lim SG, Tong MJ, Sievert W, Shiffman ML, Jeffers L, Goodman Z, Wulfsohn MS, Xiong S, Fry J, Brosgart CL; Adefovir Dipivoxil 437 Study Group. Adefovir dipivoxil for the treatment of hepatitis B e antigen-positive chronic hepatitis B. N Engl J Med. 2003 Feb 27;348(9):808-16. doi: 10.1056/NEJMoa020681.
- Background: PubMed 12829991Westland CE, Yang H, Delaney WE 4th, Gibbs CS, Miller MD, Wulfsohn M, Fry J, Brosgart CL, Xiong S; 437 and 438 Study Teams. Week 48 resistance surveillance in two phase 3 clinical studies of adefovir dipivoxil for chronic hepatitis B. Hepatology. 2003 Jul;38(1):96-103. doi: 10.1053/jhep.2003.50288.
- Gilead's websiteLink provided by the sponsor.
- Study ResultsLink provided by the sponsor.
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Chronic Hepatitis B
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Adefovir Dipivoxil for oral suspension, 2 mg/mL in people with Chronic Hepatitis B, run by Gilead Sciences at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Oct 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00071201, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Oct 2013.