Once-Daily Drug Regimen for HIV-Infected Patients

March 3, 2008 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

A Pilot Study of Once-Daily Therapy With Amprenavir, Ritonavir, Lamivudine and Abacavir in HIV-Infected, Antiretroviral-Naive Patients

This study will examine the safety of giving antiviral therapy for HIV infection in a once-daily dosing schedule, and assess how well patients tolerate this regimen. A once a day dosing schedule may be easier for some people to follow than one that requires taking medicine 2 or 3 times a day. The ease of treatment is important, because not following the prescribed dosing regimen may make therapy less effective or ineffective.

HIV-infected patients 18 years and older who have never been treated for their infection may be eligible for this study. Candidates will be screened with a history and physical examination, including blood tests. Participants will take the following medications once a day: 1200 mg of amprenavir (8 capsules); 300 mg of ritonavir (3 capsules); 600 mg of abacavir (2 pills); and 300 mg of lamivudine (2 pills). Patients will have routine blood tests and be seen by a nurse or doctor, or both, at follow-up visits at weeks 2, 4, 8, 12, and 16; then every 8 weeks until week 48; and then every 3 months for up to 3 years. At week 2, a special blood test will be done over the course of a day to measure blood drug levels. For this test, blood samples will be drawn 8 times over a 24-hour period. A heparin lock (a device that allows the needle to remain in the vein) will be used to avoid multiple needle sticks.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The development of a once-daily anti-retroviral regimen is a priority because regimen simplicity might enhance regimen adherence, and because a once-daily regimen would be useful for directly observed therapy. Pharmacokinetic modeling suggests that plasma levels of amprenavir in the presence of ritonavir, a potent inhibitor of cytochrome p450, should be high enough to support once-daily dosing. Lamivudine is currently being explored in other studies in once-daily dosing. Abacavir has not been used once daily but some in vitro studies suggest that such dosing might be appropriate. In this uncontrolled, open-label study, amprenavir 1200 mg daily, ritonavir 300 mg daily, lamivudine 300 mg daily, and abacavir 600 mg daily will be administered to up to 25 HIV-infected, anti-retroviral naive patients. The objectives are to assess the tolerability and safety of this regimen; the plasma concentrations of amprenavir; and the anti-viral response. Study evaluations include percentage of patients who have discontinued the regimen by weeks 16 and 24 for toxicity, intolerance or failure; the number of grade 3 and 4 adverse events by weeks 16 and 24; the antiviral response at weeks 16, 24, and 48 (change from baseline and percentage of patients with viral load less than 50 copies and less than 400 copies per mL), and the number (percent) of patients with trough plasma concentrations of amprenavir above 280 ng/mL.

Study Type

Interventional

Enrollment

25

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Bethesda, Maryland, United States, 20892
        • National Institute of Allergy and Infectious Diseases (NIAID)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Adults (greater than 18 years) infected with HIV-1.

Plasma viral burden greater than 8,000 and less than 60,000 RNA copies per ml. by bDNA method at screening.

CD4 cell count above 200 cells per microliter at screen.

No prior treatment with any anti-retroviral agent.

Laboratory values at screen: hemoglobin greater than 9 g per dl; granulocyte count greater than 900 cells per microliter; platelet count greater than 80,000 cells per microliter; AST (SGOT) less than 151 U/L; creatinine less than 2 mg/dL.

Must not be pregnant or breast-feeding and willing to avoid pregnancy by the use of non-hormonal methods of birth control during study participation. Pregnancy test (blood or urine) must be negative within two weeks prior to dosing with study medications.

Willing and able to provide written informed consent.

No history suggestive of malabsorption.

No chronic diarrhea.

Must not have had treatment with systemic corticosteroids at greater than physiologic replacement doses, interleukins, interferons, radiation therapy or cytotoxic chemotherapeutic agents within 30 days of study drug administration or an anticipated need for radiation or chemotherapy treatment within the next 48 weeks (with the exception of local treatment of Kaposi's sarcoma).

Must not have current or anticipated therapy with other agents with documented activity against HIV-1 in vitro.

Must not have active, untreated opportunistic infection or other major illness that would, in the opinion of the investigator, increase the risk that adverse events might pose to the patient or might render the patient too ill to return for study visits.

Must not have significant substance abuse or psychiatric illness that might interfere with assessment or compliance.

Must not have current or anticipated future need for any of the following drugs which are contraindicated with an amprenavir-ritonavir regimen because of drug-drug interactions: Terfenadine (Seldane), Astemizole (Hismanal), Cisapride (Propulsid), Triazolam (Halcion), Bepridil (Vascor), Medazolam (Versed), Rifampin (Rifadin, Rifamate, Rifater), Ergotamine/Dihydroergotamine containing regimens (Ergomar, Wygraine, Ercaf, DHE, Migranal), Amiodarone (Cordarone), Flecanaide (Tambocor), Propafenone (Rythmol), Quinidine (Quinaglute, Cardioquin), and Pimozide (Orap).

Must not have current or anticipated future need for the following anticonvulsants: phenobarbital, phenytoin, carbamazepine.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2000

Study Completion

November 1, 2000

Study Registration Dates

First Submitted

January 18, 2000

First Submitted That Met QC Criteria

December 9, 2002

First Posted (Estimate)

December 10, 2002

Study Record Updates

Last Update Posted (Estimate)

March 4, 2008

Last Update Submitted That Met QC Criteria

March 3, 2008

Last Verified

December 1, 1999

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 000053
  • 00-I-0053

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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