The Safety and Effectiveness of PMPA Prodrug in HIV-Infected Patients

The recruitment status of this study is unknown because the information has not been verified recently.
Verified November 1999 by NIH AIDS Clinical Trials Information Service.
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by:
NIH AIDS Clinical Trials Information Service
ClinicalTrials.gov Identifier:
NCT00002396
First received: November 2, 1999
Last updated: June 23, 2005
Last verified: November 1999
  Purpose

To evaluate the safety of single and multiple doses (28 daily doses) of 9-[2-(R)-[[bis[[(isopropoxycarbonyl)- oxy]methoxy]phosphinoyl]methoxy]propyl]adenine fumarate (PMPA) prodrug administered orally to HIV-infected patients. To determine the pharmacokinetics of single and multiple doses of PMPA prodrug when administered orally to HIV-infected patients. To evaluate the anti-HIV activity of PMPA prodrug, as demonstrated by increases in CD4 cell counts and decreases in HIV RNA, when administered orally as a single dose and daily for 4 weeks to HIV-infected patients with CD4 cell counts of 200 or more cells/mm3.


Condition Intervention Phase
HIV Infections
Drug: Tenofovir disoproxil fumarate
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: A Phase I/II, Randomized, Double-Blind, Placebo-Controlled Study of the Safety, Tolerance, Pharmacokinetics, and Antiviral Activity of 9-[2-(R)-[[Bis[[(Isopropoxycarbonyl)- Oxy]Methoxy]Phosphinoyl]Methoxy]Propyl]Adenine Fumarate (PMPA Prodrug) in HIV-Infected Patients

Resource links provided by NLM:


Further study details as provided by NIH AIDS Clinical Trials Information Service:

Estimated Enrollment: 60
Detailed Description:

In this double-blind, placebo-controlled study, a total of 60 patients are randomized to receive PMPA prodrug at 1 of 5 doses or matching placebo tablets.

Part A (Days 1-7): Patients receive a single dose of PMPA prodrug or matching placebo tablets administered orally followed by a 1-week observation period. Patients who complete Part A without a dose-limiting toxicity begin Part B.

Part B (Days 8-35): Patients receive either PMPA prodrug or matching placebo tablets administered orally qd for 4 weeks at the same dosage level administered in Part A.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

Patients must have:

  • HIV infection, as indicated by seropositivity for HIV infection (ELISA and Western blot), positive HIV culture, or positive plasma HIV RNA.
  • CD4 cell count of 200 or more cells/mm3 within 28 days prior to study entry.
  • Plasma HIV RNA of 10,000 or more copies/ml within 28 days of study entry.
  • Minimum life expectancy of 12 months.

Exclusion Criteria

Co-existing Condition:

Patients with any of the following symptoms or conditions are excluded:

  • Active, serious infections (other than HIV infection) that require parenteral antibiotic therapy. Patients should be considered recovered if at least 2 weeks have elapsed following the cessation of parenteral antibiotic therapy before enrollment.
  • Active clinically significant medical problems including cardiac disease (e.g., symptoms of ischemia, congestive heart failure, or arrhythmia).
  • Positive test for Hepatitis B surface antigen (HBsAg).
  • Malignancy other than basal cell carcinoma or cutaneous Kaposi's sarcoma.

Prior Medication:

Excluded:

  • Adefovir dipivoxil (bis-POM PMEA) for more than 14 days.

Within 2 weeks prior to entry:

  • Antiretroviral therapy, including nucleoside analogues, nonnucleoside reverse transcriptase inhibitors, protease inhibitors, or investigational antiretroviral agents.
  • Interferon (alpha, beta, or gamma) or interleukin (e.g., IL-2) therapy, aminoglycoside antibiotics, amphotericin B, cidofovir, diuretics, foscarnet, ganciclovir, itraconazole, fluconazole, ketoconazole (topical allowed), isoniazid, rifampin, rifabutin, clarithromycin, azithromycin, systemic chemotherapeutic agents, systemic corticosteroids, other agents with significant nephrotoxic potential, other agents that may inhibit or compete for elimination via active renal tubular secretion (e.g., probenecid), and other investigational agents.

Risk Behavior:

Excluded:

Active drug or alcohol abuse as demonstrated by a positive screening test for drugs of abuse (except marijuana or drugs used for medical indications) or substance abuse considered sufficient to hinder patient compliance.

Patients who are receiving:

  • Antiretroviral therapy, including nucleoside analogues, nonnucleoside reverse transcriptase inhibitors, protease inhibitors, or investigational antiretroviral agents. NOTE:
  • Antiretroviral therapy may be started after completion of the Day 49 follow-up visit (i.e., not earlier than 14 days after completion of dosing).
  • Interferon (alpha, beta, or gamma) or interleukin (e.g., IL-2) therapy, aminoglycoside antibiotics, amphotericin B, cidofovir, diuretics, foscarnet, ganciclovir, itraconazole, fluconazole, ketoconazole (topical allowed), isoniazid, rifampin, rifabutin, clarithromycin, azithromycin, systemic chemotherapeutic agents, systemic corticosteroids, other agents with significant nephrotoxic potential, other agents with significant nephrotoxic potential, other agents that may inhibit or compete for elimination via active renal tubular secretion (e.g., probenecid), and other investigational agents.
  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: NCT00002396

Locations
United States, California
San Francisco Gen Hosp
San Francisco, California, United States, 94115
United States, Maryland
Johns Hopkins Hosp
Baltimore, Maryland, United States, 21205
United States, Washington
Univ of Washington / AIDS Clinical Trial Unit
Seattle, Washington, United States, 98104
Sponsors and Collaborators
Gilead Sciences
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00002396     History of Changes
Other Study ID Numbers: 283A, GS-97-901
Study First Received: November 2, 1999
Last Updated: June 23, 2005
Health Authority: United States: Food and Drug Administration

Keywords provided by NIH AIDS Clinical Trials Information Service:
Dose-Response Relationship, Drug
Adenine
Anti-HIV Agents

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Tenofovir
Tenofovir disoproxil
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on July 22, 2014