The Safety and Effectiveness of FIAC in the Treatment of Cytomegalovirus (CMV) in Patients With AIDS

This study has been completed.
Sponsor:
Collaborator:
Oclassen Pharmaceuticals
Information provided by:
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000981
First received: November 2, 1999
Last updated: December 17, 2012
Last verified: December 2012
  Purpose

To find oral doses of FIAC (a pyrimidine nucleoside analog) that are effective in treating cytomegalovirus (CMV) viremia in HIV-infected immunocompromised patients; to determine tolerance and safety of FIAC in this patient population; and to determine pharmacokinetics following multiple doses of FIAC. (An example of another nucleoside analog effective against retroviruses such as HIV is zidovudine (AZT).) CMV infection is a medically significant opportunistic disease in patients with HIV-related infection. The purine nucleoside ganciclovir has been used to treat AIDS patients with CMV disease. Although ganciclovir is useful in treating CMV disease, such treatment is frequently complicated by hematologic (blood) toxicity. Also, treatment is difficult because it requires daily intravenous dosing. Test tube studies show that FIAC and its primary breakdown product FIAU are highly and specifically active against several viruses including CMV. A single-dose, pharmacokinetic (blood level) study showed that FIAC, when taken orally, is readily absorbed into the bloodstream, and most of it is converted to FIAU.


Condition Intervention Phase
Cytomegalovirus Infections
HIV Infections
Drug: Fiacitabine
Phase 2

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: Efficacy and Safety of Oral FIAC in AIDS Patients With Cytomegalovirus Infection: A Dose Ranging Study

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 78
Study Completion Date: February 1993
Detailed Description:

CMV infection is a medically significant opportunistic disease in patients with HIV-related infection. The purine nucleoside ganciclovir has been used to treat AIDS patients with CMV disease. Although ganciclovir is useful in treating CMV disease, such treatment is frequently complicated by hematologic (blood) toxicity. Also, treatment is difficult because it requires daily intravenous dosing. Test tube studies show that FIAC and its primary breakdown product FIAU are highly and specifically active against several viruses including CMV. A single-dose, pharmacokinetic (blood level) study showed that FIAC, when taken orally, is readily absorbed into the bloodstream, and most of it is converted to FIAU.

Patients are treated as outpatients if general health permits. This is continued for up to 90 days or until failure on basis of efficacy, tolerance, or toxicity. The dose escalation between groups of patients uses the formula n + 0.7n. Entry of new patients at the next higher dose is based on results of antiviral, tolerance, and safety data for the prior cohort when they have received at least 14 days of therapy. Consecutively qualifying patients are enrolled for each dose group and not based on either disease severity or expected tolerance. Although not formally randomized due to the sequential nature of the study and serious medical condition of the patients, every attempt to avoid bias in assigning a patient to a dose is made. Patients are advised to avoid heavy exercise within 24 hours of any laboratory tests.

  Eligibility

Ages Eligible for Study:   13 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

Concurrent Medication:

Allowed:

  • Pentamidine aerosol for prophylaxis of recurrent Pneumocystis carinii pneumonia (PCP) in patients currently receiving such treatment.

Prior Medication:

Allowed:

  • Zidovudine (AZT) but only if patient has been taking the drug for > 6 weeks at a dose = or < 600 mg/day, and had < 10 percent decrease in hematocrit, neutrophils, and platelets in the last 30 days. Those off AZT must have been off it for > 1 month.

Patients must:

  • Have documented cytomegalovirus (CMV) viremia or viruria.
  • Have a diagnosis of HIV infection by ELISA or Western blot.
  • Be able to participate as an outpatient.
  • Be ambulatory.
  • Grade 0 or 1 AIDS Clinical Trial Group toxicity grades for specified laboratory tests.
  • Be competent to sign informed consent.
  • Be able to cooperate with the treatment plan and evaluation schedule.

NOTE:

  • The screening tests must be initiated and completed within 4 weeks prior to the first dose of FIAC.

Concomitant diseases allowed:

  • Stable mucocutaneous Kaposi's sarcoma.
  • Superficial or uncomplicated infections such as thrush.

Exclusion Criteria

Co-existing Condition:

Patients with the following are excluded:

  • HIV wasting syndrome (involuntary weight loss > 10 percent of baseline body weight and/or chronic diarrhea or weakness and documented fever for at least 30 days).
  • Clinical or x-ray evidence of bronchitis, pneumonitis, pulmonary edema, effusion, or suspected active tuberculosis.
  • Any unstable medical condition including serious cardiovascular, infectious, oncologic, renal, or hepatic condition.
  • Cytomegalovirus end organ disease.
  • Kaposi's sarcoma requiring chemotherapy.
  • Systemic fungal infection requiring amphotericin therapy.
  • Diagnosis of idiopathic thrombocytopenic purpura (persistent platelet counts < 100000 platelets/mm3 for = or > 3 months).

Patients with the following are excluded:

  • HIV wasting syndrome.
  • Clinical or x-ray evidence of bronchitis, pneumonitis, pulmonary edema, effusion, or suspected active tuberculosis.
  • Any unstable medical condition including serious cardiovascular, infectious, oncologic, renal, or hepatic condition.
  • Cytomegalovirus (CMV) end organ disease e.g., retinitis, hepatitis, gastroenteritis.

Prior Medication:

Excluded within 4 weeks of study entry:

  • Zidovudine (AZT).
  • Acyclovir.
  • Ganciclovir (DHPG).
  • Foscarnet.
  • Interferon.
  • Other drug with putative anticytomegaloviral activity.
  • Any immunostimulating drug not specifically allowed.
  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: NCT00000981

Locations
United States, Alabama
Univ of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
United States, California
Univ of California / San Diego Treatment Ctr
San Diego, California, United States, 921036325
United States, Maryland
Natl Institute of Health
Bethesda, Maryland, United States, 20892
United States, Washington
Univ of Washington / Madison Clinic
Seattle, Washington, United States, 98122
Sponsors and Collaborators
Oclassen Pharmaceuticals
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00000981     History of Changes
Other Study ID Numbers: ACTG 122 FIAC, R89-001-01, 02, 03, 04
Study First Received: November 2, 1999
Last Updated: December 17, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Retinitis
AIDS-Related Opportunistic Infections
Pyrimidine Nucleosides
Drug Evaluation
fiacitabine
Cytomegalovirus Infections
Acquired Immunodeficiency Syndrome
Antiviral Agents

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
Communicable Diseases
Cytomegalovirus Infections
HIV Infections
Infection
DNA Virus Infections
Herpesviridae Infections
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Fiacitabine
Anti-Infective Agents
Antineoplastic Agents
Antiviral Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 29, 2014