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

Primary Purpose

Cytomegalovirus Infections, HIV Infections

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Fiacitabine
Sponsored by
National Institute of Allergy and Infectious Diseases (NIAID)
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cytomegalovirus Infections focused on measuring Retinitis, AIDS-Related Opportunistic Infections, Pyrimidine Nucleosides, Drug Evaluation, fiacitabine, Cytomegalovirus Infections, Acquired Immunodeficiency Syndrome, Antiviral Agents

Eligibility Criteria

13 Years - 65 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Univ of Alabama at Birmingham
  • Univ of California / San Diego Treatment Ctr
  • Natl Institute of Health
  • Univ of Washington / Madison Clinic

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 2, 1999
Last Updated
December 17, 2012
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Oclassen Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT00000981
Brief Title
The Safety and Effectiveness of FIAC in the Treatment of Cytomegalovirus (CMV) in Patients With AIDS
Official Title
Efficacy and Safety of Oral FIAC in AIDS Patients With Cytomegalovirus Infection: A Dose Ranging Study
Study Type
Interventional

2. Study Status

Record Verification Date
December 2012
Overall Recruitment Status
Completed
Study Start Date
undefined (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
February 1993 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Oclassen Pharmaceuticals

4. Oversight

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cytomegalovirus Infections, HIV Infections
Keywords
Retinitis, AIDS-Related Opportunistic Infections, Pyrimidine Nucleosides, Drug Evaluation, fiacitabine, Cytomegalovirus Infections, Acquired Immunodeficiency Syndrome, Antiviral Agents

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Enrollment
78 (false)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Fiacitabine

10. Eligibility

Sex
All
Minimum Age & Unit of Time
13 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Facility Information:
Facility Name
Univ of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
Univ of California / San Diego Treatment Ctr
City
San Diego
State/Province
California
ZIP/Postal Code
921036325
Country
United States
Facility Name
Natl Institute of Health
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States
Facility Name
Univ of Washington / Madison Clinic
City
Seattle
State/Province
Washington
ZIP/Postal Code
98122
Country
United States

12. IPD Sharing Statement

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

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