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Effect of Fluconazole, Clarithromycin, and Rifabutin on the Pharmacokinetics of Sulfamethoxazole-Trimethoprim and Dapsone and Their Hydroxylamine Metabolites
This study has been completed.
First Received: November 2, 1999   Last Updated: August 6, 2008   History of Changes
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000826
  Purpose

To determine the effects of fluconazole and either rifabutin or clarithromycin, alone and in combination, on the pharmacokinetics of first sulfamethoxazole-trimethoprim and then dapsone in HIV-infected patients.

Although prophylaxis for more than one opportunistic infection is emerging as a common clinical practice in patients with advanced HIV disease, little is known about possible adverse drug interactions. The need exists to define pharmacokinetics and pharmacodynamic adverse interactions of the many combination prophylactic regimens that may be prescribed.


Condition Intervention Phase
Bacterial Infections
Mycoses
HIV Infections
Drug: Clarithromycin
Drug: Rifabutin
Drug: Sulfamethoxazole-Trimethoprim
Drug: Dapsone
Drug: Fluconazole
Phase I

Study Type: Interventional
Study Design: Treatment, Open Label, Pharmacokinetics Study
Official Title: Effect of Fluconazole, Clarithromycin, and Rifabutin on the Pharmacokinetics of Sulfamethoxazole and Dapsone and Their Hydroxylamine Metabolites

Resource links provided by NLM:


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

Estimated Enrollment: 48
Detailed Description:

Although prophylaxis for more than one opportunistic infection is emerging as a common clinical practice in patients with advanced HIV disease, little is known about possible adverse drug interactions. The need exists to define pharmacokinetics and pharmacodynamic adverse interactions of the many combination prophylactic regimens that may be prescribed.

In Part A, patients receive sulfamethoxazole-trimethoprim (SMX/TMP) alone for 2 weeks, then in combination with fluconazole, rifabutin, or both drugs, each over 2-week periods in a randomly assigned order. Patients in Part B receive the same regimens except with clarithromycin substituted for rifabutin. In Part C, patients receive dapsone alone for 2 weeks, then in combination with fluconazole, rifabutin, or both drugs in the same manner as in Part A. Part D patients receive the same regimen as those in Part C, except with clarithromycin substituted for rifabutin. Patients are followed every 2 weeks.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

Concurrent Medication:

Allowed:

  • Antiretroviral therapy provided patient has been on a stable dose for at least 4 weeks prior to study entry.
  • Methadone for drug abuse programs provided patient has been on a stable dose for at least 4 weeks prior to the study.

Patients must have:

  • HIV infection.
  • CD4 count >= 200 cells/mm3.
  • No active opportunistic infection.

Prior Medication:

Allowed:

  • Antiretroviral therapy.
  • Methadone for drug abuse therapy.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

  • Suspicion of gastrointestinal malabsorption problems (at discretion of investigator).
  • Known hypersensitivity to dapsone, SMX, or other sulfonamides, trimethoprim, clarithromycin, rifabutin or other rifamycins, fluconazole, or other azoles.
  • G-6-PD deficiency or methemoglobinemia (in Part C and D patients only).

Concurrent Medication:

Excluded:

  • Cytolytic agents.
  • Amiodarone.
  • Anesthetics, general.
  • Astemizole.
  • Azithromycin.
  • Barbiturates.
  • Carbamazepine.
  • Cimetidine.
  • Ciprofloxacin.
  • Cisapride.
  • Clarithromycin (except as required on study).
  • Clotrimazole.
  • Dexamethasone.
  • Disulfiram.
  • Erythromycin.
  • Fluoroquinolones.
  • Fluoxetine.
  • Gestodene.
  • Hydrochlorothiazide.
  • Hypoglycemics, oral.
  • Isoniazid.
  • Itraconazole.
  • Ketoconazole.
  • Levomepromazine.
  • Loratadine.
  • MAO inhibitors.
  • Methoxsalen.
  • Miconazole.
  • Nafcillin.
  • Narcotic analgesics.
  • Naringenin.
  • Nifedipine.
  • Norethindrone.
  • Pentazocine.
  • Phenothiazines.
  • Phenytoin.
  • Protease inhibitors.
  • Quinidine.
  • Ranitidine.
  • Rifabutin (except as required on study).
  • Rifampin.
  • Sedative hypnotics.
  • Sulfaphenazole.
  • Terfenadine.
  • Tranquilizers (unless allowed by investigator).
  • Tricyclic and tetracyclic antidepressants.
  • Troleandomycin.
  • Warfarin.

Concurrent Treatment:

Excluded:

  • Radiation therapy.

Prior Medication:

Excluded:

  • Cytolytic agents within 5 years prior to study entry.
  • Rifabutin and/or rifampin within 4 weeks prior to study entry.
  • Fluconazoles or other azoles within 4 weeks prior to study entry.
  • Glutathione, glutathione precursors, or related prodrugs within 2 weeks prior to study entry.

Excluded within 72 hours prior to study entry:

  • Amiodarone.
  • Anesthetics, general.
  • Astemizole.
  • Azithromycin.
  • Cimetidine.
  • Ciprofloxacin.
  • Cisapride.
  • Clarithromycin.
  • Dexamethasone.
  • Disulfiram.
  • Erythromycin.
  • Fluoroquinolones.
  • Fluoxetine.
  • Hydrochlorothiazide.
  • Hypoglycemics, oral.
  • Isoniazid.
  • Levomepromazine.
  • Loratadine.
  • MAO inhibitors.
  • Methoxsalen.
  • Nafcillin.
  • Narcotic analgesics.
  • Naringenin.
  • Nifedipine.
  • Norethindrone.
  • Pentazocine.
  • Phenothiazines.
  • Phenytoin.
  • Protease inhibitors.
  • Quinidine.
  • Ranitidine.
  • Sedative hypnotics.
  • Sulfaphenazole.
  • Terfenadine.
  • Tranquilizers (unless allowed by investigator).
  • Troleandomycin.
  • Warfarin.

Excluded within 4 weeks prior to study entry:

  • Barbiturates.
  • Carbamazepine.
  • Clotrimazole.
  • Gestodene.
  • Itraconazole.
  • Ketoconazole.
  • Miconazole.
  • Omeprazole.
  • Rifabutin.
  • Rifampin.
  • Tricyclic and tetracyclic antidepressants.

Prior Treatment:

Excluded:

  • Blood transfusion within 1 week prior to study entry.
  • Radiation therapy within 5 years prior to study entry.

Active drug or alcohol abuse or dependence that would preclude completion of study.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00000826

Locations
United States, California
San Francisco Gen Hosp
San Francisco, California, United States, 941102859
United States, District of Columbia
Georgetown Univ Med Ctr
Washington, District of Columbia, United States, 20007
United States, Tennessee
Meharry Med College
Nashville, Tennessee, United States, 37203
United States, Washington
Univ of Washington
Seattle, Washington, United States, 981224304
Sponsors and Collaborators
Investigators
Study Chair: Unadkat J
Study Chair: Trapnell CB
  More Information

Additional Information:
Publications:
Study ID Numbers: ACTG 283
Study First Received: November 2, 1999
Last Updated: August 6, 2008
ClinicalTrials.gov Identifier: NCT00000826     History of Changes
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Rifabutin
Trimethoprim-Sulfamethoxazole Combination
AIDS-Related Opportunistic Infections
Dapsone
Drug Interactions
Fluconazole
Acquired Immunodeficiency Syndrome
AIDS-Related Complex
Clarithromycin
Sulfamethoxazole-Trimethoprim

Additional relevant MeSH terms:
Bacterial Infections
Anti-Infective Agents
Communicable Diseases
Sexually Transmitted Diseases, Viral
Trimethoprim
Antiprotozoal Agents
Slow Virus Diseases
Rifabutin
Molecular Mechanisms of Pharmacological Action
Trimethoprim-Sulfamethoxazole Combination
Renal Agents
Infection
Anti-Bacterial Agents
Mycoses
Clarithromycin
Antimalarials
Antiparasitic Agents
Antifungal Agents
Therapeutic Uses
Dapsone
Retroviridae Infections
Fluconazole
RNA Virus Infections
Immune System Diseases
Sulfamethoxazole
Acquired Immunodeficiency Syndrome
Anti-Infective Agents, Urinary
Enzyme Inhibitors
Folic Acid Antagonists
Pharmacologic Actions

ClinicalTrials.gov processed this record on November 27, 2009