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Effect of Fluconazole, Clarithromycin, and Rifabutin on the Pharmacokinetics of Sulfamethoxazole-Trimethoprim and Dapsone and Their Hydroxylamine Metabolites

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ClinicalTrials.gov Identifier: NCT00000826
Recruitment Status : Completed
First Posted : August 31, 2001
Last Update Posted : May 2, 2012
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Study Description
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Brief Summary:

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 or disease Intervention/treatment Phase
Bacterial Infections Mycoses HIV Infections Drug: Clarithromycin Drug: Rifabutin Drug: Sulfamethoxazole-Trimethoprim Drug: Dapsone Drug: Fluconazole Phase 1

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.


Study Design
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Study Type : Interventional  (Clinical Trial)
Enrollment : 48 participants
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Effect of Fluconazole, Clarithromycin, and Rifabutin on the Pharmacokinetics of Sulfamethoxazole and Dapsone and Their Hydroxylamine Metabolites
Actual Study Completion Date : May 1999

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS
U.S. FDA Resources

Arms and Interventions
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Outcome Measures
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Eligibility Criteria
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Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
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
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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00000826


Locations
United States, California
Ucsf Aids Crs
San Francisco, California, United States
United States, Washington
University of Washington AIDS CRS
Seattle, Washington, United States, 98122
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
Study Chair: Unadkat J
Study Chair: Trapnell CB
More Information
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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications of Results:

Other Publications:

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000826     History of Changes
Other Study ID Numbers: ACTG 283
11259 ( Registry Identifier: DAIDS ES Registry Number )
First Posted: August 31, 2001    Key Record Dates
Last Update Posted: May 2, 2012
Last Verified: May 2012

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:
Infection
Communicable Diseases
HIV Infections
Mycoses
Bacterial Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Clarithromycin
Dapsone
 Rifabutin
Trimethoprim, Sulfamethoxazole Drug Combination
Fluconazole
Trimethoprim
Sulfamethoxazole
Anti-Bacterial Agents
Anti-Infective Agents
Protein Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Antifungal Agents
14-alpha Demethylase Inhibitors
Steroid Synthesis Inhibitors