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

Primary Purpose

Bacterial Infections, Mycoses, HIV Infections

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Clarithromycin
Rifabutin
Sulfamethoxazole-Trimethoprim
Dapsone
Fluconazole
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 Bacterial Infections focused on measuring Rifabutin, Trimethoprim-Sulfamethoxazole Combination, AIDS-Related Opportunistic Infections, Dapsone, Drug Interactions, Fluconazole, Acquired Immunodeficiency Syndrome, AIDS-Related Complex, Clarithromycin, Sulfamethoxazole-Trimethoprim

Eligibility Criteria

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

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.

Sites / Locations

  • Ucsf Aids Crs
  • University of Washington AIDS CRS

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 2, 1999
Last Updated
October 27, 2021
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
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1. Study Identification

Unique Protocol Identification Number
NCT00000826
Brief Title
Effect of Fluconazole, Clarithromycin, and Rifabutin on the Pharmacokinetics of Sulfamethoxazole-Trimethoprim and Dapsone and Their Hydroxylamine Metabolites
Official Title
Effect of Fluconazole, Clarithromycin, and Rifabutin on the Pharmacokinetics of Sulfamethoxazole and Dapsone and Their Hydroxylamine Metabolites
Study Type
Interventional

2. Study Status

Record Verification Date
October 2021
Overall Recruitment Status
Completed
Study Start Date
undefined (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
May 1999 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)

4. Oversight

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bacterial Infections, Mycoses, HIV Infections
Keywords
Rifabutin, Trimethoprim-Sulfamethoxazole Combination, AIDS-Related Opportunistic Infections, Dapsone, Drug Interactions, Fluconazole, Acquired Immunodeficiency Syndrome, AIDS-Related Complex, Clarithromycin, Sulfamethoxazole-Trimethoprim

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Masking
None (Open Label)
Enrollment
48 (false)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Clarithromycin
Intervention Type
Drug
Intervention Name(s)
Rifabutin
Intervention Type
Drug
Intervention Name(s)
Sulfamethoxazole-Trimethoprim
Intervention Type
Drug
Intervention Name(s)
Dapsone
Intervention Type
Drug
Intervention Name(s)
Fluconazole

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Unadkat J
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Trapnell CB
Official's Role
Study Chair
Facility Information:
Facility Name
Ucsf Aids Crs
City
San Francisco
State/Province
California
Country
United States
Facility Name
University of Washington AIDS CRS
City
Seattle
State/Province
Washington
ZIP/Postal Code
98122
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
11362422
Citation
Cheng B. Preventing opportunistic infections. PI Perspect. 1995 May;(no 16):14-5.
Results Reference
background
PubMed Identifier
15470330
Citation
Winter HR, Trapnell CB, Slattery JT, Jacobson M, Greenspan DL, Hooton TM, Unadkat JD. The effect of clarithromycin, fluconazole, and rifabutin on sulfamethoxazole hydroxylamine formation in individuals with human immunodeficiency virus infection (AACTG 283). Clin Pharmacol Ther. 2004 Oct;76(4):313-22. doi: 10.1016/j.clpt.2004.06.002.
Results Reference
result

Learn more about this trial

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

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