Expired Study
This study is not currently recruiting Study Participants on ClinicalConnection.com. If you would like to find active studies please search for clinical trials.

Nashville, Tennessee 37203


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.


Study summary:

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.


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.


Study is Available At:


Original ID:

ACTG 283


NCT ID:

NCT00000826


Secondary ID:

11259


Study Acronym:


Brief Title:

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


Official Title:

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


Overall Status:

Completed


Study Phase:

Phase 1


Genders:

Both


Minimum Age:

18 Years


Maximum Age:

65 Years


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

National Institute of Allergy and Infectious Diseases (NIAID)


Oversight Authority:

United States: Federal Government


Reasons Why Stopped:


Study Type:

Interventional


Study Design:

Endpoint Classification: Pharmacokinetics Study,


Number of Arms:

0


Number of Groups:

0


Total Enrollment:

48


Enrollment Type:


Overall Contact Information

Official Name:Unadkat J
Study Chair

Study Dates

Completion Date:May 1999
Completion Type:Actual
Verification Date:May 2012
Last Changed Date:May 1, 2012
First Received Date:November 2, 1999

Study Outcomes

There are no available Study Outcomes

Study Interventions

Intervention Type:Drug
Name:Clarithromycin
Intervention Type:Drug
Name:Rifabutin
Intervention Type:Drug
Name:Sulfamethoxazole-Trimethoprim
Intervention Type:Drug
Name:Dapsone
Intervention Type:Drug
Name:Fluconazole

Study Arms

There are no available Study Arms

Study Agencies

Agency Class:NIH
Agency Type:Lead Sponsor
Agency Name:National Institute of Allergy and Infectious Diseases (NIAID)

Sample and Retention Information

There are no available Sample and Retention Information

Study References

Reference Type:Reference
Citation:Cheng B. Preventing opportunistic infections. PI Perspect. 1995 May;(no 16):14-5. No abstract available.
PMID:11362422
Reference Type:Results Reference
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.
PMID:15470330

Data Source: ClinicalTrials.gov

Date Processed: January 21, 2020

Modifications to this listing: Only selected fields are shown, please use the link below to view all information about this clinical trial.


This study is not currently recruiting Study Participants. The form below is not enabled.