Bacterial InfectionsPhase 1NCT00000826
Effect of Fluconazole, Clarithromycin, and Rifabutin on the Pharmacokinetics of Sulfamethoxazole-Trimethoprim and Dapsone and Their Hydroxylamine Metabolites
A Phase 1 study testing Clarithromycin, Rifabutin and Sulfamethoxazole-Trimethoprim in people with Bacterial Infections and Mycoses, run by National Institute of Allergy and Infectious Diseases (NIAID) at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Bacterial Infections, Mycoses, HIV Infections
- What is being tested?
- Clarithromycin, Rifabutin and Sulfamethoxazole-Trimethoprim
- How many people
- 48 participants
- Where
- 2 sitesUnited States
- Study dates
- Start not givento May 1999
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- CD4 count >= 200 cells/mm3.
- No active opportunistic infection.
- Prior Medication:
- Allowed:
- Antiretroviral therapy.
- Methadone for drug abuse therapy.
Who cannot join
- 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:
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- 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.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Ucsf Aids Crs
San Francisco, California
University of Washington AIDS CRS
Seattle, Washington, 98122
About this study
Official title: Effect of Fluconazole, Clarithromycin, and Rifabutin on the Pharmacokinetics of Sulfamethoxazole and Dapsone and Their Hydroxylamine Metabolites
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.
Read the 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.
- Conditions
- Bacterial Infections, Mycoses, HIV Infections
- Being tested
- Clarithromycin, Rifabutin, Sulfamethoxazole-Trimethoprim, Dapsone, Fluconazole
- Keywords
- Rifabutin, Trimethoprim-Sulfamethoxazole Combination, AIDS-Related Opportunistic Infections, Dapsone, Drug Interactions, Fluconazole, Acquired Immunodeficiency Syndrome, AIDS-Related Complex, Clarithromycin, Sulfamethoxazole-Trimethoprim
- Medical subject headings
- Bacterial Infections, Mycoses, HIV Infections, AIDS-Related Opportunistic Infections, Acquired Immunodeficiency Syndrome, AIDS-Related Complex
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ClarithromycinDrug
RifabutinDrug
Sulfamethoxazole-TrimethoprimDrug
DapsoneDrug
FluconazoleDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Aug 2001 (estimated)
- Study completionMay 1999
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Bacterial InfectionsStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Masking
- None (open label)
- Enrolment
- 48 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Unadkat J, Study chairTrapnell CB, Study chair
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00000826
- Sponsor's protocol ID
- ACTG 283
- Other IDs
- 11259
- Status last verified
- Oct 2021
- First submitted
- 2 Nov 1999
- Last updated
- 29 Oct 2021
- Results posted
- No
Publications
Cheng B. Preventing opportunistic infections. PI Perspect. 1995 May;(no 16):14-5.
PubMed 11362422Winter 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.
PubMed 15470330
Study at a glance
From the registry record, last updated by the sponsor on 29 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Fluconazole, Clarithromycin, and Rifabutin on the Pharmacokinetics of Sulfamethoxazole and Dapsone and Their Hydroxylamine Metabolites
- ClinicalTrials.gov ID
- NCT00000826
- Acronym / sponsor ID
- ACTG 283
- Conditions
- Bacterial Infections, Mycoses, HIV Infections
- Keywords
- Rifabutin, Trimethoprim-Sulfamethoxazole Combination, AIDS-Related Opportunistic Infections, Dapsone, Drug Interactions, Fluconazole, Acquired Immunodeficiency Syndrome, AIDS-Related Complex
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study completion
- May 1999 (actual)
- First posted
- 31 Aug 2001 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Masking
- None (open label)
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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.
- HIV infection.
- CD4 count >= 200 cells/mm3.
- No active opportunistic infection.
Key exclusion criteria (119 listed)
- 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).
- Cytolytic agents.
- Amiodarone.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Clarithromycin | Drug | – |
| Rifabutin | Drug | – |
| Sulfamethoxazole-Trimethoprim | Drug | – |
| Dapsone | Drug | – |
| Fluconazole | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Oct 2021.
- Background: PubMed 11362422Cheng B. Preventing opportunistic infections. PI Perspect. 1995 May;(no 16):14-5.
- Results publication: PubMed 15470330Winter 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Unadkat J study chair
Trapnell CB study chair
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Clarithromycin, Rifabutin and Sulfamethoxazole-Trimethoprim in people with Bacterial Infections and Mycoses, run by National Institute of Allergy and Infectious Diseases (NIAID) at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 119 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00000826, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Oct 2021.