A Phase II Open Randomized Comparison of 566C80 and Pentamidine Isethionate for the Treatment of Pneumocystis Carinii Pneumonia in AIDS Patients Who Are Intolerant of Trimethoprim / Sulfamethoxazole

HIV Infections Clinical Trial

Official title:

A Phase II Open Randomized Comparison of 566C80 and Pentamidine Isethionate for the Treatment of Pneumocystis Carinii Pneumonia in AIDS Patients Who Are Intolerant of Trimethoprim / Sulfamethoxazole

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00001996
• Other study ID #: 053B
• Secondary ID: 05
• Status: Completed
• Phase: Phase 2
• First received: November 2, 1999
• Last updated: June 23, 2005

Study information

• Verified date: May 1992
• Source: NIH AIDS Clinical Trials Information Service
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

To compare the safety of atovaquone (566C80) with intravenous (IV) pentamidine for the treatment of mild to moderate Pneumocystis carinii pneumonia (PCP) in AIDS patients who are intolerant of therapy with trimethoprim / sulfamethoxazole (TMP / SMX) by comparing the incidence of premature discontinuation of therapy due to toxicity. To compare the efficacy of 566C80 with intravenous (IV) pentamidine for the treatment of mild to moderate PCP in the same population.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 13 Years and older

Eligibility

Inclusion Criteria

Patients must have the following:

• History of, or are currently experiencing, intolerance to TMP / SMX, or to another sulfonamide, which required discontinuation of therapy.

• Pneumocystis carinii pneumonia (PCP).

• Willing and able to give informed consent.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions or symptoms are excluded.

• Malabsorption disorder or vomiting that would, in the judgement of the investigator, potentially limit the retention and absorption of an oral therapy.

• Concurrent bacterial, fungal, or viral pneumonitis, pulmonary Kaposi's sarcoma, or other concurrent illness, or chronic pulmonary disease that, in the investigator's opinion, would make interpretation of drug efficacy difficult.

• Present occurrences of abnormal prolongation of QT interval on standard, 12 lead EKG.

Concurrent Medication:

Excluded:

• Drugs with potential anti-pneumocystis effect (eg:

• sulfonamides, dapsone, trimethoprim, other dihydrofolate reductase (DHFR) inhibitors, primaquine, clindamycin, sulfonylureas).

• Ganciclovir.

• Zidovudine.

• Investigational agents including anti-retroviral agents (ddI, ddC, etc.). Patients receiving these drugs prior to entry must discontinue their use during the therapy phase (21 days) of the trial.

• Corticosteroids (except replacement therapy) during the 21 day treatment period (Strata A and C Patients).

• Class 1A antiarrhythmics (ie:

• quinidine, procainamide, disopyramide).

Patients with the following are excluded:

• Judged by the investigator to be in impending respiratory failure.

• Known intolerance to parenteral pentamidine isethionate, or therapeutic failure with same for treatment of current episode of PCP.

• Significant psychosis or emotional disorder that, in the investigator's opinion, would preclude the patient from adhering to the protocol.

• Inability or unwillingness to take medication orally or with food.

• Prior documented glucose-6-phosphate dehydrogenase (G6PD) deficiency.

• History, or present occurrences, of abnormal prolongation of QT interval on standard, 12 lead EKG.

• Termination from FDA 053A due to toxicity.

• For patients entering under historic intolerance criteria (Groups A and B), prior therapy for this episode of PCP is an exclusion.

Prior Medication:

Excluded:

• Treatment within 4 weeks of entry for a prior episode of PCP.

• For patients entering under historic intolerance criteria (Groups A and B), prior therapy for this episode of PCP is an exclusion.

Required:

• Adjuvant prednisone for patient enrolled in Strata B or D.

Study Design

Endpoint Classification: Safety Study, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infections
• Pneumonia
• Pneumonia, Pneumocystis
• Pneumonia, Pneumocystis Carinii

Intervention

Drug:
• Atovaquone

• Pentamidine isethionate

Locations

Country	Name	City	State
United States	Infectious Disease Research Consortium of Georgia	Atlanta	Georgia
United States	East Bay AIDS Ctr	Berkeley	California
United States	Boston City Hosp	Boston	Massachusetts
United States	Massachusetts Gen Hosp	Boston	Massachusetts
United States	Univ of Cincinnati	Cincinnati	Ohio
United States	Kaiser Foundation Hosp	Harbor City	California
United States	Baylor College of Medicine	Houston	Texas
United States	Gathe, Joseph, M.D.	Houston	Texas
United States	Cedars Sinai Med Ctr	Los Angeles	California
United States	UCLA CARE Ctr	Los Angeles	California
United States	Regional Med Ctr at Memphis	Memphis	Tennessee
United States	Beth Israel Med Ctr	New York	New York
United States	Harlem AIDS Treatment Group / Harlem Hosp Ctr	New York	New York
United States	Saint Vincent's Hosp and Med Ctr	New York	New York
United States	UCI Med Ctr	Orange	California
United States	Buckley Braffman Stern Med Associates	Philadelphia	Pennsylvania
United States	Portland Veterans Adm Med Ctr / Rsch & Education Grp	Portland	Oregon
United States	AIDS Community Research Consortium	Redwood City	California
United States	Davies Med Ctr	San Francisco	California
United States	Dr Patrick Joseph	San Ramone	California

Sponsors (1)

Lead Sponsor	Collaborator
Glaxo Wellcome

Country where clinical trial is conducted

United States, 

References & Publications (1)

Dohn M, Weinberg W, Rosenstock J, Follansbee S, Torres R, Caldwell P. Atovaquone vs. pentamidine for pneumocystis carinii pneumonia in patients with AIDS. Int Conf AIDS. 1993 Jun 6-11;9(1):372 (abstract no PO-B10-1421)