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

Sponsor

Glaxo Wellcome (Industry)

Overall Status

Completed

CT.gov ID

NCT00001996

Collaborator

(none)

Locations

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Pneumonia, Pneumocystis Carinii HIV Infections	Drug: Atovaquone Drug: Pentamidine isethionate	Phase 2

Study Design

Study Type:

Interventional

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

13 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	East Bay AIDS Ctr	Berkeley	California	United States	94704
2	Kaiser Foundation Hosp	Harbor City	California	United States	90710
3	Cedars Sinai Med Ctr	Los Angeles	California	United States	90048
4	UCLA CARE Ctr	Los Angeles	California	United States	90095
5	UCI Med Ctr	Orange	California	United States	92668
6	AIDS Community Research Consortium	Redwood City	California	United States	94063
7	Davies Med Ctr	San Francisco	California	United States	94114
8	Dr Patrick Joseph	San Ramone	California	United States	94583
9	Infectious Disease Research Consortium of Georgia	Atlanta	Georgia	United States	30345
10	Massachusetts Gen Hosp	Boston	Massachusetts	United States	02114
11	Boston City Hosp	Boston	Massachusetts	United States	02118
12	Beth Israel Med Ctr	New York	New York	United States	10003
13	Saint Vincent's Hosp and Med Ctr	New York	New York	United States	10011
14	Harlem AIDS Treatment Group / Harlem Hosp Ctr	New York	New York	United States	10037
15	Univ of Cincinnati	Cincinnati	Ohio	United States	452670405
16	Portland Veterans Adm Med Ctr / Rsch & Education Grp	Portland	Oregon	United States	97210
17	Buckley Braffman Stern Med Associates	Philadelphia	Pennsylvania	United States	19107
18	Regional Med Ctr at Memphis	Memphis	Tennessee	United States	38103
19	Gathe, Joseph, M.D.	Houston	Texas	United States	77004
20	Baylor College of Medicine	Houston	Texas	United States	77030