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

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.