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	Treatment or Intervention	Phase
Pneumonia, Pneumocystis carinii HIV Infections	Drug: Atovaquone  Drug: Pentamidine isethionate	Phase II

Ages Eligible for Study:  13 Years and above,  Genders Eligible for Study:  Both

Criteria

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.

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

Study ID Numbers:  053B; 05
Record last reviewed:  May 1992
Last Updated:  October 13, 2004
Record first received:  November 2, 1999
ClinicalTrials.gov Identifier:  NCT00001996
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-04-08