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

GlaxoSmithKline (GSK)

Status and phase: Completed; Phase 2

Conditions: Pneumonia, Pneumocystis Carinii; HIV Infections

Treatments: Drug: Pentamidine isethionate; Drug: Atovaquone

Study type: Interventional

Funder types: Industry

Identifiers

NCT00001996

053B

05

Details and patient eligibility

About

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.

Sex: All

Ages: 13+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.