Randomized Phase I Study of Trimetrexate Glucuronate (TMTX) With Leucovorin (LCV) Protection Plus Dapsone Versus Trimethoprim / Sulfamethoxazole (TMP/SMX) for Treatment of Moderately Severe Episodes of Pneumocystis Carinii Pneumonia

HIV Infections Clinical Trial

Official title:

Randomized Phase I Study of Trimetrexate Glucuronate (TMTX) With Leucovorin (LCV) Protection Plus Dapsone Versus Trimethoprim / Sulfamethoxazole (TMP/SMX) for Treatment of Moderately Severe Episodes of Pneumocystis Carinii Pneumonia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00002120
• Other study ID #: 224A
• Secondary ID: TMTX A009
• Status: Completed
• Phase: Phase 1
• First received: November 2, 1999
• Last updated: June 23, 2005

Study information

• Verified date: March 1996
• 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 evaluate the safety of the combination of trimetrexate glucuronate (TMTX) and dapsone with leucovorin protection versus trimethoprim/sulfamethoxazole (TMP/SMX) in patients with AIDS and moderately severe Pneumocystis carinii pneumonia (PCP). To determine the pharmacokinetic parameters of TMTX, leucovorin, and dapsone and of TMP/SMX when given to patients with AIDS and moderately severe PCP.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 13 Years and older

Eligibility

Inclusion Criteria

Concurrent Medication:

Allowed:

• Empiric therapy for other opportunistic pulmonary infection (TB or fungi) for the first 72 hours of study enrollment ONLY, until presence of suspected pathogens can be confidently excluded.

Patients must have:

• AIDS.

• Confirmed diagnosis of PCP.

• Alveolar-arterial differences in dissolved oxygen >= 35 mm Hg but < 55 mm Hg on room air.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

• Severe renal or hepatic dysfunction.

• Serious or life-threatening intolerance to TMP/SMX, TMTX, or dapsone.

• Concurrent pneumothorax.

• Active pulmonary tuberculosis or other inadequately treated opportunistic pulmonary infection (e.g., Cryptococcus neoforms, CMV). NOTE:

• Identification of Mycobacterium avium or CMV in sputum or BAL fluid does not exclude, since these organisms may be present without causing disease.

• Pulmonary Kaposi's sarcoma.

• Active opportunistic infections or malignancies requiring induction therapy with bone marrow suppressive drugs (e.g., ganciclovir) or hepatotoxic drugs (e.g., chemotherapy).

• Unable to have arterial blood gases on room air obtained at baseline.

• Unwilling to undergo bronchoscopy, if sputum induction does not reveal Pneumocystis carinii.

• Suspected malabsorption (e.g., ileus or severe diarrhea with > 6 stools/day).

• Known absence of G6PD activity.

• Large volume (1.0 to 1.5 liters) of intravenous fluid (5 percent in water) per 24 hours is medically inadvisable.

• Unwilling to comply with study design.

Concurrent Medication:

Excluded:

• Induction therapy with bone marrow suppressive drugs (e.g., ganciclovir) or hepatotoxic drugs (e.g., chemotherapy).

• AZT, ddI, ddC, d4T, or other antiretroviral therapy.

Patients with the following prior condition are excluded:

Prior history of serious or life-threatening intolerance to TMP/SMX. (NOTE:

• Patients with less severe reactions may be included at the discretion of the investigator and primary care provider.)

Prior Medication:

Excluded:

• More than 24 hours of systemic anti-PCP therapy within 2 weeks prior to study entry.

Study Design

Endpoint Classification: Pharmacokinetics Study, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

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

Intervention

Drug:
• Trimetrexate glucuronate

• Trimethoprim

• Sulfamethoxazole

• Dapsone

• Leucovorin calcium

Locations

Country	Name	City	State
United States	Los Angeles County / Health Research Assoc / Drew Med Ctr	Los Angeles	California

Sponsors (2)

Lead Sponsor	Collaborator
U.S. Bioscience	Jacobus Pharmaceutical

Country where clinical trial is conducted

United States,