DB289 Versus TMP-SMX for the Treatment of Acute Pneumocystis Jiroveci Pneumonia (PCP)

NCT00302341 | Terminated Phase 3 DMC

• 1 other identifier: C05-009
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 7

Brief Summary

The purpose of this study is to demonstrate the non-inferiority of pafuramidine maleate (DB289)versus trimethoprim-sulfamethoxazole (TMP-SMX)for the treatment of mild to moderately severe Pneumocystis pneumonia (PCP).

Conditions

Pneumonia, Interstitial Plasma Cell; Pneumocystis Carinii Pneumonia; Pneumonia, Pneumocystis Carinii; HIV Infections

Keywords

Pulmonary disease; Dyspnea; Hypoxemia; AIDS; Pneumocystis jiroveci

Outcome Measures

Primary Outcomes (1)

• The primary efficacy endpoint will be the proportion of subjects with clinical success at the End of Treatment (Day 22) for the Modified Intent-to-Treat population (mITT).

  Day 22

Secondary Outcomes (1)

• The secondary efficacy endpoints will be the proportion of subjects with clinical success at the End of Treatment (Day 22)for the Per Protocol population and sustained clinical success at the End of Study (Day 42)in the Per Protocol and mITT populations.

  Day 22

Study Arms (2)

1

EXPERIMENTAL

pafuramidine maleate, oral tablet, 100 mg bid X 14 days

Drug: Pafuramidine maleate (DB289)

2

ACTIVE COMPARATOR

TMP/SMX oral tablet, 15 mg/kg, split tid X 21 days

Drug: Trimethoprim-Sulfamethoxazole (TMP-SMX)

Interventions

Pafuramidine maleate (DB289) DRUG

Oral tablet, 100 mg bid, 14 days

1

Trimethoprim-Sulfamethoxazole (TMP-SMX) DRUG

15 mg/kg, oral tablet split tid X 21 days

Also known as: Bactrim

2

Eligibility Criteria

• Age: 13 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Documented or presumptive HIV infection
• Signs and symptoms of PCP present for at least 5 days
• Pneumocystis jiroveci confirmed in BAL fluid or induced sputum sample
• Suitable candidate for oral therapy
• Alveolar-arterial oxygen (A-a) gradient \< or = 45 mm Hg on room air and partial pressure of oxygen (pO2) \> or = 60 mm Hg
• No more than 48 hours of prior treatment in the preceding 7 days for PCP treatment at full doses; failure of Pneumocystis prophylaxis or use of medications recommended for treatment of PCP at doses less than recommended by the CDC Guidelines is acceptable.

You may not qualify if:

• Unwilling or unable to discontinue use of other medications with anti-PCP activity
• AIDS related cachexia (weight loss that is more than 10% of ideal body weight)
• Severe diarrhea and/or vomiting
• History of hypersensitivity or severe or life threatening toxicity to TMP-SMX, other sulfonamides or pentamidine
• Active illicit drug use
• Impending respiratory failure or need for intubation
• AST and ALT levels \> 3 times the upper limit of normal
• History of pancreatitis
• Severe PCP
• Karnofsky score \< or = 20
• Terminal HIV disease or life expectancy of less than 6 months
• Acute concurrent pulmonary pathological condition that would obscure the evaluation of response to therapy
• Concomitant use of amphotericin B, gangciclovir, cyclosporine, warfarin, thiazide diuretics, phenytoin, methotrexate, leucovorin
• Receipt of systemic corticosteroids (except replacement therapy) within 14 days of study entry at high doses for 3 or more consecutive days. Concomitant use of corticosteroids, other than replacement doses for adrenal insufficiency, is also excluded unless the patient meets the CDC criteria for use of corticosteroids for treatment of PCP
• Pregnant or lactating women

Sponsors & Collaborators

• Immtech Pharmaceuticals, Inc: lead

Study Sites (7)

University of California

San Francisco, California, 94110, United States

Location

The University of Chicago

Chicago, Illinois, 60637, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

NYU School of Medicine

New York, New York, 10016, United States

Location

UNC AIDS Clinical Trials

Chapel Hill, North Carolina, 27599-7030, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45267-0405, United States

Location

Medical University of SC

Charleston, South Carolina, 29425, United States

Location

MeSH Terms

Conditions

Pneumonia, Pneumocystis; HIV Infections; Lung Diseases; Dyspnea; Hypoxia; Acquired Immunodeficiency Syndrome

Interventions

pafuramidine; Trimethoprim, Sulfamethoxazole Drug Combination

Condition Hierarchy (Ancestors)

Lung Diseases, Fungal; Mycoses; Bacterial Infections and Mycoses; Infections; Pneumocystis Infections; Respiratory Tract Infections; Pneumonia; Respiratory Tract Diseases; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Slow Virus Diseases

Intervention Hierarchy (Ancestors)

Sulfamethoxazole; Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Sulfanilamides; Aniline Compounds; Amines; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Trimethoprim; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Judith Aberg, MD

  NYU School of Medicine

  PRINCIPAL INVESTIGATOR

• Preston Church, MD

  Medical University of South Carolina

  PRINCIPAL INVESTIGATOR

• Laurence Huang, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

• Amanda Peppercorn, MD

  UNC AIDS Clinical Trials- School of Medicine

  PRINCIPAL INVESTIGATOR

• Carl Fichtenbaum, MD

  University of Cincinnati

  PRINCIPAL INVESTIGATOR

• Kathleen Mullane, DO

  University of Chicago

  PRINCIPAL INVESTIGATOR

• Jose Vazquez, MD

  Henry Ford Health Systems

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 10, 2006
• First Posted: March 14, 2006
• Study Start: May 1, 2006
• Primary Completion: December 1, 2008
• Study Completion: December 1, 2008
• Last Updated: March 7, 2013

Record last verified: 2013-03

Locations

US (7)