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

This study has been terminated.
(FDA Clinical Hold as of 12/21/07 due to safety concerns)
Sponsor:
Information provided by (Responsible Party):
Immtech Pharmaceuticals, Inc
ClinicalTrials.gov Identifier:
NCT00302341
First received: March 10, 2006
Last updated: March 6, 2013
Last verified: March 2013
  Purpose

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).


Condition Intervention Phase
Pneumonia, Interstitial Plasma Cell
Pneumocystis Carinii Pneumonia
Pneumonia, Pneumocystis Carinii
HIV Infections
Drug: Pafuramidine maleate (DB289)
Drug: Trimethoprim-Sulfamethoxazole (TMP-SMX)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: International Randomized, Controlled Phase 3 Trial of DB289 Versus Trimethoprim-sulfamethoxazole for the Treatment of Acute Pneumocystis Jiroveci Pneumonia (PCP) in Patients With HIV/AIDS

Resource links provided by NLM:


Further study details as provided by Immtech Pharmaceuticals, Inc:

Primary Outcome Measures:
  • 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). [ Time Frame: Day 22 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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. [ Time Frame: Day 22 ] [ Designated as safety issue: No ]

Enrollment: 48
Study Start Date: May 2006
Study Completion Date: December 2008
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
pafuramidine maleate, oral tablet, 100 mg bid X 14 days
Drug: Pafuramidine maleate (DB289)
Oral tablet, 100 mg bid, 14 days
Active Comparator: 2
TMP/SMX oral tablet, 15 mg/kg, split tid X 21 days
Drug: Trimethoprim-Sulfamethoxazole (TMP-SMX)
15 mg/kg, oral tablet split tid X 21 days
Other Name: Bactrim

Detailed Description:

The gold standard treatment for PCP is trimethoprim-sulfamethoxazole (TMP-SMX). This drug is highly effective; however, a significant number of patients are unable to complete a course of therapy due to adverse events, some of which can be life-threatening. In addition, mutations that confer resistance to sulfa-based drugs in other microorganisms are increasingly being reported in P. jiroveci. A potential role of these mutations in conferring clinical resistance to PCP and in breakthroughs to prophylaxis regimens based on sulfa drugs is being actively studied. Second and third line agents or combinations for PCP treatment are also limited in efficacy and/or by adverse events.

A new agent such as pafuramidine maleate (DB289), which has well documented activity against P. carinii in animal models, documented efficacy in a preliminary study trial in HIV-infected patients with PCP that were intolerant or resistant to TMP-SMX, was well tolerated in this trial and demonstrated a low toxicity profile in Phase 1 studies, would meet a significant medical need. Furthermore, pafuramidine maleate is active against other pathogens responsible for significant morbidity and mortality in patients with AIDS in the developing world, like different strains of Plasmodium (malaria) and Cryptosporidium parvum. The decrease in the rate of PCP in countries where patients with AIDS have access to HAART will present a significant challenge to the completion of this development program. The last published trial of PCP treatment was conducted by the ACTG in 24 U.S. sites between May 1991 and june 1993. That study needed to decrease the planned sample size to 195 due to low enrollment. This represents an important challenge for our program.

  Eligibility

Ages Eligible for Study:   13 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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
  • The subject has been previously enrolled in the study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00302341

Locations
United States, California
University of California
San Francisco, California, United States, 94110
United States, Illinois
The University of Chicago
Chicago, Illinois, United States, 60637
United States, Michigan
Henry Ford Health System
Detroit, Michigan, United States, 48202
United States, New York
NYU School of Medicine
New York, New York, United States, 10016
United States, North Carolina
UNC AIDS Clinical Trials
Chapel Hill, North Carolina, United States, 27599-7030
United States, Ohio
University of Cincinnati
Cincinnati, Ohio, United States, 45267-0405
United States, South Carolina
Medical University of SC
Charleston, South Carolina, United States, 29425
Sponsors and Collaborators
Immtech Pharmaceuticals, Inc
Investigators
Principal Investigator: 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
  More Information

No publications provided

Responsible Party: Immtech Pharmaceuticals, Inc
ClinicalTrials.gov Identifier: NCT00302341     History of Changes
Other Study ID Numbers: C05-009
Study First Received: March 10, 2006
Last Updated: March 6, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Immtech Pharmaceuticals, Inc:
Pulmonary disease
Dyspnea
Hypoxemia
AIDS
Pneumocystis jiroveci

Additional relevant MeSH terms:
Lung Diseases, Interstitial
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immune System Diseases
Slow Virus Diseases
Lung Diseases
Respiratory Tract Diseases
Lung Diseases, Fungal
HIV Infections
Acquired Immunodeficiency Syndrome
Pneumonia
Pneumonia, Pneumocystis
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Immunologic Deficiency Syndromes
Respiratory Tract Infections
Mycoses
Pneumocystis Infections
Maleic acid
Trimethoprim
Sulfamethoxazole
Trimethoprim-Sulfamethoxazole Combination
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Infective Agents
Therapeutic Uses
Anti-Infective Agents, Urinary

ClinicalTrials.gov processed this record on August 28, 2014