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

March 10, 2006
March 6, 2013
May 2006
December 2008   (final data collection date for primary outcome measure)
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 ]
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).
Complete list of historical versions of study NCT00302341 on ClinicalTrials.gov Archive Site
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 ]
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.
Not Provided
Not Provided
 
DB289 Versus TMP-SMX for the Treatment of Acute Pneumocystis Jiroveci Pneumonia (PCP)
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

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).

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
  • Pneumonia, Interstitial Plasma Cell
  • Pneumocystis Carinii Pneumonia
  • Pneumonia, Pneumocystis Carinii
  • HIV Infections
  • Drug: Pafuramidine maleate (DB289)
    Oral tablet, 100 mg bid, 14 days
  • Drug: Trimethoprim-Sulfamethoxazole (TMP-SMX)
    15 mg/kg, oral tablet split tid X 21 days
    Other Name: Bactrim
  • Experimental: 1
    pafuramidine maleate, oral tablet, 100 mg bid X 14 days
    Intervention: Drug: Pafuramidine maleate (DB289)
  • Active Comparator: 2
    TMP/SMX oral tablet, 15 mg/kg, split tid X 21 days
    Intervention: Drug: Trimethoprim-Sulfamethoxazole (TMP-SMX)
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
48
December 2008
December 2008   (final data collection date for primary outcome measure)

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
Both
13 Years to 65 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00302341
C05-009
Yes
Immtech Pharmaceuticals, Inc
Immtech Pharmaceuticals, Inc
Not Provided
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
Immtech Pharmaceuticals, Inc
March 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP