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

March 6, 2013 updated by: Immtech Pharmaceuticals, Inc

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).

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

48

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • San Francisco, California, United States, 94110
        • University of California
    • Illinois
      • Chicago, Illinois, United States, 60637
        • The University of Chicago
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Henry Ford Health System
    • New York
      • New York, New York, United States, 10016
        • NYU School of Medicine
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599-7030
        • UNC AIDS Clinical Trials
    • Ohio
      • Cincinnati, Ohio, United States, 45267-0405
        • University of Cincinnati
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Medical University of SC

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

13 years to 65 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 Names:
  • Bactrim

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
Day 22

Secondary Outcome Measures

Outcome Measure
Time Frame
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
Day 22

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Immtech Pharmaceuticals, Inc

Investigators

  • Principal Investigator: Carl Fichtenbaum, MD, University of Cincinnati
  • 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: Kathleen Mullane, DO, University of Chicago
  • Principal Investigator: Jose Vazquez, MD, Henry Ford Health Systems

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2006

Primary Completion (Actual)

December 1, 2008

Study Completion (Actual)

December 1, 2008

Study Registration Dates

First Submitted

March 10, 2006

First Submitted That Met QC Criteria

March 10, 2006

First Posted (Estimate)

March 14, 2006

Study Record Updates

Last Update Posted (Estimate)

March 7, 2013

Last Update Submitted That Met QC Criteria

March 6, 2013

Last Verified

March 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • C05-009

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on HIV Infections

Clinical Trials on Pafuramidine maleate (DB289)

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Mauritania

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe