Limited Access Protocol of Posaconazole in Invasive Fungal Infections Study PO2095

• Status: Terminated
• Trial end date: 2006-11-01
• Target enrollment: 0
• Participant gender: All

Summary

Therapeutic options for serious fungal infections are limited by intrinsic and acquired resistance to existing antifungal agents. For example, zygomycetes (such as Mucor spp.) are intrinsically resistant to voriconazole and caspofungin. Yet, the only available therapeutic option, amphotericin, is associated with significant renal toxicity, even in lipid formulations. Posaconazole is a new antifungal drug, not yet Food and Drug Administration (FDA) approved, but which has excellent in vitro activity against some intrinsically resistant fungi such as the zygomycetes.

The intent of this trial is to provide access to posaconazole to patients with serious fungal infections which are refractory to standard antifungal therapies or invasive fungal infections for which there are currently no effective therapies. Secondly, the drug will also be made available to patients with invasive fungal infections who:

• have experienced serious or severe toxicities while receiving standard antifungal therapies;

• have pre-existing renal dysfunction which precludes use of standard antifungal therapies; or

• are chronically immunosuppressed with a history of invasive fungal infections previously treated with posaconazole in other clinical trials, and who require oral antifungal suppressive therapy as maintenance treatment to prevent recurrence.

This is a multicenter, open-label, non-comparative experimental treatment use protocol. The experimental treatment use protocol will provide the investigational medication posaconazole where no other drug is commercially available. Posaconazole is given as an orally or enterally administered suspension. The duration of therapy is at the discretion of the investigator. Safety assessments will include an electrocardiogram [ECG] (to ensure no QTc interval prolongation) performed at baseline and serum/urine pregnancy testing performed at baseline and every three months after initiation of therapy. Plasma concentrations will be obtained if there is evidence of clinical failure. No other tests will be performed specifically for the experimental treatment use protocol.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Pittsburgh
• Collaborator: Schering-Plough
• Treatments: Posaconazole

Criteria

Inclusion Criteria:

• A proven, probable, or possible invasive fungal infection which is refractory to standard antifungal therapies after a reasonable trial of standard antifungal therapy

• A proven, probable, or possible invasive fungal infection with a prior history of serious, severe, or life-threatening toxicities related to antifungal therapy

• A proven, probable, or possible invasive fungal infection with documented organ dysfunction (such as renal dysfunction defined as serum creatinine > 2.5 mg/dL or estimated creatinine clearance < 25 mL/minute), which precludes the continued administration of standard antifungal therapy

• A proven or probable invasive fungal infection for which there are currently no other clinically reasonable effective therapies

• A history of a proven or probable invasive fungal infection previously treated with posaconazole in a chronically immunosuppressed patient that requires oral antifungal suppressive therapy.

• A proven or probable invasive fungal infection in patients who have failed a reasonable trial of other licensed antifungal agents, either due to progression or lack of improvement of the infection

• A history of proven or probable invasive fungal infection in patients requiring ongoing antifungal therapy as chronic maintenance after initial control of disease with other antifungal agents, but who have become intolerant to licensed azoles. In these cases where long term parenteral antifungal therapy (e.g., amphotericin B or echinocandins) is not considered practical or clinically reasonable by the physician, posaconazole may be considered to be a potential treatment option.

• Patients with debilitating but no immediately life threatening fungal diseases, where significant morbidity may result in disability and where prior antifungal therapy has been unsuccessful (e.g., chronic candidiasis with dehydration and malnutrition, or cutaneous phaeohyphomycosis and mycetoma).

Exclusion Criteria:

• Females who are pregnant or who continue to breast feed infants.

• History of serious or severe hypersensitivity or idiosyncratic reactions to azole antifungals

• Subjects who require ongoing treatment with any prohibited medication and for whom an appropriate washout period has not elapsed. Those drugs known to interact with azoles and that may lead to life-threatening side effects: terfenadine, cisapride, and ebastine at entry or within 24 hours before entry, or astemizole at entry or within 10 days before entry; those known to lower the serum concentration/efficacy of azole antifungal agents: cimetidine, rifampin, carbamazepine, phenytoin, rifabutin, barbiturates, and isoniazid at entry or within 24 hours before entry; and those receiving vinca alkaloids, or anthracyclines with evidence of cardiotoxicity.

• Subjects who are in a situation or have any condition that, in the opinion of the investigator, may interfere with optimal participation in the experimental treatment use protocol, ie, any condition requiring the use of prohibited drugs or unstable medical conditions other than a hematological disorder such as unstable cardiac disorder (including acute myocardial infarction or unstable myocardial ischemia/angina within 30 days, ventricular arrhythmia within 30 days, uncontrolled atrial fibrillation, or atrial fibrillation/flutter with symptomatic bradycardia [sick sinus syndrome], or unstable congestive heart failure) or impairment expected to be unstable or progressive during the course of this experimental treatment use protocol (eg, recurrent or uncontrolled seizure disorders, demyelinating syndromes, or progressive peripheral neuropathy).

• Subjects receiving vinca alkaloids or anthracyclines within 24 hours of enrollment or requiring therapy with vinca alkaloids or anthracyclines within the next 30 days for treatment of uncontrolled (pre-existing) malignancy or requiring ongoing therapy with vinca alkaloids or anthracyclines

• Subjects requiring ongoing systemic antifungal agents in addition to investigational medication (combination use is not permitted without prior authorization of the sponsor project physician).

• Subjects with an ECG with QTc interval greater than 450 msec for men, and greater than 470 msec for women at entry or within seven days prior to entry

• Any condition requiring the use of prohibited drugs

• Hepatic function tests: alanine amino transferase (ALT) or aspartate amino transferase (AST) > 10 times upper limit of normal.