Open Label, Limited Access Protocol of Posaconazole in Invasive Fungal Infections Study PO2095
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 入组人数
- 10
- 试验地点
- 2
- 主要终点
- provide posaconazole to patients with invasive fungal infections
研究概览
简要总结
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.
详细描述
This is an open-label, multi-center limited access experimental treatment use protocol of Posaconazole in the treatment of Invasive Fungal Infections. This experimental treatment use protocol is projected to begin enrollment in September 2001.
Screening:
- complete medical history, including a review of the subject's fungal infection and the antifungal treatment(s)
- women of childbearing potential, will have a serum (blood) or urine pregnancy test before the experimental medication (posaconazole) is administered. This test requires a sample of blood to be drawn (10 mL or 1 tablespoon of blood or about 10 ml or 1 tablespoon of urine). The subject will not be able to participate in this experimental treatment use protocol if pregnant. In addition, while participating in this experimental treatment use protocol, women of childbearing potential, will have serum (blood) or urine pregnancy tests performed every 3 months.
- Electrocardiogram- ECG
The total time for all these screening tests will be one hour and will be carried out in the subject's hospital room.
Experimental Procedures: the following procedures that are not part of the subject's standard medical care. This experimental treatment use protocol will be conducted worldwide. This experimental treatment use protocol is open ended so no set subject enrollment has been set by Schering Plough. It is anticipated that sites may be opened for a single patient, and we anticipate enrolling up to two patients at UPMC. All subjects enrolled in this open-label experimental treatment use protocol will receive treatment with posaconazole as outlined previously. Subject identification numbers will be assigned sequentially within each site starting with Subject No. 1. There will be no randomization. Primary efficacy endpoint is the global response (microbiological and clinical) at the end of therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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).
排除标准
- •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.
结局指标
主要结局
provide posaconazole to patients with invasive fungal infections
次要结局
- posaconazole where no other drug is commercially available