Conditions: Coccidioidomycosis
Keywords: coccidioidomycosis Valley Fever nikkomycin Z
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 6
Healthy volunteers: no

Brief summary:
The purpose of this study is to determine if nikkomycin Z is safe when administered at different dose levels for 14 days. The study will also determine blood levels and urinary excretion of nikkomycin Z in relation to dose administered. Patients with mild forms of Valley Fever pneumonia will be eligible to participate and will be allocated to receive treatment with nikkomycin Z (various doses) or a placebo. A secondary goal of this study is to evaluate the effectiveness and dose response of nikkomycin Z in an exploratory analysis.

Detailed description:
Every year there are 50,000 new U.S. cases of coccidioidomycosis (Valley Fever). The majority of these illnesses occur as a result of endemic exposure in Arizona and California. The benefits of antifungal therapy for uncomplicated disease are not currently established. Current therapies for serious and complicated forms of coccidioidomycosis are only partially effective and in themselves are unable to eradicate the fungus from sites of infection, commonly resulting in breakthrough infection and/or relapse. Nikkomycin Z is effective in the mouse model and results in improved microbiological response over fluconazole.

The goals of this study include: 1) Evaluating the safety and tolerance of nikkomycin Z following administration of multiple doses (50 mg Q 12 h to 750 mg Q 8 h) for two week and 2) Evaluating the pharmacokinetics of nikkomycin Z after single and multiple doses in relationship to dose. The study will include patients with uncomplicated Coccidioides pneumonia (mild illness) which will allow exploratory analysis of efficacy and dose response based on biomarkers.

Arms:
arm 1: nikkomycin Z 50 mg BID x 14 days arm 2: nikkomycin Z nikkomycin Z 250 mg BID x 14 days arm 3: nikkomycin Z 500 mg BID x 14 days arm 4: nikkomycin Z 750 BID x 14 days arm 5: placebo BID x 14 days

Interventions: intervention 1: nikkomycin Z intervention 2: Placebo
Intervention descriptions: intervention 1: Stage I: Multiple rising doses. Doses packaged on a unit dose basis in 50 and 250 mg capsules. Subjects take 1-3 capsules per dosing block for 14 days unless ADE or study withdrawal. Dose escalation unless a dose-limiting adverse effect is noted. Subjects assigned to BID dosing will receive 28 doses and subjects assigned to TID dosing will receive 42 doses.

* 50 mg BID (n=4) vs placebo capsule BID (n=1)
* 50 mg BID (n=4) vs 250 mg BID (n=4) vs Placebo capsule BID (n=2)
* 250 mg BID (n=4) vs 500 mg BID (n=4) vs Placebo capsule BID (n=2)
* 500 mg BID (n=4) vs Placebo capsule BID (n=1)

At least 4 subjects complete lower dose before randomization includes next higher dose.

Stage II will be a single dose level selected based on pharmacodynamics and safety from Stage I for 20 additional subjects using 4:1 randomization. intervention 2: Placebo comparator

Protocol document: