Safety and PK of Nikkomycin Z for Coccidioides Pneumonia Treatment

University of Arizona

Status and phase: Terminated; Phase 2; Phase 1

Conditions: Coccidioidomycosis

Treatments: Drug: Placebo; Drug: nikkomycin Z

Study type: Interventional

Funder types: Other; Other U.S. Federal agency

Identifiers

NCT00614666

VCFE-2007-001

Details and patient eligibility

About

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.

Full 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.

Enrollment: 6 patients

Sex: All

Ages: 18 to 50 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Age >= 18 years and <= 50 years
• Male or Female (if female, must have a negative pregnancy test and agree to use an acceptable contraception method)
• Able to understand study and give written informed consent
• Have a respiratory illness with at least one of the following: Cough, chest pain dyspnea or tachypnea, sputum production, or fever/chills/night sweats
• Have a new or suspected new pulmonary infiltrate on Chest X-ray
• Have a positive coccidioidal serology by EIA or immunodiffusion

Exclusion criteria

• Patients under the age of 18 years or over 50 years
• Patients with a prior history of confirmed coccidioidal infection
• Laboratory diagnosis of another etiology for the inclusion-defining illness
• Inability to comprehend study and provide informed consent
• History of or current evidence of major organ disease
• Concomitant use of prednisone and other corticosteroids not permitted
• Concomitant immunosuppressive therapy is not permitted
• Concomitant antibacterial therapy is not permitted

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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6 participants in 5 patient groups, including a placebo group

A - First dose level (n=5)

Experimental group

Description:

nikkomycin Z 50 mg BID x 14 days

Treatment:

Drug: nikkomycin Z

B - Second Dose Level (n=10)

Experimental group

Description:

nikkomycin Z nikkomycin Z 250 mg BID x 14 days

Treatment:

Drug: nikkomycin Z

C - Third Dose Level (n=10)

Experimental group

Description:

nikkomycin Z 500 mg BID x 14 days

Treatment:

Drug: nikkomycin Z

D - Fourth Dose Level (n=5)

Experimental group

Description:

nikkomycin Z 750 BID x 14 days

Treatment:

Drug: nikkomycin Z

Placebo

Placebo Comparator group

Description:

placebo BID x 14 days

Treatment:

Drug: Placebo