Safety and PK of Nikkomycin Z for Coccidioides Pneumonia Treatment

NCT ID: NCT00614666

Last Updated: 2025-04-16

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-09-30
• Study Completion Date: 2009-09-30

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.

Conditions

Coccidioidomycosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

A - First dose level (n=5)

nikkomycin Z 50 mg BID x 14 days

Group Type: EXPERIMENTAL

nikkomycin Z

Intervention Type: DRUG

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.

B - Second Dose Level (n=10)

nikkomycin Z nikkomycin Z 250 mg BID x 14 days

Group Type: EXPERIMENTAL

nikkomycin Z

Intervention Type: DRUG

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.

C - Third Dose Level (n=10)

nikkomycin Z 500 mg BID x 14 days

Group Type: EXPERIMENTAL

nikkomycin Z

Intervention Type: DRUG

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.

D - Fourth Dose Level (n=5)

nikkomycin Z 750 BID x 14 days

Group Type: EXPERIMENTAL

nikkomycin Z

Intervention Type: DRUG

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.

Placebo

placebo BID x 14 days

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo comparator

Interventions

nikkomycin Z

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 Type: DRUG

Placebo

Placebo comparator

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

FDA Office of Orphan Products Development

FED

Sponsor Role: collaborator

University of Arizona

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David E Nix, Pharm D

Role: PRINCIPAL_INVESTIGATOR

University of Arizona

Locations

Clinical & Translational Research Center - University of Arizona

Tucson, Arizona, United States

Countries

United States

Related Links

http://www.vfce.arizona.edu

The Valley Fever Center for Excellence

Other Identifiers

VCFE-2007-001

Identifier Type: -

Identifier Source: org_study_id