Safety and PK of Nikkomycin Z for Coccidioides Pneumonia Treatment

Phase I/II Evaluation of the Safety, Pharmacokinetics, and Preliminary Effectiveness of Nikkomycin Z in the Treatment of Patients With Uncomplicated Coccidioides Pneumonia

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.

Study Overview

• Status: Terminated
• Conditions: Coccidioidomycosis
• Intervention / Treatment: Drug: Placebo; Drug: nikkomycin Z

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.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85721
      • Clinical & Translational Research Center - University of Arizona

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A - First dose level (n=5); nikkomycin Z 50 mg BID x 14 days	Drug: 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.
Experimental: B - Second Dose Level (n=10); nikkomycin Z nikkomycin Z 250 mg BID x 14 days	Drug: 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.
Experimental: C - Third Dose Level (n=10); nikkomycin Z 500 mg BID x 14 days	Drug: 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.
Experimental: D - Fourth Dose Level (n=5); nikkomycin Z 750 BID x 14 days	Drug: 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.
Placebo Comparator: Placebo; placebo BID x 14 days	Drug: Placebo; Placebo comparator

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Concentration of Nikkomycin Z in the Blood Over Time (AUC)	0, 0.25, 0.5, 0.75, 1.0, 1.5, 2 , 3, 4, 6, 8 and 12 h hours post-dose on Day 1 and Day 14
Highest Concentration of Nikkomycin Z in the Blood (Cmax)	0, 0.25, 0.5, 0.75, 1.0, 1.5, 2 , 3, 4, 6, 8 and 12 h hours post-dose on Day 1 and Day 14

Secondary Outcome Measures

Outcome Measure	Time Frame
Evaluate the multiple dose pharmacokinetics of nikkomycin Z in patients with uncomplicated coccidioidal pneumonia	2 weeks

Collaborators and Investigators

• Sponsor: University of Arizona
• Collaborators: FDA Office of Orphan Products Development
• Investigators: Principal Investigator: David E Nix, Pharm D, University of Arizona

Publications and helpful links

Helpful Links

• The Valley Fever Center for Excellence

Study record dates

Study Major Dates

• Study Start: September 1, 2007
• Primary Completion (Actual): September 1, 2009
• Study Completion (Actual): September 1, 2009

Study Registration Dates

• First Submitted: January 31, 2008
• First Submitted That Met QC Criteria: February 12, 2008
• First Posted (Estimated): February 13, 2008

Study Record Updates

• Last Update Posted (Actual): April 16, 2025
• Last Update Submitted That Met QC Criteria: March 27, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: coccidioidomycosis; Valley Fever; nikkomycin Z
• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; Respiratory Tract Diseases; Lung Diseases; Protozoan Infections; Parasitic Diseases; Bacterial Infections and Mycoses; Mycoses; Pneumonia; Coccidioidomycosis; Coccidiosis; Anti-Infective Agents; Antifungal Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Nikkomycin
• Other Study ID Numbers: VCFE-2007-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified data may be shared for legitimate use to further nikkomycin Z development.
• IPD Sharing Time Frame: Study was terminated due to poor enrollment. Study report was not generated beyond safety data.
• IPD Sharing Access Criteria: Contact Valley fever Solutions - current license for development.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF