Clinical trial NCT00614666: Safety and PK of Nikkomycin Z for Coccidioides Pneumonia Treatment
Official title: Phase I/II Evaluation of the Safety, Pharmacokinetics, and Preliminary Effectiveness of Nikkomycin Z in the Treatment of Patients With Uncomplicated Coccidioides Pneumonia
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Coccidioidomycosis
Keywords: coccidioidomycosis
Valley Fever
nikkomycin Z
Lead sponsor: University of Arizona
Sponsor class: OTHER
Collaborators: name: FDA Office of Orphan Products Development
First posted: 2008-02-13
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Concentration of Nikkomycin Z in the Blood Over Time (AUC)
timeFrame: 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
measure: Highest Concentration of Nikkomycin Z in the Blood (Cmax)
timeFrame: 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 outcomes:
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Clinical & Translational Research Center - University of Arizona
state: Arizona
Study officials:
affiliation: University of Arizona
name: David E Nix, Pharm D
role: PRINCIPAL_INVESTIGATOR
References: