Safety and PK of Nikkomycin Z for Coccidioides Pneumonia Treatment

Coccidioidomycosis Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00614666
• Other study ID #: VCFE-2007-001
• Status: Terminated
• Phase: Phase 1/Phase 2
• First received: January 31, 2008
• Last updated: February 12, 2013
• Start date: September 2007
• Est. completion date: September 2009

Study information

• Verified date: August 2009
• Source: University of Arizona
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 6
• Est. completion date: September 2009
• Est. primary completion date: September 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 50 Years

Eligibility

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 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 Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Coccidioidomycosis

Intervention

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=8) vs placebo capsule BID (n=2) 250 mg BID (n=8) vs Placebo capsule BID (n=2) 500 mg BID (n=8) vs Placebo capsule BID (n=2) 750 mg TID (n=8) vs Placebo capsule TID (n=2) At least 4 subjects complete lower dose before randomization includes next higher dose, thus there are 4 arms for active intervention and corresponding placebos. 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.

Locations

Country	Name	City	State
United States	Clinical & Translational Research Center - University of Arizona	Tucson	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
University of Arizona	FDA Office of Orphan Products Development

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determine safety and tolerance of nikkomycin Z in relatively healthy subjects following administration of multiple doses.		four weeks	Yes
Secondary	Evaluate the multiple dose pharmacokinetics of nikkomycin Z in patients with uncomplicated coccidioidal pneumonia		2 weeks	No

External Links

•   The Valley Fever Center for Excellence