Safety and PK of Nikkomycin Z for Coccidioides Pneumonia Treatment - Full Text View

Sponsors and Collaborators:	University of Arizona FDA Office of Orphan Products Development
Information provided by:	University of Arizona
ClinicalTrials.gov Identifier:	NCT00614666

Purpose

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.

Condition	Intervention	Phase
Coccidioidomycosis	Drug: nikkomycin Z	Phase I Phase II

MedlinePlus related topics: Fever Pneumonia

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator), Dose Comparison, Parallel Assignment, Safety Study
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

Further study details as provided by University of Arizona:

Primary Outcome Measures:

Determine safety and tolerance of nikkomycin Z in relatively healthy subjects following administration of multiple doses. [ Time Frame: four weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Evaluate the multiple dose pharmacokinetics of nikkomycin Z in patients with uncomplicated coccidioidal pneumonia [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment:	60
Study Start Date:	September 2007
Estimated Study Completion Date:	October 2010
Estimated Primary Completion Date:	October 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
A: Experimental nikkomycin Z 50 mg BID versus placebo 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=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.
B: Experimental nikkomycin Z 250 mg BID versus placebo 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=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.
C: Experimental nikkomycin Z 500 mg BID versus placebo 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=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.
D: Experimental nikkomycin Z 750 mg TID versus placebo TID 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=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.

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

Ages Eligible for Study:	18 Years to 50 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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 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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00614666

Contacts

Contact: David E Nix, Pharm D	520-626-4814	nix@pharmacy.arizona.edu
Contact: Hoover Susan, MD, PhD	520-626-6887	shoover@DeptOfMed.arizona.edu

Locations

United States, Arizona
Clinical & Translational Research Center - University of Arizona	Recruiting
Tucson, Arizona, United States, 85721
Principal Investigator: David E Nix, Pharm D

Sponsors and Collaborators

University of Arizona

FDA Office of Orphan Products Development

Investigators

Principal Investigator:

David E Nix, Pharm D

University of Arizona

More Information

The Valley Fever Center for Excellence This link exits the ClinicalTrials.gov site

Responsible Party:	University of Arizona ( John N Galgiani, MD )
Study ID Numbers:	VCFE-2007-001
Study First Received:	January 31, 2008
Last Updated:	February 2, 2009
ClinicalTrials.gov Identifier:	NCT00614666
Health Authority:	United States: Food and Drug Administration

Keywords provided by University of Arizona:

coccidioidomycosis
Valley Fever
nikkomycin Z

Study placed in the following topic categories:

Fever
Mycoses
Clotrimazole
Miconazole

Coccidioidomycosis
Tioconazole
Nikkomycin
Pneumonia

Additional relevant MeSH terms:

Anti-Infective Agents
Molecular Mechanisms of Pharmacological Action
Therapeutic Uses
Antifungal Agents

Antibiotics, Antifungal
Enzyme Inhibitors
Pharmacologic Actions

ClinicalTrials.gov processed this record on February 11, 2009