- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00614666
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
Study Overview
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
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
Arizona
-
Tucson, Arizona, United States, 85721
- Clinical & Translational Research Center - University of Arizona
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
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 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
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: A
nikkomycin Z 50 mg BID versus placebo BID x 14 days
|
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.
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. |
Experimental: B
nikkomycin Z 250 mg BID versus placebo BID x 14 days
|
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.
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. |
Experimental: C
nikkomycin Z 500 mg BID versus placebo BID x 14 days
|
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.
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. |
Experimental: D
nikkomycin Z 750 mg TID versus placebo TID x 14 days
|
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.
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. |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Determine safety and tolerance of nikkomycin Z in relatively healthy subjects following administration of multiple doses.
Time Frame: four weeks
|
four weeks
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Evaluate the multiple dose pharmacokinetics of nikkomycin Z in patients with uncomplicated coccidioidal pneumonia
Time Frame: 2 weeks
|
2 weeks
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: David E Nix, Pharm D, University of Arizona
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Infections
- Respiratory Tract Infections
- Respiratory Tract Diseases
- Lung Diseases
- Bacterial Infections and Mycoses
- Parasitic Diseases
- Protozoan Infections
- Mycoses
- Pneumonia
- Coccidioidomycosis
- Coccidiosis
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Enzyme Inhibitors
- Antifungal Agents
- Nikkomycin
Other Study ID Numbers
- VCFE-2007-001
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Coccidioidomycosis
-
National Institute of Allergy and Infectious Diseases...Completed
-
University of California, San FranciscoWithdrawnCoccidioidomycosis
-
George R ThompsonMayne Pharma International Pty LtdWithdrawnCoccidioidomycosis | Valley FeverUnited States
-
Merck Sharp & Dohme LLCCompleted
-
Nielsen BioSciences, Inc.Sr Consultants Inc.Completed
-
National Institute of Allergy and Infectious Diseases...University of ArizonaRecruitingCoccidioidomycosisUnited States
-
University of ArizonaTerminatedCoccidioidomycosis | Valley FeverUnited States
-
PfizerCompletedHIV Infections | Mycoses | CoccidioidomycosisUnited States
-
National Institute of Allergy and Infectious Diseases...Completed
-
National Institute of Allergy and Infectious Diseases...TerminatedCoccidioidomycosisUnited States
Clinical Trials on nikkomycin Z
-
University of ArizonaTerminated
-
University of ArizonaCompleted
-
University of California, DavisCompleted
-
University of OxfordUnknownEbola Virus DiseaseUnited Kingdom
-
Jürgen WeissUnknown
-
Zeria PharmaceuticalCompletedAdvanced Hepatocellular CarcinomaJapan
-
Zeria PharmaceuticalCompletedPrimary Hypophosphatemic RicketsJapan
-
University of WashingtonCompletedHypertrophic Scarring After Burn InjuryUnited States
-
Everfront Biotech Co., Ltd.Active, not recruitingAmyotrophic Lateral SclerosisTaiwan
-
Tarsus UniversityNot yet recruiting