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Safety and PK of Nikkomycin Z for Coccidioides Pneumonia Treatment

Primary Purpose

Coccidioidomycosis

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
nikkomycin Z
Sponsored by
University of Arizona
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Coccidioidomycosis focused on measuring coccidioidomycosis, Valley Fever, nikkomycin Z

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Clinical & Translational Research Center - University of Arizona

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

A

B

C

D

Arm Description

nikkomycin Z 50 mg BID versus placebo BID x 14 days

nikkomycin Z 250 mg BID versus placebo BID x 14 days

nikkomycin Z 500 mg BID versus placebo BID x 14 days

nikkomycin Z 750 mg TID versus placebo TID x 14 days

Outcomes

Primary Outcome Measures

Determine safety and tolerance of nikkomycin Z in relatively healthy subjects following administration of multiple doses.

Secondary Outcome Measures

Evaluate the multiple dose pharmacokinetics of nikkomycin Z in patients with uncomplicated coccidioidal pneumonia

Full Information

First Posted
January 31, 2008
Last Updated
February 12, 2013
Sponsor
University of Arizona
Collaborators
FDA Office of Orphan Products Development
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1. Study Identification

Unique Protocol Identification Number
NCT00614666
Brief Title
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

2. Study Status

Record Verification Date
August 2009
Overall Recruitment Status
Terminated
Why Stopped
Recruitment challenges and lack of funding caused an early end to this study
Study Start Date
September 2007 (undefined)
Primary Completion Date
September 2009 (Actual)
Study Completion Date
September 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Arizona
Collaborators
FDA Office of Orphan Products Development

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Coccidioidomycosis
Keywords
coccidioidomycosis, Valley Fever, nikkomycin Z

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
6 (Actual)

8. Arms, Groups, and Interventions

Arm Title
A
Arm Type
Experimental
Arm Description
nikkomycin Z 50 mg BID versus placebo BID x 14 days
Arm Title
B
Arm Type
Experimental
Arm Description
nikkomycin Z 250 mg BID versus placebo BID x 14 days
Arm Title
C
Arm Type
Experimental
Arm Description
nikkomycin Z 500 mg BID versus placebo BID x 14 days
Arm Title
D
Arm Type
Experimental
Arm Description
nikkomycin Z 750 mg TID versus placebo TID x 14 days
Intervention Type
Drug
Intervention Name(s)
nikkomycin Z
Intervention Description
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.
Primary Outcome Measure Information:
Title
Determine safety and tolerance of nikkomycin Z in relatively healthy subjects following administration of multiple doses.
Time Frame
four weeks
Secondary Outcome Measure Information:
Title
Evaluate the multiple dose pharmacokinetics of nikkomycin Z in patients with uncomplicated coccidioidal pneumonia
Time Frame
2 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
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 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David E Nix, Pharm D
Organizational Affiliation
University of Arizona
Official's Role
Principal Investigator
Facility Information:
Facility Name
Clinical & Translational Research Center - University of Arizona
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85721
Country
United States

12. IPD Sharing Statement

Links:
URL
http://www.vfce.arizona.edu
Description
The Valley Fever Center for Excellence

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Safety and PK of Nikkomycin Z for Coccidioides Pneumonia Treatment

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