Safety and PK of Nikkomycin Z for Coccidioides Pneumonia Treatment

February 12, 2013 updated by: University of Arizona

Phase I/II Evaluation of the Safety, Pharmacokinetics, and Preliminary Effectiveness of Nikkomycin Z in the Treatment of Patients With Uncomplicated Coccidioides Pneumonia

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Actual)

6

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Arizona
      • Tucson, Arizona, United States, 85721
        • Clinical & Translational Research Center - University of Arizona

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 50 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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.

  • 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.

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.

  • 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.

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.

  • 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.

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.

  • 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.

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

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: David E Nix, Pharm D, University of Arizona

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2007

Primary Completion (Actual)

September 1, 2009

Study Completion (Actual)

September 1, 2009

Study Registration Dates

First Submitted

January 31, 2008

First Submitted That Met QC Criteria

February 12, 2008

First Posted (Estimate)

February 13, 2008

Study Record Updates

Last Update Posted (Estimate)

February 15, 2013

Last Update Submitted That Met QC Criteria

February 12, 2013

Last Verified

August 1, 2009

More Information

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.

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