Safety and PK of Nikkomycin Z for Coccidioides Pneumonia Treatment

This study has been terminated.
(Recruitment challenges and lack of funding caused an early end to this study)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Arizona
ClinicalTrials.gov Identifier:
NCT00614666
First received: January 31, 2008
Last updated: February 12, 2013
Last verified: August 2009
  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 1
Phase 2

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

Resource links provided by NLM:


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 ]

Enrollment: 6
Study Start Date: September 2007
Study Completion Date: September 2009
Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A
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.

Experimental: B
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.

Experimental: C
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.

Experimental: D
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
United States, Arizona
Clinical & Translational Research Center - University of Arizona
Tucson, Arizona, United States, 85721
Sponsors and Collaborators
University of Arizona
Investigators
Principal Investigator: David E Nix, Pharm D University of Arizona
  More Information

Additional Information:
No publications provided

Responsible Party: University of Arizona
ClinicalTrials.gov Identifier: NCT00614666     History of Changes
Other Study ID Numbers: VCFE-2007-001
Study First Received: January 31, 2008
Last Updated: February 12, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Arizona:
coccidioidomycosis
Valley Fever
nikkomycin Z

Additional relevant MeSH terms:
Coccidioidomycosis
Coccidiosis
Pneumonia
Mycoses
Protozoan Infections
Parasitic Diseases
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Nikkomycin
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 20, 2014