Safety and PK of Nikkomycin Z in Healthy Subjects

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University of Arizona
ClinicalTrials.gov Identifier:
NCT00834184
First received: February 2, 2009
Last updated: February 12, 2013
Last verified: January 2010
  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. Healthy patients will be eligible to participate and will be allocated to receive nikkomycin Z (various doses) or a placebo.


Condition Intervention Phase
Healthy
Drug: nikkomycin Z
Phase 1

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, Randomized, Double-blind, Placebo Controlled, Multiple-dose Evaluation of the Safety Tolerance and Pharmacokinetics of Nikkomycin Z in Healthy Subjects

Further study details as provided by University of Arizona:

Primary Outcome Measures:
  • Determine safety and tolerance of nikkomycin Z in 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 healthy subjects [ Time Frame: two weeks ] [ Designated as safety issue: No ]

Enrollment: 33
Study Start Date: October 2008
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 250 mg BID versus placebo BID x 14 days
Drug: nikkomycin Z

Multiple rising doses. Doses packaged on a unit dose basis in 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.

250 mg BID (n=6) vs Placebo capsule BID (n=2), 500 mg BID (n=6) vs Placebo capsule BID (n=2), 750 mg BID (n=6) vs Placebo capsule BID (n=2), 750 mg TID (n=6) 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.

Experimental: B
nikkomycin Z 500 mg BID versus placebo BID x 14 days
Drug: nikkomycin Z

Multiple rising doses. Doses packaged on a unit dose basis in 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.

250 mg BID (n=6) vs Placebo capsule BID (n=2), 500 mg BID (n=6) vs Placebo capsule BID (n=2), 750 mg BID (n=6) vs Placebo capsule BID (n=2), 750 mg TID (n=6) 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.

Experimental: C
nikkomycin Z 750 mg BID versus placebo BID x 14 days
Drug: nikkomycin Z

Multiple rising doses. Doses packaged on a unit dose basis in 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.

250 mg BID (n=6) vs Placebo capsule BID (n=2), 500 mg BID (n=6) vs Placebo capsule BID (n=2), 750 mg BID (n=6) vs Placebo capsule BID (n=2), 750 mg TID (n=6) 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.

Experimental: D
nikkomycin Z 750 mg TID versus placebo TID x 14 days
Drug: nikkomycin Z

Multiple rising doses. Doses packaged on a unit dose basis in 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.

250 mg BID (n=6) vs Placebo capsule BID (n=2), 500 mg BID (n=6) vs Placebo capsule BID (n=2), 750 mg BID (n=6) vs Placebo capsule BID (n=2), 750 mg TID (n=6) 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.


Detailed Description:

This protocol will serve as a Phase I, randomized, double-blind, placebo controlled, multiple-dose study to evaluate the safety, tolerance and pharmacokinetics of nikkomycin Z. Nikkomycin Z has previously been studied in a single dose protocol in healthy male subjects. This study is designed to run in parallel to protocol VFCE-2007-001 to provide additional data on safety and pharmacokinetics. The study will involve a total of 32 subjects (6 active/2 placebo per group) with a multiple, rising dose strategy.

  Eligibility

Ages Eligible for Study:   18 Years to 40 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Age >= 18 years and <= 40 years
  • Male or Female (if female, must have a negative pregnancy test and agrees to use an acceptable contraception method)
  • Able to understand study and give written informed consent
  • Be determined healthy based on a medical and laboratory evaluation

Exclusion Criteria:

  • Patients under the age of 18 years or over 40 years
  • Inability to comprehend study and provide written informed consent
  • Inability to comply with the study requirements
  • History of or current evidence of major organ disease including:
  • Renal disease - serum creatinine > 1.5 mg/dL, significant hematuria or proteinuria, known structural abnormality or chronic kidney disease
  • Hepatic disease - active viral hepatitis, history of hepatitis B or hepatitis C, bilirubin > 2.0, ALT or AST above normal upper limit for laboratory, alcoholic liver disease, other chronic liver disease
  • CNS disease or cognitive dysfunction - any past history of epilepsy, CNS infections, stroke, CNS bleed, severe headaches, major psychiatric illness, or current mental status changes
  • Lung disease - history of severe asthma, COPD, pulmonary tuberculosis, or other major lung disease
  • Cardiac disease - history or current evidence of ischemic coronary artery disease, myocardial infarction, heart failure, significant arrhythmia
  • Gastrointestinal disease - presence of inflammatory bowel disease, difficulty swallowing, or any gastrointestinal problem that would limit taking oral medications or that may compromise absorption of oral medications
  • Cancer - History of hematologic malignancy or solid tumor excluding basal cell carcinoma limited to the skin within the past 5 years
  • History of autoimmune or inflammatory disease such as rheumatoid arthritis and lupus
  • Any other history or evidence of disease that in the opinion of the physician would increase the risk for the subject for clinical trial participation
  • Immunocompromised state - solid organ transplant, cancer chemotherapy, BMT with graft versus host disease, immunosuppressive therapy, or HIV infection
  • Recent weight loss of greater than 10%
  • Regular use of prescription medications, over-the-counter medications, or dietary/herbal supplements within 14 days of day 1. Occasional use of acetaminophen or over-the-counter NSAID within the 14 day window may be allowed at the P.I.'s discretion
  • Subjects who received another investigational drug within 30 days of enrollment
  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: NCT00834184

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

No publications provided

Responsible Party: University of Arizona
ClinicalTrials.gov Identifier: NCT00834184     History of Changes
Other Study ID Numbers: VFCE-2008-002
Study First Received: February 2, 2009
Last Updated: February 12, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Arizona:
nikkomycin Z
evaluate safety, tolerance and pharmacokinetics of nikkomycin Z

Additional relevant MeSH terms:
Nikkomycin
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 20, 2014