Clinical trial NCT00834184: Safety and PK of Nikkomycin Z in Healthy Subjects
Official title: Phase I, Randomized, Double-blind, Placebo Controlled, Multiple-dose Evaluation of the Safety Tolerance and Pharmacokinetics of Nikkomycin Z in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: nikkomycin Z
pharmacokinetics
toxicity
Lead sponsor: University of Arizona
Sponsor class: OTHER
First posted: 2009-02-03
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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. Healthy patients will be eligible to participate and will be allocated to receive nikkomycin Z (various doses) or a placebo.

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 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

Primary outcomes:
measure: Determine safety and tolerance of nikkomycin Z in healthy subjects following administration of multiple doses.
timeFrame: four weeks
Secondary outcomes:
measure: Evaluate the multiple dose pharmacokinetics of nikkomycin Z in healthy subjects
timeFrame: two weeks
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Clinical & Translational Research Center - University of Arizona
state: Arizona
Study officials:
affiliation: University of Arizona
name: David E Nix, Pharm D
role: PRINCIPAL_INVESTIGATOR
References: