Healthy
Conditions
Keywords
nikkomycin Z, pharmacokinetics, toxicity
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.
Interventions
DRUGnikkomycin 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.
Sponsors
University of Arizona
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 40 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Determine safety and tolerance of nikkomycin Z in healthy subjects following administration of multiple doses. | four weeks |
Secondary
| Measure | Time frame |
|---|---|
| Evaluate the multiple dose pharmacokinetics of nikkomycin Z in healthy subjects | two weeks |
Countries
United States
Outcome results
None listed