Safety and PK of Nikkomycin Z in Healthy Subjects - Full Text View

Sponsored by:	University of Arizona
Information provided by:	University of Arizona
ClinicalTrials.gov Identifier:	NCT00834184

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 I

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator), Parallel Assignment, Safety Study
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 ]

Estimated Enrollment:	32
Study Start Date:	October 2008
Estimated Study Completion Date:	October 2010
Estimated Primary Completion Date:	October 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
A: Experimental 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.
B: Experimental 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.
C: Experimental 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.
D: Experimental 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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00834184

Contacts

Contact: David E Nix, Pharm D	520-626-4814	nix@pharmacy.arizona.edu
Contact: Susan Hoover, MD, PhD	520-626-6887	shoover@DeptOfMed.arizona.edu

Locations

United States, Arizona
Clinical & Translational Research Center - University of Arizona	Recruiting
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 ( John Galgiani; Director: Valley Fever Center for Excellence )
Study ID Numbers:	VFCE-2008-002
Study First Received:	February 2, 2009
Last Updated:	February 2, 2009
ClinicalTrials.gov Identifier:	NCT00834184 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by University of Arizona:

nikkomycin Z
evaluate safety, tolerance and pharmacokinetics of nikkomycin Z

Study placed in the following topic categories:

Anti-Bacterial Agents
Clotrimazole
Miconazole
Antifungal Agents

Tioconazole
Healthy
Nikkomycin

Additional relevant MeSH terms:

Anti-Infective Agents
Molecular Mechanisms of Pharmacological Action
Therapeutic Uses
Antifungal Agents

Antibiotics, Antifungal
Enzyme Inhibitors
Nikkomycin
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 07, 2009