Clinical Trial: Safety, Tolerability and PK 3-Period Crossover Study Comparing 2 Single Doses of ZTI-01 and Monurol® in Healthy Subjects

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Randomized, Safety, Tolerability and Pharmacokinetics 3-Period Crossover Study Comparing 2 Single Doses of ZTI-01 and Monurol® in Healthy Subjects

Brief Summary: The objective is to determine the safety, tolerability and pharmacokinetics (PK) of 2 single doses of ZTI-01 (1g and 8g infused over 1-hr) and a single dose of the Reference Label Drug, Monurol® (oral sachet, 3g). Subjects will be randomized to a treatment sequence prior to dosing on Day 1 of Period 1 prior to study screening.

Detailed Summary: This is a Phase 1 single-dose, randomized, 3-Period, crossover study conducted at a single center. A total of 30 healthy subjects, aged 18-45years, will be randomized to receive one of 3 treatment sequences. The duration of study will be approximately 18-26 days and subject participation will be the duration of study. Each treatment sequence will be enrolled in parallel and each subject will receive all 3 treatments in crossover fashion. Each subject will complete Screening, Baseline, and Treatment Phases. The Screening Phase will be conducted on an outpatient basis within 35 days of admission (Day -1 of Period 1). All subjects admitted to the study center the day before dosing in each treatment period (Day -1; check-in) for pre-dosing assessments and will remain in the study center through 48 hours post-dose for each Period. Final baseline qualification will only be evaluated prior to randomization for Treatment Period 1. Each one of the periods will be separated by a 3 (minimum) to 7 days (maximum) washout period. The Treatment Phase will be comprised of 3 crossover periods (duration Day-1 to 48 hours post dose). Each crossover period will include a single dose of study drug under fasting conditions followed by post-dose safety assessments and blood and urine collection for PK measures through 48 hours post-dose; each period will be separated by a 3 to 7 days washout. Subjects will remain in the study center for all 3- study treatment periods (Day -1 to 48 hours post dosing) and will be discharged after the 48-hour sampling timepoint (if safety parameters are acceptable to the Investigator on Day 3).
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Current Primary Outcome:

  • Pharmacokinetics: Maximum measured plasma concentration (Cmax), area under the concentration versus time curve (AUC0-t and AUC0-inf), time to peak concentration (tmax), terminal elimination half-life (t1/2), terminal-phase elimination rate constant). [ Time Frame: Study periods 1, 2 and 3, Day 1 through Day 3 ]
  • Pharmacokinetics: Volume of distribution (Vd) or apparent volume of distribution (Vd/F) as appropriate, clearance (CL) or apparent Clearance (CL/F) as appropriate, renal Clearance (CLr) and Fraction Bioavailable as appropriate [ Time Frame: Study periods 1, 2 and 3, Day 1 through Day 3 ]
  • Adverse events (AEs) will be monitored and recorded [ Time Frame: Study periods 1, 2 and 3, screening through Day 3, including washout periods ]
  • Assessed safety and tolerability via physical examinations, vital signs, standard 12-lead electrocardiograms, and clinical laboratory tests [ Time Frame: Study periods 1, 2 and 3, screening through Day 3 ]


Original Primary Outcome:

  • Pharmacokinetics: Volume of distribution (Vd) or apparent volume of distribution (Vd/F) as appropriate, clearance (CL) or apparent Clearance (CL/F) as appropriate, renal Clearance (CLr) and Fraction Bioavailable as appropriate [ Time Frame: Study periods 1, 2 and 3, Day 1 through Day 3 ]
  • Pharmacokinetics: Maximum measured plasma concentration (Cmax), area under the concentration versus time curve (AUC0-t and AUC0-inf), time to peak concentration (tmax), terminal elimination half-life (t1/2), terminal-phase elimination rate constant). [ Time Frame: Study periods 1, 2 and 3, Day 1 through Day 3 ]
  • Adverse events (AEs) will be monitored and recorded [ Time Frame: Study periods 1, 2 and 3, screening through Day 3, including washout periods ]
  • Assessed safety and tolerability via physical examinations, vital signs, standard 12-lead electrocardiograms, and clinical laboratory tests [ Time Frame: Study periods 1, 2 and 3, screening through Day 3 ]


Current Secondary Outcome:

Original Secondary Outcome:

Information By: National Institute of Allergy and Infectious Diseases (NIAID)

Dates:
Date Received: June 26, 2014
Date Started: August 2014
Date Completion:
Last Updated: March 31, 2016
Last Verified: January 2015