Clinical Trial: The Pharmacokinetics of Extended Duration High-dose Cefixime for the Decreased Susceptibility of Neisseria Gonorrhoeae: A Phase I Pilot Study

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

Official Title: The Pharmacokinetics of Extended Duration High-Dose Cefixime for the Decreased Susceptibility of Neisseria Gonorrhoeae: A Phase I Pilot Study

Brief Summary: This study is a Phase I, open label, non-randomized, dose-frequency escalation pharmacokinetics study among 24 healthy male and female subjects, aged 18 to 45 years to determine the pharmacokinetics and safety of high-, multi-dose cefixime for the treatment of reduced susceptibility gonorrhea. Stage 1(Cohorts A and B) will examine the pharmacokinetics of single 400mg and 800mg dose of cefixime. Stage 2(Cohorts C and D) subjects will take 800mg of cefixime every 12 hours for 2 doses. If that dosing regimen is well tolerated, the dose-frequency will escalate to 800mg every 8 hours for 3 doses, and serum levels of cefixime will be measured. Study duration is approximately 47 weeks.

Detailed Summary: This study is a Phase I, open label, non-randomized, dose-frequency escalation pharmacokinetics study among 24 healthy male and female subjects, aged 18 to 45 years to determine the pharmacokinetics and safety of high multi-dose cefixime for the treatment of reduced susceptibility gonorrhea. The study will occur in two stages as described below. Stage 1: Confirm/establish the pharmacokinetics (PK) of 400mg and 800mg doses of cefixime tablet. Stage 2: Define dosing frequency necessary to achieve total serum cefixime levels that exceed 2.0 mcg/mL for over 20 hours. Stage 1 (Cohorts A and B): Six subjects will be admitted to the Johns Hopkins Bayview Clinic Trials Unit to assess each dosing regimen, for a total of 12 subjects. At time=0, subjects will undergo baseline serum cefixime levels, followed by ingestion of cefixime. Serum collections will occur at times 0, 1, 2, 4, 8, 12, 16, 20, and 24 hours. Cohort B will have the same serum collection time points as Cohort A. Cohorts A & B will be run nearly simultaneously as logistically feasible. Stage 2 (Cohorts C and D): After determining the PK parameters of single dose 800mg, the PK simulation model will be repeated, adjusting the model as needed based on findings from study Stage 1. Assuming there are no major discrepancies between Figure 2 (above) and the new PK simulations, the following regimens will be tested, beginning with Cohort C. Six subjects per dosing regimen, Cohorts C and D, will be admitted to the Johns Hopkins Bayview Medical Center, for a total of 12 subjects. The 800mg q12 hour x 2 regimen (Cohort C) will be tested first. For Cohort C, serum cefixime levels will be drawn at 12, 16, and 26 hours. If the q12 regimen is deemed safe and tolerable after review by the SMC, Cohort D will commence with the 800mg q8 hour x 3 regimen. Total serum cefixime levels will be drawn for Cohort D at 8, 16, 20 and 26 hours (see Section 7.2). All Stages, All Cohorts: All samples collected for PK analysis will be shi
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Current Primary Outcome:

  • Pharmacokinetic curves of cefixime levels versus time: total time that cefixime levels exceed 4x the MIC of 0.5 mcg/mL(serum level of 2.0 mcg/mL) [ Time Frame: Day 0-1, 2 and Day 7 ]
  • Pharmacokinetic curves of cefixime levels versus time: time to peak drug level, half-life, and elimination rate [ Time Frame: Day 0-1, 2 and Day 7 ]
  • Pharyngeal fluid concentrations of cefixime for Cohorts C - D: Cmax and ratio of fluid to serum concentration [ Time Frame: Day 0-1 ]
  • Total serum concentrations of cefixime at multiple time points for both individuals and cohorts in total [ Time Frame: Day 1, 2 and Day 7 ]
  • Safety and tolerability assessed by laboratory monitoring, targeted clinical evaluations,: serum chemistries, liver functions tests (LFTs), hematology panel, coagulation panel, and urinalysis [ Time Frame: Screening to Day 7 ]
  • Assess subject reported adverse events, unsolicited symptoms and discomforts [ Time Frame: Up to Day 30 ]
  • Pharmacokinetic curves of cefixime levels versus time: peak cefixime level. [ Time Frame: Day 0-1, 2 and Day 7 ]
  • Pharmacokinetic curves of cefixime levels versus time: total area under the curve (AUC) [ Time Frame: Day 0-1, 2 and Day 7 ]


Original Primary Outcome:

  • Pharmacokinetic curves of cefixime levels versus time: peak cefixime level, total area under the curve (AUC), time to peak drug level, half-life, elimination rate, total time that cefixime levels exceed 4x the MIC of 0.5 mcg/mL(serum level of 2.0 mcg/mL) [ Time Frame: Day 0-1, 2 and Day 7 ]
  • Assess subject reported adverse events, unsolicited symptoms and discomforts [ Time Frame: Up to Day 30 ]
  • Safety and tolerability assessed by laboratory monitoring, targeted clinical evaluations,: serum chemistries, liver functions tests (LFTs), hematology panel, coagulation panel, and urinalysis [ Time Frame: Screening to Day 7 ]
  • Total serum concentrations of cefixime at multiple time points for both individuals and cohorts in total [ Time Frame: Day 1, 2 and Day 7 ]


Current Secondary Outcome:

Original Secondary Outcome:

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

Dates:
Date Received: September 19, 2013
Date Started: December 2013
Date Completion:
Last Updated: March 26, 2015
Last Verified: March 2015