The Pharmacokinetics of Extended Duration High-dose Cefixime for the Decreased Susceptibility of Neisseria Gonorrhoeae: A Phase I Pilot Study
Condition: Gonorrhoea
MeSH terms: Gonorrhea
Study type: Interventional
Phase: Phase 1

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 description: 
      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 shipped to the University of Toledo, Dr. Jeffrey Blumer's HPLC lab for
      processing. Specimens will be analyzed by high performance liquid chromatography (HPLC) for
      total cefixime concentration levels. Targeted clinical evaluations will be used to monitor
      for subject reported side effects. Subjects will be asked about specific symptoms they may
      have experienced, including abdominal pain, nausea, vomiting, diarrhea, flatulence, headache,
      and rash, or any other symptoms. Additionally, subjects will be asked to maintain a Subject
      Diary (Appendix E) from Study Day 0 through Day 7 to record information about any symptoms
      experienced or medications taken. Study duration is approximately 47 weeks.
    

Intervention name(s): Cefixime
Intervention type(s): Drug
Intervention description(s): Cefixime is an FDA approved oral semi-synthetic cephalosporin antibiotic. The standard dose (400mg), high dose (800mg and 1200mg), and multiple 800mg and 1200mg doses given over a 24-hour period using a dose-frequency escalation method. Cohort A receives 400 mg orally once, Cohort B receives 800 mg orally once; Cohort C receives 1200 mg orally once; Cohort D receives 800 mg orally 3 times (every 8 hrs)
Intervention MeSH terms: Cefixime
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Gonococcal Infections, Cefixime, Neisseria gonorrhoeae, Azithromycin, antibiotic, cephalosporin