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

Gonorrhoea Clinical Trial

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

Status Completed

Clinical Trial 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.

Clinical Trial 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. ;

Related Conditions & MeSH terms

• Disease Susceptibility
• Gonorrhea
• Gonorrhoea

• NCT number: NCT01949363
• Study type: Interventional
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Status: Completed
• Phase: Phase 1
• Start date: December 2013
• Completion date: December 2015