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

• Status: Completed
• Trial end date: 2015-12-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Treatments: Cefixime; Cephalosporins

Criteria

Inclusion Criteria:

• Healthy male or female subjects between 18 and 45 years, inclusive

• Ability to understand the consent process and procedures

• Informed consent obtained and signed

• Body mass index (BMI) < 35 kg/m^2

• Subjects agree to be available for all study visits

• Negative Breathalyzer

• Agreement by female subjects with reproductive potential to use an adequate method of contraception during the study and for 30 days after study drug administration. Female subjects must agree to the use of TWO reliable methods of contraception while receiving study drug and for 30 days after study drug administration if sexually active, which can include: condoms, spermicidal gel, diaphragm, hormonal or non-hormonal intrauterine device, surgical sterilization, oral contraceptive pill (OCP), and depot progesterone injections.

Exclusion Criteria:

• Subjects who take any prescription medication on a regular basis (except oral contraceptives, OCPs), including but not limited to, anti-psychotics, anti-depressants, anti-epileptics, cardiac medications, anti-hypertensives etc.

• Medical condition that precludes participation, including the following:

• Hypertension with confirmed systolic blood pressure >140 mmHg or confirmed diastolic blood pressure >90 mmHg, measured after 10 - 15 minutes of rest

• Morbid obesity (BMI>/=35)

• Current diagnosis of pulmonary disease

• History of or current diagnosis of diabetes

• Autoimmune disorder, such as lupus, Wegener's, rheumatoid arthritis

• History of malignancy except low-grade skin cancer, (i.e., basal cell carcinoma thought to be cured)

• Known diagnosis of prolonged QT interval

• History of alcohol abuse

• History of seizure disorder

• History of renal disease

• Chronic renal, hepatic, or pulmonary disease or other condition that could interfere with the absorption of the study drug or predispose to adverse gastrointestinal events (e.g., surgical resection of significant proportions of the stomach or bowel, gastric bypass, gastric banding, irritable bowel syndrome, inflammatory bowel disease)

• Positive serology results for HIV, HBsAg, or HCV antibodies

• Subjects who have taken any prescription drugs in the previous 14 days or within 5 half-lives before dosing

• Ingestion of over the counter medications or herbal supplements within 7 days of dosing

• Positive urine toxicology for marijuana, cocaine, amphetamines, opiates, PCP, barbiturates or benzodiazepines

• History of allergic reaction or intolerance to cephalosporins

• History of allergic reaction to penicillin (all stages)

• Subjects with an allergy to macrolides may not participate in Stage 3

• Subjects with QTc >450ms (Fridericia's correction) on screening ECG may not participate in Stage 3.

• Positive pregnancy test; pregnant or nursing women

• Screening laboratory tests outside of the acceptable limits presented in Appendix C

• Any specific condition that, in the judgment of the Investigator, precludes participation because it could affect subject safety