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

NCT01949363 | Completed Phase 1

• 2 other identifiers: 12-0025HHSN272201500007I
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

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.

Conditions

Gonorrhoea

Keywords

Gonococcal Infections, Cefixime, Neisseria gonorrhoeae, Azithromycin, antibiotic, cephalosporin

Outcome Measures

Primary Outcomes (8)

• Total serum concentrations of cefixime at multiple time points for both individuals and cohorts in total

  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

  Screening to Day 7

• Pharmacokinetic curves of cefixime levels versus time: time to peak drug level, half-life, and elimination rate

  Day 0-1, 2 and Day 7

• 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)

  Day 0-1, 2 and Day 7

• Pharmacokinetic curves of cefixime levels versus time: total area under the curve (AUC)

  Day 0-1, 2 and Day 7

• Pharmacokinetic curves of cefixime levels versus time: peak cefixime level.

  Day 0-1, 2 and Day 7

• Pharyngeal fluid concentrations of cefixime for Cohorts C - D: Cmax and ratio of fluid to serum concentration

  Day 0-1

• Assess subject reported adverse events, unsolicited symptoms and discomforts

  Up to Day 30

Study Arms (2)

Stage 2 (Cohorts C and D)

EXPERIMENTAL

Cohort C will first be given 1200mg cefixime orally once; Cohort D will be given 800mg cefixime orally three times (every 8 hours); 6 subjects in each cohort

Drug: Cefixime

Stage 1 (Cohorts A and B)

EXPERIMENTAL

Cohort A will be given 400mg of cefixime orally once; Cohort B will be given 800mg of cefixime given orally once; 6 subjects in each cohort

Drug: Cefixime

Interventions

Cefixime DRUG

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)

Stage 1 (Cohorts A and B); Stage 2 (Cohorts C and D)

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

Johns Hopkins Bayview Medical Center - Infectious Diseases

Baltimore, Maryland, 21224-2735, United States

Location

Related Publications (1)

• Barbee LA, Nayak SU, Blumer JL, O'Riordan MA, Gray W, Zenilman JM, Golden MR, Griffiss JM. A Phase 1 Pharmacokinetic and Safety Study of Extended-Duration, High-dose Cefixime for Cephalosporin-resistant Neisseria gonorrhoeae in the Pharynx. Sex Transm Dis. 2018 Oct;45(10):677-683. doi: 10.1097/OLQ.0000000000000844.

  PMID: 29624558 DERIVED

MeSH Terms

Conditions

Gonorrhea

Interventions

Cefixime

Condition Hierarchy (Ancestors)

Neisseriaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Sexually Transmitted Diseases, Bacterial; Sexually Transmitted Diseases; Communicable Diseases; Genital Diseases; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Cefotaxime; Cephacetrile; Cephalosporins; beta-Lactams; Lactams; Amides; Organic Chemicals; Thiazines; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 19, 2013
• First Posted: September 24, 2013
• Study Start: December 1, 2013
• Primary Completion: February 1, 2015
• Study Completion: December 1, 2015
• Last Updated: January 17, 2019

Record last verified: 2015-06

Locations

US (1)