Pharmacokinetic and Safety Study of HYLENEX Recombinant-Augmented Subcutaneous Ceftriaxone Administration
Phase 1
Completed
- Conditions
- Healthy
- Interventions
- Registration Number
- NCT00493220
- Lead Sponsor
- Baxter Healthcare Corporation
- Brief Summary
The objectives of this study are:
* to establish the safety of subcutaneous administration of ceftriaxone at different concentrations, with and without HYLENEX recombinant, and to determine the maximum tolerated concentration;
* and to establish the pharmacokinetic comparability of subcutaneous administration of ceftriaxone with HYLENEX recombinant to subcutaneous administration without HYLENEX recombinant and to IV administration.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 30
Inclusion Criteria
- Male or female, 18-65 years of age
- If female: non-lactating; non-pregnant; and incapable of becoming pregnant, or taking specific precautions to avoid becoming pregnant before and during study
- Normal clinical laboratory parameters
- Adequate venous access in both upper extremities
- Agreeing to refrain from smoking and from ingesting any alcohol or caffeine-containing products before and during the study
- Good health based on medical history, physical examination and laboratory tests
- Non-smoking; or smoking less than 10 cigarettes per day and willing to refrain from use of nicotine products before and during study
Exclusion Criteria
- Received a cephalosporin within the 21 days prior to study or anticipated to receive non-study cephalosporin during study
- Pregnant or breast-feeding.
- Previously exposed to a hyaluronidase drug product
- Medical condition presenting unacceptable safety risk or likely to prevent completion of study
- Known hypersensitivity to hyaluronidase or any other ingredient in HYLENEX recombinant
- Contraindication to ceftriaxone, including known allergy to beta-lactam antibiotics
- Local condition precluding subcutaneous injection or injection site evaluation
- History of gastrointestinal disease (in particular colitis)
- Consumption of caffeine- or other methylxanthine-containing beverage within 24 hours before and/or during the PK sampling period
- Participation in study of any investigational drug or device within 30 days before this study
- Serum hemoglobin <12 g/dL.
- Blood donation or significant loss of blood within 56 days, or plasma donation within 7 days, prior to study
- Medical history/condition, screening physical examination finding or clinical laboratory result precluding safe participation in study, or which might adversely effect interpretation of study results
- History of drug or alcohol abuse within 2 years prior to study
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description HYLENEX SC, IV, Placebo SC IV Ceftriaxone subcutaneous HYLENEX and ceftriaxone as 1st intervention, IV ceftriaxone as 2nd intervention, subcutaneous placebo and ceftriaxone as 3rd intervention Placebo SC, HYLENEX SC, IV IV Ceftriaxone subcutaneous placebo and ceftriaxone as 1st intervention, subcutaneous HYLENEX and ceftriaxone as 2nd intervention, IV ceftriaxone as 3rd intervention Placebo SC, IV, HYLENEX SC IV Ceftriaxone subcutaneous placebo and ceftriaxone as 1st intervention, IV ceftriaxone as 2nd intervention, subcutaneous HYLENEX and ceftriaxone as 3rd intervention HYLENEX SC, IV, Placebo SC SC Placebo and Ceftriaxone subcutaneous HYLENEX and ceftriaxone as 1st intervention, IV ceftriaxone as 2nd intervention, subcutaneous placebo and ceftriaxone as 3rd intervention HYLENEX SC, Placebo SC, IV SC HYLENEX and Ceftriaxone subcutaneous HYLENEX and ceftriaxone as 1st intervention, subcutaneous placebo and ceftriaxone as 2nd intervention, IV ceftriaxone as 3rd intervention HYLENEX SC, Placebo SC, IV SC Placebo and Ceftriaxone subcutaneous HYLENEX and ceftriaxone as 1st intervention, subcutaneous placebo and ceftriaxone as 2nd intervention, IV ceftriaxone as 3rd intervention HYLENEX SC, Placebo SC, IV IV Ceftriaxone subcutaneous HYLENEX and ceftriaxone as 1st intervention, subcutaneous placebo and ceftriaxone as 2nd intervention, IV ceftriaxone as 3rd intervention HYLENEX SC, IV, Placebo SC SC HYLENEX and Ceftriaxone subcutaneous HYLENEX and ceftriaxone as 1st intervention, IV ceftriaxone as 2nd intervention, subcutaneous placebo and ceftriaxone as 3rd intervention Placebo SC, HYLENEX SC, IV SC HYLENEX and Ceftriaxone subcutaneous placebo and ceftriaxone as 1st intervention, subcutaneous HYLENEX and ceftriaxone as 2nd intervention, IV ceftriaxone as 3rd intervention Placebo SC, HYLENEX SC, IV SC Placebo and Ceftriaxone subcutaneous placebo and ceftriaxone as 1st intervention, subcutaneous HYLENEX and ceftriaxone as 2nd intervention, IV ceftriaxone as 3rd intervention Placebo SC, IV, HYLENEX SC SC HYLENEX and Ceftriaxone subcutaneous placebo and ceftriaxone as 1st intervention, IV ceftriaxone as 2nd intervention, subcutaneous HYLENEX and ceftriaxone as 3rd intervention Placebo SC, IV, HYLENEX SC SC Placebo and Ceftriaxone subcutaneous placebo and ceftriaxone as 1st intervention, IV ceftriaxone as 2nd intervention, subcutaneous HYLENEX and ceftriaxone as 3rd intervention IV, HYLENEX SC, Placebo SC SC HYLENEX and Ceftriaxone IV ceftriaxone as 1st intervention, subcutaneous HYLENEX and ceftriaxone as 2nd intervention, subcutaneous placebo and ceftriaxone as 3rd intervention IV, HYLENEX SC, Placebo SC SC Placebo and Ceftriaxone IV ceftriaxone as 1st intervention, subcutaneous HYLENEX and ceftriaxone as 2nd intervention, subcutaneous placebo and ceftriaxone as 3rd intervention IV, HYLENEX SC, Placebo SC IV Ceftriaxone IV ceftriaxone as 1st intervention, subcutaneous HYLENEX and ceftriaxone as 2nd intervention, subcutaneous placebo and ceftriaxone as 3rd intervention IV, Placebo SC, HYLENEX SC SC HYLENEX and Ceftriaxone IV ceftriaxone as 1st intervention, subcutaneous placebo and ceftriaxone as 2nd intervention, subcutaneous HYLENEX and ceftriaxone as 3rd intervention IV, Placebo SC, HYLENEX SC SC Placebo and Ceftriaxone IV ceftriaxone as 1st intervention, subcutaneous placebo and ceftriaxone as 2nd intervention, subcutaneous HYLENEX and ceftriaxone as 3rd intervention IV, Placebo SC, HYLENEX SC IV Ceftriaxone IV ceftriaxone as 1st intervention, subcutaneous placebo and ceftriaxone as 2nd intervention, subcutaneous HYLENEX and ceftriaxone as 3rd intervention
- Primary Outcome Measures
Name Time Method AUC0-t Start of ceftriaxone administration through time of last measureable plasma ceftriaxone concentration Area under the drug concentration-time curve from time zero to the time of the last measurable concentration (calculated by the linear trapezoidal method)
AUC0-inf from the start of ceftriaxone administration to infinity Area under the drug concentration-time curve from time zero to infinity, calculated as AUC0-t + Ct/kel (Ct = time of last measurable concentration; kel = terminal elimination rate constant)
- Secondary Outcome Measures
Name Time Method Cmax at the time of the highest measured plasma ceftriaxone concentration Maximum measured plasma ceftriaxone concentration
Tmax from start of ceftriaxone administration until time of maximum measured plasma ceftriaxone concentration Time to maximum measured plasma ceftriaxone concentration