Clinical trial NCT00493220: Pharmacokinetic and Safety Study of HYLENEX Recombinant-Augmented Subcutaneous Ceftriaxone Administration
Official title: INcreased Flow Utilizing Subcutaneously-Enabled Ceftriaxone (INFUSE-Ceftriaxone) Study: A Phase I Study Comparing the Safety and Pharmacokinetics of Ceftriaxone Administered Subcutaneously With and Without Human Recombinant Hyaluronidase (HYLENEX Recombinant) and Intravenously in Human Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: ceftriaxone
cephalosporins
pharmacokinetics
subcutaneous
hyaluronoglucosaminidase
hyaluronidase
hyaluronan
rHuPH20
Lead sponsor: Baxter Healthcare Corporation
Sponsor class: INDUSTRY
Collaborators: name: Halozyme Therapeutics
First posted: 2007-06-28
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: AUC0-t
timeFrame: Start of ceftriaxone administration through time of last measureable plasma ceftriaxone concentration
measure: AUC0-inf
timeFrame: from the start of ceftriaxone administration to infinity
Secondary outcomes:
measure: Cmax
timeFrame: at the time of the highest measured plasma ceftriaxone concentration
measure: Tmax
timeFrame: from start of ceftriaxone administration until time of maximum measured plasma ceftriaxone concentration
Other outcomes:
Locations:
Study officials:
affiliation: Baxter Healthcare Corporation
name: George E Harb, MD
role: STUDY_DIRECTOR
References:
citation: Harb G, Lebel F, Battikha J, Thackara JW. Safety and pharmacokinetics of subcutaneous ceftriaxone administered with or without recombinant human hyaluronidase (rHuPH20) versus intravenous ceftriaxone administration in adult volunteers. Curr Med Res Opin. 2010 Feb;26(2):279-88. doi: 10.1185/03007990903432900.