Pharmacokinetic and Safety Study of HYLENEX Recombinant-Augmented Subcutaneous Ceftriaxone Administration

Condition(s) targeted: Healthy

Intervention: hyaluronidase (human recombinant) and ceftriaxone (Drug); placebo and ceftriaxone (Drug); ceftriaxone (Drug)

Phase: Phase 1

Status: Completed

Sponsored by: Baxter Healthcare Corporation

Official(s) and/or principal investigator(s):
John M Zahradnik, MD, Study Director, Affiliation: Baxter Healthcare Corporation

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 (MTC);

- and to establish the pharmacokinetic comparability of subcutaneous administration of

ceftriaxone with HYLENEX recombinant to subcutaneous administration without HYLENEX recombinant and to IV 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 design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Crossover Assignment, Pharmacokinetics Study

Primary outcome:

Comparison of the pharmacokinetic parameters for ceftriaxone after subcutaneous administration, with and without HYLENEX recombinant, and after IV administration

Safety and tolerability (injection site reactions, adverse events, physical examinations, vital signs) of subcutaneous administration of ceftriaxone, with and without HYLENEX recombinant

Minimum age: 18 Years. Maximum age: 65 Years. Gender(s): Both.

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

Starting date: June 2007
Ending date: September 2007
Last updated: March 20, 2008