Pharmacokinetic and Safety Study of HYLENEX Recombinant-Augmented Subcutaneous Ceftriaxone Administration
Condition: Healthy
Intervention: SC HYLENEX and Ceftriaxone; SC Placebo and Ceftriaxone; IV Ceftriaxone
Intervention description: single, subcutaneous, 150 U dose of HYLENEX; followed by single, subcutaneous, 1 gm dose of ceftriaxone (350 mg/mL solution administered at 2.5 mL/min over 1.14 minutes); single, subcutaneous injection of 1 mL 0.9% sodium chloride solution; followed by single, subcutaneous, 1 gm dose of ceftriaxone (350 mg/mL solution administered at 2.5 mL/min over 1.14 minutes); single, intravenous infusion of 1 gm ceftriaxone (40 mg/mL solution administered at 0.83 mL/min over 30 minutes)
Intervention MeSH terms: Ceftriaxone
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 30.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: ceftriaxone; cephalosporins; pharmacokinetics; subcutaneous; hyaluronoglucosaminidase; hyaluronidase; hyaluronan; rHuPH20

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