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”

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.

Intervention(s) in this Clinical Trial

• Drug: SC HYLENEX and Ceftriaxone
  • 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)
• Drug: SC Placebo and Ceftriaxone
  • 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)
• Drug: IV Ceftriaxone
  • single, intravenous infusion of 1 gm ceftriaxone (40 mg/mL solution administered at 0.83 mL/min over 30 minutes)

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: HYLENEX SC, Placebo SC, IV
  • subcutaneous HYLENEX and ceftriaxone as 1st intervention, subcutaneous placebo and ceftriaxone as 2nd intervention, IV ceftriaxone as 3rd intervention
• Experimental: HYLENEX SC, IV, Placebo SC
  • subcutaneous HYLENEX and ceftriaxone as 1st intervention, IV ceftriaxone as 2nd intervention, subcutaneous placebo and ceftriaxone as 3rd intervention
• Experimental: Placebo SC, HYLENEX SC, IV
  • subcutaneous placebo and ceftriaxone as 1st intervention, subcutaneous HYLENEX and ceftriaxone as 2nd intervention, IV ceftriaxone as 3rd intervention
• Experimental: Placebo SC, IV, HYLENEX SC
  • subcutaneous placebo and ceftriaxone as 1st intervention, IV ceftriaxone as 2nd intervention, subcutaneous HYLENEX and ceftriaxone as 3rd intervention
• Experimental: IV, HYLENEX SC, Placebo SC
  • IV ceftriaxone as 1st intervention, subcutaneous HYLENEX and ceftriaxone as 2nd intervention, subcutaneous placebo and ceftriaxone as 3rd intervention
• Experimental: IV, Placebo SC, HYLENEX SC
  • IV ceftriaxone as 1st intervention, subcutaneous placebo and ceftriaxone as 2nd intervention, subcutaneous HYLENEX and ceftriaxone as 3rd intervention

Primary Measures

• AUC0-t
  • Time Frame: Start of ceftriaxone administration through time of last measureable plasma ceftriaxone concentration
    Safety Issue?: No
• AUC0-inf
  • Time Frame: from the start of ceftriaxone administration to infinity
    Safety Issue?: No

Secondary Measures

• Cmax
  • Time Frame: at the time of the highest measured plasma ceftriaxone concentration
    Safety Issue?: No
• Tmax
  • Time Frame: from start of ceftriaxone administration until time of maximum measured plasma ceftriaxone concentration
    Safety Issue?: No

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 65 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Investigator: Baxter Healthcare Corporation Industry

Overall Clinical Trial Officials and Contacts

George E Harb, MD Study Director Baxter Healthcare Corporation  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00493220

Study ID Number: 1838-004

ClinicalTrials.gov Identifier: NCT00493220

Health Authority: United States: Food and Drug Administration