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Pharmacokinetic and Safety Study of HYLENEX Recombinant-Augmented Subcutaneous Ceftriaxone Administration (INFUSE-Cftrx)

This study has been completed.
Sponsor:
Collaborator:
Halozyme Therapeutics
Information provided by:
Baxter Healthcare Corporation
ClinicalTrials.gov Identifier:
NCT00493220
First received: June 26, 2007
Last updated: October 24, 2011
Last verified: October 2011
History of Changes
  Purpose

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.

Condition Intervention Phase
Healthy
 Drug: SC HYLENEX and Ceftriaxone
Drug: SC Placebo and Ceftriaxone
Drug: IV Ceftriaxone
 Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Baxter Healthcare Corporation:

Primary Outcome Measures:
  • AUC0-t [ Time Frame: Start of ceftriaxone administration through time of last measureable plasma ceftriaxone concentration ] [ Designated as safety issue: No ]
    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 [ Time Frame: from the start of ceftriaxone administration to infinity ] [ Designated as safety issue: No ]
    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:
  • Cmax [ Time Frame: at the time of the highest measured plasma ceftriaxone concentration ] [ Designated as safety issue: No ]
    Maximum measured plasma ceftriaxone concentration

  • Tmax [ Time Frame: from start of ceftriaxone administration until time of maximum measured plasma ceftriaxone concentration ] [ Designated as safety issue: No ]
    Time to maximum measured plasma ceftriaxone concentration


Enrollment: 30
Study Start Date: June 2007
Study Completion Date: September 2007
Primary Completion Date: September 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
 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)
Other Names:
  • HYLENEX recombinant
  • hyaluronoglucosaminidase
  • hyaluronidase
  • rHuPH20
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)
Other Names:
  • saline
  • normal saline
  • 0.9% sodium chloride injection
Drug: IV Ceftriaxone
single, intravenous infusion of 1 gm ceftriaxone (40 mg/mL solution administered at 0.83 mL/min over 30 minutes)
Other Name: ceftriaxone
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
 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)
Other Names:
  • HYLENEX recombinant
  • hyaluronoglucosaminidase
  • hyaluronidase
  • rHuPH20
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)
Other Names:
  • saline
  • normal saline
  • 0.9% sodium chloride injection
Drug: IV Ceftriaxone
single, intravenous infusion of 1 gm ceftriaxone (40 mg/mL solution administered at 0.83 mL/min over 30 minutes)
Other Name: ceftriaxone
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
 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)
Other Names:
  • HYLENEX recombinant
  • hyaluronoglucosaminidase
  • hyaluronidase
  • rHuPH20
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)
Other Names:
  • saline
  • normal saline
  • 0.9% sodium chloride injection
Drug: IV Ceftriaxone
single, intravenous infusion of 1 gm ceftriaxone (40 mg/mL solution administered at 0.83 mL/min over 30 minutes)
Other Name: ceftriaxone
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
 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)
Other Names:
  • HYLENEX recombinant
  • hyaluronoglucosaminidase
  • hyaluronidase
  • rHuPH20
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)
Other Names:
  • saline
  • normal saline
  • 0.9% sodium chloride injection
Drug: IV Ceftriaxone
single, intravenous infusion of 1 gm ceftriaxone (40 mg/mL solution administered at 0.83 mL/min over 30 minutes)
Other Name: ceftriaxone
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
 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)
Other Names:
  • HYLENEX recombinant
  • hyaluronoglucosaminidase
  • hyaluronidase
  • rHuPH20
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)
Other Names:
  • saline
  • normal saline
  • 0.9% sodium chloride injection
Drug: IV Ceftriaxone
single, intravenous infusion of 1 gm ceftriaxone (40 mg/mL solution administered at 0.83 mL/min over 30 minutes)
Other Name: ceftriaxone
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
 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)
Other Names:
  • HYLENEX recombinant
  • hyaluronoglucosaminidase
  • hyaluronidase
  • rHuPH20
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)
Other Names:
  • saline
  • normal saline
  • 0.9% sodium chloride injection
Drug: IV Ceftriaxone
single, intravenous infusion of 1 gm ceftriaxone (40 mg/mL solution administered at 0.83 mL/min over 30 minutes)
Other Name: ceftriaxone

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00493220

Sponsors and Collaborators
Baxter Healthcare Corporation
Halozyme Therapeutics
Investigators
Study Director: George E Harb, MD Baxter Healthcare Corporation
  More Information

Publications:

Responsible Party: Geroge E. Harb, MD, Baxter Healthcare Corporation
ClinicalTrials.gov Identifier: NCT00493220     History of Changes
Other Study ID Numbers: 1838-004
Study First Received: June 26, 2007
Results First Received: September 12, 2011
Last Updated: October 24, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Baxter Healthcare Corporation:
ceftriaxone
cephalosporins
pharmacokinetics
subcutaneous
 hyaluronoglucosaminidase
hyaluronidase
hyaluronan
rHuPH20

Additional relevant MeSH terms:
Ceftriaxone
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 22, 2013