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

Sponsor:	Baxter Healthcare Corporation
Collaborator:	Halozyme Therapeutics
Information provided by:	Baxter Healthcare Corporation
ClinicalTrials.gov Identifier:	NCT00493220

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 I

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:

Drug Information available for: Chlorides Ceftriaxone Ceftriaxone Sodium Hyaluronidase Sodium chloride

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:

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.

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 February 12, 2012