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

NCT ID: NCT00493220

Last Updated: 2011-12-02

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-06-30

Study Completion Date

2007-09-30

Brief Summary

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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.

Detailed Description

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Conditions

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Healthy

Keywords

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ceftriaxone cephalosporins pharmacokinetics subcutaneous hyaluronoglucosaminidase hyaluronidase hyaluronan rHuPH20

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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HYLENEX SC, Placebo SC, IV

subcutaneous HYLENEX and ceftriaxone as 1st intervention, subcutaneous placebo and ceftriaxone as 2nd intervention, IV ceftriaxone as 3rd intervention

Group Type EXPERIMENTAL

SC HYLENEX and Ceftriaxone

Intervention Type DRUG

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)

SC Placebo and Ceftriaxone

Intervention Type DRUG

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)

IV Ceftriaxone

Intervention Type DRUG

single, intravenous infusion of 1 gm ceftriaxone (40 mg/mL solution administered at 0.83 mL/min over 30 minutes)

HYLENEX SC, IV, Placebo SC

subcutaneous HYLENEX and ceftriaxone as 1st intervention, IV ceftriaxone as 2nd intervention, subcutaneous placebo and ceftriaxone as 3rd intervention

Group Type EXPERIMENTAL

SC HYLENEX and Ceftriaxone

Intervention Type DRUG

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)

SC Placebo and Ceftriaxone

Intervention Type DRUG

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)

IV Ceftriaxone

Intervention Type DRUG

single, intravenous infusion of 1 gm ceftriaxone (40 mg/mL solution administered at 0.83 mL/min over 30 minutes)

Placebo SC, HYLENEX SC, IV

subcutaneous placebo and ceftriaxone as 1st intervention, subcutaneous HYLENEX and ceftriaxone as 2nd intervention, IV ceftriaxone as 3rd intervention

Group Type EXPERIMENTAL

SC HYLENEX and Ceftriaxone

Intervention Type DRUG

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)

SC Placebo and Ceftriaxone

Intervention Type DRUG

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)

IV Ceftriaxone

Intervention Type DRUG

single, intravenous infusion of 1 gm ceftriaxone (40 mg/mL solution administered at 0.83 mL/min over 30 minutes)

Placebo SC, IV, HYLENEX SC

subcutaneous placebo and ceftriaxone as 1st intervention, IV ceftriaxone as 2nd intervention, subcutaneous HYLENEX and ceftriaxone as 3rd intervention

Group Type EXPERIMENTAL

SC HYLENEX and Ceftriaxone

Intervention Type DRUG

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)

SC Placebo and Ceftriaxone

Intervention Type DRUG

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)

IV Ceftriaxone

Intervention Type DRUG

single, intravenous infusion of 1 gm ceftriaxone (40 mg/mL solution administered at 0.83 mL/min over 30 minutes)

IV, HYLENEX SC, Placebo SC

IV ceftriaxone as 1st intervention, subcutaneous HYLENEX and ceftriaxone as 2nd intervention, subcutaneous placebo and ceftriaxone as 3rd intervention

Group Type EXPERIMENTAL

SC HYLENEX and Ceftriaxone

Intervention Type DRUG

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)

SC Placebo and Ceftriaxone

Intervention Type DRUG

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)

IV Ceftriaxone

Intervention Type DRUG

single, intravenous infusion of 1 gm ceftriaxone (40 mg/mL solution administered at 0.83 mL/min over 30 minutes)

IV, Placebo SC, HYLENEX SC

IV ceftriaxone as 1st intervention, subcutaneous placebo and ceftriaxone as 2nd intervention, subcutaneous HYLENEX and ceftriaxone as 3rd intervention

Group Type EXPERIMENTAL

SC HYLENEX and Ceftriaxone

Intervention Type DRUG

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)

SC Placebo and Ceftriaxone

Intervention Type DRUG

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)

IV Ceftriaxone

Intervention Type DRUG

single, intravenous infusion of 1 gm ceftriaxone (40 mg/mL solution administered at 0.83 mL/min over 30 minutes)

Interventions

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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)

Intervention Type 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)

Intervention Type DRUG

IV Ceftriaxone

single, intravenous infusion of 1 gm ceftriaxone (40 mg/mL solution administered at 0.83 mL/min over 30 minutes)

Intervention Type DRUG

Other Intervention Names

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HYLENEX recombinant hyaluronoglucosaminidase hyaluronidase rHuPH20 saline normal saline 0.9% sodium chloride injection ceftriaxone

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Halozyme Therapeutics

INDUSTRY

Sponsor Role collaborator

Baxter Healthcare Corporation

INDUSTRY

Sponsor Role lead

Responsible Party

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Baxter Healthcare Corporation

Principal Investigators

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George E Harb, MD

Role: STUDY_DIRECTOR

Baxter Healthcare Corporation

Countries

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United States

References

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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. doi: 10.1185/03007990903432900.

Reference Type RESULT
PMID: 19947907 (View on PubMed)

Other Identifiers

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1838-004

Identifier Type: -

Identifier Source: org_study_id