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

NCT00493220 | Completed Phase 1 Results

• 1 other identifier: 1838-004
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Healthy

Keywords

ceftriaxone; cephalosporins; pharmacokinetics; subcutaneous; hyaluronoglucosaminidase; hyaluronidase; hyaluronan; rHuPH20

Outcome Measures

Primary Outcomes (2)

• AUC0-t

  Area under the drug concentration-time curve from time zero to the time of the last measurable concentration (calculated by the linear trapezoidal method)

  Start of ceftriaxone administration through time of last measureable plasma ceftriaxone concentration

• AUC0-inf

  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)

  from the start of ceftriaxone administration to infinity

Secondary Outcomes (2)

• Cmax

  at the time of the highest measured plasma ceftriaxone concentration

• Tmax

  from start of ceftriaxone administration until time of maximum measured plasma ceftriaxone concentration

Study Arms (6)

HYLENEX SC, Placebo SC, IV

EXPERIMENTAL

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

Drug: SC HYLENEX and Ceftriaxone; Drug: SC Placebo and Ceftriaxone; Drug: IV Ceftriaxone

HYLENEX SC, IV, Placebo SC

EXPERIMENTAL

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

Drug: SC HYLENEX and Ceftriaxone; Drug: SC Placebo and Ceftriaxone; Drug: IV Ceftriaxone

Placebo SC, HYLENEX SC, IV

EXPERIMENTAL

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

Drug: SC HYLENEX and Ceftriaxone; Drug: SC Placebo and Ceftriaxone; Drug: IV Ceftriaxone

Placebo SC, IV, HYLENEX SC

EXPERIMENTAL

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

Drug: SC HYLENEX and Ceftriaxone; Drug: SC Placebo and Ceftriaxone; Drug: IV Ceftriaxone

IV, HYLENEX SC, Placebo SC

EXPERIMENTAL

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

Drug: SC HYLENEX and Ceftriaxone; Drug: SC Placebo and Ceftriaxone; Drug: IV Ceftriaxone

IV, Placebo SC, HYLENEX SC

EXPERIMENTAL

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

Drug: SC HYLENEX and Ceftriaxone; Drug: SC Placebo and Ceftriaxone; Drug: IV Ceftriaxone

Interventions

SC HYLENEX and Ceftriaxone 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)

Also known as: HYLENEX recombinant, hyaluronoglucosaminidase, hyaluronidase, rHuPH20

HYLENEX SC, IV, Placebo SC; HYLENEX SC, Placebo SC, IV; IV, HYLENEX SC, Placebo SC; IV, Placebo SC, HYLENEX SC; Placebo SC, HYLENEX SC, IV; Placebo SC, IV, HYLENEX SC

SC Placebo and Ceftriaxone 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)

Also known as: saline, normal saline, 0.9% sodium chloride injection

HYLENEX SC, IV, Placebo SC; HYLENEX SC, Placebo SC, IV; IV, HYLENEX SC, Placebo SC; IV, Placebo SC, HYLENEX SC; Placebo SC, HYLENEX SC, IV; Placebo SC, IV, HYLENEX SC

IV Ceftriaxone DRUG

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

Also known as: ceftriaxone

HYLENEX SC, IV, Placebo SC; HYLENEX SC, Placebo SC, IV; IV, HYLENEX SC, Placebo SC; IV, Placebo SC, HYLENEX SC; Placebo SC, HYLENEX SC, IV; Placebo SC, IV, HYLENEX SC

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Baxter Healthcare Corporation: lead
• Halozyme Therapeutics: collaborator

Related Publications (1)

• 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.

  PMID: 19947907 RESULT

MeSH Terms

Interventions

Ceftriaxone; Hyaluronoglucosaminidase; Sodium Chloride; Saline Solution

Intervention Hierarchy (Ancestors)

Cefotaxime; Cephacetrile; Cephalosporins; beta-Lactams; Lactams; Amides; Organic Chemicals; Thiazines; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glycoside Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Polysaccharide-Lyases; Carbon-Oxygen Lyases; Lyases; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Results Point of Contact

• Title: George Harb, MD, MPH
• Organization: Baxter Healthcare Corporation

george_harb@baxter.com

Study Officials

• George E Harb, MD

  Baxter Healthcare Corporation

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: June 26, 2007
• First Posted: June 28, 2007
• Study Start: June 1, 2007
• Primary Completion: September 1, 2007
• Study Completion: September 1, 2007
• Last Updated: December 2, 2011
• Results First Posted: December 2, 2011

Record last verified: 2011-10