Phase 1 Safety, Tolerability and PK Study of Ondansetron and Hylenex Recombinant in Healthy Volunteers

This is a randomized, open label, 4 way crossover Phase 1 study of the pharmacokinetics, safety and tolerability of a 4 mg dose of ondansetron administered subcutaneously with Hylenex recombinant compared to 4 mg doses of ondansetron administered intravenously and intramuscularly and an 8 mg dose of ondansetron administered orally.

• Ondansetron (Drug), also known as Zofran: Ondansetron solution 4 mg single administration
• Ondansetron + Hylenex (Drug), also known as Zofran: Ondansetron solution (4 mg) single administration + Hylenex recombinant (150 U) single administration
• Zofran ODT (Drug), also known as ondansetron disintegrating tablet - oral: Zofran ODT (8 mg) single administration
• Ondansetron solution (Drug), also known as Zofran: Ondansetron solution (4 mg) single administration

Primary outcomes

• Evaluation of Overall Safety [Days 1-31]: Investigator assessment of infusion site observations for parenteral administration; Subject assessment of pain using the verbal response scale for parenteral administration; Subject assessment of pain using the visual analog scale for parenteral administration; Investigator assessment of systemic adverse events

Secondary outcomes

• Evaluation of Pharmacokinetics [Days 1-5]: Area of under the plasma concentration time curve (AUC); Time to achieve maximum plasma concentration (tmax); Maximum plasma concentration (Cmax); Plasma elimination half-life (t1/2); Relative bioavailability, ondansentron SC with Hylenex recombinant relative to ondansetron alone IV, IM, and PO

Sex: All, ages: 19 Years to 65 Years, accepts healthy volunteers

Inclusion Criteria:

* Male or female volunteers 19-65 years old
* Females must be nonlactating and nonpregnant (negative serum pregnancy test at screening)and agree to practice effective birth control for at least 30 days after study completion
* Nonsmoker or no tobacco/nicotine use in previous 6 months
* Intact normal skin without obscuring tattoos, pigmentation or lesions
* Adequate venous access in upper extremities
* Normal vital signs, ECG, and labs or assessed by the Investigator as NCS
* Serum hemoglobin within site's normal range
* Negative drug and alcohol screen
* Able to make decisions and comply with study requirements

Exclusion Criteria:

* History of drug or alcohol abuse or positive drug and alcohol screen
* Abdominal surgery within the last 30 days
* Phenylketonuria
* Tobacco or nicotine use within previous 6 months
* Hypersensitivity or contraindication to ondansetron or other 5-HT3 receptor agonists
* Received ondansetron within 4 days prior to Day 1
* Known allergy to hyaluronidase or other ingredient in Hylenex recombinant
* Lower extremity edema
* Creatinine clearance < 60 mL/min
* Dehydration (Grade 2 or higher)
* Hypersensitivity or contraindication to heparin
* Abnormal ECG with clinically significant QT prolongation or history of
* Female who is pregnant or breastfeeding
* Participation in a clinical trial (drug or device) within 30 days of enrollment
* Clinically significant medical history, major systemic disease, intercurrent illness, physical examination finding, or clinical laboratory test result that risks the subject's safety or interfere with interpretation of study results
* Not able to comply with study requirements

• Results publication: Dychter SS, Harrigan R, Bahn JD, Printz MA, Sugarman BJ, DeNoia E, Haughey DB, Fellows D, Maneval DC. Tolerability and pharmacokinetic properties of ondansetron administered subcutaneously with recombinant human hyaluronidase in minipigs and healthy volunteers. Clin Ther. 2014 Feb 1;36(2):211-24. doi: 10.1016/j.clinthera.2013.12.013. Epub 2014 Jan 31. PMID 24486335

• Samuel S Dychter, MD, Study director, Halozyme Therapeutics