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

Study Overview
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Brief Summary
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This is a randomized, open-label Phase 1 pharmacokinetic, tolerability, and safety study of ondansetron and Hylenex given subcutaneously compared to ondansetron given intravenously, intramuscularly, and orally in normal healthy volunteers.

Detailed Description
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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.

Official Title
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Phase 1 Open-Label Randomized 4 Period Crossover Study Comparing Safety, Tolerability and PK of Ondansetron Given Subcutaneously With Hylenex Recombinant and Given Alone Intramuscularly, Intravenously and Orally in Healthy Volunteers

Conditions
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Healthy

Intervention / Treatment
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* Drug: Ondansetron
* Drug: Ondansetron + Hylenex
* Drug: Zofran ODT
* Drug: Ondansetron solution


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Subcutaneous Administration<br>Ondansetron + Hylenex administered subcutaneously | Drug: Ondansetron + Hylenex<br>* Ondansetron solution (4 mg) single administration + Hylenex recombinant (150 U) single administration<br>* Other names: Zofran;|
| Experimental: Oral Administration<br>Ondansetron administered orally | Drug: Zofran ODT<br>* Zofran ODT (8 mg) single administration<br>* Other names: ondansetron disintegrating tablet - oral;|
| Experimental: Intramuscular Administration<br>Ondansetron administered intramuscularly | Drug: Ondansetron<br>* Ondansetron solution 4 mg single administration<br>* Other names: Zofran;|
| Experimental: Intravenous Administration<br>Ondansetron administered intravenously | Drug: Ondansetron solution<br>* Ondansetron solution (4 mg) single administration<br>* Other names: Zofran;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of Overall Safety | 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 | Days 1-31 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of Pharmacokinetics | 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 | Days 1-5 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pharmacokinetics, Safety, Healthy Volunteers, tolerability