Study of Subcutaneous Hydration Enabled by Human Recombinant Hyaluronidase (Hylenex)

Study Overview
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Brief Summary
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Randomized, double-blinded study that will evaluate the tolerability, safety, and flow rates of different solutions subcutaneously (SC) infused and preceded by human recombinant hyaluronidase (hylenex) 150 units. In Stage 1, the comparison will be Normal Saline (NS) solution to Lactated Ringer's (LR) solution. Each subject will receive 500 milliliters (mL) of solution, consisting of NS in one thigh and LR in the other thigh. Immediately prior to the infusions, each thigh will have 150 units of hylenex. In Stage 2, the comparison will be NS solution and buffered NS solution.

Detailed Description
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This Phase IV, randomized, double-blinded study in volunteer subjects to evaluate the tolerability, safety, and flow rates of different solutions subcutaneously (SC) infused and preceded by human recombinant hyaluronidase (hylenex) 150 units. The study will be conducted in two sequential stages. In Stage 1, the comparison will be NS solution to LR solution. Each subject will receive simultaneous SC infusions of 500 mL (from a 500 mL bag) of solution in each anterior thigh, consisting of NS in one thigh and LR in the other thigh. The thighs (left vs. right) to receive NS and LR will be randomized and double blinded. Immediately prior to the infusions, each thigh will have 150 units of hylenex simultaneously injected. Tolerability will be assessed based on the subject's self-assessment of discomfort on a visual analog scale (VAS). Safety will be assessed by physical examination targeted at infusion sites, vital signs, and adverse events. The amount of fluid infused will be assessed by weighing the infusion bag, fluid and tubing at designated time points, and allowing the determination of flow rate. Stage 2 will be conducted only if the observed Stage 1 VAS mean maximum pain score is at least 25 mm higher for one solution compared to the other. Stage 2 will evaluate the tolerability, safety, and flow rates of subcutaneously infused NS solution and buffered NS solution.

Official Title
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The INcreased Flow Utilizing Subcutaneously-Enabled Normal Saline and Lactated Ringer's (INFUSE-NSLR) Study: A Phase IV, Double-Blind, Randomized Study of Subcutaneous Hydration Enabled by Human Recombinant Hyaluronidase (Hylenex) in Volunteer Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: recombinant human hyaluronidase


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, 18 to 60 years of age. Intact normal skin without in the areas intended for infusion. No fluid intake for 12 hours prior to the start of the study infusion. Vital signs (Blood Pressure (BP), Heart Rate (HR), Respiratory Rate (RR)) within normal range. Metabolic panel within normal range. A negative urine or serum pregnancy test. Signed, written Institutional Review Board (IRB)-approved informed consent. Exclusion Criteria: Lower extremity edema. Lower extremity pathology that could interfere with study outcome. Rales on lung auscultation. History of cardiovascular disease. Allergy to hyaluronidase. Allergy to bee or vespid venom. Pregnancy or breast-feeding woman. Use of any investigational drug or device within 30 days of enrollment.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NS Infusion Group<br>Normal Saline (NS) and Hylenex | Drug: recombinant human hyaluronidase<br>* 150 Units in 1mL<br>* Other names: Hylenex;|
| Experimental: LR Infusion Group<br>Lactated Ringer's (LR) and Hylenex | Drug: recombinant human hyaluronidase<br>* 150 Units in 1mL<br>* Other names: Hylenex;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Participant's Assessment of Discomfort at the Infusion Site on a Visual Analog Scale (VAS) | Participant's self-assessment of discomfort at the infusion site by means of a validated VAS with a range of 0 millimeters (mm) (no discomfort) to 100 mm (worst possible discomfort), for the comparison of subcutaneous (SC) infusion of normal saline (NS) versus Lactated Ringer's (LR), each following an SC slow-push injection of 150 Units (U) Hylenex. | Approximate times which ranged from zero minutes at baseline to maximal post-infusion of 240 minutes on Day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Assessed for Safety Measures | Safety outcome measures included adverse events (AEs), physical examinations (targeted physical examination included lung auscultation for rales, checking for edema, evaluation of infusion sites, positives on a review of systems, and follow-up of findings from previous physical examinations), and vital signs (systolic blood pressure, diastolic blood pressure, heart rate, and respiration rate). | Baseline, Mid-Infusion Right and Left, Post-Infusion Right and Left, Discharge Right and Left (up to approximately 8 days) | 
| Average Infusion Flow Rate (Milliliters Per Hour [mL/hr]) Derived From the Time to Infuse up to 500 mL of Solution | The infusion flow rate (mL/h) was derived from the time to subcutaneously (SC) infuse up to 500 mL of NS or LR solution (following SC injection of 150 Units hylenex) by measuring the change in weight of the infusion bag, fluid, and tubing. | During infusion on Day 1 | 
| Percent Change From Baseline Thigh Circumference to Maximum Post-Baseline Thigh Circumference at Infusion Sites | Thigh circumference was measured in centimeters at 7 time points before, during, and after subcutaneous infusion of 500 mL NS or LR solution. | Before the infusion, during the infusion, after the infusion, and discharge (Day 1) | 
| Time From the Beginning of Infusion Until the Thigh Circumference Returns to Within 5% of Baseline Circumference | Thigh circumference was measured at the level of the angiocatheter with a flexible measuring tape prior to infusion initiation (Baseline), at the midpoint for each infusion, and at the end of each infusion. | Before the infusion (Baseline) until discharge (Day 1) | 
| Number of Participant's With the Indicated Global Preference for Infusion (Left Versus Right Thigh) | Participants blinded to the type of infusion were asked to state their preference for the left or right infusion following all infusion day (Day 1) activities and assessments. The preference for the left or right infusion indicated which infusion was preferred: NS or LR. | End of infusion (Day 1) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hylenex, subcutaneous infusion, hyaluronidase, rHuPH20, recombinant human hyaluronidase