Study of In-line Pressure Using Various Techniques of Subcutaneous Administration of Fluids Enabled by Human Recombinant Hyaluronidase (INFUSE-AT1A)

Study Overview
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Brief Summary
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The purpose is to characterize the in-line pressure profiles associated with several infusion technique factors during subcutaneous (SC) infusion of Lactated Ringer's solution, preceded by recombinant human hyaluronidase (hylenex). The safety and tolerability of hylenex-augmented SC infusion of Lactated Ringer's solution fluid is also being evaluated.

Official Title
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The INcreased Flow Utilizing Subcutaneously-Enabled Fluids Administration Technique 1A Study (INFUSE-AT 1A): A Randomized, Parallel Group Study to Evaluate the In-line Pressure, Flow Rate, Safety and Tolerability of Hylenex-facilitated Subcutaneous Fluid Administration In Healthy Volunteers Using Various Subcutaneous Infusion Techniques

Conditions
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Dehydration

Intervention / Treatment
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* Drug: Subcutaneous HYLENEX (recombinant human hyaluronidase) and Lactated Ringer's solution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, aged 18 to 60 years, inclusive. Body mass index 19.0 to 35.0 kg/m2 Intact normal skin without potentially obscuring tattoos, pigmentation, or lesions on the upper back in the area intended for infusion Free from any clinically significant abnormality on the basis of medical/medication history or physical examination Vital signs and clinical laboratory parameters within normal range or, if outside normal range, deemed not clinically significant Negative urine drug and alcohol screens. Exclusion Criteria: Upper back pathology that could interfere with study outcome. History of congestive heart failure, known coronary heart disease, active or recent pulmonary disease, or renal insufficiency. Rales on lung auscultation. Known allergy to hyaluronidase or any other ingredient in the formulation of hylenex recombinant Treatment with furosemide, benzodiazepines, or phenytoin. Pregnancy or breastfeeding. Exposure to any experimental drug within 30 days prior to study admission, or previous participation in this study. Any other reason which, in the investigator's opinion, would prevent the safe participation in the study.

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 24 ga catheter, dose flush, single-step rate scheme<br>Single 150 U subcutaneous (SC) dose of HYLENEX and 3 mL Lactated Ringer's solution flush administered through 24 gauge plastic catheter; followed by SC infusion of 1000 mL Lactated Ringer's solution via large-volume infusion pump at 250 mL/h for the first hour and 200 mL/hr for the remainder of the infusion. | Drug: Subcutaneous HYLENEX (recombinant human hyaluronidase) and Lactated Ringer's solution<br>* Subcutaneous administration of 150 U HYLENEX, followed by 1000 mL Lactated Ringer's solution<br>* Other names: LR solution;|
| Experimental: 24 ga catheter, no dose flush, single-step rate scheme<br>Single 150 U subcutaneous (SC) dose of HYLENEX (without a Lactated Ringer's solution flush) administered through 24 gauge plastic catheter; followed by SC infusion of 1000 mL Lactated Ringer's solution via large-volume infusion pump at 250 mL/h for the first hour and 200 mL/hr for the remainder of the infusion. | Drug: Subcutaneous HYLENEX (recombinant human hyaluronidase) and Lactated Ringer's solution<br>* Subcutaneous administration of 150 U HYLENEX, followed by 1000 mL Lactated Ringer's solution<br>* Other names: LR solution;|
| Experimental: 24 ga catheter, dose flush, up-titrated rate scheme<br>Single 150 U subcutaneous (SC) dose of HYLENEX and 3 mL Lactated Ringer's solution flush administered through 24 gauge plastic catheter; followed by SC infusion of 1000 mL Lactated Ringer's solution via large-volume infusion pump at 50 mL/h for the first 5 min, 100 mL/h for the next 5 min, 285 mL/h for the next 50 min and 200 mL/h for the remainder of the infusion. | Drug: Subcutaneous HYLENEX (recombinant human hyaluronidase) and Lactated Ringer's solution<br>* Subcutaneous administration of 150 U HYLENEX, followed by 1000 mL Lactated Ringer's solution<br>* Other names: LR solution;|
| Experimental: 24 ga catheter, no dose flush, up-titrated rate scheme<br>Single 150 U subcutaneous (SC) dose of HYLENEX (without a Lactated Ringer's solution flush) administered through 24 gauge plastic catheter; followed by SC infusion of 1000 mL Lactated Ringer's solution via large-volume infusion pump at 50 mL/h for the first 5 min, 100 mL/h for the next 5 min, 285 mL/h for the next 50 min and 200 mL/h for the remainder of the infusion. | Drug: Subcutaneous HYLENEX (recombinant human hyaluronidase) and Lactated Ringer's solution<br>* Subcutaneous administration of 150 U HYLENEX, followed by 1000 mL Lactated Ringer's solution<br>* Other names: LR solution;|
| Experimental: 25 ga needle, dose flush, single-step rate scheme<br>Single 150 U subcutaneous (SC) dose of HYLENEX and 3 mL Lactated Ringer's solution flush administered through 25 gauge metal butterfly needle; followed by SC infusion of 1000 mL Lactated Ringer's solution via large-volume infusion pump at 250 mL/h for the first hour and 200 mL/hr for the remainder of the infusion. | Drug: Subcutaneous HYLENEX (recombinant human hyaluronidase) and Lactated Ringer's solution<br>* Subcutaneous administration of 150 U HYLENEX, followed by 1000 mL Lactated Ringer's solution<br>* Other names: LR solution;|
| Experimental: 25 ga needle, no dose flush, single-step rate scheme<br>Single 150 U subcutaneous (SC) dose of HYLENEX (without a Lactated Ringer's solution flush) administered through 25 gauge metal butterfly needle; followed by SC infusion of 1000 mL Lactated Ringer's solution via large-volume infusion pump at 250 mL/h for the first hour and 200 mL/hr for the remainder of the infusion. | Drug: Subcutaneous HYLENEX (recombinant human hyaluronidase) and Lactated Ringer's solution<br>* Subcutaneous administration of 150 U HYLENEX, followed by 1000 mL Lactated Ringer's solution<br>* Other names: LR solution;|
| Experimental: 25 ga needle, dose flush, up-titrated rate scheme<br>Single 150 U subcutaneous (SC) dose of HYLENEX and 3 mL Lactated Ringer's solution flush administered through 25 gauge metal butterfly needle; followed by SC infusion of 1000 mL Lactated Ringer's solution via large-volume infusion pump at 50 mL/h for the first 5 min, 100 mL/h for the next 5 min, 285 mL/h for the next 50 min and 200 mL/h for the remainder of the infusion. | Drug: Subcutaneous HYLENEX (recombinant human hyaluronidase) and Lactated Ringer's solution<br>* Subcutaneous administration of 150 U HYLENEX, followed by 1000 mL Lactated Ringer's solution<br>* Other names: LR solution;|
| Experimental: 25 ga needle, no dose flush, up-titrated rate scheme<br>Single 150 U subcutaneous (SC) dose of HYLENEX (without a Lactated Ringer's solution flush) administered through 25 gauge metal butterfly needle; followed by SC infusion of 1000 mL Lactated Ringer's solution via large-volume infusion pump at 50 mL/h for the first 5 min, 100 mL/h for the next 5 min, 285 mL/h for the next 50 min and 200 mL/h for the remainder of the infusion. | Drug: Subcutaneous HYLENEX (recombinant human hyaluronidase) and Lactated Ringer's solution<br>* Subcutaneous administration of 150 U HYLENEX, followed by 1000 mL Lactated Ringer's solution<br>* Other names: LR solution;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Measured In-line Fluid Pressure | Maximum fluid pressure measured (15 sec period) in delivery line during subcutaneous fluid infusion at specified time point after start of infusion | each minute for the first 15 minutes of fluid infusion, every 5 minutes for the next 45 minutes of infusion, and every 15 minutes thereafter until the end of infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Attempts Needed for Successful Subcutaneous Catheter/Needle Placement |  | end of catheter/needle placement | 
| Cumulative Fluid Volume Delivered |  | each minute for the first 15 minutes of fluid infusion, every 5 minutes for the next 45 minutes of infusion, and every 15 minutes thereafter until the end of infusion | 
| Technical Challenges Encountered During Fluid Infusion | Observed challenges, including catheter kinking, catheter/needle dislodgement/pull-out, infusion pump alarm, other technical problems | at any occurence of a defined challenge or at end of infusion if no challenges occurred | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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dehydration, fluid therapy, hyaluronoglucosaminidase, hyaluronidase, hypodermoclysis, clysis, subcutaneous hydration, subcutaneous rehydration, hyaluronan, rHuPH20