Trial Outcomes & Findings for Study of Subcutaneous Hydration Enabled by Human Recombinant Hyaluronidase (Hylenex) (NCT NCT00656370)

NCT ID: NCT00656370

Last Updated: 2018-10-17

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 15 participants
• Primary outcome timeframe: Approximate times which ranged from zero minutes at baseline to maximal post-infusion of 240 minutes on Day 1
• Results posted on: 2018-10-17

Participant Flow

The first subject entered screening on 19 DEC 2007 and the last subject entered screening on 23 JAN 2008. A total of 25 subjects were assessed for eligibility and signed an Informed Consent Form.

Seven subjects were excluded during screening: 6 did not meet inclusion criteria and 1 withdrew consent. An additional 3 subjects were screened as alternates, but were not enrolled. 15 subjects were randomized and completed stage 1.

Participant milestones

Measure	NS, LR 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.
Overall Study STARTED	25
Overall Study COMPLETED	15
Overall Study NOT COMPLETED	10

Reasons for withdrawal

Measure	NS, LR 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.
Overall Study Screen Failures	7
Overall Study Alternates	3

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	NS, LR n=15 Participants 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.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	15 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	41 years STANDARD_DEVIATION 14.9 • n=5 Participants
Sex: Female, Male Female	14 Participants n=5 Participants
Sex: Female, Male Male	1 Participants n=5 Participants
Region of Enrollment United States	15 participants n=5 Participants

PRIMARY outcome

Timeframe: Approximate times which ranged from zero minutes at baseline to maximal post-infusion of 240 minutes on Day 1

Population: 15 subjects were randomized and completed stage 1

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.

Outcome measures

Measure	NS Infusion Group n=15 Participants Normal Saline (NS) and Hylenex recombinant human hyaluronidase: 150 Units in 1mL	LR Infusion Group n=15 Participants Lactated Ringer's (LR) and Hylenex recombinant human hyaluronidase: 150 Units in 1mL
The Participant's Assessment of Discomfort at the Infusion Site on a Visual Analog Scale (VAS)	20.0 mm Standard Deviation 19.4	9.4 mm Standard Deviation 18.3

SECONDARY outcome

Timeframe: Baseline, Mid-Infusion Right and Left, Post-Infusion Right and Left, Discharge Right and Left (up to approximately 8 days)

Population: 15 participants were randomized and completed stage 1

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).

Outcome measures

Measure	NS Infusion Group n=15 Participants Normal Saline (NS) and Hylenex recombinant human hyaluronidase: 150 Units in 1mL	LR Infusion Group Lactated Ringer's (LR) and Hylenex recombinant human hyaluronidase: 150 Units in 1mL
Number of Participants Assessed for Safety Measures	15 participants	—

SECONDARY outcome

Timeframe: During infusion on Day 1

Population: 15 participants were randomized and completed stage 1

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.

Outcome measures

Measure	NS Infusion Group n=15 Participants Normal Saline (NS) and Hylenex recombinant human hyaluronidase: 150 Units in 1mL	LR Infusion Group n=15 Participants Lactated Ringer's (LR) and Hylenex recombinant human hyaluronidase: 150 Units in 1mL
Average Infusion Flow Rate (Milliliters Per Hour [mL/hr]) Derived From the Time to Infuse up to 500 mL of Solution	384.1 mL/hr Standard Deviation 118.1	395.8 mL/hr Standard Deviation 132.8

SECONDARY outcome

Timeframe: Before the infusion, during the infusion, after the infusion, and discharge (Day 1)

Population: 15 participants were randomized and completed stage 1

Thigh circumference was measured in centimeters at 7 time points before, during, and after subcutaneous infusion of 500 mL NS or LR solution.

Outcome measures

Measure	NS Infusion Group n=15 Participants Normal Saline (NS) and Hylenex recombinant human hyaluronidase: 150 Units in 1mL	LR Infusion Group n=15 Participants Lactated Ringer's (LR) and Hylenex recombinant human hyaluronidase: 150 Units in 1mL
Percent Change From Baseline Thigh Circumference to Maximum Post-Baseline Thigh Circumference at Infusion Sites	5.2 percent change Standard Deviation 1.6	5.3 percent change Standard Deviation 1.5

SECONDARY outcome

Timeframe: Before the infusion (Baseline) until discharge (Day 1)

Population: 15 participants were randomized and completed stage 1. Only those participants who experienced a 5% or greater increase in thigh circumference for both infusions were included in the analysis.

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.

Outcome measures

Measure	NS Infusion Group n=4 Participants Normal Saline (NS) and Hylenex recombinant human hyaluronidase: 150 Units in 1mL	LR Infusion Group n=4 Participants Lactated Ringer's (LR) and Hylenex recombinant human hyaluronidase: 150 Units in 1mL
Time From the Beginning of Infusion Until the Thigh Circumference Returns to Within 5% of Baseline Circumference	147.3 minutes Standard Deviation 35.6	123.5 minutes Standard Deviation 9.7

SECONDARY outcome

Timeframe: End of infusion (Day 1)

Population: 15 participants were randomized and completed stage 1

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.

Outcome measures

Measure	NS Infusion Group n=15 Participants Normal Saline (NS) and Hylenex recombinant human hyaluronidase: 150 Units in 1mL	LR Infusion Group n=15 Participants Lactated Ringer's (LR) and Hylenex recombinant human hyaluronidase: 150 Units in 1mL
Number of Participant's With the Indicated Global Preference for Infusion (Left Versus Right Thigh)	0 Participants	15 Participants

Adverse Events

NS, LR

Serious events: 0 serious events

Other events: 15 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	NS, LR n=15 participants at risk 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.
General disorders Injection site pain	73.3% 11/15 • Number of events 16
General disorders Injection site erythema	46.7% 7/15 • Number of events 9
General disorders Injection site irritation	26.7% 4/15 • Number of events 7
General disorders Injection site pruritus	13.3% 2/15 • Number of events 3
General disorders Injection site bruising	6.7% 1/15 • Number of events 1
General disorders Oedema peripheral	6.7% 1/15 • Number of events 1
General disorders Pain	6.7% 1/15 • Number of events 1
Infections and infestations Bronchitis	6.7% 1/15 • Number of events 1
Infections and infestations Nasopharyngitis	6.7% 1/15 • Number of events 1
Infections and infestations Tooth infection	6.7% 1/15 • Number of events 1
Nervous system disorders Headache	13.3% 2/15 • Number of events 2

Additional Information

Dimitrios Chondros, M.D., Chief Medical Officer

Halozyme Therapeutics

Phone: 858-794-8889

Email: dchondros@halozyme.com

Results disclosure agreements

• Principal investigator is a sponsor employee The Investigator agrees to use the information for the purpose of carrying out this study and for no other purpose, unless prior written permission from the Sponsor (Halozyme) is obtained.
• Publication restrictions are in place

Restriction type: OTHER