Healthy
Conditions
Keywords
Hylenex, subcutaneous infusion, hyaluronidase, rHuPH20, recombinant human hyaluronidase
Brief summary
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
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.
Interventions
150 Units in 1mL
Sponsors
Baxter Healthcare Corporation
Halozyme Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
1. Male or female, 18 to 60 years of age. 2. Intact normal skin without in the areas intended for infusion. 3. No fluid intake for 12 hours prior to the start of the study infusion. 4. Vital signs (Blood Pressure (BP), Heart Rate (HR), Respiratory Rate (RR)) within normal range. 5. Metabolic panel within normal range. 6. A negative urine or serum pregnancy test. 7. Signed, written Institutional Review Board (IRB)-approved informed consent.
Exclusion criteria
1. Lower extremity edema. 2. Lower extremity pathology that could interfere with study outcome. 3. Rales on lung auscultation. 4. History of cardiovascular disease. 5. Allergy to hyaluronidase. 6. Allergy to bee or vespid venom. 7. Pregnancy or breast-feeding woman. 8. Use of any investigational drug or device within 30 days of enrollment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Participant's Assessment of Discomfort at the Infusion Site on a Visual Analog Scale (VAS) | Approximate times which ranged from zero minutes at baseline to maximal post-infusion of 240 minutes on Day 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Assessed for Safety Measures | Baseline, Mid-Infusion Right and Left, Post-Infusion Right and Left, Discharge Right and Left (up to approximately 8 days) | 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). |
| Average Infusion Flow Rate (Milliliters Per Hour [mL/hr]) Derived From the Time to Infuse up to 500 mL of Solution | During infusion on Day 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. |
| Percent Change From Baseline Thigh Circumference to Maximum Post-Baseline Thigh Circumference at Infusion Sites | Before the infusion, during the infusion, after the infusion, and discharge (Day 1) | Thigh circumference was measured in centimeters at 7 time points before, during, and after subcutaneous infusion of 500 mL NS or LR solution. |
| Time From the Beginning of Infusion Until the Thigh Circumference Returns to Within 5% of Baseline Circumference | Before the infusion (Baseline) until discharge (Day 1) | 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. |
| Number of Participant's With the Indicated Global Preference for Infusion (Left Versus Right Thigh) | End of infusion (Day 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. |
Countries
United States
Participant flow
Recruitment details
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.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 15 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Alternates | 3 |
| Overall Study | Screen Failures | 7 |
Baseline characteristics
| Characteristic | NS, LR |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants |
| Age, Continuous | 41 years STANDARD_DEVIATION 14.9 |
| Region of Enrollment United States | 15 participants |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 15 / 15 |
| serious Total, serious adverse events | 0 / 15 |
Outcome results
Primary
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.
Time frame: 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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NS Infusion Group | The Participant's Assessment of Discomfort at the Infusion Site on a Visual Analog Scale (VAS) | 20.0 mm | Standard Deviation 19.4 |
| LR Infusion Group | The Participant's Assessment of Discomfort at the Infusion Site on a Visual Analog Scale (VAS) | 9.4 mm | Standard Deviation 18.3 |
Secondary
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.
Time frame: During infusion on Day 1
Population: 15 participants were randomized and completed stage 1
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NS Infusion Group | 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 |
| LR Infusion Group | Average Infusion Flow Rate (Milliliters Per Hour [mL/hr]) Derived From the Time to Infuse up to 500 mL of Solution | 395.8 mL/hr | Standard Deviation 132.8 |
p-value: 0.93Wilcoxon signed rank test
Secondary
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).
Time frame: 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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NS Infusion Group | Number of Participants Assessed for Safety Measures | 15 participants |
Secondary
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.
Time frame: End of infusion (Day 1)
Population: 15 participants were randomized and completed stage 1
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| NS Infusion Group | Number of Participant's With the Indicated Global Preference for Infusion (Left Versus Right Thigh) | 0 Participants |
| LR Infusion Group | Number of Participant's With the Indicated Global Preference for Infusion (Left Versus Right Thigh) | 15 Participants |
Secondary
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.
Time frame: Before the infusion, during the infusion, after the infusion, and discharge (Day 1)
Population: 15 participants were randomized and completed stage 1
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NS Infusion Group | Percent Change From Baseline Thigh Circumference to Maximum Post-Baseline Thigh Circumference at Infusion Sites | 5.2 percent change | Standard Deviation 1.6 |
| LR Infusion Group | Percent Change From Baseline Thigh Circumference to Maximum Post-Baseline Thigh Circumference at Infusion Sites | 5.3 percent change | Standard Deviation 1.5 |
p-value: 0.67Wilcoxon signed rank test
Secondary
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NS Infusion Group | Time From the Beginning of Infusion Until the Thigh Circumference Returns to Within 5% of Baseline Circumference | 147.3 minutes | Standard Deviation 35.6 |
| LR Infusion Group | Time From the Beginning of Infusion Until the Thigh Circumference Returns to Within 5% of Baseline Circumference | 123.5 minutes | Standard Deviation 9.7 |