INFUSE-NSLR: Study of Subcutaneous Hydration Enabled by Human Recombinant Hyaluronidase (Hylenex)
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 4 |
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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: NS Infusion Group Normal Saline (NS) and Hylenex |
Drug: recombinant human hyaluronidase
150 Units in 1mL
Other Names:
|
Experimental: LR Infusion Group Lactated Ringer's (LR) and Hylenex |
Drug: recombinant human hyaluronidase
150 Units in 1mL
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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.
Eligibility Criteria
Criteria
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.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Jasper Clinic | Kalamazoo | Michigan | United States | 49007 |
Sponsors and Collaborators
- Halozyme Therapeutics
- Baxter Healthcare Corporation
Investigators
- Principal Investigator: Shanthini Daniel, M.D., Jasper Clinic, Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- HZ2-07-03
Study Results
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 Detail | 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. |
Arm/Group Title | NS, LR |
---|---|
Arm/Group Description | 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. |
Period Title: Overall Study | |
STARTED | 25 |
COMPLETED | 15 |
NOT COMPLETED | 10 |
Baseline Characteristics
Arm/Group Title | NS, LR |
---|---|
Arm/Group Description | 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 Participants | 15 |
Age (Count of Participants) | |
<=18 years |
0
0%
|
Between 18 and 65 years |
15
100%
|
>=65 years |
0
0%
|
Age (years) [Mean (Standard Deviation) ] | |
Mean (Standard Deviation) [years] |
41
(14.9)
|
Sex: Female, Male (Count of Participants) | |
Female |
14
93.3%
|
Male |
1
6.7%
|
Region of Enrollment (participants) [Number] | |
United States |
15
100%
|
Outcome Measures
Title | The Participant's Assessment of Discomfort at the Infusion Site on a Visual Analog Scale (VAS) |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
15 subjects were randomized and completed stage 1 |
Arm/Group Title | NS Infusion Group | LR Infusion Group |
---|---|---|
Arm/Group Description | Normal Saline (NS) and Hylenex recombinant human hyaluronidase: 150 Units in 1mL | Lactated Ringer's (LR) and Hylenex recombinant human hyaluronidase: 150 Units in 1mL |
Measure Participants | 15 | 15 |
Mean (Standard Deviation) [mm] |
20.0
(19.4)
|
9.4
(18.3)
|
Title | Number of Participants Assessed for Safety Measures |
---|---|
Description | 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) |
Outcome Measure Data
Analysis Population Description |
---|
15 participants were randomized and completed stage 1 |
Arm/Group Title | NS, LR |
---|---|
Arm/Group Description | 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. |
Measure Participants | 15 |
Number [participants] |
15
100%
|
Title | Average Infusion Flow Rate (Milliliters Per Hour [mL/hr]) Derived From the Time to Infuse up to 500 mL of Solution |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
15 participants were randomized and completed stage 1 |
Arm/Group Title | NS Infusion Group | LR Infusion Group |
---|---|---|
Arm/Group Description | Normal Saline (NS) and Hylenex recombinant human hyaluronidase: 150 Units in 1mL | Lactated Ringer's (LR) and Hylenex recombinant human hyaluronidase: 150 Units in 1mL |
Measure Participants | 15 | 15 |
Mean (Standard Deviation) [mL/hr] |
384.1
(118.1)
|
395.8
(132.8)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | NS Infusion Group, LR Infusion Group |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.93 |
Comments | ||
Method | Wilcoxon signed rank test | |
Comments |
Title | Percent Change From Baseline Thigh Circumference to Maximum Post-Baseline Thigh Circumference at Infusion Sites |
---|---|
Description | 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) |
Outcome Measure Data
Analysis Population Description |
---|
15 participants were randomized and completed stage 1 |
Arm/Group Title | NS Infusion Group | LR Infusion Group |
---|---|---|
Arm/Group Description | Normal Saline (NS) and Hylenex recombinant human hyaluronidase: 150 Units in 1mL | Lactated Ringer's (LR) and Hylenex recombinant human hyaluronidase: 150 Units in 1mL |
Measure Participants | 15 | 15 |
Mean (Standard Deviation) [percent change] |
5.2
(1.6)
|
5.3
(1.5)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | NS Infusion Group, LR Infusion Group |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.67 |
Comments | ||
Method | Wilcoxon signed rank test | |
Comments |
Title | Time From the Beginning of Infusion Until the Thigh Circumference Returns to Within 5% of Baseline Circumference |
---|---|
Description | 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) |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | NS Infusion Group | LR Infusion Group |
---|---|---|
Arm/Group Description | Normal Saline (NS) and Hylenex recombinant human hyaluronidase: 150 Units in 1mL | Lactated Ringer's (LR) and Hylenex recombinant human hyaluronidase: 150 Units in 1mL |
Measure Participants | 4 | 4 |
Mean (Standard Deviation) [minutes] |
147.3
(35.6)
|
123.5
(9.7)
|
Title | Number of Participant's With the Indicated Global Preference for Infusion (Left Versus Right Thigh) |
---|---|
Description | 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) |
Outcome Measure Data
Analysis Population Description |
---|
15 participants were randomized and completed stage 1 |
Arm/Group Title | NS Infusion Group | LR Infusion Group |
---|---|---|
Arm/Group Description | Normal Saline (NS) and Hylenex recombinant human hyaluronidase: 150 Units in 1mL | Lactated Ringer's (LR) and Hylenex recombinant human hyaluronidase: 150 Units in 1mL |
Measure Participants | 15 | 15 |
Count of Participants [Participants] |
0
0%
|
15
NaN
|
Adverse Events
Time Frame | ||
---|---|---|
Adverse Event Reporting Description | ||
Arm/Group Title | NS, LR | |
Arm/Group Description | 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. | |
All Cause Mortality |
||
NS, LR | ||
Affected / at Risk (%) | # Events | |
Total | / (NaN) | |
Serious Adverse Events |
||
NS, LR | ||
Affected / at Risk (%) | # Events | |
Total | 0/15 (0%) | |
Other (Not Including Serious) Adverse Events |
||
NS, LR | ||
Affected / at Risk (%) | # Events | |
Total | 15/15 (100%) | |
General disorders | ||
Injection site pain | 11/15 (73.3%) | 16 |
Injection site erythema | 7/15 (46.7%) | 9 |
Injection site irritation | 4/15 (26.7%) | 7 |
Injection site pruritus | 2/15 (13.3%) | 3 |
Injection site bruising | 1/15 (6.7%) | 1 |
Oedema peripheral | 1/15 (6.7%) | 1 |
Pain | 1/15 (6.7%) | 1 |
Infections and infestations | ||
Bronchitis | 1/15 (6.7%) | 1 |
Nasopharyngitis | 1/15 (6.7%) | 1 |
Tooth infection | 1/15 (6.7%) | 1 |
Nervous system disorders | ||
Headache | 2/15 (13.3%) | 2 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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.
Results Point of Contact
Name/Title | Dimitrios Chondros, M.D., Chief Medical Officer |
---|---|
Organization | Halozyme Therapeutics |
Phone | 858-794-8889 |
dchondros@halozyme.com |
- HZ2-07-03