INFUSE-NSLR: Study of Subcutaneous Hydration Enabled by Human Recombinant Hyaluronidase (Hylenex)

Sponsor
Halozyme Therapeutics (Industry)
Overall Status
Completed
CT.gov ID
NCT00656370
Collaborator
Baxter Healthcare Corporation (Industry)
15
1
2
2
7.6

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
  • Drug: recombinant human hyaluronidase
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

Study Type:
Interventional
Actual Enrollment :
15 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
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
Study Start Date :
Dec 1, 2007
Actual Primary Completion Date :
Jan 30, 2008
Actual Study Completion Date :
Jan 30, 2008

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:
  • Hylenex
  • Experimental: LR Infusion Group

    Lactated Ringer's (LR) and Hylenex

    Drug: recombinant human hyaluronidase
    150 Units in 1mL
    Other Names:
  • Hylenex
  • Outcome Measures

    Primary Outcome Measures

    1. 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

    1. 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).

    2. 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.

    3. 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.

    4. 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.

    5. 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

    Ages Eligible for Study:
    18 Years to 60 Years
    Sexes Eligible for Study:
    All
    Accepts 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.

    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.
    Responsible Party:
    Halozyme Therapeutics
    ClinicalTrials.gov Identifier:
    NCT00656370
    Other Study ID Numbers:
    • HZ2-07-03
    First Posted:
    Apr 11, 2008
    Last Update Posted:
    Oct 17, 2018
    Last Verified:
    Sep 1, 2018

    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

    1. Primary Outcome
    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)
    2. Secondary Outcome
    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%
    3. Secondary Outcome
    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
    4. Secondary Outcome
    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
    5. Secondary Outcome
    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)
    6. Secondary Outcome
    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

    [Not Specified]

    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
    Email dchondros@halozyme.com
    Responsible Party:
    Halozyme Therapeutics
    ClinicalTrials.gov Identifier:
    NCT00656370
    Other Study ID Numbers:
    • HZ2-07-03
    First Posted:
    Apr 11, 2008
    Last Update Posted:
    Oct 17, 2018
    Last Verified:
    Sep 1, 2018