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CompletedNCT01526733Updated Feb 26, 2019Results posted

Randomized, Double Blind, 2 Way Crossover Study of CSII With, Versus Without, Pretreatment With Human Hyaluronidase

A Phase 4 interventional study of Sham Injection and Recombinant human hyaluronidase PH20 in Type 1 Diabetes Mellitus, sponsored by Halozyme Therapeutics. Completed at 1 site in United States. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2019-02-26.

Sponsored by Halozyme Therapeutics · Phase 4, Interventional, and Treatment

Phase
Phase 4
Study type
Interventional
Enrollment
25
Allocation
Randomized
Ages
18 Years to 65 Years
Sex
All
01

Study summary

The purpose of this study is to evaluate consistency of accelerated insulin absorption and onset-of-action and shortened duration of action for bolus insulin infusions after pretreatment with 150 units (U) of Hylenex® (recombinant human hyaluronidase PH20 [rHuPH20]) injection at the time of infusion set insertion compared to sham injection.

02

Conditions studied

  • Type 1 Diabetes Mellitus

Keywords

  • Type 1 Diabetes
  • Continuous Subcutaneous Insulin Infusion (CSII)
03

In context

Diabetes Mellitus, Type 1

3,522 studies on the registry are indexed under Diabetes Mellitus, Type 1; 576 are open to participants now.

This study's enrollment of 25 is below the median of 40 across 2,648 interventional studies indexed under Diabetes Mellitus, Type 1.

Browse Diabetes Mellitus, Type 1 studies →

Lead sponsor

Halozyme Therapeutics is the lead sponsor of 33 studies on the registry; 1 is open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 65 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. Males or females of age 18 to 65 years, inclusive. Females of child-bearing potential must use a standard and effective means of birth control for the duration of the study.
  2. Non-smoking participants with Type 1 diabetes mellitus (T1DM) treated with insulin for ≥12 months. Nonsmoking means abstinence from cigarettes and cigars for 3 months and negative cotinine screening tests at screening.
  3. Body mass index (BMI) 18.0 to 35.0 kilograms per meter squared (kg/m²), inclusive.
  4. Glycosylated hemoglobin A1c (HbA1c) ≤10% based on local laboratory results.
  5. Fasting connecting peptide of insulin (C-peptide) \<0.6 nanograms per milliliter (ng/mL).
  6. Current treatment with insulin \<90 units per day (U/d).
  7. Current use of rapid acting insulin analog.
  8. Routine use of CSII as the primary route of insulin administration for at least 3 months prior to screening
  9. Participants should be in good general health based on medical history and physical examination without medical conditions that might prevent the completion of study drug infusions and assessments required in the study protocol.

Exclusion criteria

Exclusion Criteria:

  1. Known or suspected allergy to any component of any of the study drugs in this study.
  2. Previous enrollment in this study.
  3. Use of drugs that may interfere with the interpretation of study results or are known to cause clinically relevant interference with insulin action, glucose utilization, or recovery from hypoglycemia. Participants taking maintenance doses of blood thinners (for example, coumadin or heparin) will be excluded.
  4. Use of any long-acting insulin injection within 72 hours of Study Day 1; participants will continue to refrain from use throughout the duration of the study (Phases I and II).
  5. Recurrent major hypoglycemia or hypoglycemic unawareness, as judged by the Investigator.
  6. Current addiction to alcohol or substances of abuse as determined by the Investigator.
  7. Blood donation or phlebotomy (>500 milliliters [mL]) within the previous 8 weeks of the Screening Visit(s) in this study.
  8. Pregnancy, breastfeeding, the intention of becoming pregnant, or not using adequate contraceptive measures (adequate contraceptive measures consist of sterilization, intra-uterine device [IUD], oral or injectable contraceptives, or barrier methods).
  9. Symptomatic gastroparesis.
  10. Receipt of any investigational drug within 4 weeks of Study Day 1.
05

Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Crossover assignment
Masking
Triple (Participant, Care provider, Investigator)
Enrollment
25 participants (actual)

Study arms

  • Sham comparator
    Insulin (Aspart or Lispro)-Sham

    In Phase I or Phase II of the study, participants received 0.15 units per kilogram (U/kg) insulin (either insulin aspart or insulin lispro) as a continuous subcutaneous insulin infusion (CSII) for 16 days, with sham injections administered prior to outpatient euglycemic clamps on Days 1 and 4 and prior to outpatient meal test procedures on Days 7, 10, 13, and 16. Each Phase was separated by a washout period of 5 to 21 days.

    Drug: Sham Injection · Drug: Insulin aspart · Drug: Insulin lispro

  • Experimental
    Insulin (Aspart or Lispro)-rHuPH20

    In Phase I or Phase II of the study, participants received 0.15 U/kg insulin (either insulin aspart or insulin lispro) as a CSII for 16 days. Prior to outpatient euglycemic clamps on Days 1 and 4 and prior to outpatient meal test procedures on Days 7, 10, 13, and 16, participants received a 1 mL (150 U) injection of recombinant human hyaluronidase (rHuPH20). Each Phase was separated by a washout period of 5 to 21 days.

    Drug: Recombinant human hyaluronidase PH20 · Drug: Insulin aspart · Drug: Insulin lispro

Interventions

  • DrugSham Injection
  • DrugRecombinant human hyaluronidase PH20

    Also known as: rHuPH20, PH20, Hylenex

  • DrugInsulin aspart

    Also known as: Novolog, Aspart

  • DrugInsulin lispro

    Also known as: Humalog, Lispro

06

What researchers measure

Primary outcomes

  1. Early Insulin Exposure (%AUC[0-60])

    Early insulin exposure, defined as the percentage of total insulin exposure (area under the insulin concentration curve \[AUC{0 360}\]) that occurs within the first hour following bolus dose of insulin during the 2 euglycemic clamps is presented. Blood samples were collected 10 minutes predose and at 0, 5, 10, 15, 20, 30, 45, and 60 minutes postdose during a euglycemic clamp.

    Time frame: 10 minutes predose; 0, 5, 10, 15, 20, 30, 45, and 60 minutes postdose on Days 1 and 4

Secondary outcomes

  1. Maximum Glucose Infusion Rate (GIRmax)

    Blood samples were collected at 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose during a euglycemic clamp.

    Time frame: 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose on Days 1 and 4

  2. Time to First Occurrence of Maximum Glucose Infusion Rate (tGIRmax)

    Blood samples were collected at 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose during a euglycemic clamp.

    Time frame: 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose on Days 1 and 4

  3. Time to 50% Maximum Glucose Infusion Rate (tGIR50%Max)

    Early and late tGIR50%max are presented. Blood samples were collected at 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose during a euglycemic clamp.

    Time frame: 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose on Days 1 and 4

  4. Time to 50% Total Glucose Infused (50%Gtot)

    Blood samples were collected at 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose during a euglycemic clamp.

    Time frame: 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose on Days 1 and 4

  5. Area Under the Glucose Concentration Curve (AUC[0-360])

    Area under the glucose concentration curve from 0 to 360 minutes (AUC\[0-360\]) is presented. Blood samples were collected 30 and 10 minutes prior to insulin bolus and at 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose during a euglycemic clamp.

    Time frame: 30 minutes and 10 minutes predose; 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose on Days 1 and 4

  6. Duration of Insulin Action (AUMC[0-360]/AUC[0-360])

    Duration of insulin action was calculated by dividing the area under the first moment curve (AUMC\[0-360\]) by the area under the concentration versus time curve (AUC\[0-360\]). AUCM is the total area under the first moment curve. First moment curve is obtained by plotting concentration-time versus time. It can be used to measure how long a drug stays in the body. Blood samples were collected 10 minutes predose and at 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose during a euglycemic clamp.

    Time frame: 10 minutes predose; 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose on Days 1 and 4

07

Results

Posted Sep 29, 2014

Participant flow

Phase 1
Participant flow — Phase 1
MilestoneInsulin-rHuPH20, Then Insulin-shamInsulin-sham, Then Insulin-rHuPH20
Started1213
Received at least 1 dose of study drug1213
Completed1012
Not completed21
Withdrew: Protocol violation10
Withdrew: Withdrawal by subject11
Washout Period of 5 to 21 Days
Participant flow — Washout Period of 5 to 21 Days
MilestoneInsulin-rHuPH20, Then Insulin-shamInsulin-sham, Then Insulin-rHuPH20
Started1012
Completed1012
Not completed00
Phase 2
Participant flow — Phase 2
MilestoneInsulin-rHuPH20, Then Insulin-shamInsulin-sham, Then Insulin-rHuPH20
Started1012
Completed1012
Not completed00

Outcome measures

PrimaryEarly Insulin Exposure (%AUC[0-60])

Early insulin exposure, defined as the percentage of total insulin exposure (area under the insulin concentration curve \[AUC{0 360}\]) that occurs within the first hour following bolus dose of insulin during the 2 euglycemic clamps is presented. Blood samples were collected 10 minutes predose and at 0, 5, 10, 15, 20, 30, 45, and 60 minutes postdose during a euglycemic clamp.

Time frame:
10 minutes predose; 0, 5, 10, 15, 20, 30, 45, and 60 minutes postdose on Days 1 and 4
Reported as:
Mean · percentage of AUC(0-60)
Early Insulin Exposure (%AUC[0-60])
percentage of AUC(0-60)Insulin (Aspart or Lispro)-rHuPH20Insulin (Aspart or Lispro)-Sham
Day 133.53 ± 11.8117.85 ± 8.24
Day 439.45 ± 9.7233.52 ± 10.78
Statistical analysis
  • Insulin (Aspart or Lispro)-rHuPH20 vs Insulin (Aspart or Lispro)-Sham · Mixed Models Analysis · p = <0.0001 (Comparison of Day 1 Insulin (Aspart or Lispro)-rHuPH20 versus Day 1 Insulin-sham.) · Geometric least squares mean ratio: 2.15 · 90% CI 1.71 to 2.71A mixed model with fixed effects for treatment, day, and interaction of treatment with day was performed using a compound symmetric covariance matrix.
  • Insulin (Aspart or Lispro)-rHuPH20 vs Insulin (Aspart or Lispro)-Sham · Mixed Models Analysis · p = <0.0001 (Comparison of Day 4 Insulin (Aspart or Lispro)-rHuPH20 versus Day 1 Insulin-sham.) · Geometric least squares mean ratio: 2.62 · 90% CI 2.08 to 3.29A mixed model with fixed effects for treatment, day, and interaction of treatment with day was performed using a compound symmetric covariance matrix.
SecondaryMaximum Glucose Infusion Rate (GIRmax)

Blood samples were collected at 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose during a euglycemic clamp.

Time frame:
0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose on Days 1 and 4
Reported as:
Mean · milligrams/kilogram/minute
Maximum Glucose Infusion Rate (GIRmax)
milligrams/kilogram/minuteInsulin (Aspart or Lispro)-rHuPH20Insulin (Aspart or Lispro)-Sham
Day 113.47 ± 5.4611.14 ± 4.21
Day 410.75 ± 3.7311.83 ± 3.26
SecondaryTime to First Occurrence of Maximum Glucose Infusion Rate (tGIRmax)

Blood samples were collected at 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose during a euglycemic clamp.

Time frame:
0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose on Days 1 and 4
Reported as:
Mean · minutes
Time to First Occurrence of Maximum Glucose Infusion Rate (tGIRmax)
minutesInsulin (Aspart or Lispro)-rHuPH20Insulin (Aspart or Lispro)-Sham
Day 178.95 ± 37.16132.62 ± 55.07
Day 481.86 ± 45.9997.38 ± 47.31
SecondaryTime to 50% Maximum Glucose Infusion Rate (tGIR50%Max)

Early and late tGIR50%max are presented. Blood samples were collected at 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose during a euglycemic clamp.

Time frame:
0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose on Days 1 and 4
Reported as:
Mean · minutes
Time to 50% Maximum Glucose Infusion Rate (tGIR50%Max)
minutesInsulin (Aspart or Lispro)-rHuPH20Insulin (Aspart or Lispro)-Sham
Early tGIR50%, Day 140.33 ± 20.1354.67 ± 33.97
Late tGIR50%, Day 1114.52 ± 54.33152.14 ± 61.00
Early tGIR50%, Day 432.57 ± 14.5039.67 ± 15.51
Late tGIR50%, Day 4113.24 ± 48.72126.71 ± 50.37
SecondaryTime to 50% Total Glucose Infused (50%Gtot)

Blood samples were collected at 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose during a euglycemic clamp.

Time frame:
0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose on Days 1 and 4
Reported as:
Mean · minutes
Time to 50% Total Glucose Infused (50%Gtot)
minutesInsulin (Aspart or Lispro)-rHuPH20Insulin (Aspart or Lispro)-Sham
Day 140.33 ± 20.1332.57 ± 14.50
Day 454.67 ± 54.6739.67 ± 15.51
SecondaryArea Under the Glucose Concentration Curve (AUC[0-360])

Area under the glucose concentration curve from 0 to 360 minutes (AUC\[0-360\]) is presented. Blood samples were collected 30 and 10 minutes prior to insulin bolus and at 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose during a euglycemic clamp.

Time frame:
30 minutes and 10 minutes predose; 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose on Days 1 and 4
Reported as:
Mean · picomoles*minutes/liter
Area Under the Glucose Concentration Curve (AUC[0-360])
picomoles*minutes/literInsulin (Aspart or Lispro)-rHuPH20Insulin (Aspart or Lispro)-Sham
Day 11312.41 ± 627.331199.54 ± 535.80
Day 41063.77 ± 500.061139.65 ± 414.94
SecondaryDuration of Insulin Action (AUMC[0-360]/AUC[0-360])

Duration of insulin action was calculated by dividing the area under the first moment curve (AUMC\[0-360\]) by the area under the concentration versus time curve (AUC\[0-360\]). AUCM is the total area under the first moment curve. First moment curve is obtained by plotting concentration-time versus time. It can be used to measure how long a drug stays in the body. Blood samples were collected 10 minutes predose and at 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose during a euglycemic clamp.

Time frame:
10 minutes predose; 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose on Days 1 and 4
Reported as:
Mean · ratio
Duration of Insulin Action (AUMC[0-360]/AUC[0-360])
ratioInsulin (Aspart or Lispro)-rHuPH20Insulin (Aspart or Lispro)-Sham
Day 1119.02 ± 21.18154.03 ± 27.58
Day 4111.25 ± 20.59120.57 ± 20.85

Adverse events

Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Insulin (Aspart or Lispro)-rHuPH20—0/24 (0%)13/24 (54.2%)
Insulin (Aspart or Lispro)-Sham—0/23 (0%)9/23 (39.1%)
Most frequent other events
Showing 10 of 20
Most frequent other events
EventInsulin (Aspart or Lispro)-rHuPH20Insulin (Aspart or Lispro)-Sham
AnaemiaBlood and lymphatic system disorders2/244/23
HeadacheNervous system disorders2/243/23
Injection site painGeneral disorders3/241/23
Injection site pruritusGeneral disorders1/242/23
NauseaGastrointestinal disorders2/241/23
VomitingGastrointestinal disorders2/240/23
Injection site inflammationGeneral disorders0/241/23
TendernessGeneral disorders0/241/23
Upper respiratory tract infectionInfections and infestations1/241/23
Clavicle fractureInjury, poisoning and procedural complications0/241/23

Baseline characteristics

All enrolled participants.

Age, Continuous
Age, Continuous(years)All Enrolled Participants
Mean31.6 ± 9.13
Sex: Female, Male
Sex: Female, Male(Participants)All Enrolled Participants
Female14
Male11
Race (NIH/OMB)
Race (NIH/OMB)(Participants)All Enrolled Participants
American Indian or Alaska Native0
Asian0
Native Hawaiian or Other Pacific Islander2
Black or African American0
White23
More than one race0
Unknown or Not Reported0
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)All Enrolled Participants
Hispanic or Latino2
Not Hispanic or Latino23
Unknown or Not Reported0
Region of Enrollment
Region of Enrollment(participants)All Enrolled Participants
United States25
08

Study locations

1 site
  • Profil Institute for Clinical Research
    Chula Vista, California 91911, United States
09

References and documents

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Feb 26, 2019, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT01526733
Lead sponsor
Halozyme Therapeutics
Responsible party
Sponsor
First posted
Feb 6, 2012
Start date
Dec 2011
Primary completion
Aug 2012
Completion
Sep 2013
Results posted
Sep 29, 2014
Last update
Feb 26, 2019

Study contacts

Linda Morrow, MD
principal investigator · Profil Institute for Clinical Research, Inc.

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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