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Trial record 81 of 447 for:    subcutaneous | "Diabetes Mellitus, Insulin-Dependent"

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

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ClinicalTrials.gov Identifier: NCT01526733
Recruitment Status : Completed
First Posted : February 6, 2012
Results First Posted : September 29, 2014
Last Update Posted : February 26, 2019
Sponsor:
Information provided by (Responsible Party):
Halozyme Therapeutics

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Type 1 Diabetes Mellitus
Interventions Drug: Sham Injection
Drug: Recombinant human hyaluronidase PH20
Drug: Insulin aspart
Drug: Insulin lispro
Enrollment 25
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Insulin-rHuPH20, Then Insulin-sham Insulin-sham, Then Insulin-rHuPH20
Hide Arm/Group Description

In Phase I, 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. 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 milliliter (mL) (150 U) injection of recombinant human hyaluronidase PH20 (rHuPH20).

In Phase II, participants received 0.15 U/kg insulin (either insulin aspart or insulin lispro) as a CSII for 16 days, with a 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.

Phase I and II were separated by a washout period of 5 to 21 days.

In Phase I, participants received 0.15 U/kg insulin (either insulin aspart or insulin lispro) as a CSII for 16 days, with a sham injection 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.

In Phase II, 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 rHuPH20.

Phase I and Phase II were separated by a washout period of 5 to 21 days.

Period Title: Phase 1
Started 12 13 [1]
Received at Least 1 Dose of Study Drug 12 13
Completed 10 12
Not Completed 2 1
Reason Not Completed
Protocol Violation             1             0
Withdrawal by Subject             1             1
[1]
One participant discontinued after receiving insulin-sham and before receiving insulin-rHuPH20.
Period Title: Washout Period of 5 to 21 Days
Started 10 12
Completed 10 12
Not Completed 0 0
Period Title: Phase 2
Started 10 12
Completed 10 12
Not Completed 0 0
Arm/Group Title All Enrolled Participants
Hide Arm/Group Description All participants enrolled in the study.
Overall Number of Baseline Participants 25
Hide Baseline Analysis Population Description
All enrolled participants.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 25 participants
31.6  (9.13)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 25 participants
Female
14
  56.0%
Male
11
  44.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 25 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
2
   8.0%
Black or African American
0
   0.0%
White
23
  92.0%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 25 participants
Hispanic or Latino
2
   8.0%
Not Hispanic or Latino
23
  92.0%
Unknown or Not Reported
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 25 participants
25
1.Primary Outcome
Title Early Insulin Exposure (%AUC[0-60])
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who completed both phases of the study and with evaluable %AUC(0-60) data.
Arm/Group Title Insulin (Aspart or Lispro)-rHuPH20 Insulin (Aspart or Lispro)-Sham
Hide Arm/Group Description:

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 rHuPH20.

Each Phase was separated by a washout period of 5 to 21 days.

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, 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.

Overall Number of Participants Analyzed 21 21
Mean (Standard Deviation)
Unit of Measure: percentage of AUC(0-60)
Day 1 33.53  (11.81) 17.85  (8.24)
Day 4 39.45  (9.72) 33.52  (10.78)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Insulin (Aspart or Lispro)-rHuPH20, Insulin (Aspart or Lispro)-Sham
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Comparison of Day 1 Insulin (Aspart or Lispro)-rHuPH20 versus Day 1 Insulin-sham.
Method Mixed Models Analysis
Comments A mixed model with fixed effects for treatment, day, and interaction of treatment with day was performed using a compound symmetric covariance matrix.
Method of Estimation Estimation Parameter Geometric Least Squares Mean Ratio
Estimated Value 2.15
Confidence Interval (2-Sided) 90%
1.71 to 2.71
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Insulin (Aspart or Lispro)-rHuPH20, Insulin (Aspart or Lispro)-Sham
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Comparison of Day 4 Insulin (Aspart or Lispro)-rHuPH20 versus Day 1 Insulin-sham.
Method Mixed Models Analysis
Comments A mixed model with fixed effects for treatment, day, and interaction of treatment with day was performed using a compound symmetric covariance matrix.
Method of Estimation Estimation Parameter Geometric Least Squares Mean Ratio
Estimated Value 2.62
Confidence Interval (2-Sided) 90%
2.08 to 3.29
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Maximum Glucose Infusion Rate (GIRmax)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who completed both phases of the study and with evaluable GIRmax data.
Arm/Group Title Insulin (Aspart or Lispro)-rHuPH20 Insulin (Aspart or Lispro)-Sham
Hide Arm/Group Description:

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 rHuPH20.

Each Phase was separated by a washout period of 5 to 21 days.

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, 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.

Overall Number of Participants Analyzed 21 21
Mean (Standard Deviation)
Unit of Measure: milligrams/kilogram/minute
Day 1 13.47  (5.46) 11.14  (4.21)
Day 4 10.75  (3.73) 11.83  (3.26)
3.Secondary Outcome
Title Time to First Occurrence of Maximum Glucose Infusion Rate (tGIRmax)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who completed both phases of the study and with evaluable tGIRmax data.
Arm/Group Title Insulin (Aspart or Lispro)-rHuPH20 Insulin (Aspart or Lispro)-Sham
Hide Arm/Group Description:

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 rHuPH20.

Each Phase was separated by a washout period of 5 to 21 days.

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, 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.

Overall Number of Participants Analyzed 21 21
Mean (Standard Deviation)
Unit of Measure: minutes
Day 1 78.95  (37.16) 132.62  (55.07)
Day 4 81.86  (45.99) 97.38  (47.31)
4.Secondary Outcome
Title Time to 50% Maximum Glucose Infusion Rate (tGIR50%Max)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who completed both phases of the study and with evaluable early and late tGIR50%max data.
Arm/Group Title Insulin (Aspart or Lispro)-rHuPH20 Insulin (Aspart or Lispro)-Sham
Hide Arm/Group Description:

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 rHuPH20.

Each Phase was separated by a washout period of 5 to 21 days.

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, 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.

Overall Number of Participants Analyzed 21 21
Mean (Standard Deviation)
Unit of Measure: minutes
Early tGIR50%, Day 1 40.33  (20.13) 54.67  (33.97)
Late tGIR50%, Day 1 114.52  (54.33) 152.14  (61.00)
Early tGIR50%, Day 4 32.57  (14.50) 39.67  (15.51)
Late tGIR50%, Day 4 113.24  (48.72) 126.71  (50.37)
5.Secondary Outcome
Title Time to 50% Total Glucose Infused (50%Gtot)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who completed both phases of the study and with evaluable 50%Gtot data.
Arm/Group Title Insulin (Aspart or Lispro)-rHuPH20 Insulin (Aspart or Lispro)-Sham
Hide Arm/Group Description:

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) rHuPH20.

Each Phase was separated by a washout period of 5 to 21 days.

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, 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.

Overall Number of Participants Analyzed 21 21
Mean (Standard Deviation)
Unit of Measure: minutes
Day 1 40.33  (20.13) 32.57  (14.50)
Day 4 54.67  (54.67) 39.67  (15.51)
6.Secondary Outcome
Title Area Under the Glucose Concentration Curve (AUC[0-360])
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who completed both phases of the study and with evaluable AUC(0-360) data.
Arm/Group Title Insulin (Aspart or Lispro)-rHuPH20 Insulin (Aspart or Lispro)-Sham
Hide Arm/Group Description:

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 rHuPH20.

Each Phase was separated by a washout period of 5 to 21 days.

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, 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.

Overall Number of Participants Analyzed 21 21
Mean (Standard Deviation)
Unit of Measure: picomoles*minutes/liter
Day 1 1312.41  (627.33) 1199.54  (535.80)
Day 4 1063.77  (500.06) 1139.65  (414.94)
7.Secondary Outcome
Title Duration of Insulin Action (AUMC[0-360]/AUC[0-360])
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who completed both phases of the study and with evaluable AUMC(0-360)/AUC(0-360) data.
Arm/Group Title Insulin (Aspart or Lispro)-rHuPH20 Insulin (Aspart or Lispro)-Sham
Hide Arm/Group Description:

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 rHuPH20.

Each Phase was separated by a washout period of 5 to 21 days.

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, 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.

Overall Number of Participants Analyzed 21 21
Mean (Standard Deviation)
Unit of Measure: ratio
Day 1 119.02  (21.18) 154.03  (27.58)
Day 4 111.25  (20.59) 120.57  (20.85)
Time Frame [Not Specified]
Adverse Event Reporting Description Insulin was not considered a study drug for safety assessments and causality assessments were done for rHuPH20 only.
 
Arm/Group Title Insulin (Aspart or Lispro)-rHuPH20 Insulin (Aspart or Lispro)-Sham
Hide Arm/Group Description

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 rHuPH20.

Each Phase was separated by a washout period of 5 to 21 days.

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, 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.

All-Cause Mortality
Insulin (Aspart or Lispro)-rHuPH20 Insulin (Aspart or Lispro)-Sham
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Insulin (Aspart or Lispro)-rHuPH20 Insulin (Aspart or Lispro)-Sham
Affected / at Risk (%) Affected / at Risk (%)
Total   0/24 (0.00%)   0/23 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Insulin (Aspart or Lispro)-rHuPH20 Insulin (Aspart or Lispro)-Sham
Affected / at Risk (%) Affected / at Risk (%)
Total   13/24 (54.17%)   9/23 (39.13%) 
Blood and lymphatic system disorders     
Anaemia  1  2/24 (8.33%)  4/23 (17.39%) 
Gastrointestinal disorders     
Nausea  1  2/24 (8.33%)  1/23 (4.35%) 
Vomiting  1  2/24 (8.33%)  0/23 (0.00%) 
Constipation  1  1/24 (4.17%)  0/23 (0.00%) 
General disorders     
Injection site pain  1  3/24 (12.50%)  1/23 (4.35%) 
Injection site pruritus  1  1/24 (4.17%)  2/23 (8.70%) 
Injection site haemorrhage  1  1/24 (4.17%)  0/23 (0.00%) 
Injection site haematoma  1  1/24 (4.17%)  0/23 (0.00%) 
Injection site induration  1  1/24 (4.17%)  0/23 (0.00%) 
Injection site inflammation  1  0/24 (0.00%)  1/23 (4.35%) 
Tenderness  1  0/24 (0.00%)  1/23 (4.35%) 
Infections and infestations     
Upper respiratory tract infection  1  1/24 (4.17%)  1/23 (4.35%) 
Injury, poisoning and procedural complications     
Clavicle fracture  1  0/24 (0.00%)  1/23 (4.35%) 
Sunburn  1  1/24 (4.17%)  0/23 (0.00%) 
Musculoskeletal and connective tissue disorders     
Neck pain  1  0/24 (0.00%)  1/23 (4.35%) 
Nervous system disorders     
Headache  1  2/24 (8.33%)  3/23 (13.04%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  1/24 (4.17%)  0/23 (0.00%) 
Dysphonia  1  1/24 (4.17%)  0/23 (0.00%) 
Oropharyngeal pain  1  1/24 (4.17%)  0/23 (0.00%) 
Skin and subcutaneous tissue disorders     
Ecchymosis  1  1/24 (4.17%)  0/23 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (12.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
All information obtained as a result of this study or during the conduct of this study will be regarded as confidential. 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: Vice President, Endocrinology Clinical Development
Organization: Halozyme Therapeutics, Inc
Phone: 858-794-8889
Responsible Party: Halozyme Therapeutics
ClinicalTrials.gov Identifier: NCT01526733     History of Changes
Other Study ID Numbers: Halo-117-401
First Submitted: January 31, 2012
First Posted: February 6, 2012
Results First Submitted: September 23, 2014
Results First Posted: September 29, 2014
Last Update Posted: February 26, 2019