Randomized, Double-blind, Crossover, Pharmacokinetic (PK) and Glucodynamic (GD) Study of Continuous Subcutaneous Insulin Infusion (CSII) in Participants With Type 1 Diabetes Mellitus (T1DM)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Halozyme Therapeutics
ClinicalTrials.gov Identifier:
NCT01275131
First received: January 10, 2011
Last updated: June 26, 2014
Last verified: June 2014
Results First Received: June 26, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Pharmacokinetics/Dynamics Study;   Intervention Model: Crossover Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator);   Primary Purpose: Basic Science
Condition: Type 1 Diabetes Mellitus
Interventions: Drug: Insulin aspart
Drug: Recombinant human hyaluronidase PH20 (rHuPH20)

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Stage 1: Insulin Aspart First, Then Insulin Aspart-rHuPH20

Participants first received 0.15 units per kilogram (U/kg) insulin aspart administered as a continuous subcutaneous insulin infusion (CSII), for 4 days (Days 1-4; Period 1), including during a 6-hour (hr) euglycemic clamp on Days 2 and 4.

After a 5- to 14-day washout period, participants received 0.15 U/kg insulin aspart and 5-micrograms per milliliter (μg/mL) recombinant human hyaluronidase PH20 (rHuPH20) (insulin aspart-rHuPH20) coadministered as a CSII, for 4 days (Days 5-8; Period 2), including during a 6-hr euglycemic clamp on Days 6 and 8.

Stage 1: Insulin Aspart-rHuPH20 First, Then Insulin Aspart

Participants first received 0.15 units per kilogram (U/kg) insulin aspart and 5 micrograms per milliliter (μg/mL) recombinant human hyaluronidase PH20 (rHuPH20) (insulin aspart-rHuPH20) coadministered as a continuous subcutaneous insulin infusion (CSII), for 4 days (Days 1-4; Period 1), including during a 6-hour (hr) euglycemic clamp on Days 2 and 4.

After a 5- to 14-day washout period, participants received 0.15 U/kg insulin aspart alone as a CSII, for 4 days (Days 5-8; Period 2), including during a 6-hr euglycemic clamp on Days 6 and 8.

Stage 3: Insulin Aspart First, Then Insulin Aspart + rHuPH20

Participants first received 0.12 units per kilogram (U/kg) insulin aspart administered as a continuous subcutaneous insulin infusion (CSII), for 5 days (Days 1-5; Period 1), including during a 6-hour (hr) euglycemic clamp on Days 2, 3, and 5. On Day 2 only, a sham injection was administered 2.5 hr prior to the 6-hr euglycemic clamp.

After a 5- to 14-day washout period, participants received 0.12 U/kg insulin aspart administered as a CSII, for 5 days (Days 6-10; Period 2), including during a 6-hr euglycemic clamp on Days 7, 8, and 10. On Day 7 only, a 1.0 milliliter (mL) subcutaneous (SC) injection of 1.25 micrograms per milliliter (μg/mL) recombinant human hyaluronidase PH20 (rHuPH20) was administered 2.5 hr prior to the 6-hr euglycemic clamp.

Stage 3: Insulin Aspart + rHuPH20 First, Then Insulin Aspart

Participants first received 0.12 units per kilogram (U/kg) insulin aspart administered as a continuous subcutaneous insulin infusion (CSII), for 5 days (Days 1-5; Period 1), including during a 6-hour (hr) euglycemic clamp on Days 2, 3, and 5. On Day 2 only, a 1.0 milliliter (mL) subcutaneous (SC) injection of 1.25 micrograms per milliliter (μg/mL) recombinant human hyaluronidase PH20 (rHuPH20) was administered 2.5 hr prior to the 6-hr euglycemic clamp .

After a 5- to 14-day washout period, participants received 0.12 U/kg insulin aspart administered as a CSII, for 5 days (Days 6-10; Period 2), including during a 6-hr euglycemic clamp on Days 7, 8, and 10. On Day 7 only, a sham injection was administered 2.5 hr prior to the 6-hr euglycemic clamp.


Participant Flow for 3 periods

Period 1:   Period 1
    Stage 1: Insulin Aspart First, Then Insulin Aspart-rHuPH20     Stage 1: Insulin Aspart-rHuPH20 First, Then Insulin Aspart     Stage 3: Insulin Aspart First, Then Insulin Aspart + rHuPH20     Stage 3: Insulin Aspart + rHuPH20 First, Then Insulin Aspart  
STARTED     11     9     13     12  
Received at Least One Dose of Study Drug     11     9     13     12  
COMPLETED     9     9     10     10  
NOT COMPLETED     2     0     3     2  
Withdrawal by Subject                 1                 0                 3                 2  
Physician Decision                 1                 0                 0                 0  

Period 2:   5- to 14-Day Washout Period
    Stage 1: Insulin Aspart First, Then Insulin Aspart-rHuPH20     Stage 1: Insulin Aspart-rHuPH20 First, Then Insulin Aspart     Stage 3: Insulin Aspart First, Then Insulin Aspart + rHuPH20     Stage 3: Insulin Aspart + rHuPH20 First, Then Insulin Aspart  
STARTED     9     9     10     10  
COMPLETED     9     9     10     10  
NOT COMPLETED     0     0     0     0  

Period 3:   Period 2 (Crossover)
    Stage 1: Insulin Aspart First, Then Insulin Aspart-rHuPH20     Stage 1: Insulin Aspart-rHuPH20 First, Then Insulin Aspart     Stage 3: Insulin Aspart First, Then Insulin Aspart + rHuPH20     Stage 3: Insulin Aspart + rHuPH20 First, Then Insulin Aspart  
STARTED     9     9     10     10  
COMPLETED     8     8     9     8  
NOT COMPLETED     1     1     1     2  
Adverse Event                 0                 1                 0                 0  
Withdrawal by Subject                 1                 0                 1                 2  



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants who received at least one dose of study drug.

Reporting Groups
  Description
Stage 1: Insulin Aspart First, Then Insulin Aspart-rHuPH20

Participants first received 0.15 units per kilogram (U/kg) insulin aspart, administered as a continuous subcutaneous insulin infusion (CSII), for 4 days (Days 1-4; Period 1), including during a 6-hour (hr) euglycemic clamp on Days 2 and 4.

After a 5- to 14-day washout period, participants received 0.15 U/kg insulin aspart and 5 micrograms per milliliter (μg/mL) recombinant human hyaluronidase PH20 (rHuPH20) (insulin aspart-rHuPH20) coadministered as a CSII, for 4 days (Days 5-8; Period 2), including during a 6-hr euglycemic clamp on Days 6 and 8.

Stage 1: Insulin Aspart-rHuPH20 First, Then Insulin Aspart

Participants first received 0.15 units per kilogram (U/kg) insulin aspart and 5 micrograms per milliliter (μg/mL) recombinant human hyaluronidase PH20 (rHuPH20) (insulin aspart-rHuPH20) coadministered as a continuous subcutaneous insulin infusion (CSII), for 4 days (Days 1-4; Period 1), including during a 6-hour (hr) euglycemic clamp on Days 2 and 4.

After a 5- to 14-day washout period, participants received 0.15 U/kg insulin aspart alone as a CSII, for 4 days (Days 5-8; Period 2), including during a 6-hr euglycemic clamp on Days 6 and 8.

Stage 3: Insulin Aspart First, Then Insulin Aspart + rHuPH20

Participants first received 0.12 units per kilogram (U/kg) insulin aspart administered as a continuous subcutaneous insulin infusion (CSII), for 5 days (Days 1-5; Period 1), including during a 6-hour (hr) euglycemic clamp on Days 2, 3, and 5. On Day 2 only, a sham injection was administered 2.5 hr prior to the 6-hr euglycemic clamp.

After a 5- to 14-day washout period, participants received 0.12 U/kg insulin aspart administered as a CSII for 5 days (Days 6-10; Period 2), including during a 6-hr euglycemic clamp on Days 7, 8, and 10. On Day 7 only, a 1.0-milliliter (mL) subcutaneous (SC) injection of 1.25 micrograms per milliliter (μg/mL) recombinant human hyaluronidase PH20 (rHuPH20) was administered 2.5 hr prior to a 6-hr euglycemic clamp.

Stage 3: Insulin Aspart + rHuPH20 First, Then Insulin Aspart

Participants first received 0.12 units per kilogram (U/kg) insulin aspart administered as a continuous subcutaneous insulin infusion (CSII), for 5 days (Days 1-5; Period 1), including during a 6-hour (hr) euglycemic clamp on Days 2, 3, and 5. On Day 2 only, a 1.0-milliliter (mL) subcutaneous (SC) injection of 1.25 micrograms per milliliter (μg/mL) recombinant human hyaluronidase PH20 (rHuPH20) was administered 2.5 hr prior to the euglycemic clamp .

After a 5- to 14-day washout period, participants received 0.12 U/kg insulin aspart administered as a CSII, for 5 days (Days 6-10; Period 2), including during a 6-hr euglycemic clamp on Days 7, 8, and 10. On Day 7 only, a sham injection was administered 2.5 hr prior to a 6-hr euglycemic clamp.

Total Total of all reporting groups

Baseline Measures
    Stage 1: Insulin Aspart First, Then Insulin Aspart-rHuPH20     Stage 1: Insulin Aspart-rHuPH20 First, Then Insulin Aspart     Stage 3: Insulin Aspart First, Then Insulin Aspart + rHuPH20     Stage 3: Insulin Aspart + rHuPH20 First, Then Insulin Aspart     Total  
Number of Participants  
[units: participants]
  11     9     13     12     45  
Age  
[units: Years]
Mean ± Standard Deviation
  31.3  ± 6.39     44.6  ± 9.00     35.5  ± 9.50     32.3  ± 10.29     35.44  ± 9.95  
Gender  
[units: Participants]
         
Female     6     3     7     6     22  
Male     5     6     6     6     23  
Race (NIH/OMB)  
[units: Participants]
         
American Indian or Alaska Native     0     0     0     0     0  
Asian     0     0     0     0     0  
Native Hawaiian or Other Pacific Islander     0     0     0     0     0  
Black or African American     0     0     1     1     2  
White     11     9     11     11     42  
More than one race     0     0     0     0     0  
Unknown or Not Reported     0     0     1     0     1  
Ethnicity (NIH/OMB)  
[units: Participants]
         
Hispanic or Latino     1     1     0     0     2  
Not Hispanic or Latino     10     8     13     12     43  
Unknown or Not Reported     0     0     0     0     0  
Region of Enrollment  
[units: Participants]
         
United States     11     9     13     12     45  



  Outcome Measures
  Hide All Outcome Measures

1.  Primary:   Early Insulin Exposure (%AUC[0-60]), Stage 1   [ Time Frame: 10 minutes predose up to 60 minutes postdose ]

Measure Type Primary
Measure Title Early Insulin Exposure (%AUC[0-60]), Stage 1
Measure 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, 60, 120, 150, 180, 240, 300, and 360 minutes postdose during the euglycemic clamp.
Time Frame 10 minutes predose up to 60 minutes postdose  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants who completed all study periods within a given stage with evaluable early insulin exposure (%AUC[0-60]) data.

Reporting Groups
  Description
Stage 1: Insulin Aspart Alone Participants received 0.15 units per kilogram (U/kg) insulin aspart, administered as a continuous subcutaneous insulin infusion (CSII), for 4 days (Days 1-4 or 5-8), including during a 6-hour (hr) euglycemic clamp on Days 2 and 4 of Period 1 or Days 6 and 8 of Period 2
Stage 1: Insulin Aspart-rHuPH20 Participants received 0.15 units per kilogram (U/kg) insulin aspart and 5 micrograms per milliliter (μg/mL) recombinant human hyaluronidase PH20 (rHuPH20) (insulin aspart-rHuPH20) coadministered as a continuous subcutaneous insulin infusion (CSII), for 4 days (Days 1-4 or 5-8), including during a 6-hour (hr) euglycemic clamp on Days 2 and 4 of Period 1 or Days 6 and 8 of Period 2

Measured Values
    Stage 1: Insulin Aspart Alone     Stage 1: Insulin Aspart-rHuPH20  
Number of Participants Analyzed  
[units: participants]
  16     16  
Early Insulin Exposure (%AUC[0-60]), Stage 1  
[units: Percentage of AUC(0-360)]
Mean ± Standard Deviation
   
Stage 1, Day 2/6     20.99  ± 6.37     34.94  ± 9.48  
Stage 1, Day 4/8     32.83  ± 14.66     50.97  ± 13.91  


Statistical Analysis 1 for Early Insulin Exposure (%AUC[0-60]), Stage 1
Groups [1] All groups
Method [2] Mixed Models Analysis
P Value [3] 0.0009
Least Squares Mean Difference [4] 13.95
90% Confidence Interval ( 7.37 to 20.54 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Comparison at Stage 1, Day 2/6
[2] Other relevant method information, such as adjustments or degrees of freedom:
  A mixed model with fixed effects for treatment, day, and interaction of treatment with day was performed using a compound symmetric covariance matrix.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Early Insulin Exposure (%AUC[0-60]), Stage 1
Groups [1] All groups
Method [2] Mixed Models Analysis
P Value [3] <0.0001
Least Squares Mean Difference [4] 18.14
90% Confidence Interval ( 11.55 to 24.72 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Comparison at Stage 1, Day 4/8
[2] Other relevant method information, such as adjustments or degrees of freedom:
  A mixed model with fixed effects for treatment, day, and interaction of treatment with day was performed using a compound symmetric covariance matrix.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



2.  Primary:   Early Exposure to Insulin (%AUC[0-60]), Stage 3   [ Time Frame: 10 minutes predose up to 60 minutes postdose on Days 2/7, 3/8, and 5/10 ]

Measure Type Primary
Measure Title Early Exposure to Insulin (%AUC[0-60]), Stage 3
Measure 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, 60, 120, 150, 180, 240, 300, and 360 minutes postdose during the euglycemic clamp.
Time Frame 10 minutes predose up to 60 minutes postdose on Days 2/7, 3/8, and 5/10  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants who completed all periods of study within a given stage with evaluable %AUC(0-60) data.

Reporting Groups
  Description
Stage 3: Insulin Aspart Alone Participants received 0.12 units per kilogram (U/kg) insulin aspart administered as a continuous subcutaneous insulin infusion (CSII), for 5 days (Days 1-5 or 6-10), including during a 6-hour (hr) euglycemic clamp on Days 2, 3, and 5 of Period 1, or on Days 7, 8, and 10 of Period 2. On Day 2 or Day 7 only, a sham injection was administered 2.5 hr prior to the 6-hr euglycemic clamp.
Stage 3: Insulin Aspart + rHuPH20 Participants received 0.12 units per kilogram (U/kg) insulin aspart administered as a continuous subcutaneous insulin infusion (CSII), for 5 days (Days 1-5 or 6-10), including during a 6-hour (hr) euglycemic clamp on Days 2, 3, and 5 of Period 1, or on Days 7, 8, and 10 of Period 2. On Day 2 or Day 7 only, a 1 milliliter (mL) subcutaneous (SC) injection of 1.25 micrograms per milliliter (μg/mL) recombinant human hyaluronidase PH20 (rHuPH20) was administered 2.5 hr prior to the 6-hr euglycemic clamp.

Measured Values
    Stage 3: Insulin Aspart Alone     Stage 3: Insulin Aspart + rHuPH20  
Number of Participants Analyzed  
[units: participants]
  17     17  
Early Exposure to Insulin (%AUC[0-60]), Stage 3  
[units: Percentage of AUC(0-360)]
Mean ± Standard Deviation
   
Stage 3, Day 2/7     15.70  ± 6.38     32.11  ± 10.91  
Stage 3, Day 3/8     22.29  ± 5.43     36.39  ± 9.43  
Stage 3, Day 5/10     27.31  ± 10.49     32.64  ± 11.32  


Statistical Analysis 1 for Early Exposure to Insulin (%AUC[0-60]), Stage 3
Groups [1] All groups
Method [2] Mixed Models Analysis
P Value [3] <0.0001
Least Squares Mean Difference [4] 16.41
90% Confidence Interval ( 11.86 to 20.97 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Comparison at Stage 3, Day 2/7
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Mixed model with fixed effects for treatment, day, and interaction of treatment with day. A compound symmetric covariance matrix was assumed.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Early Exposure to Insulin (%AUC[0-60]), Stage 3
Groups [1] All groups
Method [2] Mixed Models Analysis
P Value [3] <0.0001
Least Squares Mean Difference [4] 14.10
90% Confidence Interval ( 9.55 to 18.65 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Comparison at Stage 3, Day 3/8
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Mixed model with fixed effects for treatment, day, and interaction of treatment with day. A compound symmetric covariance matrix was assumed.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 3 for Early Exposure to Insulin (%AUC[0-60]), Stage 3
Groups [1] All groups
Method [2] Mixed Models Analysis
P Value [3] 0.0552
Least Squares Mean Difference [4] 5.32
90% Confidence Interval ( 0.77 to 9.88 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Comparison at Stage 3, Day 5/10
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Mixed model with fixed effects for treatment, day, and interaction of treatment with day. A compound symmetric covariance matrix was assumed.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



3.  Secondary:   Maximum Glucose Infusion Rate (GIRmax), Stage 1   [ Time Frame: 0 up to 360 minutes postdose on Day 2/6 and Day 4/8 ]

Measure Type Secondary
Measure Title Maximum Glucose Infusion Rate (GIRmax), Stage 1
Measure Description Maximum glucose infusion rates (GIRmax) for Stage1 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 up to 360 minutes postdose on Day 2/6 and Day 4/8  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants who completed all periods of study within a given stage with evaluable GIRmax data.

Reporting Groups
  Description
Stage 1: Insulin Aspart Alone Participants received 0.15 units per kilogram (U/kg) insulin aspart, administered as a continuous subcutaneous insulin infusion (CSII), for 4 days (Days 1-4 or 5-8), including during a 6-hour (hr) euglycemic clamp on Days 2 and 4 of Period 1 or Day 6 and 8 of Period 2.
Stage 1: Insulin Aspart-rHuPH20 Participants received 0.15 units per kilogram (U/kg) insulin aspart and 5 micrograms per milliliter (μg/mL) recombinant human hyaluronidase PH20 (rHuPH20) (insulin aspart-rHuPH20) administered together as a continuous subcutaneous insulin infusion (CSII), for 4 days (Days 1-4 or 5-8), including during a 6-hour (hr) euglycemic clamp on Days 2 and 4 of Period 1 or Days 6 and 8 of Period 2.

Measured Values
    Stage 1: Insulin Aspart Alone     Stage 1: Insulin Aspart-rHuPH20  
Number of Participants Analyzed  
[units: participants]
  16     16  
Maximum Glucose Infusion Rate (GIRmax), Stage 1  
[units: Milligrams/kilogram/minute]
Mean ± Standard Deviation
   
Stage 1, Day 2/6     13.37  ± 4.23     12.51  ± 3.19  
Stage 1, Day 4/8     11.88  ± 3.64     11.52  ± 3.67  

No statistical analysis provided for Maximum Glucose Infusion Rate (GIRmax), Stage 1



4.  Secondary:   Maximum Glucose Infusion Rate (GIRmax), Stage 3   [ Time Frame: 0 up to 360 minutes postdose on Days 2/7, 3/8, and 5/10 ]

Measure Type Secondary
Measure Title Maximum Glucose Infusion Rate (GIRmax), Stage 3
Measure Description Maximum glucose infusion rates (GIRmax) for Stage 3 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 up to 360 minutes postdose on Days 2/7, 3/8, and 5/10  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants who completed all periods of study within a given stage with evaluable GIRmax data.

Reporting Groups
  Description
Stage 3: Insulin Aspart Alone Participants received 0.12 units per kilogram (U/kg) insulin aspart administered as a continuous subcutaneous insulin infusion (CSII), for 5 days (Days 1-5 or 6-10), including during a 6-hour (hr) euglycemic clamp on Days 2, 3, and 5 of Period 1, or Days 7, 8, and 10 of Period 2. On Day 2 or Day 7 only, a sham injection was administered 2.5 hr prior to the 6-hr euglycemic clamp.
Stage 3: Insulin Aspart + rHuPH20 Participants received 0.12 units per kilogram (U/kg) insulin aspart administered as a continuous subcutaneous insulin infusion (CSII), for 5 days (Days 1-5 or 6-10), including during a 6-hour (hr) euglycemic clamp on Days 2, 3, and 5 of Period 1, or on Days 7, 8, and 10 of Period 2. On Day 2 or Day 7 only, a 1-milliliter (mL) subcutaneous (SC) injection of 1.25 micrograms per milliliter (μg/mL) recombinant human hyaluronidase PH20 (rHuPH20) was administered 2.5 hr prior to the 6-hr euglycemic clamp.

Measured Values
    Stage 3: Insulin Aspart Alone     Stage 3: Insulin Aspart + rHuPH20  
Number of Participants Analyzed  
[units: participants]
  17     17  
Maximum Glucose Infusion Rate (GIRmax), Stage 3  
[units: Milligrams/kilogram/minute]
Mean ± Standard Deviation
   
Stage 3, Day 2/7     9.58  ± 2.28     12.63  ± 3.88  
Stage 3, Day 3/8     10.07  ± 3.36     12.4  ± 3.39  
Stage 3, Day 5/10     9.97  ± 3.53     10.76  ± 3.35  

No statistical analysis provided for Maximum Glucose Infusion Rate (GIRmax), Stage 3



5.  Secondary:   Time to First Occurrence of Maximum Glucose Infusion Rate (tGIRmax), Stage 1   [ Time Frame: 0 up to 360 minutes postdose on Day 2/6 and Day 4/8 ]

Measure Type Secondary
Measure Title Time to First Occurrence of Maximum Glucose Infusion Rate (tGIRmax), Stage 1
Measure Description Time to first occurrence of maximum glucose infusion rate (tGIRmax) for Stage 1 is 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 up to 360 minutes postdose on Day 2/6 and Day 4/8  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants who completed all periods of study within a given stage with evaluable tGIRmax data.

Reporting Groups
  Description
Stage 1: Insulin Aspart Alone Participants received 0.15 units per kilogram (U/kg) insulin aspart, administered as a continuous subcutaneous insulin infusion (CSII), for 4 days (Days 1-4 or 5-8), including during a 6-hour (hr) euglycemic clamp on Days 2 and 4 of Period 1 or Days 6 and 8 of Period 2.
Stage 1: Insulin Aspart-rHuPH20 Participants received 0.15 units per kilogram (U/kg) insulin aspart and 5 micrograms per milliliter (μg/mL) recombinant human hyaluronidase PH20 (rHuPH20) (insulin aspart-rHuPH20) administered together as a continuous subcutaneous insulin infusion (CSII), for 4 days (Days 1-4 or 5-8), including during a 6-hour (hr) euglycemic clamp on Days 2 and 4 of Period 1 or Days 6 and 8 of Period 2.

Measured Values
    Stage 1: Insulin Aspart Alone     Stage 1: Insulin Aspart-rHuPH20  
Number of Participants Analyzed  
[units: participants]
  16     16  
Time to First Occurrence of Maximum Glucose Infusion Rate (tGIRmax), Stage 1  
[units: Minutes]
Mean ± Standard Deviation
   
Stage 1, Day 2/6     115.38  ± 59.21     102.38  ± 38.28  
Stage 1, Day 4/8     92.50  ± 24.71     84.31  ± 25.89  

No statistical analysis provided for Time to First Occurrence of Maximum Glucose Infusion Rate (tGIRmax), Stage 1



6.  Secondary:   Time to First Occurrence of Maximum Glucose Infusion Rate (tGIRmax), Stage 3   [ Time Frame: 0 up to 360 minutes postdose on Days 2/7, 3/8, and 5/10 ]

Measure Type Secondary
Measure Title Time to First Occurrence of Maximum Glucose Infusion Rate (tGIRmax), Stage 3
Measure Description Time to first occurrence of maximum glucose infusion rate (tGIRmax) for Stage 3 is 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 up to 360 minutes postdose on Days 2/7, 3/8, and 5/10  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants who completed all periods of study within a given stage with evaluable tGIRmax data.

Reporting Groups
  Description
Stage 3: Insulin Aspart Alone Participants received 0.12 units per kilogram (U/kg) insulin aspart administered as a continuous subcutaneous insulin infusion (CSII), for 5 days (Days 1-5 or 6-10), including during a 6-hour (hr) euglycemic clamp on Days 2, 3, and 5 of Period 1, or Days 7, 8, and 10 of Period 2. On Day 2 or Day 7 only, a sham injection was administered 2.5 hr prior to the 6-hr euglycemic clamp.
Stage 3: Insulin Aspart + rHuPH20 Participants received 0.12 units per kilogram (U/kg) insulin aspart administered as a continuous subcutaneous insulin infusion (CSII), for 5 days (Days 1-5 or 6-10), including during a 6-hour (hr) euglycemic clamp on Days 2, 3, and 5 of Period 1, or on Days 7, 8, and 10 of Period 2. On Day 2 or Day 7 only, a 1-milliliter (mL) subcutaneous (SC) injection of 1.25 micrograms per milliliter (μg/mL) recombinant human hyaluronidase PH20 (rHuPH20) was administered 2.5 hr prior to the 6-hr euglycemic clamp.

Measured Values
    Stage 3: Insulin Aspart Alone     Stage 3: Insulin Aspart + rHuPH20  
Number of Participants Analyzed  
[units: participants]
  17     17  
Time to First Occurrence of Maximum Glucose Infusion Rate (tGIRmax), Stage 3  
[units: Minutes]
Mean ± Standard Deviation
   
Stage 3, Day 2/7     127.65  ± 60.02     78.53  ± 27.04  
Stage 3, Day 3/8     135.24  ± 73.00     79.47  ± 42.57  
Stage 3, Day 5/10     117.76  ± 75.20     79.53  ± 42.99  

No statistical analysis provided for Time to First Occurrence of Maximum Glucose Infusion Rate (tGIRmax), Stage 3



7.  Secondary:   Time to 50% Maximum Glucose Infusion Rate (tGIR50%Max), Stage 1   [ Time Frame: 0 up to 360 minutes postdose on day 2/6 and Day 4/8 ]

Measure Type Secondary
Measure Title Time to 50% Maximum Glucose Infusion Rate (tGIR50%Max), Stage 1
Measure Description Early and late times to 50% maximum glucose infusion rate (tGIR50%max) for Stage 1 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 up to 360 minutes postdose on day 2/6 and Day 4/8  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants who completed all periods of study within a given stage with evaluable early or late tGIR50%max data.

Reporting Groups
  Description
Stage 1: Insulin Aspart Alone Participants received 0.15 units per kilogram (U/kg) insulin aspart, administered as a continuous subcutaneous insulin infusion (CSII), for 4 days (Days 1-4 or 5-8), including during a 6-hour (hr) euglycemic clamp on Days 2 and 4 of Period 1 or Days 6 and 8 of Period 2.
Stage 1: Insulin Aspart-rHuPH20 Participants received 0.15 units per kilogram (U/kg) insulin aspart and 5 micrograms per milliliter (μg/mL) recombinant human hyaluronidase PH20 (rHuPH20) (insulin aspart-rHuPH20) administered together as a continuous subcutaneous insulin infusion (CSII), for 4 days, including during a 6-hour (hr) euglycemic clamp on Days 2 and 4 or Days 6 and 8.

Measured Values
    Stage 1: Insulin Aspart Alone     Stage 1: Insulin Aspart-rHuPH20  
Number of Participants Analyzed  
[units: participants]
  16     16  
Time to 50% Maximum Glucose Infusion Rate (tGIR50%Max), Stage 1  
[units: Minutes]
Mean ± Standard Deviation
   
Early tGIR50%max, Stage 1, Day 2/6     46.50  ± 18.08     34.88  ± 17.92  
Late tGIR50%max, Stage 1, Day 2/6     162.19  ± 56.78     158.06  ± 52.58  
Early tGIR50%max, Stage 1, Day 4/8     35.19  ± 28.54     39.75  ± 18.71  
Late tGIR50%max, Stage 1, Day 4/8     132.63  ± 47.37     114.19  ± 29.05  

No statistical analysis provided for Time to 50% Maximum Glucose Infusion Rate (tGIR50%Max), Stage 1



8.  Secondary:   Time to 50% Maximum Glucose Infusion Rate (tGIR50%Max), Stage 3   [ Time Frame: 0 up to 360 minutes postdose on Days 2/7, 3/8, and 5/10 ]

Measure Type Secondary
Measure Title Time to 50% Maximum Glucose Infusion Rate (tGIR50%Max), Stage 3
Measure Description Early and late time to 50% maximum glucose infusion rates (tGIR50%max) for Stage 3 studies 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 up to 360 minutes postdose on Days 2/7, 3/8, and 5/10  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants who completed all periods of study within a given stage with evaluable early and late tGIR50%max data.

Reporting Groups
  Description
Stage 3: Insulin Aspart Alone Participants received 0.12 units per kilogram (U/kg) insulin aspart administered as a continuous subcutaneous insulin infusion (CSII), for 5 days (Days 1-5 or 6-10), including during a 6 hour (hr) euglycemic clamp on Days 2, 3, and 5 of Period 1, or Days 7, 8, and 10 of Period 2. On Day 2 or Day 7 only, a sham injection was administered 2.5 hr prior to the 6-hr euglycemic clamp.
Stage 3: Insulin Aspart + rHuPH20 Participants received 0.12 units per kilogram (U/kg) insulin aspart administered as a continuous subcutaneous insulin infusion (CSII), for 5 days (Days 1-5 or 6-10), including during a 6-hour (hr) euglycemic clamp on Days 2, 3, and 5 of Period 1, or on Days 7, 8, and 10 of Period 2. On Day 2 or Day 7 only, a 1 milliliter (mL) subcutaneous (SC) injection of 1.25 micrograms per milliliter (μg/mL) recombinant human hyaluronidase PH20 (rHuPH20) was administered 2.5 hr prior to the 6-hr euglycemic clamp.

Measured Values
    Stage 3: Insulin Aspart Alone     Stage 3: Insulin Aspart + rHuPH20  
Number of Participants Analyzed  
[units: participants]
  17     17  
Time to 50% Maximum Glucose Infusion Rate (tGIR50%Max), Stage 3  
[units: Minutes]
Mean ± Standard Deviation
   
Early tGIR50%max, Stage 3, Day 2/7     58.47  ± 17.53     31.06  ± 20.73  
Late tGIR50%max, Stage 3, Day 2/7     144.18  ± 61.44     98.71  ± 39.87  
Early tGIR50%max, Stage 3, Day 3/8     32.59  ± 22.88     31.53  ± 21.27  
Late tGIR50%max, Stage 3, Day 3/8     153.41  ± 65.35     102.88  ± 44.57  
Early tGIR50%max, Stage 3, Day 5/10     27.29  ± 18.40     28.88  ± 21.97  
Late tGIR50%max, Stage 3, Day 5/10     136.88  ± 73.39     110.59  ± 55.10  

No statistical analysis provided for Time to 50% Maximum Glucose Infusion Rate (tGIR50%Max), Stage 3



9.  Secondary:   Time to 50% Total Glucose Infused (50%Gtot), Stage 1   [ Time Frame: 0 up to 360 minutes postdose on Day 2/6 and Day 4/8 ]

Measure Type Secondary
Measure Title Time to 50% Total Glucose Infused (50%Gtot), Stage 1
Measure Description Time to 50% total glucose infused (50%Gtot) is presented for Stage 1. 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 up to 360 minutes postdose on Day 2/6 and Day 4/8  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants who completed all periods of study within a given stage with evaluable 50%Gtot data.

Reporting Groups
  Description
Stage 1: Insulin Aspart Alone Participants received 0.15 units per kilogram (U/kg) insulin aspart, administered as a continuous subcutaneous insulin infusion (CSII), for 4 days (Days 1-4 or 5-8), including during a 6-hour (hr) euglycemic clamp on Days 2 and 4 of Period 1 or Days 6 and 8 of Period 2.
Stage 1: Insulin Aspart-rHuPH20 Participants received 0.15 units per kilogram (U/kg) insulin aspart and 5 micrograms per milliliter (μg/mL) recombinant human hyaluronidase PH20 (rHuPH20) (insulin aspart-rHuPH20) administered together as a continuous subcutaneous insulin infusion (CSII), for 4 days (Days 1-4 or 5-8), including during a 6-hour (hr) euglycemic clamp on Days 2 and 4 of Period 1 or Days 6 and 8 of Period 2.

Measured Values
    Stage 1: Insulin Aspart Alone     Stage 1: Insulin Aspart-rHuPH20  
Number of Participants Analyzed  
[units: participants]
  16     16  
Time to 50% Total Glucose Infused (50%Gtot), Stage 1  
[units: Minutes]
Mean ± Standard Deviation
   
Stage 1, Day 2/6     156.13  ± 18.70     134.94  ± 18.28  
Stage 1, Day 4/8     137.38  ± 22.21     115.25  ± 14.50  

No statistical analysis provided for Time to 50% Total Glucose Infused (50%Gtot), Stage 1



10.  Secondary:   Time to 50% Total Glucose Infused (50%Gtot), Stage 3   [ Time Frame: 0 up to 360 minutes postdose on Days 2/7, 3/8, and 5/10 ]

Measure Type Secondary
Measure Title Time to 50% Total Glucose Infused (50%Gtot), Stage 3
Measure Description Time to 50% of total glucose infused (50%Gtot) is presented for Stage 3. 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 up to 360 minutes postdose on Days 2/7, 3/8, and 5/10  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants who completed all periods of study within a given stage with evaluable 50%Gtot data.

Reporting Groups
  Description
Stage 3: Insulin Aspart Alone Participants received 0.12 units per kilogram (U/kg) insulin aspart administered as a continuous subcutaneous insulin infusion (CSII), for 5 days (Days 1-5 or 6-10), including during a 6-hour (hr) euglycemic clamp on Days 2, 3, and 5 of Period 1, or Days 7, 8, and 10 of Period 2. On Day 2 or Day 7 only, a sham injection was administered 2.5 hr prior to the 6-hr euglycemic clamp.
Stage 3: Insulin Aspart + rHuPH20 Participants received 0.12 units per kilogram (U/kg) insulin aspart administered as a continuous subcutaneous insulin infusion (CSII), for 5 days (Days 1-5 or 6-10), including during a 6-hour (hr) euglycemic clamp on Days 2, 3, and 5 of Period 1, or on Days 7, 8, and 10 of Period 2. On Day 2 or Day 7 only, a 1-milliliter (mL) subcutaneous (SC) injection of 1.25 micrograms per milliliter (μg/mL) recombinant human hyaluronidase PH20 (rHuPH20) was administered 2.5 hr prior to the 6-hr euglycemic clamp.

Measured Values
    Stage 3: Insulin Aspart Alone     Stage 3: Insulin Aspart + rHuPH20  
Number of Participants Analyzed  
[units: participants]
  17     17  
Time to 50% Total Glucose Infused (50%Gtot), Stage 3  
[units: Minutes]
Mean ± Standard Deviation
   
Stage 3, Day 2/7     174.59  ± 25.86     124.18  ± 22.03  
Stage 3, Day 3/8     154.06  ± 24.02     120.00  ± 17.12  
Stage 3, Day 5/10     146.59  ± 28.63     130.18  ± 23.54  

No statistical analysis provided for Time to 50% Total Glucose Infused (50%Gtot), Stage 3



11.  Secondary:   Area Under the Glucose Concentration Curve (AUC[0-360]), Stage 1   [ Time Frame: 30 minutes predose up to 360 minutes postdose on Day 2/6 and Day 4/8 ]

Measure Type Secondary
Measure Title Area Under the Glucose Concentration Curve (AUC[0-360]), Stage 1
Measure Description Area under the glucose concentration curve for 0 to 360 minutes (AUC[0-360]) from Stage 1 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 predose up to 360 minutes postdose on Day 2/6 and Day 4/8  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants who completed all periods of study within a given stage with evaluable AUC(0-360) data.

Reporting Groups
  Description
Stage 1: Insulin Aspart Alone Participants received 0.15 units per kilogram (U/kg) insulin aspart, administered as a continuous subcutaneous insulin infusion (CSII), for 4 days (Days 1-4 or 5-8), including during a 6-hour (hr) euglycemic clamp on Days 2 and 4 of Period 1 or Days 6 and 8 of Period 2.
Stage 1: Insulin Aspart-rHuPH20 Participants received 0.15 units per kilogram (U/kg) insulin aspart and 5 micrograms per milliliter (μg/mL) recombinant human hyaluronidase PH20 (rHuPH20) (insulin aspart-rHuPH20) administered together as a continuous subcutaneous insulin infusion (CSII), for 4 days (Days 1-4 or 5-8), including during a 6-hour (hr) euglycemic clamp on Days 2 and 4 of Period 1 or Days 6 and 8 of Period 2.

Measured Values
    Stage 1: Insulin Aspart Alone     Stage 1: Insulin Aspart-rHuPH20  
Number of Participants Analyzed  
[units: participants]
  16     16  
Area Under the Glucose Concentration Curve (AUC[0-360]), Stage 1  
[units: Picomoles*minutes/liter]
Mean ± Standard Deviation
   
Stage 1, Day 2/6     1978.08  ± 631.89     1977.02  ± 795.79  
Stage 1, Day 4/8     1598.40  ± 546.00     1324.31  ± 500.04  

No statistical analysis provided for Area Under the Glucose Concentration Curve (AUC[0-360]), Stage 1



12.  Secondary:   Area Under the Glucose Concentration Curve (AUC[0-360]), Stage 3   [ Time Frame: 30 minutes predose up to 360 minutes postdose Days 2/7, 3/8, and 5/10 ]

Measure Type Secondary
Measure Title Area Under the Glucose Concentration Curve (AUC[0-360]), Stage 3
Measure Description Area under the glucose concentration curve from 0 to 360 minutes (AUC[0-360]) for Stage 3 studies 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 predose up to 360 minutes postdose Days 2/7, 3/8, and 5/10  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants who completed all periods of study within a given stage with evaluable AUC(0-360) data.

Reporting Groups
  Description
Stage 3: Insulin Aspart Alone Participants received 0.12 units per kilogram (U/kg) insulin aspart administered as a continuous subcutaneous insulin infusion (CSII), for 5 days (Days 1-5 or 6-10), including during a 6-hour (hr) euglycemic clamp on Days 2, 3, and 5 of Period 1, or Days 7, 8, and 10 of Period 2. On Day 2 or Day 7 only, a sham injection was administered 2.5 hr prior to the 6-hr euglycemic clamp.
Stage 3: Insulin Aspart + rHuPH20 Participants received 0.12 units per kilogram (U/kg) insulin aspart administered as a continuous subcutaneous insulin infusion (CSII), for 5 days (Days 1-5 or 6-10), including during a 6-hour (hr) euglycemic clamp on Days 2, 3, and 5 of Period 1, or on Days 7, 8, and 10 of Period 2. On Day 2 or Day 7 only, a 1-milliliter (mL) subcutaneous (SC) injection of 1.25 micrograms per milliliter (μg/mL) recombinant human hyaluronidase PH20 (rHuPH20) was administered 2.5 hr prior to the 6-hr euglycemic clamp.

Measured Values
    Stage 3: Insulin Aspart Alone     Stage 3: Insulin Aspart + rHuPH20  
Number of Participants Analyzed  
[units: participants]
  17     17  
Area Under the Glucose Concentration Curve (AUC[0-360]), Stage 3  
[units: Picomoles*minutes/liter]
Mean ± Standard Deviation
   
Stage 3, Day 2/7     1197.60  ± 385.44     1509.38  ± 541.45  
Stage 3, Day 3/8     1368.81  ± 424.16     1405.75  ± 516.85  
Stage 3, Day 5/10     1289.22  ± 486.03     1369.97  ± 462.78  

No statistical analysis provided for Area Under the Glucose Concentration Curve (AUC[0-360]), Stage 3



13.  Secondary:   Duration of Insulin Action (AUMC[0-360]/AUC[0-360]), Stage 1   [ Time Frame: 10 minutes predose up to 360 minutes postdose on Day 2/6 and Day 4/8 ]

Measure Type Secondary
Measure Title Duration of Insulin Action (AUMC[0-360]/AUC[0-360]), Stage 1
Measure 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]) for Stage 1. 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 up to 360 minutes postdose on Day 2/6 and Day 4/8  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants who completed all periods of study within a given stage with evaluable AUMC(0-360)/AUC(0-360) data.

Reporting Groups
  Description
Stage 1: Insulin Aspart Alone Participants received 0.15 units per kilogram (U/kg) insulin aspart, administered as a continuous subcutaneous insulin infusion (CSII), for 4 days (Days 1-4 or 5-8), including during a 6 hour (hr) euglycemic clamp on Days 2 and 4 of Period 1 or Days 6 and 8 of Period 2.
Stage 1: Insulin Aspart-rHuPH20 Participants received 0.15 units per kilogram (U/kg) insulin aspart and 5 micrograms per milliliter (μg/mL) recombinant human hyaluronidase PH20 (rHuPH20) (insulin aspart-rHuPH20) administered together as a continuous subcutaneous insulin infusion (CSII), for 4 days (Days 1-4 or 5-8), including during a 6-hour (hr) euglycemic clamp on Days 2 and 4 of Period 1 or Days 6 and 8 of Period 2.

Measured Values
    Stage 1: Insulin Aspart Alone     Stage 1: Insulin Aspart-rHuPH20  
Number of Participants Analyzed  
[units: participants]
  16     16  
Duration of Insulin Action (AUMC[0-360]/AUC[0-360]), Stage 1  
[units: Ratio]
Mean ± Standard Deviation
   
Stage 1, Day 2/6     163.63  ± 14.70     146.51  ± 16.30  
Stage 1, Day 4/8     147.50  ± 23.86     132.60  ± 15.55  

No statistical analysis provided for Duration of Insulin Action (AUMC[0-360]/AUC[0-360]), Stage 1



14.  Secondary:   Duration of Insulin Action (AUMC[0-360]/AUC[0-360]), Stage 3   [ Time Frame: 10 minutes predose up to 360 minutes postdose on Days 2/7, 3/8, and 5/10 ]

Measure Type Secondary
Measure Title Duration of Insulin Action (AUMC[0-360]/AUC[0-360]), Stage 3
Measure 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]) for Stage 3. 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 up to 360 minutes postdose on Days 2/7, 3/8, and 5/10  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants who completed all periods of study within a given stage with evaluable AUMC(0-360)/AUC(0-360) data.

Reporting Groups
  Description
Stage 3: Insulin Aspart Alone Participants received 0.12 units per kilogram (U/kg) insulin aspart administered as a continuous subcutaneous insulin infusion (CSII), for 5 days (Days 1-5 or 6-10), including during a 6-hour (hr) euglycemic clamp on Days 2, 3, and 5 of Period 1, or Days 7, 8, and 10 of Period 2. On Day 2 or Day 7 only, a sham injection was administered 2.5 hr prior to the 6-hr euglycemic clamp.
Stage 3: Insulin Aspart + rHuPH20 Participants received 0.12 units per kilogram (U/kg) insulin aspart administered as a continuous subcutaneous insulin infusion (CSII), for 5 days (Days 1-5 or 6-10), including during a 6-hour (hr) euglycemic clamp on Days 2, 3, and 5 of Period 1, or on Days 7, 8, and 10 of Period 2. On Day 2 or Day 7 only, a 1-milliliter (mL) subcutaneous (SC) injection of 1.25 micrograms per milliliter (μg/mL) recombinant human hyaluronidase PH20 (rHuPH20) was administered 2.5 hr prior to the 6-hr euglycemic clamp.

Measured Values
    Stage 3: Insulin Aspart Alone     Stage 3: Insulin Aspart + rHuPH20  
Number of Participants Analyzed  
[units: participants]
  17     17  
Duration of Insulin Action (AUMC[0-360]/AUC[0-360]), Stage 3  
[units: ratio]
Mean ± Standard Deviation
   
Stage 3, Day 2/7     180.39  ± 18.72     138.59  ± 18.41  
Stage 3, Day 3/8     164.65  ± 19.97     135.71  ± 17.30  
Stage 3, Day 5/10     156.14  ± 26.38     145.81  ± 16.42  

No statistical analysis provided for Duration of Insulin Action (AUMC[0-360]/AUC[0-360]), Stage 3




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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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.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Vice President, Endocrinology Clinical Development
Organization: Halozyme Therapeutics, Inc
phone: (858)794-8889


No publications provided


Responsible Party: Halozyme Therapeutics
ClinicalTrials.gov Identifier: NCT01275131     History of Changes
Other Study ID Numbers: HALO-117-105
Study First Received: January 10, 2011
Results First Received: June 26, 2014
Last Updated: June 26, 2014
Health Authority: United States: Food and Drug Administration