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Safety/Efficacy Study of Subcutaneously Injected Prandial Insulins Compared to Insulin Lispro Alone in Participants With Type 1 Diabetes Mellitus

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Halozyme Therapeutics
ClinicalTrials.gov Identifier:
NCT01194245
First received: August 31, 2010
Last updated: August 1, 2014
Last verified: August 2014
Results First Received: August 1, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Crossover Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Diabetes Mellitus, Type 1
Interventions: Drug: Insulin lispro
Drug: recombinant human hyaluronidase PH20
Drug: Insulin aspart
Drug: Insulin glulisine
Drug: Insulin glargine

  Participant Flow
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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
The study included an open-label titration period of at least 4 weeks and up to 6 weeks prior to randomization at Week 0.

Reporting Groups
  Description
All Enrolled Participants

Prior to randomization, all enrolled participants underwent a titration period of 4-6 weeks in which they received 100 units per milliliter (U/mL) insulin glulisine, injected subcutaneously (SC), pre-meals, with doses titrated to each participant individually.

Participants requiring basal insulin used twice daily SC injections of 100 U/mL insulin glargine.

Lispro-PH20 First, Then Insulin Lispro

Following a titration period of 4 to 6 weeks, participants were randomly assigned to Treatment A for the first 3-month treatment cycle, followed by Treatment B for the second 3-month treatment cycle.

Lispro-PH20 (Treatment A): 100 units per milliliter (U/mL) insulin lispro with 5.0 micrograms per milliliter (µg/mL) recombinant human hyaluronidase PH20, injected subcutaneously (SC), pre-meals, with doses titrated to each participant individually

Insulin Lispro (Treatment B): 100 U/mL insulin lispro, injected SC, pre-meals, with doses titrated to each participant individually

Throughout the study, participants requiring basal insulin used twice daily SC injections of 100 U/mL insulin glargine.

Insulin Lispro First, Then Lispro-PH20

Following a titration period of 4 to 6 weeks, participants were randomly assigned to Treatment B for the first 3-month treatment cycle, followed by Treatment A for the second 3-month treatment cycle.

Insulin Lispro (Treatment B): 100 units per milliliter (U/mL) insulin lispro, injected subcutaneously (SC), pre-meals, with doses titrated to each participant individually

Lispro-PH20 (Treatment A): 100 U/mL insulin lispro with 5.0 micrograms per milliliter (µg/mL) recombinant human hyaluronidase PH20, injected SC, pre-meals, with doses titrated to each participant individually

Throughout the study, participants requiring basal insulin used twice daily SC injections of 100 U/mL insulin glargine.

Aspart-PH20 First, Then Insulin Lispro

Following a titration period of 4 to 6 weeks, participants were randomly assigned to Treatment A for the first 3-month treatment cycle, followed by Treatment B for the second 3-month treatment cycle.

Aspart-PH20 (Treatment A): 100 units per milliliter (U/mL) insulin aspart with 5.0 micrograms per milliliter (µg/mL) recombinant human hyaluronidase PH20, injected subcutaneously (SC), pre-meals, with doses titrated to each participant individually

Insulin Lispro (Treatment B): 100 U/mL insulin lispro, injected SC, pre-meals, with doses titrated to each participant individually

Throughout the study, participants requiring basal insulin used twice daily SC injections of 100 U/mL insulin glargine.

Insulin Lispro First, Then Aspart-PH20

Following a titration period of 4 to 6 weeks, participants were randomly assigned to Treatment B for the first 3-month treatment cycle, followed by Treatment A for the second 3-month treatment cycle.

Insulin Lispro (Treatment B): 100 units per milliliter (U/mL) insulin lispro, injected subcutaneously (SC), pre-meals, with doses titrated to each participant individually

Aspart-PH20 (Treatment A): 100 U/mL insulin aspart with 5.0 micrograms per milliliter (µg/mL) recombinant human hyaluronidase PH20, injected SC, pre-meals, with doses titrated to each participant individually

Throughout the study, participants requiring basal insulin used twice daily SC injections of 100 U/mL insulin glargine.


Participant Flow for 3 periods

Period 1:   Titration Period (4 to 6 Weeks)
    All Enrolled Participants     Lispro-PH20 First, Then Insulin Lispro     Insulin Lispro First, Then Lispro-PH20     Aspart-PH20 First, Then Insulin Lispro     Insulin Lispro First, Then Aspart-PH20  
STARTED     135     0     0     0     0  
COMPLETED     117 [1]   0     0     0     0  
NOT COMPLETED     18     0     0     0     0  
Withdrawal by Subject                 5                 0                 0                 0                 0  
Physician Decision                 3                 0                 0                 0                 0  
Titration Failure                 3                 0                 0                 0                 0  
Did Not Meet Randomization Criteria                 7                 0                 0                 0                 0  
[1] Participants that completed the Titration Period were randomized to Treatment Period 1.

Period 2:   Treatment Period 1 (Weeks 0 to 12)
    All Enrolled Participants     Lispro-PH20 First, Then Insulin Lispro     Insulin Lispro First, Then Lispro-PH20     Aspart-PH20 First, Then Insulin Lispro     Insulin Lispro First, Then Aspart-PH20  
STARTED     0     29     28     30     30  
Received at Least 1 Dose of Study Drug     0     29     28     30     30  
COMPLETED     0     29     27     29     28  
NOT COMPLETED     0     0     1     1     2  
Lost to Follow-up                 0                 0                 0                 0                 1  
Withdrawal by Subject                 0                 0                 1                 1                 1  

Period 3:   Treatment Period 2 (Weeks 12 to 24)
    All Enrolled Participants     Lispro-PH20 First, Then Insulin Lispro     Insulin Lispro First, Then Lispro-PH20     Aspart-PH20 First, Then Insulin Lispro     Insulin Lispro First, Then Aspart-PH20  
STARTED     0     29     27     29     28  
COMPLETED     0     29     27     29     28  
NOT COMPLETED     0     0     0     0     0  



  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 enrolled participants.

Reporting Groups
  Description
Non-randomized Participants

Participants underwent a titration period of 4-6 weeks in which they received 100 units per milliliter (U/mL) insulin glulisine, injected subcutaneously (SC), pre-meals, with doses titrated to each participant individually. Participants requiring basal insulin used twice daily SC injections of 100 U/mL insulin glargine.

Participants did not complete the titration period or did not meet one or more randomization criteria and, therefore, were not randomized.

Lispro-PH20 First, Then Insulin Lispro

Following a titration period of 4 to 6 weeks, participants were randomly assigned to Treatment A for the first 3-month treatment cycle, followed by Treatment B for the second 3-month treatment cycle.

Lispro-PH20 (Treatment A): 100 units per milliliter (U/mL) insulin lispro with 5.0 micrograms per milliliter (µg/mL) recombinant human hyaluronidase PH20, injected subcutaneously (SC), pre-meals, with doses titrated to each participant individually

Insulin Lispro (Treatment B): 100 U/mL insulin lispro, injected SC, pre-meals, with doses titrated to each participant individually

Throughout the study, participants requiring basal insulin used twice daily SC injections of 100 U/mL insulin glargine.

Insulin Lispro First, Then Lispro-PH20

Following a titration period of 4 to 6 weeks, participants were randomly assigned to Treatment B for the first 3-month treatment cycle, followed by Treatment A for the second 3-month treatment cycle.

Insulin Lispro (Treatment B): 100 units per milliliter (U/mL) insulin lispro, injected subcutaneously (SC), pre-meals, with doses titrated to each participant individually

Lispro-PH20 (Treatment A): 100 U/mL insulin lispro with 5.0 micrograms per milliliter (µg/mL) recombinant human hyaluronidase PH20, injected SC, pre-meals, with doses titrated to each participant individually

Throughout the study, participants requiring basal insulin used twice daily SC injections of 100 U/mL insulin glargine.

Aspart-PH20 First, Then Insulin Lispro

Following a titration period of 4 to 6 weeks, participants were randomly assigned to Treatment A for the first 3-month treatment cycle, followed by Treatment B for the second 3-month treatment cycle.

Aspart-PH20 (Treatment A): 100 units per milliliter (U/mL) insulin aspart with 5.0 micrograms per milliliter (µg/mL) recombinant human hyaluronidase PH20, injected subcutaneously (SC), pre-meals, with doses titrated to each participant individually

Insulin Lispro (Treatment B): 100 U/mL insulin lispro, injected SC, pre-meals, with doses titrated to each participant individually

Throughout the study, participants requiring basal insulin used twice daily SC injections of 100 U/mL insulin glargine.

Insulin Lispro First, Then Aspart-PH20

Following a titration period of 4 to 6 weeks, participants were randomly assigned to Treatment B for the first 3-month treatment cycle, followed by Treatment A for the second 3-month treatment cycle.

Insulin Lispro (Treatment B): 100 units per milliliter (U/mL) insulin lispro, injected subcutaneously (SC), pre-meals, with doses titrated to each participant individually

Aspart-PH20 (Treatment A): 100 U/mL insulin aspart with 5.0 micrograms per milliliter (µg/mL) recombinant human hyaluronidase PH20, injected SC, pre-meals, with doses titrated to each participant individually

Throughout the study, participants requiring basal insulin used twice daily SC injections of 100 U/mL insulin glargine.

Total Total of all reporting groups

Baseline Measures
    Non-randomized Participants     Lispro-PH20 First, Then Insulin Lispro     Insulin Lispro First, Then Lispro-PH20     Aspart-PH20 First, Then Insulin Lispro     Insulin Lispro First, Then Aspart-PH20     Total  
Number of Participants  
[units: participants]
  18     29     28     30     30     135  
Age  
[units: years]
Mean ± Standard Deviation
  34.8  ± 11.71     44.6  ± 14.56     45.7  ± 14.94     42.8  ± 14.13     42.5  ± 14.70     42.6  ± 14.41  
Gender  
[units: participants]
           
Female     6     13     13     14     15     61  
Male     12     16     15     16     15     74  
Race (NIH/OMB)  
[units: participants]
           
American Indian or Alaska Native     0     0     0     0     0     0  
Asian     1     0     0     0     0     1  
Native Hawaiian or Other Pacific Islander     0     0     0     0     0     0  
Black or African American     0     0     1     0     2     3  
White     17     27     27     30     28     129  
More than one race     0     2     0     0     0     2  
Unknown or Not Reported     0     0     0     0     0     0  
Ethnicity (NIH/OMB)  
[units: participants]
           
Hispanic or Latino     4     1     2     2     1     10  
Not Hispanic or Latino     14     28     26     28     29     125  
Unknown or Not Reported     0     0     0     0     0     0  
Region of Enrollment  
[units: participants]
           
United States     18     29     28     30     30     135  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Change From Baseline in Glycosylated Hemoglobin A1C (HbA1c) at the End of Each Treatment Period   [ Time Frame: Baseline, Week 12 and Week 24 ]

2.  Secondary:   Mean Daily Insulin Dose   [ Time Frame: Week 10 and Week 22 ]

3.  Secondary:   Percentage of Participants Meeting Glucose Targets   [ Time Frame: Baseline through Week 24, excluding 10-point glucose monitoring days ]

4.  Secondary:   Rates of Hypoglycemia at the End of Each Treatment Period   [ Time Frame: Week 12 and Week 24 ]

5.  Secondary:   Change From Baseline in Body Weight at the End of Each Treatment Period   [ Time Frame: Baseline, Week 12 and Week 24 ]

6.  Secondary:   Mean Daily Postprandial Glucose (PPG) Excursions   [ Time Frame: Week 10 and Week 22 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

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
No text entered.


  More Information
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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: NCT01194245     History of Changes
Other Study ID Numbers: HALO-117-205
Study First Received: August 31, 2010
Results First Received: August 1, 2014
Last Updated: August 1, 2014
Health Authority: United States: Food and Drug Administration