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Safety/Efficacy Study of Subcutaneously Injected Prandial Insulins Compared to Insulin Lispro Alone in Patients With Type 2 Diabetes Mellitus

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Halozyme Therapeutics
ClinicalTrials.gov Identifier:
NCT01194258
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 II
Interventions: Drug: Insulin lispro
Drug: Insulin aspart
Drug: Recombinant human hyaluronidase PH20
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 to 6 weeks in which they received 100 U/mL insulin glulisine, injected 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.

Insulin Lispro, Then Lispro-PH20

Participants received a subcutaneous (SC) injection of 100 units per milliliter (U/mL) insulin lispro alone pre-meals for 12 weeks during Treatment Period 1 of the study.

Then, participants received a SC injection of 100 U insulin lispro and 5 micrograms (µg) recombinant human hyaluronidase PH20 (rHuPH20) (combined: Lispro-PH20) pre-meals for 12 weeks during Treatment Period 2 of the study.

Lispro-PH20, Then Insulin Lispro

Participants received a SC injection of 100 U/mL insulin lispro and 5 µg rHuPH20 (Lispro-PH20) pre-meals for 12 weeks during Treatment Period 1 of the study.

Then, participants received a SC injection of 100 U/mL insulin lispro alone pre-meals for 12 weeks during Treatment Period 2 of the study.

Insulin Lispro, Then Aspart-PH20

Participants received a SC injection of 100 U/mL insulin lispro alone pre-meals for 12 weeks during Treatment Period 1 of the study.

Then, participants received a SC injection of 100 U/mL insulin aspart and 5 µg rHuPH20 (combined: Aspart-PH20) pre-meals for 12 weeks during Treatment Period 2 of the study.

Aspart-PH20, Then Insulin Lispro

Participants received SC injection of 100 U/mL insulin aspart and 5 µg rHuPH20 (Aspart-PH20) pre-meals for 12 weeks during Treatment Period 1 of the study.

Then, participants received a SC injection of 100 U/mL insulin lispro alone pre-meals for 12 weeks during Treatment Period 2 of the study.


Participant Flow for 3 periods

Period 1:   Titration Period
    All Enrolled Participants     Insulin Lispro, Then Lispro-PH20     Lispro-PH20, Then Insulin Lispro     Insulin Lispro, Then Aspart-PH20     Aspart-PH20, Then Insulin Lispro  
STARTED     132     0     0     0     0  
COMPLETED     121     0     0     0     0  
NOT COMPLETED     11     0     0     0     0  
Withdrawal by Subject                 6                 0                 0                 0                 0  
Lost to Follow-up                 2                 0                 0                 0                 0  
Titration failure                 3                 0                 0                 0                 0  

Period 2:   Period 1 (12 Weeks)
    All Enrolled Participants     Insulin Lispro, Then Lispro-PH20     Lispro-PH20, Then Insulin Lispro     Insulin Lispro, Then Aspart-PH20     Aspart-PH20, Then Insulin Lispro  
STARTED     0 [1]   29 [2]   30 [3]   29 [4]   33 [5]
Received at Least 1 Dose of Study Drug     0     29     30     29     33  
COMPLETED     0     29     30     29     32  
NOT COMPLETED     0     0     0     0     1  
Death                 0                 0                 0                 0                 1  
[1] Participants were randomized to the Insulin lispro or an Analog-PH20 group after titration.
[2] After the titration phase, 29 participants were randomized to the Insulin lispro/Lispro-PH20 group.
[3] After the titration phase, 30 participants were randomized to the Lispro-PH20/Insulin lispro group.
[4] After the titration phase, 29 participants were randomized to the Insulin lispro/Aspart-PH20 group.
[5] After the titration phase, 33 participants were randomized to the Aspart-PH20/Insulin lispro group.

Period 3:   Period 2 (12 Weeks)
    All Enrolled Participants     Insulin Lispro, Then Lispro-PH20     Lispro-PH20, Then Insulin Lispro     Insulin Lispro, Then Aspart-PH20     Aspart-PH20, Then Insulin Lispro  
STARTED     0     29     30     29     32  
COMPLETED     0     27     29     29     30  
NOT COMPLETED     0     2     1     0     2  
Lost to Follow-up                 0                 0                 0                 0                 2  
Adverse Event                 0                 1                 0                 0                 0  
Withdrawal by Subject                 0                 1                 1                 0                 0  



  Baseline Characteristics
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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 in the study, including those who were enrolled but were not randomized.

Reporting Groups
  Description
All Study Participants All participants in the study, including those who were enrolled but were not randomized.

Baseline Measures
    All Study Participants  
Number of Participants  
[units: participants]
  132  
Age  
[units: years]
Mean ± Standard Deviation
  58.7  ± 9.85  
Gender  
[units: participants]
 
Female     53  
Male     79  
Race (NIH/OMB)  
[units: participants]
 
American Indian or Alaska Native     0  
Asian     3  
Native Hawaiian or Other Pacific Islander     1  
Black or African American     10  
White     115  
More than one race     1  
Unknown or Not Reported     2  
Ethnicity (NIH/OMB)  
[units: participants]
 
Hispanic or Latino     19  
Not Hispanic or Latino     113  
Unknown or Not Reported     0  
Region of Enrollment  
[units: participants]
 
United States     132  



  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 as Recorded During 10-Point Glucose Monitoring   [ Time Frame: Week 10 and Week 22 ]

3.  Secondary:   Percentage of Participants Meeting Glucose Targets at Least 2/3 of the Time   [ 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 ]
  Hide Outcome Measure 5

Measure Type Secondary
Measure Title Change From Baseline in Body Weight at the End of Each Treatment Period
Measure Description Change from baseline in body weight at the end of each treatment period (Week 12 and Week 24) is presented. Data are presented by combined treatment group (Lispro-PH20 + Aspart-PH20 = Analog-PH20) and combined comparator drug (Insulin lispro from both cohorts).
Time Frame Baseline, Week 12 and Week 24  
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.
All participants who completed both Period 1 and Period 2 with evaluable body weight data.

Reporting Groups
  Description
Analog-PH20 100 U/mL insulin analog (Insulin lispro or insulin aspart) with 5.0 µg/mL rHuPH20, injected SC, pre-meals, with doses titrated to each participant individually, for 12 weeks
Insulin-lispro 100 U/mL insulin lispro, injected SC, pre-meals, with doses titrated to each participant individually, for 12 weeks

Measured Values
    Analog-PH20     Insulin-lispro  
Number of Participants Analyzed  
[units: participants]
  115     115  
Change From Baseline in Body Weight at the End of Each Treatment Period  
[units: pounds]
Mean ± Standard Deviation
  3.35  ± 5.466     3.44  ± 5.852  

No statistical analysis provided for Change From Baseline in Body Weight at the End of Each Treatment Period



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


  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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  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
phone: 858-794-8889


No publications provided


Responsible Party: Halozyme Therapeutics
ClinicalTrials.gov Identifier: NCT01194258     History of Changes
Other Study ID Numbers: HALO-117-206
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