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Lispro Mid Mixture (MM) Intensive Mixture Therapy With Progressive Dose-Titration of Lispro Low Mixture (LM) or Biphasic Insulin Aspart 30/70 (S019)

This study has been completed.
Sponsor:
Information provided by:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00393705
First received: October 26, 2006
Last updated: July 15, 2010
Last verified: July 2010
History of Changes
Results First Received: March 31, 2010  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Diabetes Mellitus, Type 2
Interventions: Drug: Insulin Biphasic Aspart 30/70
Drug: insulin lispro LM
Drug: insulin lispro MM

  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
No text entered.

Reporting Groups
  Description
Insulin Lispro LM + Insulin Lispro MM

Three times per day insulin lispro mid mixture (MM) with the possiblity to change the evening injection of MM to insulin lispro low mixture (LM) if fasting blood glucose target is not achieved.

Insulin lispro mid mixture (MM): Participant adjusted dose, three times per day, injected subcutaneously for 16 weeks.

Insulin lispro low mixture (LM): Participant adjusted dose, possibly in the evening.
Insulin Biphasic Aspart 30/70 or Insulin Lispro LM

Twice daily treatment of either biphasic insulin aspart 30/70 or insulin lispro LM (continuation of analogue formulation used before study enrollment).

Insulin Biphasic Aspart 30/70: Participant adjusted dose, twice daily, injected subcutaneously for 16 weeks.

Insulin Lispro LM: Participant adjusted dose, twice daily, injected subcutaneously for 16 weeks.

Participant Flow:   Overall Study
    Insulin Lispro LM + Insulin Lispro MM     Insulin Biphasic Aspart 30/70 or Insulin Lispro LM  
STARTED     151     151  
Received at Least One Dose of Study Drug     139     139  
COMPLETED     128     128  
NOT COMPLETED     23     23  
Adverse Event                 0                 2  
Death                 0                 1  
Lost to Follow-up                 2                 2  
Entry Criteria Not Met                 10                 10  
Protocol Violation                 4                 3  
Withdrawal by Subject                 5                 3  
Physician Decision                 2                 2  



  Baseline Characteristics
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Reporting Groups
  Description
Insulin Lispro LM + Insulin Lispro MM

Three times per day insulin lispro mid mixture (MM) with the possiblity to change the evening injection of MM to insulin lispro low mixture (LM) if fasting blood glucose target is not achieved.

Insulin lispro mid mixture (MM): Participant adjusted dose, three times per day, injected subcutaneously for 16 weeks.

Insulin lispro low mixture (LM): Participant adjusted dose, possibly in the evening.
Insulin Biphasic Aspart 30/70 or Insulin Lispro LM

Twice daily treatment of either biphasic insulin aspart 30/70 or insulin lispro LM (continuation of analogue formulation used before study enrollment).

Insulin Biphasic Aspart 30/70: Participant adjusted dose, twice daily, injected subcutaneously for 16 weeks.

Insulin Lispro LM: Participant adjusted dose, twice daily, injected subcutaneously for 16 weeks.
Total Total of all reporting groups

Baseline Measures
    Insulin Lispro LM + Insulin Lispro MM     Insulin Biphasic Aspart 30/70 or Insulin Lispro LM     Total  
Number of Participants  
[units: participants]
 		  151     151     302  
Age  
[units: years]
Mean ± Standard Deviation 		  57.0  ± 9.50     58.4  ± 9.01     57.7  ± 9.27  
Gender  
[units: participants]
 		     
Female     92     82     174  
Male     59     69     128  
Race/Ethnicity, Customized  
[units: participants]
 		     
Caucasian     150     149     299  
African     1     2     3  
Region of Enrollment  
[units: participants]
 		     
Poland     33     33     66  
Croatia     7     11     18  
Turkey     33     45     78  
Romania     37     28     65  
South Africa     12     13     25  
Hungary     29     21     50  
Body Mass Index (BMI) [1]
[units: kilograms per square meter (kg/m^2)]
Mean ± Standard Deviation 		  32.3  ± 4.11     31.0  ± 4.27     31.7  ± 4.23  
Daily Dose of Antihyperglycaemic Therapy Prior to Study (International Units [IU])  
[units: International Units (IU)]
Mean ± Standard Deviation 		     
Insulin Lispro Dose (n=61, n=57)     45.8  ± 16.87     39.7  ± 13.79     42.9  ± 15.69  
Biphasic Insulin Aspart 30/70 Dose (n=90, n=94)     47.5  ± 20.31     44.0  ± 17.79     45.7  ± 19.09  
Daily Dose of Metformin Treatment Prior to Study (milligrams [mg])  
[units: milligrams (mg)]
Mean ± Standard Deviation 		  1898.8  ± 402.99     1863.9  ± 379.00     1881.4  ± 390.92  
Duration of Antihyperglycaemic Therapy Prior to Study  
[units: months]
Mean ± Standard Deviation 		     
Insulin Treatment     42.8  ± 41.65     43.7  ± 51.50     43.3  ± 46.76  
Premixed Insulin Analogue Treatment     16.4  ± 17.61     16.1  ± 22.42     16.3  ± 20.12  
Oral Hypoglycemic Treatment     54.7  ± 56.55     58.9  ± 64.56     56.8  ± 60.62  
Duration of Diabetes  
[units: years]
Mean ± Standard Deviation 		  10.9  ± 5.66     11.5  ± 7.19     11.2  ± 6.47  
Fasting Plasma Glucose  
[units: milligrams per deciliter (mg/dL)]
Mean ± Standard Deviation 		  182.6  ± 46.15     185.4  ± 59.22     184.0  ± 53.04  
Height  
[units: centimeters (cm)]
Mean ± Standard Deviation 		  165.4  ± 9.47     165.4  ± 9.82     165.4  ± 9.63  
Hemoglobin A1c (HbA1c)  
[units: percent HbA1c]
Mean ± Standard Deviation 		  8.6  ± 1.27     8.5  ± 1.20     8.5  ± 1.23  
Weight  
[units: kilograms (kg)]
Mean ± Standard Deviation 		  88.6  ± 14.97     85.1  ± 14.45     86.8  ± 14.79  
[1] Body mass index is an estimate of body fat based on body weight divided by height squared.



  Outcome Measures
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1.  Primary:   Hemoglobin A1c (HbA1c) at 16 Week Endpoint   [ Time Frame: 16 weeks ]
  Show Outcome Measure 1

2.  Secondary:   Percentage of Patients Achieving Hemoglobin A1c (HbA1c) <7% and HbA1c ≤6.5% at 16 Week Endpoint   [ Time Frame: 16 weeks ]
  Show Outcome Measure 2

3.  Secondary:   Change From Baseline in Hemoglobin A1c (HbA1c) at 16 Week Endpoint   [ Time Frame: Baseline, 16 Weeks ]
  Show Outcome Measure 3

4.  Secondary:   2-hour Postprandial Plasma Glucose Concentrations After the Midday Meal From Self-monitored 7-point Plasma Glucose at 16 Week Endpoint   [ Time Frame: 16 weeks ]
  Show Outcome Measure 4

5.  Secondary:   Mean 2-hour Postprandial Blood Glucose Excursions After Midday Meal at 16 Week Endpoint   [ Time Frame: 16 weeks ]
  Show Outcome Measure 5

6.  Secondary:   Mean Daily Blood Glucose Values at 16 Week Endpoint   [ Time Frame: 16 weeks ]
  Show Outcome Measure 6

7.  Secondary:   Number of Patients With Self-reported Hypoglycemic Episodes   [ Time Frame: Baseline through 16 weeks ]
  Show Outcome Measure 7

8.  Secondary:   30-Day Adjusted Rate of Hypoglycemic Events   [ Time Frame: Baseline through 16 weeks ]
  Show Outcome Measure 8

9.  Secondary:   Change From Baseline in Weight at 16 Week Endpoint   [ Time Frame: Baseline, 16 weeks ]
  Show Outcome Measure 9

10.  Secondary:   Total Daily Insulin Dose at 4 Weeks and 12 Weeks   [ Time Frame: 4 weeks and 12 weeks ]
  Hide Outcome Measure 10

Measure Type Secondary
Measure Title Total Daily Insulin Dose at 4 Weeks and 12 Weeks
Measure Description No text entered.
Time Frame 4 weeks and 12 weeks  
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.
Number of patients who received at least one dose of study drug and had a post-baseline insulin measurement at week 4 and week 12.

Reporting Groups
  Description
Insulin Lispro LM + Insulin Lispro MM

Three times per day insulin lispro mid mixture (MM) with the possiblity to change the evening injection of MM to insulin lispro low mixture (LM) if fasting blood glucose target is not achieved.

Insulin lispro mid mixture (MM): Participant adjusted dose, three times per day, injected subcutaneously for 16 weeks.

Insulin lispro low mixture (LM): Participant adjusted dose, possibly in the evening.
Insulin Biphasic Aspart 30/70 or Insulin Lispro LM

Twice daily treatment of either biphasic insulin aspart 30/70 or insulin lispro LM (continuation of analogue formulation used before study enrollment).

Insulin Biphasic Aspart 30/70: Participant adjusted dose, twice daily, injected subcutaneously for 16 weeks.

Insulin Lispro LM: Participant adjusted dose, twice daily, injected subcutaneously for 16 weeks.

Measured Values
    Insulin Lispro LM + Insulin Lispro MM     Insulin Biphasic Aspart 30/70 or Insulin Lispro LM  
Number of Participants Analyzed  
[units: participants]
 		  134     135  
Total Daily Insulin Dose at 4 Weeks and 12 Weeks  
[units: International Units (IU)]
Mean ± Standard Deviation 		   
4 Weeks (n=134, n=135)     57.1  ± 22.32     51.4  ± 18.90  
12 Weeks (n=130, n=131)     64.4  ± 25.63     58.0  ± 22.90  


Statistical Analysis 1 for Total Daily Insulin Dose at 4 Weeks and 12 Weeks
Groups [1] All groups
Method [2] ANCOVA
P Value [3] 0.0056
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  Model: Value = Treatment + Lead-in + Treatment*Lead-in + Visit + Treatment*Visit + Value at baseline + error.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  P-value for Week 4

Statistical Analysis 2 for Total Daily Insulin Dose at 4 Weeks and 12 Weeks
Groups [1] All groups
Method [2] ANCOVA
P Value [3] 0.0421
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  Model: Value = Treatment + Lead-in + Treatment*Lead-in + Visit + Treatment*Visit + Value at baseline + error.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  P-value for Week 12




  Serious Adverse Events
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  Other Adverse Events
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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 Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.


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.  


Results Point of Contact:  
Name/Title: Chief Medical Officer
Organization: Eli Lilly and Company
phone: 800-545-5979


No publications provided


Responsible Party: Chief Medical Officer, Eli Lilly
ClinicalTrials.gov Identifier: NCT00393705     History of Changes
Other Study ID Numbers: 10916, F3Z-VI-S019
Study First Received: October 26, 2006
Results First Received: March 31, 2010
Last Updated: July 15, 2010
Health Authority: Poland: Ministry of Science and Higher Education