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Study of Insulin Lispro in Participants With Inadequately Controlled Type 2 Diabetes (AUTONOMY)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01215955
First received: September 30, 2010
Last updated: April 3, 2014
Last verified: April 2014
Results First Received: January 9, 2014  
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 lispro
Drug: 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
Protocol had 2 independent studies (Study A, Study B) from which data was analyzed separately and independently: Participants were randomized to 1of the 2 treatment arms (Q1D, Q3D) at the site level. Sites were assigned to a study according to an allocation plan that was pre-specified before initiation of the study.

Reporting Groups
  Description
Study A Q1D

Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose reading from the previous day (Q1D).

Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks.

Participants were randomized to Q1D at the site level: sites were assigned to Study A according to an allocation plan that was pre-specified before initiation of Study A.

Study A Q3D

Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose readings from the past 3 days (Q3D).

Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks.

Participants were randomized to Q3D at the site level: sites were assigned to Study A according to an allocation plan that was pre-specified before initiation of Study A.

Study B Q1D

Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose reading from the previous day (Q1D).

Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks.

Participants were randomized to Q1D at the site level: sites were assigned to Study B according to an allocation plan that was pre-specified before initiation of Study B.

Study B Q3D

Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose readings from the past 3 days (Q3D).

Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks.

Participants were randomized to Q3D at the site level: sites were assigned to Study B according to an allocation plan that was pre-specified before initiation of Study B.


Participant Flow:   Overall Study
    Study A Q1D   Study A Q3D   Study B Q1D   Study B Q3D
STARTED   268   263   292 [1]   294 [2] 
Received at Least 1 Dose of Study Drug   267   261   288   290 
COMPLETED   223   210   244   241 
NOT COMPLETED   45   53   48   53 
Adverse Event                1                4                2                3 
Death                2                0                1                3 
Entry Criteria Not Met                1                3                4                7 
Lack of Efficacy                1                2                1                0 
Lost to Follow-up                4                4                8                9 
Physician Decision                4                10                8                11 
Protocol Violation                17                13                8                8 
Sponsor Decision                1                2                0                1 
Withdrawal by Subject                14                15                13                9 
Quality Issues                0                0                3                2 
[1] Three (3) participants from 1 site were excluded due to quality issues and validity of data.
[2] Two (2) participants from 1 site were excluded due to quality issues and validity of the data.



  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.
Full Analysis Set-all participants who entered this study, completed the lead-in period (if applicable), were randomized and received ≥1 dose of study insulin, except the participants from the site excluded due to quality issues and data validity.

Reporting Groups
  Description
Study A Q1D

Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose reading from the previous day (Q1D).

Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks.

Participants were randomized to Q1D at the site level: sites were assigned to Study A according to an allocation plan that was pre-specified before initiation of Study A.

Study A Q3D

Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated based dose was on blood glucose readings from the past 3 days (Q3D).

Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks.

Participants were randomized to Q3D at the site level: sites were assigned to Study A according to an allocation plan that was pre-specified before initiation of Study A.

Study B Q1D

Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose reading from the previous day (Q1D).

Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks.

Participants were randomized to Q1D at the site level: sites were assigned to Study B according to an allocation plan that was pre-specified before initiation of Study B.

Study B Q3D

Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose readings from the past 3 days (Q3D).

Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks.

Participants were randomized to Q3D at the site level: sites were assigned to Study B according to an allocation plan that was pre-specified before initiation of Study B.

Total Total of all reporting groups

Baseline Measures
   Study A Q1D   Study A Q3D   Study B Q1D   Study B Q3D   Total 
Overall Participants Analyzed 
[Units: Participants]
 267   261   288   290   1106 
Age 
[Units: Years]
Mean (Standard Deviation)
 57.89  (10.25)   58.82  (9.46)   57.71  (9.71)   57.01  (10.61)   57.83  (10.03) 
Gender 
[Units: Participants]
         
Female   133   138   155   155   581 
Male   134   123   133   135   525 
Ethnicity (NIH/OMB) 
[Units: Participants]
         
Hispanic or Latino   100   96   91   95   382 
Not Hispanic or Latino   150   153   182   177   662 
Unknown or Not Reported   17   12   15   18   62 
Race (NIH/OMB) 
[Units: Participants]
         
American Indian or Alaska Native   22   20   11   11   64 
Asian   4   4   8   2   18 
Native Hawaiian or Other Pacific Islander   0   2   0   0   2 
Black or African American   20   15   35   29   99 
White   219   218   228   240   905 
More than one race   1   2   4   6   13 
Unknown or Not Reported   1   0   2   2   5 
Region of Enrollment 
[Units: Participants]
         
Argentina   28   28   37   38   131 
Austria   0   1   4   1   6 
Brazil   2   4   11   14   31 
Canada   5   6   7   11   29 
Croatia   3   3   4   5   15 
Denmark   5   0   1   0   6 
France   3   0   1   3   7 
Lithuania   2   4   4   5   15 
Mexico   31   31   21   25   108 
Poland   9   8   15   15   47 
Puerto Rico   26   19   7   7   59 
Romania   9   6   11   10   36 
Russian Federation   12   13   15   16   56 
South Africa   1   2   11   13   27 
United States   131   136   139   127   533 


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Change From Baseline to 24 Week Endpoint in Glycated Hemoglobin (HbA1c)   [ Time Frame: Baseline, 24 weeks ]

2.  Secondary:   Percentage of Participants Achieving Glycated Hemoglobin (HbA1c) Target Values   [ Time Frame: 24-week endpoint ]

3.  Secondary:   Percentage of Participants ≥65 Years of Age Achieving Glycated Hemoglobin (HbA1c) Target Concentration   [ Time Frame: 24-week endpoint ]

4.  Secondary:   Change From Baseline to 24 Week Endpoint in Body Weight   [ Time Frame: Baseline, 24-weeks ]

5.  Secondary:   Time to Reach Glycated Hemoglobin (HbA1c) Target Values   [ Time Frame: Baseline through 24 weeks ]

6.  Secondary:   Change From Baseline to 24 Week Endpoint in Fasting Glucose   [ Time Frame: Baseline, 24 weeks ]

7.  Secondary:   Change From Baseline to 24 Week Endpoint in Fasting Glucose in Participants ≥65 Years of Age   [ Time Frame: Baseline, 24 weeks ]

8.  Secondary:   Change From Baseline to 24 Week Endpoint in 1,5-anhydroglucitol (1,5-AG)   [ Time Frame: Baseline, 24 weeks ]

9.  Secondary:   Change From Baseline to 24 Weeks in 7-Point Self-Monitored Blood Glucose (SMBG) Profile   [ Time Frame: Baseline, 24 weeks ]

10.  Secondary:   Daily Dose of Insulin: Total, Basal and Prandial (Bolus)   [ Time Frame: 24 weeks ]

11.  Secondary:   Daily Dose of Insulin Per Kilogram of Body Weight: Total, Basal and Prandial (Bolus)   [ Time Frame: 24 weeks ]

12.  Secondary:   The Number of Participants With a Hypoglycemic Episode (Incidence)   [ Time Frame: Randomization through 24 weeks overall ]

13.  Secondary:   The Number of Participants ≥65 Years of Age With Hypoglycemic Episodes (Incidence)   [ Time Frame: Randomization through 24 weeks overall ]

14.  Secondary:   The Rate of Hypoglycemic Episodes   [ Time Frame: Randomization through 24 weeks overall ]

15.  Secondary:   Percentage of Participants With Severe Hypoglycemic Episodes   [ Time Frame: Randomization up to 24 weeks ]


  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
Five (5) randomized participants (3 Study B Q1D, 2 Study B Q3D) from 1 site were excluded from efficacy and safety analyses due to quality issues and validity of the data at that site.


  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.


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



Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01215955     History of Changes
Other Study ID Numbers: 13460
F3Z-MC-IOQC ( Other Identifier: Eli Lilly and Company )
Study First Received: September 30, 2010
Results First Received: January 9, 2014
Last Updated: April 3, 2014
Health Authority: Argentina: Ministry of Health
Austria: Federal Office for Safety in Health Care
Brazil: Ethics Committee
Brazil: Ministry of Health
Canada: Canadian Institutes of Health Research
Zanzibar: Ministry of Health and Social Welfare
Denmark: Danish Medicines Agency
France: Ministry of Health
Lithuania: State Medicine Control Agency - Ministry of Health
Mexico: Federal Commission for Protection Against Health Risks
Poland: Ministry of Health
Romania: National Medicines Agency
Russia: Ministry of Health of the Russian Federation
South Africa: Medicines Control Council
Spain: Ministry of Health
United States: Food and Drug Administration