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Efficacy and Safety of BI 1356 in Combination With Metformin in Patients With Type 2 Diabetes

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ClinicalTrials.gov Identifier: NCT00622284
Recruitment Status : Completed
First Posted : February 25, 2008
Results First Posted : February 20, 2012
Last Update Posted : January 29, 2014
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double;   Primary Purpose: Treatment
Condition: Diabetes Mellitus, Type 2
Interventions: Drug: Placebo identical to BI 1356 5mg
Drug: Placebo identical to Glimepiride 1mg or 2mg or 3mg or 4 mg
Drug: BI 1356
Drug: Glimepiride

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
There were in total 1560 patients randomised in the study. Of these, 1 patient was not treated. The remaining 8 patients not accounted for in the treated set were removed from all study analyses (explained in trial report) due to major good-clinical-practice violations at the site, and the inability to verify the validity of any patient level data.

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
Linagliptin Patients randomized to receive Linagliptin 5mg and metformin
Glimepiride Patients randomized to receive Glimepiride 1-4mg and metformin

Participant Flow:   Overall Study
    Linagliptin   Glimepiride
STARTED   776 [1]   775 [2] 
COMPLETED   587 [3]   604 [3] 
NOT COMPLETED   189   171 
Lack of Efficacy                45                15 
Adverse Event                61                90 
Protocol Violation                12                5 
Lost to Follow-up                11                13 
Withdrawal by Subject                27                24 
Other reason (not specified)                33                24 
[1] Number who started treatment. One patient in the Linagliptin group was randomized but not treated.
[2] Number who started treatment.
[3] Number who completed treatment.



  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.
No text entered.

Reporting Groups
  Description
Linagliptin Patients randomized to receive Linagliptin 5mg and metformin
Glimepiride Patients randomized to receive Glimepiride 1-4mg and metformin
Total Total of all reporting groups

Baseline Measures
   Linagliptin   Glimepiride   Total 
Overall Participants Analyzed 
[Units: Participants]
 		 776   775   1551 
Age 
[Units: Years]
Mean (Standard Deviation) 		 59.8  (9.4)   59.8  (9.4)   59.8  (9.4) 
Gender 
[Units: Patients]
 		     
Female   314   304   618 
Male   462   471   933 
Body mass index (BMI) continuous 
[Units: Kg/m^2]
Mean (Standard Deviation) 		 30.21  (4.77)   30.31  (4.57)   30.26  (4.67) 
Weight 
[Units: Kg]
Mean (Standard Deviation) 		 86.14  (17.57)   86.77  (16.69)   86.46  (17.14) 
Glycosylated haemoglobin (HbA1c) [1] 
[Units: Percent]
Mean (Standard Deviation) 		 7.69  (0.88)   7.69  (0.86)   7.69  (0.87) 
[1] Baseline HbA1c was available for 1519 patients in the Full Analysis Set (FAS), 764 treated with Linagliptin and 755 patients treated with Glimepiride.
Fasting blood plasma glucose (FPG) [1] 
[Units: mg/dL]
Mean (Standard Deviation) 		 164.46  (42.83)   166.09  (42.05)   165.27  (42.43) 
[1] Baseline fasting plasma glucose (FPG) was available for 1475 patients in the FAS, 740 treated with Linagliptin and 735 patients treated with Glimepiride.


  Outcome Measures

1.  Primary:   HbA1c Change From Baseline at Week 52   [ Time Frame: Baseline and week 52 ]
  Show Outcome Measure 1

2.  Primary:   HbA1c Change From Baseline at Week 104   [ Time Frame: Baseline and week 104 ]
  Show Outcome Measure 2

3.  Secondary:   Body Weight Change From Baseline at Week 52   [ Time Frame: Baseline and week 52 ]
  Show Outcome Measure 3

4.  Secondary:   Body Weight Change From Baseline at Week 104   [ Time Frame: Baseline and week 104 ]
  Show Outcome Measure 4

5.  Secondary:   Incidence of Hypoglycaemic Events up to 52 Weeks   [ Time Frame: Week 52 ]
  Show Outcome Measure 5

6.  Secondary:   Incidence of Hypoglycaemic Events up to 104 Weeks   [ Time Frame: Week 104 ]
  Show Outcome Measure 6

7.  Secondary:   Fasting Plasma Glucose (FPG) Change From Baseline at Week 52   [ Time Frame: Baseline and week 52 ]
  Show Outcome Measure 7

8.  Secondary:   Fasting Plasma Glucose (FPG) Change From Baseline at Week 104   [ Time Frame: Baseline and week 104 ]
  Show Outcome Measure 8

9.  Secondary:   Percentage of Patients With HbA1c <7.0% at Week 52   [ Time Frame: Week 52 ]
  Show Outcome Measure 9

10.  Secondary:   Percentage of Patients With HbA1c <7.0% at Week 104   [ Time Frame: Week 104 ]
  Show Outcome Measure 10

11.  Secondary:   Percentage of Patients With HbA1c <6.5% at Week 52   [ Time Frame: Week 52 ]
  Show Outcome Measure 11

12.  Secondary:   Percentage of Patients With HbA1c <6.5% at Week 104   [ Time Frame: Week 104 ]
  Show Outcome Measure 12

13.  Secondary:   Percentage of Patients With HbA1c Lowering by 0.5% at Week 104   [ Time Frame: Week 104 ]
  Show Outcome Measure 13

14.  Secondary:   2 hr Postprandial Glucose (PPG) Change From Baseline at Week 104   [ Time Frame: Baseline and week 104 ]
  Show Outcome Measure 14

15.  Secondary:   HbA1c Change at Week 4   [ Time Frame: Baseline and week 4 ]
  Show Outcome Measure 15

16.  Secondary:   HbA1c Change at Week 8   [ Time Frame: Baseline and week 8 ]
  Show Outcome Measure 16

17.  Secondary:   HbA1c Change at Week 12   [ Time Frame: Baseline and week 12 ]
  Show Outcome Measure 17

18.  Secondary:   HbA1c Change at Week 16   [ Time Frame: Baseline and week 16 ]
  Show Outcome Measure 18

19.  Secondary:   HbA1c Change at Week 28   [ Time Frame: Baseline and week 28 ]
  Show Outcome Measure 19

20.  Secondary:   HbA1c Change at Week 40   [ Time Frame: Baseline and week 40 ]
  Hide Outcome Measure 20

Measure Type Secondary
Measure Title HbA1c Change at Week 40
Measure Description No text entered.
Time Frame Baseline and week 40  

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.
The Full Analysis Set (FAS) included all treated and randomized patients with a baseline and at least one on-treatment HbA1c measurement. Last observation carried forward (LOCF) was used as imputation rule.

Reporting Groups
  Description
Linagliptin Patients randomized to receive Linagliptin 5mg and metformin
Glimepiride Patients randomized to receive Glimepiride 1-4mg and metformin

Measured Values
   Linagliptin   Glimepiride 
Participants Analyzed 
[Units: Participants]
 		 764   755 
HbA1c Change at Week 40 
[Units: Percent]
Mean (Standard Deviation) 		 -0.42  (0.77)   -0.69  (0.83) 

No statistical analysis provided for HbA1c Change at Week 40



21.  Secondary:   HbA1c Change at Week 52   [ Time Frame: Baseline and week 52 ]
  Show Outcome Measure 21

22.  Secondary:   HbA1c Change at Week 65   [ Time Frame: Baseline and week 65 ]
  Show Outcome Measure 22

23.  Secondary:   HbA1c Change at Week 78   [ Time Frame: Baseline and week 78 ]
  Show Outcome Measure 23

24.  Secondary:   HbA1c Change at Week 91   [ Time Frame: Baseline and week 91 ]
  Show Outcome Measure 24

25.  Secondary:   HbA1c Change at Week 104   [ Time Frame: Baseline and week 104 ]
  Show Outcome Measure 25

26.  Secondary:   Change in Baseline Lipid Parameter Cholesterol at Week 104   [ Time Frame: Baseline and week 104 ]
  Show Outcome Measure 26

27.  Secondary:   Change in Baseline Lipid Parameter HDL at Week 104   [ Time Frame: Baseline and week 104 ]
  Show Outcome Measure 27

28.  Secondary:   Change in Baseline Lipid Parameter Low Density Lipoprotein (LDL) at Week 104   [ Time Frame: Baseline and week 104 ]
  Show Outcome Measure 28

29.  Secondary:   Change in Baseline Lipid Parameter Triglyceride at Week 104   [ Time Frame: Baseline and week 104 ]
  Show Outcome Measure 29


  Serious Adverse Events


  Other Adverse Events


  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
With the exception of HbA1c<6.5% and HbA1c<7.0% at Week52, all other endpoints are presented in the Week52 repeated analysis within the final clinical trial report, where discrepancies between interim and final results are also explained.


  More Information