Treatment of Type 2 Diabetes With Linagliptin 2.5 mg Bid + Metformin 500 or 1000 mg Bid and Metformin 1000 mg Bid

Study Overview
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Brief Summary
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A phase III randomised, double-blind parallel group extension study to investigate the efficacy and safety of twice daily administration of the free combination of linagliptin 2.5 mg + metformin 500 mg or of linagliptin 2.5 mg + metformin 1000 mg versus monotherapy with metformin 1000 mg twice daily over 54 weeks in type 2 diabetic patients previously completing the double-blind part of study 1218.46

Official Title
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Extension Study Linagliptin 2.5 mg Bid + Metformin 500 or 1000 mg Bid Versus Metformin 1000 mg Bid

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Linagliptin + metformin
* Drug: Linagliptin+metformin
* Drug: Metformin


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Signed and dated written informed consent, at the latest by the date of Visit 1 Patients completing the entire treatment period of the double-blind study 1218.46, who are not treated with rescue medication (Visit 7) Exclusion criteria: Patients who meet one or more of the withdrawal criteria of the treatment period of the previous study 1218.46 Pre-menopausal women (last menstruation equal or less than 1 year prior to signing informed consent) who: are nursing or pregnant, or are of child-bearing potential and are not practicing an acceptable method of birth control, or do not plan to continue using this method throughout the study and do not agree to submit to periodic pregnancy testing during participation in the trial. Acceptable methods of birth control include transdermal patch, intra uterine devices/systems (IUDs/IUSs), oral, implantable or injectable contraceptives, sexual abstinence and vasectomised partner and in addition for male partners a barrier method, such as the use of condom with spermicide. No exception will be made. Alcohol abuse within the 3 months prior to informed consent that would interfere with study participation Drug abuse that in the opinion of the investigator would interfere with trial participation Any other clinical condition which, in the opinion of the investigator, would not allow safe completion of the protocol and safe administration of the study medication

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Linagliptin + metformin bid<br>Linagliptin low dose + metformin 500 mg, bid | Drug: Linagliptin + metformin<br>* Linagliptin tablet low dose + metformin tablet 500 mg bid<br>|
| Experimental: Linagliptin+ metformin bid<br>Linagliptin low dose + metformin 1000 mg bid | Drug: Linagliptin+metformin<br>* Linagliptin low dose tablet + metformin 1000 mg tablet bid<br>|
| Active Comparator: Metformin bid<br>Metformin 1000 mg bid | Drug: Metformin<br>* Metformin 1000 mg tablet bid<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of Patients With Adverse Events (AEs) | This includes any AEs detected during routine physical examination and electrocardiogram (ECG) procedures. | 54 weeks | 
| Change From Baseline at Week 54 in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | Baseline is defined as Visit 1 of 1218.52. | 54 weeks | 
| Change From Baseline at Week 54 in Pulse Rate | Baseline is defined as Visit 1 of 1218.52. | 54 weeks | 
| Frequency of Patients With Possibly Clinically Significant Abnormal Laboratory Parameters: Haematology |  | 54 weeks | 
| Possibly Clinically Significant Abnormal Laboratory Parameters: Clinical Chemistry | ULN means upper limit of normal | 54 weeks | 
| Clinical Relevant Drug-related Abnormal Findings in Physical Examination and ECG as Reported as AE | Frequency of patients with adverse events by treatment, primary system organ class and preferred term | Baseline and drug stop (up to 54 weeks) + 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in HbA1c From Baseline Over Time | HbA1c is measured as a percentage. Thus, this change from baseline reflects the visit HbA1c percent minus the baseline HbA1c percent. Baseline is defined as visit 1 of 1218.52. | 54 weeks | 
| Number of Patients With HbA1c <7.0% After 54 Weeks |  | 54 weeks | 
| Number of Patients With HbA1c <6.5% Over Time |  | 54 weeks | 
| Number of Patients With HbA1c of at Least <0.5% Over Time |  | 54 weeks | 
| Change in FPG From Baseline Over Time | Baseline is defined as visit 1 of 1218.52. | 54 weeks | 
| Number of Patients With Rescue Therapy |  | 54 weeks | 
| Change in HbA1c From Baseline Over Time | HbA1c is measured as a percentage. Thus, this change from baseline reflects the visit HbA1c percent minus the baseline HbA1c percent. Baseline is defined as visit 3 from study 1218.46 (NCT00915772). | 78 weeks |