Linagliptin as Add on Therapy to Empagliflozin 10 mg or 25 mg With Background Metformin in Patient With Type 2 Diabetes

Study Overview
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Brief Summary
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The objective of the study is to investigate the efficacy, safety and tolerability of linagliptin 5 mg qd compared to placebo given for 24 weeks in inadequately controlled T2DM patients on empagliflozin 10 mg or 25 mg and maximum tolerated dose of metformin. The primary objective of efficacy evaluation is planned after 24 weeks of treatment. The study is designed to show superiority of the combination of empagliflozin and linagliptin over empagliflozin alone.

Official Title
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A Phase III, Randomized, Double-blind, Parallel Group Study to Evaluate the Efficacy and Safety of Linagliptin 5 mg Compared to Placebo, Administered as Oral Fixed Dose Combination With Empagliflozin 10 mg or 25 mg for 24 Weeks, in Patients With Type 2 Diabetes Mellitus and Insufficient Glycaemic Control After 16 Weeks of Treatment With Empagliflozin 10 mg or 25 mg on Metformin Background Therapy

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: BI 10773
* Drug: BI 10773 Placebo
* Drug: BI 10773 / BI 1356
* Drug: BI 10773
* Drug: BI 10773 / BI 1356
* Drug: BI 10773 / BI 1356 Placebo
* Drug: BI 10773
* Drug: BI 10773
* Drug: BI 10773
* Drug: BI 10773 / BI 1356 Placebo
* Drug: BI 10773 Placebo
* Drug: BI 10773 / BI 1356 Placebo
* Drug: BI 10773
* Drug: BI 10773 / BI 1356 Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Signed and dated ICF (Informed Consent Form) Male or female on diet and exercise regime and on stable background metformin > or equal to 1500 mg or maximun dose according to local label HBA1c (Glicoslated Hemoglobin) > or equal to 8% and < or equal to 10.5 % at Visit 1 HbA1c > or equal to 7 and < or equal to 10.5 at Visit 4 Age > or equal to 18 years BMI (Body Mass Index) < or equal to 45 Exclusion criteria: Uncontrolled hyperglycemia during open label period and placebo add on run-in period Use of any other antidiabetic Renal function below 60 ml/min/1.73 m2 Antiobesity drugs or aggresive diets Gastorintestinal surgeries Current systemic steroids or uncontrolled endocrine disorders other than Diabetes Type 2 Acute coronary syndrome and stroke within 3 months of informed consent Known allergies to DPP-IV (Dypeptidil Peptidase IV) or SGLT-2 (Sodium Glucose Transporter 2) inhibitors

Ages Eligible for Study
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Minimum Age: 18 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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Empagliflozin 10 mg dose<br>Empagliflozin open label treatment period | Drug: BI 10773<br>* Empagliflozin active<br>|
| Experimental: Placebo add on 10 mg dose<br>Empagliflozin / Linagliptin 10/5 mg Dose FDC placebo add on run-in | Drug: BI 10773 / BI 1356 Placebo<br>* Empagliflozin / Linagliptin 10/5 mg Dose placebo FDC<br>Drug: BI 10773<br>* Empagliflozin active<br>|
| Experimental: Empagliflozin/Linagliptin 25/5 mg Dose<br>Empagliflozin / Linagliptin 25/5 mg Dose FDC active | Drug: BI 10773 / BI 1356<br>* Empagliflozin / Linagliptin 25/5 mg Dose FDC active<br>Drug: BI 10773 Placebo<br>* Empagliflozin placebo<br>|
| Experimental: Empagliflozin/Linagliptin 10/5 mg Dose.<br>Empagliflozin / Linagliptin 10/5 mg Dose FDC placebo | Drug: BI 10773 / BI 1356 Placebo<br>* Empagliflozin / Linagliptin 10/5 mg Dose FDC placebo<br>Drug: BI 10773<br>* Empagliflozin active<br>|
| Experimental: Empagliflozin/Linagliptin 10/5 mg Dose<br>Empagliflozin / Linagliptin 10/5 mg Dose FDC active | Drug: BI 10773 Placebo<br>* Empagliflozin placebo<br>Drug: BI 10773 / BI 1356<br>* Empagliflozin / Linagliptin 10/5 mg Dose FDC active<br>|
| Experimental: Empagliflozin 25 mg dose<br>Empagliflozin open label treatment period | Drug: BI 10773<br>* Empagliflozin active<br>|
| Experimental: Empagliflozin/Linagliptin 25/5 mg Dose.<br>Empagliflozin / Linagliptin 25/5 mg Dose FDC placebo | Drug: BI 10773<br>* Empagliflozin active<br>Drug: BI 10773 / BI 1356 Placebo<br>* Empagliflozin / Linagliptin 25/5 mg Dose FDC placebo<br>|
| Experimental: Placebo add on 25 mg dose<br>Empagliflozin / Linagliptin 25/5 mg Dose FDC placebo add on run-in | Drug: BI 10773<br>* Empagliflozin active<br>Drug: BI 10773 / BI 1356 Placebo<br>* Empagliflozin / Linagliptin 25/5 mg Dose FDC placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline of HbA1c After 24 Weeks of Treatment. | Change from baseline in Glycated haemoglobin (HbA1c) [%] after 24 weeks of treatment with double-blind trial medication, i.e. HbA1c change from baseline at Week 24. The term baseline was not used to refer to measurements prior to the administration of open-label medication. Such measurements were referred to as pre-treatment. Analyses of change from pre-treatment used the last value before first administration of open-label medication as point of reference. Observed Case (OC): This method analyse only available data that were observed while patients were on treatment, i.e., excluding the missing data. All values measured after rescue medication taken were set to missing. Full Analysis Set (FAS): Includes all patients in the Treated set who had a baseline HbA1c assessment and at least 1 on-treatment HbA1c assessment during the double-blind part of the trial. | Baseline and 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fasting Plasma Glucose (FPG) Change From Baseline at 24 Weeks. | Change from baseline FPG (mmol/L) after 24 weeks of treatment with double-blind trial medication, i.e. FPG change from baseline at Week 24. | Baseline and 24 weeks |