Safety and Efficacy of Empagliflozin (BI 10773) and Sitagliptin Versus Placebo Over 76 Weeks in Patients With Type 2 Diabetes

Study Overview
=================
Brief Summary
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This study will investigate the efficacy and long term safety and tolerability of BI 10773 in type 2 diabetic patients.

Official Title
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A Phase III Double-blind, Extension, Placebo-controlled Parallel Group Safety and Efficacy Trial of BI 10773 (10 and 25mg Once Daily) and Sitagliptin (100mg Once Daily) Given for Minimum 76 Weeks (Incl. 24 Weeks of Preceding Trial) as Monotherapy or With Different Back-ground Therapies in Patients With Type 2 Diabetes Mellitus Previously Completing Trial 1245.19, 1245.20 or 1245.23

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: BI 10773
* Drug: Placebo
* Drug: Placebo
* Drug: Placebo
* Drug: Placebo
* Drug: Placebo
* Drug: BI 10773
* Drug: Placebo
* Drug: Placebo
* Drug: BI 10773
* Drug: Placebo
* Drug: Placebo
* Drug: Placebo
* Drug: BI 10773
* Drug: BI 10773
* Drug: BI 10773
* Drug: Placebo
* Drug: BI 10773
* Drug: Placebo
* Drug: Placebo
* Drug: Placebo
* Drug: Sitagliptin 100mg
* Drug: BI 10773
* Drug: Placebo
* Drug: Placebo
* Drug: Placebo
* Drug: Placebo
* Drug: Placebo
* Drug: Placebo
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Patients completing the entire treatment period of the preceding double-blind trial 1245.19, 1245.20 or 1245.23 with or without rescue therapy. Signed and dated written informed consent by date of Visit 1 in accordance with Good Clinical Practice and local legislation. Exclusion criteria: Patient who meet one or more of the withdrawal criteria of the treatment period of the previous trial 1245.19, 1245.20 or 1245.23. Indication of liver disease, defined by serum levels of either alanine aminotransferase , aspartate aminotransferase, or alkaline phosphatase above 3 x upper limit of normal as determined during last visit of preceding trial. Impaired renal function defined as glomerular filtration rate<30 ml/min (severe renal impairment, Modification of Diet in Renal Disease formula) as determined during last visit of preceding trial. Contraindications to sitagliptin, pioglitazone, metformin or sulfonylurea according to local label, which started during trial participation in 1245.19, 1245.20 or 1245.23 Pre-menopausal women (last menstruation < or = 1 year prior to 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 tubal ligation, transdermal patch, intra uterine devices/systems, oral, implantable or injectable contraceptives, sexual abstinence (if acceptable by local authorities), double barrier method and vasectomised partner. Alcohol or drug abuse within the 3 months prior to informed consent that would interfere with trial participation or any ongoing condition leading to a decreased compliance to study procedures or study drug intake. Participation in another trial with an investigational drug within 30 days prior to informed consent (except 1245.19, 1245.20 and 1245.23). Any other clinical condition that would jeopardize patient's safety while participating in this clinical trial.

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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BI 10773 low (drug naive)<br>BI 10773 tablets once daily | Drug: BI 10773<br>* BI 10773 tablets once daily<br>Drug: Placebo<br>* Placebo matching Sitagliptin<br>Drug: Placebo<br>* Placebo matching BI 10773 high dose<br>|
| Experimental: BI 10773 high (drug naive)<br>BI 10773 tablets once daily | Drug: Placebo<br>* Placebo matching Sitagliptin<br>Drug: BI 10773<br>* BI 10773 tablets once daily<br>Drug: Placebo<br>* Placebo matching BI 10773 low dose<br>|
| Placebo Comparator: Placebo (drug naive)<br>Placebo tablets matching BI 10773 / Sitagliptin once daily | Drug: Placebo<br>* Placebo matching BI 10773 low dose<br>Drug: Placebo<br>* Placebo matching Sitagliptin<br>Drug: Placebo<br>* Placebo matching BI 10773 high dose<br>|
| Active Comparator: Sitagliptin 100mg (drug naive)<br>Sitagliptin once daily | Drug: Placebo<br>* Placebo matching BI 10773 high dose<br>Drug: Placebo<br>* Placebo matching BI 10773 low dose<br>Drug: Sitagliptin 100mg<br>* Sitagliptin once daily<br>|
| Experimental: BI 10773 low (pioglitazone)<br>BI 10773 tablets once daily | Drug: BI 10773<br>* BI 10773 tablets once daily<br>Drug: Placebo<br>* Placebo matching BI 10773 high dose<br>|
| Experimental: BI 10773 high (pioglitazone)<br>BI 10773 tablets once daily | Drug: BI 10773<br>* BI 10773 tablets once daily<br>Drug: Placebo<br>* Placebo matching BI 10773 low dose<br>|
| Placebo Comparator: Placebo (pioglitazone)<br>Placebo tablets matching BI 10773 once daily | Drug: Placebo<br>* Placebo matching BI 10773 low dose<br>Drug: Placebo<br>* Placebo matching BI 10773 high dose<br>|
| Experimental: BI 10773 low (metformin)<br>BI 10773 tablets once daily | Drug: Placebo<br>* Placebo matching BI 10773 high dose<br>Drug: BI 10773<br>* BI 10773 tablets once daily<br>|
| Experimental: BI 10773 high (metformin)<br>BI 10773 tablets once daily | Drug: BI 10773<br>* BI 10773 tablets once daily<br>Drug: Placebo<br>* Placebo matching BI 10773 low dose<br>|
| Placebo Comparator: Placebo (metformin)<br>Placebo tablets matching BI 10773 once daily | Drug: Placebo<br>* Placebo matching BI 10773 low dose<br>Drug: Placebo<br>* Placebo matching BI 10773 high dose<br>|
| Experimental: BI 10773 low (metformin+sulfonylurea)<br>BI 10773 tablets once daily | Drug: BI 10773<br>* BI 10773 tablets once daily<br>Drug: Placebo<br>* Placebo matching BI 10773 high dose<br>|
| Experimental: BI 10773 high (metformin+sulfonylurea)<br>BI 10773 tablets once daily | Drug: BI 10773<br>* BI 10773 tablets once daily<br>Drug: Placebo<br>* Placebo matching BI 10773 low dose<br>|
| Placebo Comparator: Placebo (metformin+sulfonylurea)<br>Placebo tablets matching BI 10773 | Drug: Placebo<br>* Placebo matching BI 10773 low dose<br>Drug: Placebo<br>* Placebo matching BI 10773 high dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes From Baseline in Glycosylated Haemoglobin (HbA1c) (%) After 52 Weeks of Treatment | Change from baseline in HbA1c after 52 weeks | Baseline and 52 weeks | 
| Changes From Baseline in HbA1c (%) After 76 Weeks of Treatment | Change from baseline in HbA1c after 76 weeks | Baseline and 76 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HbA1c (%) Changes From Baseline After 76 Weeks of Treatment | Change from baseline in HbA1c (%) after 76 weeks using MMRM approach | Baseline and 76 weeks | 
| Systolic Blood Pressure: Change From Baseline After 52 Weeks of Treatment | Systolic blood pressure - change from baseline after 52 weeks of treatment | Baseline and 52 weeks | 
| Systolic Blood Pressure: Change From Baseline After 76 Weeks of Treatment | Systolic blood pressure - change from baseline after 76 weeks of treatment | Baseline and 76 weeks | 
| Diastolic Blood Pressure: Change From Baseline After 52 Weeks of Treatment | Diastolic blood pressure - change from baseline after 52 weeks of treatment | Baseline and 52 weeks | 
| Diastolic Blood Pressure: Change From Baseline After 76 Weeks of Treatment | Diastolic blood pressure - change from baseline after 76 weeks of treatment | Baseline and 76 weeks | 
| Body Weight (kg) Change From Baseline After 52 Weeks of Treatment | Body Weight (kg) - Change From Baseline After 52 Weeks of Treatment | Baseline and 52 weeks | 
| Body Weight (kg) Change From Baseline After 76 Weeks of Treatment | Body Weight (kg) - Change From Baseline After 76 Weeks of Treatment | Baseline and 76 weeks | 
| Waist Circumference (cm) Change From Baseline After 52 Weeks of Treatment | Waist circumference (cm) - change from baseline after 52 weeks of treatment | Baseline and 52 weeks | 
| Waist Circumference (cm) Change From Baseline After 76 Weeks of Treatment | Waist circumference (cm) - change from baseline after 76 weeks of treatment | Baseline and 76 weeks | 
| Fasting Plasma Glucose Change From Baseline After 52 Weeks of Treatment | Fasting plasma glucose - change from baseline after 52 weeks of treatment | Baseline and 52 weeks | 
| Fasting Plasma Glucose Change From Baseline After 76 Weeks of Treatment | Fasting plasma glucose - change from baseline after 76 weeks of treatment | Baseline and 76 weeks |