Efficacy and Safety of Empagliflozin (BI 10773) / Linagliptin (BI 1356) Fixed Dose Combination in Treatment naïve and Metformin Treated Type 2 Diabetes Patients

This study has been completed.
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01422876
First received: August 23, 2011
Last updated: April 1, 2015
Last verified: March 2015
Results First Received: January 15, 2015  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double-Blind;   Primary Purpose: Treatment
Condition: Diabetes Mellitus, Type 2
Interventions: Drug: high dose FDC
Drug: BI 10773 high dose
Drug: high dose FDC placebo
Drug: low dose FDC placebo
Drug: high dose BI 10773 placebo
Drug: low dose FDC
Drug: BI 10773 low dose
Drug: linagliptin
Drug: linagliptin placebo
Drug: BI 10773 low dose placebo
Drug: low dose BI 10773 placebo

  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
Of the 1405 patients enrolled and randomized the data for 42 randomized patients were excluded from all analyses due to serious non-compliance. Therefore, 1363 patients were included in the analyses.

Reporting Groups
  Description
Metformin Background: Empagliflozin 25 mg/Linagliptin 5 mg Study population on a stable background of metformin defined as pre-treated with metformin (≥1500 mg/day or on the maximum tolerated dose or the maximum dose according to local label) unchanged for 12 weeks prior to randomisation. Test product: Empagliflozin/linagliptin FDC tablets dose: 25 mg/5 mg q.d. mode of admin: Oral
Metformin Background: Empagliflozin 10 mg/Linagliptin 5 mg

Study population on a stable background of metformin defined as pre-treated with metformin (≥1500 mg/day or on the maximum tolerated dose or the maximum dose according to local label) unchanged for 12 weeks prior to randomisation.

Test product: Empagliflozin/linagliptin FDC tablets dose: 10 mg/5 mg q.d. mode of admin.: Oral

Metformin Background: Empagliflozin 25 mg

Study population on a stable background of metformin defined as pre-treated with metformin (≥1500 mg/day or on the maximum tolerated dose or the maximum dose according to local label) unchanged for 12 weeks prior to randomisation.

Reference therapy 1: Empagliflozin tablets dose: 25 mg q.d. mode of admin.: Oral

Metformin Background: Empagliflozin 10 mg

Study population on a stable background of metformin defined as pre-treated with metformin (≥1500 mg/day or on the maximum tolerated dose or the maximum dose according to local label) unchanged for 12 weeks prior to randomisation.

Reference therapy 1: Empagliflozin tablets dose: 10 mg q.d. mode of admin.: Oral

Metformin Background: Linagliptin 5 mg

Study population on a stable background of metformin defined as pre-treated with metformin (≥1500 mg/day or on the maximum tolerated dose or the maximum dose according to local label) unchanged for 12 weeks prior to randomisation.

Reference therapy 2: Linagliptin tablets dose: 5 mg q.d. mode of admin.: Oral

Treatment Naive: Empagliflozin 25 mg/Linagliptin 5 mg

Study population treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation.

Test product: Empagliflozin/linagliptin FDC tablets dose: 25 mg/5 mg q.d. mode of admin.: Oral

Treament Naive: Empagliflozin 10 mg/Linagliptin 5 mg

Study population treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation.

Test product: Empagliflozin/linagliptin FDC tablets dose: 10 mg/5 mg q.d. mode of admin.: Oral

Treatment Naive: Empagliflozin 25 mg

Study population treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation.

Reference therapy 1: Empagliflozin tablets dose: 25 mg q.d. mode of admin.: Oral

Treatment Naive: Empagliflozin 10 mg

Study population treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation.

Reference therapy 1: Empagliflozin tablets dose: 10 mg q.d. mode of admin.: Oral

Treatment Naive: Linagliptin 5 mg

Study population treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation.

Reference therapy 2: Linagliptin tablets dose: 5 mg q.d. mode of admin.: Oral


Participant Flow for 2 periods

Period 1:   Week 24
    Metformin Background: Empagliflozin 25 mg/Linagliptin 5 mg     Metformin Background: Empagliflozin 10 mg/Linagliptin 5 mg     Metformin Background: Empagliflozin 25 mg     Metformin Background: Empagliflozin 10 mg     Metformin Background: Linagliptin 5 mg     Treatment Naive: Empagliflozin 25 mg/Linagliptin 5 mg     Treament Naive: Empagliflozin 10 mg/Linagliptin 5 mg     Treatment Naive: Empagliflozin 25 mg     Treatment Naive: Empagliflozin 10 mg     Treatment Naive: Linagliptin 5 mg  
STARTED     137     136     141     140     132     137     136     135     134     135  
COMPLETED     131     133     136     132     125     131     130     128     128     125  
NOT COMPLETED     6     3     5     8     7     6     6     7     6     10  
Lost to Follow-up                 1                 1                 2                 4                 2                 0                 1                 3                 3                 4  
Consent withdrawn                 5                 1                 3                 4                 5                 6                 5                 4                 3                 6  
Death                 0                 1                 0                 0                 0                 0                 0                 0                 0                 0  

Period 2:   Week 52
    Metformin Background: Empagliflozin 25 mg/Linagliptin 5 mg     Metformin Background: Empagliflozin 10 mg/Linagliptin 5 mg     Metformin Background: Empagliflozin 25 mg     Metformin Background: Empagliflozin 10 mg     Metformin Background: Linagliptin 5 mg     Treatment Naive: Empagliflozin 25 mg/Linagliptin 5 mg     Treament Naive: Empagliflozin 10 mg/Linagliptin 5 mg     Treatment Naive: Empagliflozin 25 mg     Treatment Naive: Empagliflozin 10 mg     Treatment Naive: Linagliptin 5 mg  
STARTED     137     136     141     140     132     137     136     135     134     135  
COMPLETED     125     126     128     122     117     120     120     112     113     118  
NOT COMPLETED     12     10     13     18     15     17     16     23     21     17  
Lost to Follow-up                 3                 5                 7                 5                 8                 5                 5                 8                 7                 8  
Consent withdrawn                 9                 4                 6                 12                 7                 12                 10                 12                 13                 9  
Death                 0                 1                 0                 1                 0                 0                 1                 3                 1                 0  



  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.
FAS

Reporting Groups
  Description
Metformin Background: Empagliflozin 25 mg/Linagliptin 5 mg

Study population on a stable background of metformin defined as pre-treated with metformin (≥1500 mg/day or on the maximum tolerated dose or the maximum dose according to local label) unchanged for 12 weeks prior to randomisation and treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation.

. Test product: Empagliflozin/linagliptin FDC tablets dose: 25 mg/5 mg q.d. mode of admin.: Oral

Metformin Background: Empagliflozin 10 mg/Linagliptin 5 mg

Study population on a stable background of metformin defined as pre-treated with metformin (≥1500 mg/day or on the maximum tolerated dose or the maximum dose according to local label) unchanged for 12 weeks prior to randomisation and treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation.

Test product: Empagliflozin/linagliptin FDC tablets dose: 10 mg/5 mg q.d. mode of admin.: Oral

Metformin Background: Empagliflozin 25 mg

Study population on a stable background of metformin defined as pre-treated with metformin (≥1500 mg/day or on the maximum tolerated dose or the maximum dose according to local label) unchanged for 12 weeks prior to randomisation and treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation.

Reference therapy 1: Empagliflozin tablets dose: 25 mg q.d. mode of admin.: Oral

Metformin Background: Empagliflozin 10 mg

Study population on a stable background of metformin defined as pre-treated with metformin (≥1500 mg/day or on the maximum tolerated dose or the maximum dose according to local label) unchanged for 12 weeks prior to randomisation and treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation.

Reference therapy 1: Empagliflozin tablets dose: 10 mg q.d. mode of admin.: Oral

Metformin Background: Linagliptin 5 mg

Study population on a stable background of metformin defined as pre-treated with metformin (≥1500 mg/day or on the maximum tolerated dose or the maximum dose according to local label) unchanged for 12 weeks prior to randomisation and treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation.

Reference therapy 2: Linagliptin tablets dose: 5 mg q.d. mode of admin.: Oral

Treatment Naive: Empagliflozin 25 mg/Linagliptin 5 mg

Study population treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation.

Test product: Empagliflozin/linagliptin FDC tablets dose: 25 mg/5 mg q.d. mode of admin.: Oral

Treament Naive: Empagliflozin 10 mg/Linagliptin 5 mg

Study population treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation.

Test product: Empagliflozin/linagliptin FDC tablets dose: 10 mg/5 mg q.d. mode of admin.: Oral

Treatment Naive: Empagliflozin 25 mg

Study population treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation.

Reference therapy 1: Empagliflozin tablets dose: 25 mg q.d. mode of admin.: Oral

Treatment Naive: Empagliflozin 10 mg

Study population treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation.

Reference therapy 1: Empagliflozin tablets dose: 10 mg q.d. mode of admin.: Oral

Treatment Naive: Linagliptin 5 mg

Study population treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation.

Reference therapy 2: Linagliptin tablets dose: 5 mg q.d. mode of admin.: Oral

Total Total of all reporting groups

Baseline Measures
    Metformin Background: Empagliflozin 25 mg/Linagliptin 5 mg     Metformin Background: Empagliflozin 10 mg/Linagliptin 5 mg     Metformin Background: Empagliflozin 25 mg     Metformin Background: Empagliflozin 10 mg     Metformin Background: Linagliptin 5 mg     Treatment Naive: Empagliflozin 25 mg/Linagliptin 5 mg     Treament Naive: Empagliflozin 10 mg/Linagliptin 5 mg     Treatment Naive: Empagliflozin 25 mg     Treatment Naive: Empagliflozin 10 mg     Treatment Naive: Linagliptin 5 mg     Total  
Number of Participants  
[units: participants]
  134     135     140     137     128     134     135     133     132     133     1341  
Age  
[units: years]
Mean (Standard Deviation)
  57.1  (10.2)     56.2  (10.3)     55.5  (10.0)     56.1  (10.5)     56.2  (10.0)     54.2  (10.0)     55.2  (9.8)     56.0  (9.3)     53.9  (10.5)     53.8  (11.5)     55.4  (10.2)  
Gender  
[units: participants]
                     
Female     62     52     75     59     64     64     62     56     68     58     620  
Male     72     83     65     78     64     70     73     77     64     75     721  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Change From Baseline in Glycosylated Hemoglobin (HbA1c) for Metformin Background Patients   [ Time Frame: Baseline and 24 weeks ]

2.  Primary:   Change From Baseline in Glycosylated Hemoglobin (HbA1c) for Treatment Naive Patients   [ Time Frame: Baseline and 24 weeks ]

3.  Secondary:   Change From Baseline in Fasting Plasma Glucose at Week 24 for Metformin Background Patients   [ Time Frame: Baseline and 24 Weeks ]

4.  Secondary:   Change From Baseline in Fasting Plasma Glucose at Week 24 for Treatment Naive Patients   [ Time Frame: Baseline and 24 Weeks ]

5.  Secondary:   Change From Baseline in Body Weight for Metformin Background Patients   [ Time Frame: Baseline and 24 Weeks ]

6.  Secondary:   Change From Baseline in Body Weight for Treatment Naive Patients   [ Time Frame: Baseline and 24 Weeks ]

7.  Secondary:   Occurrence of Treat to Target Efficacy Response for Metformin Background Patients   [ Time Frame: 24 Weeks ]

8.  Secondary:   Occurrence of Treat to Target Efficacy Response for Treatment Naive Patients   [ Time Frame: 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
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  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 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 more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Boehringer Ingelheim Call Center
Organization: Boehringer Ingelheim
phone: 1-800-243-0127
e-mail: clintriage.rdg@boehringer-ingelheim.com


No publications provided by Boehringer Ingelheim

Publications automatically indexed to this study:

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01422876     History of Changes
Other Study ID Numbers: 1275.1, 2011-000383-10
Study First Received: August 23, 2011
Results First Received: January 15, 2015
Last Updated: April 1, 2015
Health Authority: Argentina: Ministry of Health
Australia: Human Research Ethics Committee
Brazil: National Committee of Ethics in Research
Bulgaria: Bulgarian Drug Agency
Canada: Health Canada
Colombia: Instituto Nacional de Vigilancia de Medicamentos y Alimentos
Denmark: The Danish Health and Medicines Authority
Estonia: The State Agency of Medicine
Hungary: National Institute of Pharmacy
Italy: Ethics Committee
Lebanon: Ministry of Public Health
Malaysia: Ministry of Health
Mexico: Federal Commission for Protection Against Health Risks
Peru: Ministry of Health
Philippines: Bureau of Food and Drugs
Poland: Registration Medicinal Product Medical Device Biocidal Product
Romania: National Medicines Agency
Russia: Pharmacological Committee, Ministry of Health
Spain: Spanish Agency of Medicines
Sweden: Medical Products Agency
Taiwan : Food and Drug Administration
United States: Food and Drug Administration