Safety and Efficacy of the Combination of Empagliflozin and Linagliptin Compared to Linagliptin Alone Over 24 Weeks in Patients With Type 2 Diabetes

This study has been completed.
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01734785
First received: November 16, 2012
Last updated: June 9, 2016
Last verified: June 2016
Results First Received: March 17, 2016  
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: Linagliptin
Drug: Empagliflozin + Linagliptin
Drug: Empaglifozin placebo + Linagliptin 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
16-week open-label (OL) lina 5 period followed by a 1-week OL period with additional placebo administration preceded randomisation to double-blind treatment. Patients were randomised to double blind treatment only when they had not met glycaemic control criteria after the 16-week OL period. All treatments were administered in addition to metformin.

Reporting Groups
  Description
Empagliflozin 25 mg Patients received 1 fixed dose combination (FDC) Empagliflozin (empa) 25/lina 5 mg tablet and two placebo tablet (1 matching placebo tablet to lina 5 and 1 matching placebo tablet to FDC empa 10/lina 5), administered orally, once every day for 24 weeks during the double blind treatment period.
Empagliflozin 10 mg Patients received 1 FDC empa 10/lina 5 mg tablet and two placebo tablet (1 matching placebo tablet to lina 5 and 1 matching placebo tablet to FDC empa 25/lina 5), administered orally, once every day for 24 weeks during the double blind treatment period.
Placebo Patients received 1 lina 5 mg tablet and two placebo tablet (1 matching placebo tablet to FDC empa 25/lina 5 and 1 matching placebo tablet to FDC empa 10/lina 5), administered orally, once every day for 24 weeks during the double blind treatment period.
Linagliptin 5 mg Patients received 5mg dose of Linagliptin (lina 5), administered orally, once daily for 16 weeks during the OL treatment period, thereafter patients received 1 matching placebo tablet to FDC empa 25/lina 5, and 1 matching placebo tablet to FDC empa 10/lina 5 per day in addition to lina 5 OL, for 1 week during the open-label placebo add-on treatment period.

Participant Flow for 2 periods

Period 1:   Open−Label Period
    Empagliflozin 25 mg     Empagliflozin 10 mg     Placebo     Linagliptin 5 mg  
STARTED     0     0     0     606  
COMPLETED     0     0     0     333  
NOT COMPLETED     0     0     0     273  
Adverse Event                 0                 0                 0                 9  
Lack of Efficacy                 0                 0                 0                 1  
Protocol Violation                 0                 0                 0                 13  
Lost to Follow-up                 0                 0                 0                 14  
Withdrawal by Subject                 0                 0                 0                 12  
Other Reasons                 0                 0                 0                 224  

Period 2:   Double−Blind Period
    Empagliflozin 25 mg     Empagliflozin 10 mg     Placebo     Linagliptin 5 mg  
STARTED     111     112     110     0  
COMPLETED     106     103     105     0  
NOT COMPLETED     5     9     5     0  
Adverse Event                 0                 3                 2                 0  
Lack of Efficacy                 0                 1                 0                 0  
Protocol Violation                 0                 1                 1                 0  
Lost to Follow-up                 2                 4                 2                 0  
Withdrawal by Subject                 2                 0                 0                 0  
Not treated                 1                 0                 0                 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.
The treated set (TS) consisted of all patients who were randomised and treated with at least 1 dose of study drug during the double-blind part of the trial.

Reporting Groups
  Description
Empagliflozin 25 mg Patients received 1 FDC Empagliflozin (empa) 25/lina 5 mg tablet and two placebo tablet (1 matching placebo tablet to lina 5 and 1 matching placebo tablet to FDC empa 10/lina 5), administered orally, once every day for 24 weeks during the double blind treatment period.
Empagliflozin 10 mg Patients received 1 FDC empa 10/lina 5 mg tablet and two placebo tablet (1 matching placebo tablet to lina 5 and 1 matching placebo tablet to FDC empa 25/lina 5), administered orally, once every day for 24 weeks during the double blind treatment period.
Placebo Patients received 1 lina 5 mg tablet and two placebo tablet (1 matching placebo tablet to FDC empa 25/lina 5 and 1 matching placebo tablet to FDC empa 10/lina 5), administered orally, once every day for 24 weeks during the double blind treatment period.
Total Total of all reporting groups

Baseline Measures
    Empagliflozin 25 mg     Empagliflozin 10 mg     Placebo     Total  
Number of Participants  
[units: participants]
  110     112     110     332  
Age  
[units: Years]
Mean (Standard Deviation)
  55.4  (9.9)     54.3  (9.5)     55.9  (9.6)     55.2  (9.7)  
Gender  
[units: Participants]
       
Female     39     46     49     134  
Male     71     66     61     198  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   HbA1c Change From Baseline After 24 Weeks Double-blind Randomized Treatment   [ Time Frame: Baseline and 24 weeks ]

2.  Secondary:   Fasting Plasma Glucose (FPG) Change From Baseline After 24 Weeks of Double-blind Treatment.   [ Time Frame: Baseline and 24 weeks ]

3.  Secondary:   Body Weight Change From Baseline After 24 Weeks of Double-blind Treatment   [ Time Frame: Baseline and 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



Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01734785     History of Changes
Other Study ID Numbers: 1275.9
2012-002270-31 ( EudraCT Number: EudraCT )
Study First Received: November 16, 2012
Results First Received: March 17, 2016
Last Updated: June 9, 2016
Health Authority: Australia: Dept of Health and Ageing Therapeutic Goods Administration
Brazil: Ministry of Health
Canada: Health Canada
France: Agence Nationale de Sécurité du Médicament et des produits de santé
New Zealand: Medsafe
Norway: Norwegian Medicines Agency
South Korea: Ministry of Food and Drug Safety (MFDS)
Spain: Spanish Agency of Medicines
Taiwan : Food and Drug Administration
United States: Food and Drug Administration