Safety and Efficacy Study of Empagliflozin and Metformin for 24 Weeks in Treatment Naive 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:
NCT01719003
First received: October 30, 2012
Last updated: January 22, 2016
Last verified: January 2016
Results First Received: November 23, 2015  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double-Blind;   Primary Purpose: Treatment
Conditions: Diabetes Mellitus, Type 2
Hyperglycemia
Interventions: Drug: Metformin 500 mg bid
Drug: Metformin 1000 mg bid
Drug: Empagliflozin low dose qd
Drug: Empagliflozin high dose qd
Drug: Empagliflozin low dose bid
Drug: Empagliflozin high dose bid

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
With the first global protocol amendment (13-Dec-2012), the HbA1c inclusion criterion changed and further enrolment in the open label (OL) group was stopped, but the patients already entered in the OL group could continue until the scheduled end of the study.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Patients with an (Glycosylated Haemoglobin) HbA1c >10.0% at screening and meeting all other inclusion criteria were initially directly included in an OL treatment group

Reporting Groups
  Description
Empagliflozin 12.5 mg Bid+ Metformin 1000 mg Bid Oral administration of Empagliflozin 12.5 mg and Metformin 1000 mg twice daily (bid)
Empagliflozin 12.5 mg Bid+ Metformin 500 mg Bid Oral administration of Empagliflozin 12.5 mg and Metformin 500 mg bid
Empagliflozin 5 mg Bid + Metformin 1000 mg Bid Oral administration of Empagliflozin 5 mg and Metformin 1000 mg bid
Empagliflozin 5 mg Bid + Metformin 500 mg Bid Oral administration of Empagliflozin 5 mg and Metformin 500 mg bid
Empagliflozin 25 mg qd Oral administration of Empagliflozin 25 mg once daily (qd)
Empagliflozin 10 mg qd Oral administration of Empagliflozin 10 mg qd
Metformin 1000 mg Bid Oral administration of Metformin 1000 mg bid
Metformin 500 mg Bid Oral administration of Metformin 500 mg bid
Empagliflozin 12.5 mg Bid + Metformin 1000 mg Bid OL Oral administration of Empagliflozin 12.5 mg and Metformin 1000 mg bid in an open label (OL)

Participant Flow:   Overall Study
    Empagliflozin 12.5 mg Bid+ Metformin 1000 mg Bid     Empagliflozin 12.5 mg Bid+ Metformin 500 mg Bid     Empagliflozin 5 mg Bid + Metformin 1000 mg Bid     Empagliflozin 5 mg Bid + Metformin 500 mg Bid     Empagliflozin 25 mg qd     Empagliflozin 10 mg qd     Metformin 1000 mg Bid     Metformin 500 mg Bid     Empagliflozin 12.5 mg Bid + Metformin 1000 mg Bid OL  
STARTED     170     170     171     169     167     172     170     171     53  
COMPLETED     161     153     154     156     150     160     150     151     49  
NOT COMPLETED     9     17     17     13     17     12     20     20     4  
Non compliant with protocol                 1                 1                 0                 1                 2                 1                 2                 3                 0  
Adverse Event                 6                 5                 4                 3                 4                 3                 6                 5                 0  
Lost to Follow-up                 0                 6                 7                 2                 3                 4                 3                 2                 2  
Refusal to continue, not due to AE                 2                 5                 4                 4                 4                 3                 8                 7                 1  
Reason other than those specified                 0                 0                 2                 3                 4                 1                 0                 3                 1  
Lack of Efficacy                 0                 0                 0                 0                 0                 0                 1                 0                 0  



  Baseline Characteristics
  Hide Baseline Characteristics

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.
Full analysis set (FAS): FAS comprised all randomised patients treated with at least 1 dose of trial medication, with a baseline and at least 1 on-treatment HbA1c assessment.

Reporting Groups
  Description
Empagliflozin 12.5 mg Bid+ Metformin 1000 mg Bid Oral administration of Empagliflozin 12.5 mg and Metformin 1000 mg twice daily (bid)
Empagliflozin 12.5 mg Bid+ Metformin 500 mg Bid Oral administration of Empagliflozin 12.5 mg and Metformin 500 mg bid
Empagliflozin 5 mg Bid + Metformin 1000 mg Bid Oral administration of Empagliflozin 5 mg and Metformin 1000 mg bid
Empagliflozin 5 mg Bid + Metformin 500 mg Bid Oral administration of Empagliflozin 5 mg and Metformin 500 mg bid
Empagliflozin 25 mg qd Oral administration of Empagliflozin 25 mg once daily (qd)
Empagliflozin 10 mg qd Oral administration of Empagliflozin 10 mg qd
Metformin 1000 mg Bid Oral administration of Metformin 1000 mg bid
Metformin 500 mg Bid Oral administration of Metformin 500 mg bid
Total Total of all reporting groups

Baseline Measures
    Empagliflozin 12.5 mg Bid+ Metformin 1000 mg Bid     Empagliflozin 12.5 mg Bid+ Metformin 500 mg Bid     Empagliflozin 5 mg Bid + Metformin 1000 mg Bid     Empagliflozin 5 mg Bid + Metformin 500 mg Bid     Empagliflozin 25 mg qd     Empagliflozin 10 mg qd     Metformin 1000 mg Bid     Metformin 500 mg Bid     Total  
Number of Participants  
[units: participants]
  169     165     167     161     164     169     164     168     1327  
Age  
[units: years]
Mean (Standard Deviation)
  53.6  (10.7)     51.0  (10.7)     52.3  (11.3)     52.2  (11.7)     53.3  (10.7)     53.1  (10.7)     51.6  (10.8)     53.4  (10.9)     52.6  (10.9)  
Gender  
[units: participants]
                 
Female     81     60     68     64     81     72     72     82     580  
Male     88     105     99     97     83     97     92     86     747  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   HbA1c (Glycosylated Haemoglobin) Change From Baseline at Week 24   [ Time Frame: baseline and 24 weeks ]

2.  Secondary:   FPG (Fasting Plasma Glucose) Change From Baseline at Week 24   [ Time Frame: baseline and 24 weeks ]

3.  Secondary:   Body Weight Change From Baseline at Week 24   [ Time Frame: baseline and 24 weeks ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

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
No text entered.


  More Information
  Hide More Information

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: 800-243-0127 ext +1
e-mail: clintriage.rdg@boehringer-ingelheim.com



Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01719003     History of Changes
Other Study ID Numbers: 1276.1
2010-021375-92 ( EudraCT Number: EudraCT )
Study First Received: October 30, 2012
Results First Received: November 23, 2015
Last Updated: January 22, 2016
Health Authority: Brazil: Ministry of Health
Canada: Health Canada
Czech Republic: State Institute for Drug Control
Egypt: Ministry of Health, Drug Policy and Planning Center
France: Ministry of Health
Germany: Federal Institute for Drugs and Medical Devices
Guatemala: Ministry of Public Health and Social Assistance
Lebanon: Institutional Review Board
Malaysia: Ministry of Health
Mexico: Ministry of Health
Peru: General Directorate of Pharmaceuticals, Devices, and Drugs
Philippines: Bureau of Food and Drugs
Russia: Pharmacological Committee, Ministry of Health
Serbia and Montenegro: Agency for Drugs and Medicinal Devices
South Korea: Ministry of Food and Drug Safety (MFDS)
Spain: Spanish Agency of Medicines
Taiwan: Department of Health
Thailand: Food and Drug Administration
Turkey: Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration