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Efficacy and Safety of Empagliflozin (BI 10773) With Metformin 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:
NCT01167881
First received: July 15, 2010
Last updated: July 28, 2016
Last verified: July 2016
Results First Received: July 17, 2014  
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: BI 10773
Drug: Glimepiride
Drug: 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
An optional 2-year extension was implemented in this trial through a protocol amendment, which brought the total length of treatment to 4 years. However, some sites did not participate in the 2-year extension, and so considered patients to have completed treatment after 2 years.

Reporting Groups
  Description
Empaglifozin 25 mg

Patients received one Empagliflozin 25 mg tablet and one placebo Glimepiride capsule orally once daily.

Empagliflozin: 25 mg once daily

Placebo: Placebo matching Glimepiride

Glimepiride

Patients received one Glimepiride capsule and one placebo Empagliflozin tablet orally once daily.

Glimepiride: 1-4 mg once daily

Placebo: Placebo matching Empagliflozin


Participant Flow:   Overall Study
    Empaglifozin 25 mg     Glimepiride  
STARTED     769     780  
Completed After 2 Years Treatment     95     127  
Completed After 4 Years Treatment     515     462  
COMPLETED     610     589  
NOT COMPLETED     159     191  
Adverse Event                 47                 51  
Lack of Efficacy                 4                 7  
Non compliant with protocol                 9                 18  
Lost to Follow-up                 19                 20  
Patient refusal to cont., not due to AE                 45                 40  
Not treated                 4                 0  
Other not defined above                 31                 55  



  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.
Full Analysis Set (FAS), All patients randomised, treated with at least one dose of study drug, and with a baseline HbA1c value.

Reporting Groups
  Description
Empaglifozin 25 mg

Patients received one Empagliflozin 25 mg tablet and one placebo Glimepiride capsule orally once daily.

Empagliflozin: 25 mg once daily

Placebo: Placebo matching Glimepiride

Glimepiride

Patients received one Glimepiride capsule and one placebo Empagliflozin tablet orally once daily.

Glimepiride: 1-4 mg once daily

Placebo: Placebo matching Empagliflozin

Total Total of all reporting groups

Baseline Measures
    Empaglifozin 25 mg     Glimepiride     Total  
Number of Participants  
[units: participants]
  765     780     1545  
Age  
[units: years]
Mean (Standard Deviation)
  56.2  (10.3)     55.7  (10.4)     55.9  (10.4)  
Gender  
[units: participants]
     
Female     333     359     692  
Male     432     421     853  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   The Change From Baseline in Glycosylated Haemoglobin (HbA1c) After 104 Weeks of Treatment.   [ Time Frame: Baseline and 104 weeks ]

2.  Secondary:   The Change in Body Weight From Baseline After 104 Weeks of Treatment.   [ Time Frame: baseline and 104 weeks ]

3.  Secondary:   The Occurrence of Confirmed Hypoglycaemic Events During 104 Weeks of Treatment.   [ Time Frame: baseline and 104 weeks ]

4.  Secondary:   The Change in Systolic Blood Pressure (SBP) From Baseline After 104 Weeks of Treatment.   [ Time Frame: baseline and 104 weeks ]

5.  Secondary:   The Change in Diastolic Blood Pressure (DBP) From Baseline After 104 Weeks of Treatment.   [ Time Frame: baseline and 104 weeks ]

6.  Secondary:   The Change From Baseline in HbA1c After 52 Weeks of Treatment.   [ Time Frame: baseline and 52 weeks ]

7.  Secondary:   The Change in Body Weight From Baseline After 52 Weeks of Treatment.   [ Time Frame: baseline and 52 weeks ]

8.  Secondary:   The Occurrence of Confirmed Hypoglycaemic Events During 52 Weeks of Treatment.   [ Time Frame: baseline and 52 weeks ]

9.  Secondary:   The Change in Systolic Blood Pressure (SBP) From Baseline After 52 Weeks of Treatment.   [ Time Frame: baseline and 52 weeks ]

10.  Secondary:   The Change in Diastolic Blood Pressure (DBP) From Baseline After 52 Weeks of Treatment.   [ Time Frame: baseline and 52 weeks ]


  Serious Adverse Events
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Time Frame Up to 4 years.
Additional Description All adverse events (AE), serious and non-serious, occurring during the course of the clinical trial were collected, documented, and reported to the sponsor by the investigator on the appropriate case report form (CRF) or serious adverse event (SAE) reporting forms.

Reporting Groups
  Description
Empa 25mg Patients received one Empagliflozin 25 mg tablet and one placebo Glimepiride capsule orally once daily. Empagliflozin: 25 mg once daily Placebo: Placebo matching Glimepiride
Glimepiride Patients received one Glimepiride capsule and one placebo Empagliflozin tablet orally once daily. Glimepiride: 1-4 mg once daily Placebo: Placebo matching Empagliflozin

Serious Adverse Events
    Empa 25mg     Glimepiride  
Total, serious adverse events      
# participants affected / at risk     161/765 (21.05%)     153/780 (19.62%)  
Blood and lymphatic system disorders      
Anaemia † 1    
# participants affected / at risk     1/765 (0.13%)     2/780 (0.26%)  
Iron deficiency anaemia † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Thrombocytopenia † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Cardiac disorders      
Coronary artery disease † 1    
# participants affected / at risk     3/765 (0.39%)     8/780 (1.03%)  
Acute myocardial infarction † 1    
# participants affected / at risk     1/765 (0.13%)     7/780 (0.90%)  
Angina unstable † 1    
# participants affected / at risk     4/765 (0.52%)     4/780 (0.51%)  
Atrial fibrillation † 1    
# participants affected / at risk     4/765 (0.52%)     2/780 (0.26%)  
Myocardial infarction † 1    
# participants affected / at risk     0/765 (0.00%)     3/780 (0.38%)  
Myocardial ischaemia † 1    
# participants affected / at risk     1/765 (0.13%)     3/780 (0.38%)  
Angina pectoris † 1    
# participants affected / at risk     1/765 (0.13%)     2/780 (0.26%)  
Cardiac failure † 1    
# participants affected / at risk     2/765 (0.26%)     1/780 (0.13%)  
Cardiac failure congestive † 1    
# participants affected / at risk     0/765 (0.00%)     2/780 (0.26%)  
Palpitations † 1    
# participants affected / at risk     2/765 (0.26%)     0/780 (0.00%)  
Acute coronary syndrome † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Arrhythmia † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Arteriosclerosis coronary artery † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Cardiac disorder † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Cardiac tamponade † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Tachycardia † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Ventricle rupture † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Ventricular tachycardia † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Congenital, familial and genetic disorders      
Phimosis † 1    
# participants affected / at risk     2/765 (0.26%)     0/780 (0.00%)  
Ear and labyrinth disorders      
Otosclerosis † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Tinnitus † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Vertigo † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Endocrine disorders      
Goitre † 1    
# participants affected / at risk     1/765 (0.13%)     1/780 (0.13%)  
Pituitary-dependent Cushing's syndrome † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Eye disorders      
Retinal detachment † 1    
# participants affected / at risk     1/765 (0.13%)     3/780 (0.38%)  
Cataract † 1    
# participants affected / at risk     0/765 (0.00%)     2/780 (0.26%)  
Diabetic retinopathy † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Endocrine ophthalmopathy † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Open angle glaucoma † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Retinal neovascularisation † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Vitreous haemorrhage † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Gastrointestinal disorders      
Inguinal hernia † 1    
# participants affected / at risk     4/765 (0.52%)     0/780 (0.00%)  
Gastrointestinal haemorrhage † 1    
# participants affected / at risk     3/765 (0.39%)     0/780 (0.00%)  
Abdominal pain † 1    
# participants affected / at risk     2/765 (0.26%)     2/780 (0.26%)  
Abdominal pain upper † 1    
# participants affected / at risk     2/765 (0.26%)     0/780 (0.00%)  
Dyspepsia † 1    
# participants affected / at risk     0/765 (0.00%)     2/780 (0.26%)  
Pancreatitis acute † 1    
# participants affected / at risk     0/765 (0.00%)     2/780 (0.26%)  
Umbilical hernia † 1    
# participants affected / at risk     2/765 (0.26%)     1/780 (0.13%)  
Vomiting † 1    
# participants affected / at risk     2/765 (0.26%)     0/780 (0.00%)  
Abdominal hernia † 1    
# participants affected / at risk     1/765 (0.13%)     1/780 (0.13%)  
Anorectal varices † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Anorectal varices haemorrhage † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Colitis † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Crohn's disease † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Diverticulum intestinal † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Enterocolitis haemorrhagic † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Gastric ulcer † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Gastritis † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Haemorrhoids † 1    
# participants affected / at risk     1/765 (0.13%)     1/780 (0.13%)  
Hiatus hernia † 1    
# participants affected / at risk     1/765 (0.13%)     1/780 (0.13%)  
Impaired gastric emptying † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Incarcerated inguinal hernia † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Intestinal obstruction † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Large intestine polyp † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Oesophageal varices haemorrhage † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Pancreatitis † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Proctitis haemorrhagic † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Rectal haemorrhage † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Rectal polyp † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Volvulus † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
General disorders      
Chest pain † 1    
# participants affected / at risk     1/765 (0.13%)     5/780 (0.64%)  
Non-cardiac chest pain † 1    
# participants affected / at risk     1/765 (0.13%)     2/780 (0.26%)  
Cyst † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Hernia † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Multi-organ failure † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Pain † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Pyrexia † 1    
# participants affected / at risk     1/765 (0.13%)     1/780 (0.13%)  
Sudden death † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Hepatobiliary disorders      
Cholelithiasis † 1    
# participants affected / at risk     4/765 (0.52%)     5/780 (0.64%)  
Cholecystitis acute † 1    
# participants affected / at risk     1/765 (0.13%)     2/780 (0.26%)  
Cholangitis † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Cholangitis acute † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Cholecystitis † 1    
# participants affected / at risk     1/765 (0.13%)     1/780 (0.13%)  
Cholecystitis chronic † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Drug-induced liver injury † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Hepatic cirrhosis † 1    
# participants affected / at risk     1/765 (0.13%)     1/780 (0.13%)  
Hepatic failure † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Hepatitis acute † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Liver disorder † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Non-alcoholic steatohepatitis † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Portal hypertension † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Immune system disorders      
Drug hypersensitivity † 1    
# participants affected / at risk     0/765 (0.00%)     3/780 (0.38%)  
Infections and infestations      
Gastroenteritis † 1    
# participants affected / at risk     4/765 (0.52%)     0/780 (0.00%)  
Cellulitis † 1    
# participants affected / at risk     3/765 (0.39%)     0/780 (0.00%)  
Diverticulitis † 1    
# participants affected / at risk     3/765 (0.39%)     0/780 (0.00%)  
Viral infection † 1    
# participants affected / at risk     3/765 (0.39%)     0/780 (0.00%)  
Bronchitis † 1    
# participants affected / at risk     0/765 (0.00%)     2/780 (0.26%)  
Erysipelas † 1    
# participants affected / at risk     1/765 (0.13%)     2/780 (0.26%)  
Post procedural infection † 1    
# participants affected / at risk     0/765 (0.00%)     2/780 (0.26%)  
Sepsis † 1    
# participants affected / at risk     1/765 (0.13%)     2/780 (0.26%)  
Abscess limb † 1    
# participants affected / at risk     1/765 (0.13%)     1/780 (0.13%)  
Appendicitis † 1    
# participants affected / at risk     1/765 (0.13%)     1/780 (0.13%)  
Bacteraemia † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Cystitis † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Cystitis escherichia † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Dengue fever † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Diarrhoea infectious † 1    
# participants affected / at risk     1/765 (0.13%)     1/780 (0.13%)  
Escherichia bacteraemia † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Febrile infection † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Gastroenteritis salmonella † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Hepatitis E † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Infectious mononucleosis † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Kidney infection † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Liver abscess † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Lobar pneumonia † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Localised infection † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Lower respiratory tract infection † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Lung infection † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Nasopharyngitis † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Osteomyelitis † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Pelvic abscess † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Peritonitis bacterial † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Pneumonia bacterial † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Pneumonia legionella † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Pyelonephritis † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Pyelonephritis acute † 1    
# participants affected / at risk     1/765 (0.13%)     1/780 (0.13%)  
Salmonellosis † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Septic shock † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Sialoadenitis † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Tuberculosis gastrointestinal † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Upper respiratory tract infection † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Urosepsis † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Injury, poisoning and procedural complications      
Fall † 1    
# participants affected / at risk     8/765 (1.05%)     1/780 (0.13%)  
Ankle fracture † 1    
# participants affected / at risk     3/765 (0.39%)     1/780 (0.13%)  
Fibula fracture † 1    
# participants affected / at risk     2/765 (0.26%)     0/780 (0.00%)  
Humerus fracture † 1    
# participants affected / at risk     2/765 (0.26%)     1/780 (0.13%)  
Incisional hernia † 1    
# participants affected / at risk     0/765 (0.00%)     2/780 (0.26%)  
Meniscus injury † 1    
# participants affected / at risk     1/765 (0.13%)     2/780 (0.26%)  
Road traffic accident † 1    
# participants affected / at risk     0/765 (0.00%)     2/780 (0.26%)  
Subdural haematoma † 1    
# participants affected / at risk     0/765 (0.00%)     2/780 (0.26%)  
Tibia fracture † 1    
# participants affected / at risk     2/765 (0.26%)     0/780 (0.00%)  
Traumatic fracture † 1    
# participants affected / at risk     2/765 (0.26%)     1/780 (0.13%)  
Burns third degree † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Comminuted fracture † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Femur fracture † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Foreign body † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Head injury † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Jaw fracture † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Joint dislocation † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Laceration † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Ligament sprain † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Limb injury † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Muscle rupture † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Overdose † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Post procedural constipation † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Post procedural haemorrhage † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Procedural headache † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Radius fracture † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Soft tissue injury † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Tendon rupture † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Investigations      
Liver function test abnormal † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Metabolism and nutrition disorders      
Obesity † 1    
# participants affected / at risk     0/765 (0.00%)     2/780 (0.26%)  
Dehydration † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Diabetes mellitus inadequate control † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Electrolyte imbalance † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Fluid overload † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Gout † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Hyperglycaemia † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Hyperkalaemia † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Hypoglycaemia † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Hypokalaemia † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Musculoskeletal and connective tissue disorders      
Osteoarthritis † 1    
# participants affected / at risk     4/765 (0.52%)     4/780 (0.51%)  
Back pain † 1    
# participants affected / at risk     2/765 (0.26%)     1/780 (0.13%)  
Foot deformity † 1    
# participants affected / at risk     2/765 (0.26%)     0/780 (0.00%)  
Intervertebral disc protrusion † 1    
# participants affected / at risk     0/765 (0.00%)     2/780 (0.26%)  
Spinal osteoarthritis † 1    
# participants affected / at risk     2/765 (0.26%)     2/780 (0.26%)  
Arthralgia † 1    
# participants affected / at risk     1/765 (0.13%)     1/780 (0.13%)  
Arthritis † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Cervical spinal stenosis † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Chondrocalcinosis pyrophosphate † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Intervertebral disc disorder † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Lumbar spinal stenosis † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Muscle twitching † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Musculoskeletal chest pain † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Neck pain † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Rotator cuff syndrome † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Spinal column stenosis † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Spinal pain † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Synovial cyst † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Synovitis † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Tendonitis † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Neoplasms benign, malignant and unspecified (incl cysts and polyps)      
Prostate cancer † 1    
# participants affected / at risk     2/765 (0.26%)     6/780 (0.77%)  
Basal cell carcinoma † 1    
# participants affected / at risk     2/765 (0.26%)     4/780 (0.51%)  
Breast cancer † 1    
# participants affected / at risk     2/765 (0.26%)     0/780 (0.00%)  
Colon cancer † 1    
# participants affected / at risk     2/765 (0.26%)     1/780 (0.13%)  
Rectal cancer † 1    
# participants affected / at risk     2/765 (0.26%)     0/780 (0.00%)  
Uterine leiomyoma † 1    
# participants affected / at risk     0/765 (0.00%)     2/780 (0.26%)  
Acute myeloid leukaemia † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Adenocarcinoma pancreas † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Endometrial adenocarcinoma † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Glioblastoma † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Hepatic cancer † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Invasive lobular breast carcinoma † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Laryngeal squamous cell carcinoma † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Lung adenocarcinoma † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Lung adenocarcinoma stage IV † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Lung neoplasm malignant † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Malignant melanoma † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Malignant melanoma in situ † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Malignant peritoneal neoplasm † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Melanoma recurrent † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Meningioma † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Metastases to bone † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Metastases to central nervous system † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Metastases to liver † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Metastatic ocular melanoma † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Nasal neoplasm benign † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Non-small cell lung cancer † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Pancreatic carcinoma † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Paranasal sinus benign neoplasm † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Renal cell carcinoma † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Renal neoplasm † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Squamous cell carcinoma † 1    
# participants affected / at risk     1/765 (0.13%)     1/780 (0.13%)  
Transitional cell carcinoma † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Uterine cancer † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Nervous system disorders      
Cerebrovascular accident † 1    
# participants affected / at risk     8/765 (1.05%)     2/780 (0.26%)  
Carpal tunnel syndrome † 1    
# participants affected / at risk     1/765 (0.13%)     2/780 (0.26%)  
Cerebral haemorrhage † 1    
# participants affected / at risk     0/765 (0.00%)     2/780 (0.26%)  
Dizziness † 1    
# participants affected / at risk     2/765 (0.26%)     0/780 (0.00%)  
Ischaemic stroke † 1    
# participants affected / at risk     2/765 (0.26%)     2/780 (0.26%)  
Transient ischaemic attack † 1    
# participants affected / at risk     2/765 (0.26%)     2/780 (0.26%)  
Brain stem infarction † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Carotid artery stenosis † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Cerebral infarction † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Cerebrovascular disorder † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Diabetic coma † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Headache † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Lacunar infarction † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Myasthenia gravis † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Myelopathy † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Optic neuritis † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Paraesthesia † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Partial seizures † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Radicular pain † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Seizure † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Subarachnoid haemorrhage † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Syncope † 1    
# participants affected / at risk     1/765 (0.13%)     1/780 (0.13%)  
Thalamic infarction † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Trigeminal neuralgia † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Psychiatric disorders      
Adjustment disorder † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Completed suicide † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Delusional disorder, unspecified type † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Depression † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Mental disorder † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Suicide attempt † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Renal and urinary disorders      
Acute kidney injury † 1    
# participants affected / at risk     0/765 (0.00%)     2/780 (0.26%)  
Nephrolithiasis † 1    
# participants affected / at risk     1/765 (0.13%)     2/780 (0.26%)  
Renal failure † 1    
# participants affected / at risk     1/765 (0.13%)     2/780 (0.26%)  
Bladder prolapse † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Calculus ureteric † 1    
# participants affected / at risk     1/765 (0.13%)     1/780 (0.13%)  
Haematuria † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Renal cyst † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Urinary tract obstruction † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Reproductive system and breast disorders      
Benign prostatic hyperplasia † 1    
# participants affected / at risk     4/765 (0.52%)     3/780 (0.38%)  
Menorrhagia † 1    
# participants affected / at risk     2/765 (0.26%)     0/780 (0.00%)  
Balanoposthitis † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Dysfunctional uterine bleeding † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Endometrial hyperplasia † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Metrorrhagia † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Prostatism † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Uterine prolapse † 1    
# participants affected / at risk     1/765 (0.13%)     1/780 (0.13%)  
Vaginal prolapse † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Respiratory, thoracic and mediastinal disorders      
Chronic obstructive pulmonary disease † 1    
# participants affected / at risk     2/765 (0.26%)     1/780 (0.13%)  
Dyspnoea † 1    
# participants affected / at risk     2/765 (0.26%)     1/780 (0.13%)  
Pulmonary embolism † 1    
# participants affected / at risk     2/765 (0.26%)     0/780 (0.00%)  
Dysphonia † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Dyspnoea exertional † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Lung consolidation † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Nasal obstruction † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Paranasal cyst † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Pleural effusion † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Pneumonia aspiration † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Pneumothorax † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Respiratory failure † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Skin and subcutaneous tissue disorders      
Diabetic foot † 1    
# participants affected / at risk     1/765 (0.13%)     1/780 (0.13%)  
Skin ulcer † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Surgical and medical procedures      
Arrhythmia prophylaxis † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Cholecystectomy † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Hip arthroplasty † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Hysterectomy † 1    
# participants affected / at risk     1/765 (0.13%)     1/780 (0.13%)  
Knee arthroplasty † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Omentectomy † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Oophorectomy bilateral † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Vascular disorders      
Deep vein thrombosis † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Hypertension † 1    
# participants affected / at risk     1/765 (0.13%)     1/780 (0.13%)  
Hypertensive emergency † 1    
# participants affected / at risk     1/765 (0.13%)     0/780 (0.00%)  
Orthostatic hypotension † 1    
# participants affected / at risk     1/765 (0.13%)     1/780 (0.13%)  
Peripheral arterial occlusive disease † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Peripheral artery stenosis † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Peripheral ischaemia † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Thrombophlebitis † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Varicose vein † 1    
# participants affected / at risk     0/765 (0.00%)     1/780 (0.13%)  
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA 18.0




  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
It should be noted that not all patients were followed up for 4 years with regard to the frequencies of adverse events presented up to 4 years.


  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


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01167881     History of Changes
Other Study ID Numbers: 1245.28
2009-016244-39 ( EudraCT Number: EudraCT )
Study First Received: July 15, 2010
Results First Received: July 17, 2014
Last Updated: July 28, 2016
Health Authority: Argentina: Admin Nacional de Medicamentos, Alimentos Tecnologia Medica
Austria: Medicines and Medical Devices Agency
Canada: Health Canada
Colombia: Instituto Nacional de Vigilancia de Medicamentos y Alimentos
Czech Republic: State Institute for Drug Control
Finland: Finnish Medicines Agency
Hong Kong: Department of Health
India: Drugs Controller General of India
Italy: Ethics Committee
Malaysia: Ministry of Health
Mexico: Federal Commission for Protection Against Health Risks
Netherlands: Central Committee Research Involving Human Subjects
Norway: Norwegian Medicines Agency
Philippines: Bureau of Food and Drugs
Portugal: National Pharmacy and Medicines Institute
South Africa: Medicines Control Council
Spain: Spanish Agency of Medicines
Sweden: Medical Products Agency
Switzerland: Swissmedic
Taiwan : Food and Drug Administration
Thailand: Ministry of Public Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration