Trial Outcomes & Findings for Efficacy and Safety Study of Empagliflozin as add-on to Insulin in Japanese Patients With Type 2 Diabetes Mellitus (NCT NCT02589639)
NCT ID: NCT02589639
Last Updated: 2019-03-27
Results Overview
The primary endpoint was the change from baseline in HbA1c after 16 weeks of treatment. The term "baseline" refers to the last observation prior to the administration of any randomised study drug. Means presented are the adjusted means.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
269 participants
Primary outcome timeframe
Baseline and 16 weeks
Results posted on
2019-03-27
Participant Flow
After screening, patients who were pre-treated with insulin and 1 oral antidiabetic drug (OAD) underwent a 10-week wash-out period. Then patients proceeded to a 2-week open-label placebo run-in period. Patients who were pre-treated with insulin alone skipped the wash-out period and proceeded to an open-label placebo run-in period.
Patients who successfully completed the periods and who still satisfied the inclusion/exclusion criteria were randomised to the 52-week double- blind treatment period of the study in which they received either 1 of the 2 doses of empagliflozin or placebo in addition to insulin.
Participant milestones
| Measure |
Placebo
Patients were orally administered Placebo matching Empagliflozin 10 milligram (mg) or 25 mg once daily for 52 weeks of double-blind treatment period
|
Empagliflozin 10 mg
Patients were orally administered Empagliflozin 10 mg film-coated tablet once daily for 52 weeks of double-blind treatment period
|
Empagliflozin 25 mg
Patients were orally administered Empagliflozin 25 mg film-coated tablet once daily for 52 weeks of double-blind treatment period
|
|---|---|---|---|
|
Overall Study
STARTED
|
90
|
89
|
90
|
|
Overall Study
Treated
|
90
|
86
|
90
|
|
Overall Study
COMPLETED
|
80
|
79
|
86
|
|
Overall Study
NOT COMPLETED
|
10
|
10
|
4
|
Reasons for withdrawal
| Measure |
Placebo
Patients were orally administered Placebo matching Empagliflozin 10 milligram (mg) or 25 mg once daily for 52 weeks of double-blind treatment period
|
Empagliflozin 10 mg
Patients were orally administered Empagliflozin 10 mg film-coated tablet once daily for 52 weeks of double-blind treatment period
|
Empagliflozin 25 mg
Patients were orally administered Empagliflozin 25 mg film-coated tablet once daily for 52 weeks of double-blind treatment period
|
|---|---|---|---|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
0
|
|
Overall Study
Protocol Violation
|
1
|
0
|
0
|
|
Overall Study
Patient withdrawal, not due to AE
|
3
|
0
|
0
|
|
Overall Study
Adverse Event
|
4
|
5
|
3
|
|
Overall Study
Other reason than specified above
|
1
|
2
|
1
|
|
Overall Study
Not Treated
|
0
|
3
|
0
|
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
Empagliflozin 10 mg
n=90 Participants
Patients were orally administered Empagliflozin 10 mg film-coated tablet once daily for 52 weeks of double-blind treatment period
|
Empagliflozin 25 mg
n=86 Participants
Patients were orally administered Empagliflozin 25 mg film-coated tablet once daily for 52 weeks of double-blind treatment period
|
Placebo
n=90 Participants
Patients were orally administered Placebo matching Empagliflozin 10 milligram (mg) or 25 mg once daily for 52 weeks of double-blind treatment period
|
Total
n=266 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
59.1 years
STANDARD_DEVIATION 10.7 • n=90 Participants
|
58.3 years
STANDARD_DEVIATION 10.0 • n=86 Participants
|
58.6 years
STANDARD_DEVIATION 9.5 • n=90 Participants
|
58.7 years
STANDARD_DEVIATION 10.0 • n=266 Participants
|
|
Sex: Female, Male
Female
|
21 Participants
n=90 Participants
|
23 Participants
n=86 Participants
|
29 Participants
n=90 Participants
|
73 Participants
n=266 Participants
|
|
Sex: Female, Male
Male
|
69 Participants
n=90 Participants
|
63 Participants
n=86 Participants
|
61 Participants
n=90 Participants
|
193 Participants
n=266 Participants
|
|
Race and Ethnicity Not Collected
|
—
|
—
|
—
|
0 Participants
Race and Ethnicity were not collected from any participant.
|
|
Baseline glycosylated haemoglobin A1c (HbA1c) [%]
|
8.70 % of HbA1c
STANDARD_DEVIATION 0.68 • n=90 Participants
|
8.83 % of HbA1c
STANDARD_DEVIATION 0.66 • n=86 Participants
|
8.74 % of HbA1c
STANDARD_DEVIATION 0.72 • n=90 Participants
|
8.75 % of HbA1c
STANDARD_DEVIATION 0.69 • n=266 Participants
|
PRIMARY outcome
Timeframe: Baseline and 16 weeksPopulation: Full analysis set (FAS) with last observation carried forward at 16 weeks (LOCF)-16; The FAS consisted of all patients in the TS who had a baseline measurement of the primary endpoint.
The primary endpoint was the change from baseline in HbA1c after 16 weeks of treatment. The term "baseline" refers to the last observation prior to the administration of any randomised study drug. Means presented are the adjusted means.
Outcome measures
| Measure |
Placebo
n=90 Participants
Patients were orally administered Placebo matching Empagliflozin 10 milligram (mg) or 25 mg once daily for 52 weeks of double-blind treatment period
|
Empagliflozin 10 mg
n=86 Participants
Patients were orally administered Empagliflozin 10 mg film-coated tablet once daily for 52 weeks of double-blind treatment period
|
Empagliflozin 25 mg
n=90 Participants
Patients were orally administered Empagliflozin 25 mg film-coated tablet once daily for 52 weeks of double-blind treatment period
|
|---|---|---|---|
|
Change From Baseline in Glycosylated Haemoglobin A1c (HbA1c) After 16 Weeks of Treatment.
|
0.00 percentage of HbA1c
Standard Error 0.07
|
-0.92 percentage of HbA1c
Standard Error 0.07
|
-1.00 percentage of HbA1c
Standard Error 0.07
|
SECONDARY outcome
Timeframe: From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeksPopulation: Treated set (TS): TS consisted of all randomised patients who were treated with at least 1 dose of the study drug during the 52-week double blind treatment period. The TS was the basis for safety analyses.
Percentage of patients with investigator defined drug-related Adverse Events (AEs) are presented
Outcome measures
| Measure |
Placebo
n=90 Participants
Patients were orally administered Placebo matching Empagliflozin 10 milligram (mg) or 25 mg once daily for 52 weeks of double-blind treatment period
|
Empagliflozin 10 mg
n=86 Participants
Patients were orally administered Empagliflozin 10 mg film-coated tablet once daily for 52 weeks of double-blind treatment period
|
Empagliflozin 25 mg
n=90 Participants
Patients were orally administered Empagliflozin 25 mg film-coated tablet once daily for 52 weeks of double-blind treatment period
|
|---|---|---|---|
|
Percentage of Patients With Investigator Defined Drug-Related Adverse Events (AEs)
|
25.6 Percentage of participants
|
43.0 Percentage of participants
|
43.3 Percentage of participants
|
Adverse Events
Placebo
Serious events: 6 serious events
Other events: 49 other events
Deaths: 0 deaths
Empagliflozin 10 mg
Serious events: 9 serious events
Other events: 45 other events
Deaths: 1 deaths
Empagliflozin 25 mg
Serious events: 8 serious events
Other events: 48 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Placebo
n=90 participants at risk
Patients were orally administered Placebo matching Empagliflozin 10 milligram (mg) or 25 mg once daily for 52 weeks of double-blind treatment period
|
Empagliflozin 10 mg
n=86 participants at risk
Patients were orally administered Empagliflozin 10 mg film-coated tablet once daily for 52 weeks of double-blind treatment period
|
Empagliflozin 25 mg
n=90 participants at risk
Patients were orally administered Empagliflozin 25 mg film-coated tablet once daily for 52 weeks of double-blind treatment period
|
|---|---|---|---|
|
Infections and infestations
Arthritis bacterial
|
0.00%
0/90 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
1.2%
1/86 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
0.00%
0/90 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
|
Infections and infestations
Chronic sinusitis
|
0.00%
0/90 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
1.2%
1/86 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
0.00%
0/90 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
|
Infections and infestations
Pyelonephritis acute
|
0.00%
0/90 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
1.2%
1/86 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
0.00%
0/90 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
|
Infections and infestations
Appendicitis
|
1.1%
1/90 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
0.00%
0/86 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
0.00%
0/90 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
|
Infections and infestations
Cellulitis
|
1.1%
1/90 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
0.00%
0/86 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
1.1%
1/90 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer
|
0.00%
0/90 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
1.2%
1/86 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
0.00%
0/90 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
|
Blood and lymphatic system disorders
Disseminated intravascular coagulation
|
0.00%
0/90 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
1.2%
1/86 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
0.00%
0/90 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
|
Psychiatric disorders
Delirium
|
0.00%
0/90 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
1.2%
1/86 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
0.00%
0/90 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
|
Nervous system disorders
Vocal cord paralysis
|
0.00%
0/90 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
1.2%
1/86 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
0.00%
0/90 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
|
Eye disorders
Glaucoma
|
0.00%
0/90 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
0.00%
0/86 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
2.2%
2/90 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
|
Eye disorders
Cataract
|
0.00%
0/90 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
0.00%
0/86 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
1.1%
1/90 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
|
Eye disorders
Dyschromatopsia
|
0.00%
0/90 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
0.00%
0/86 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
1.1%
1/90 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
|
Ear and labyrinth disorders
Sudden hearing loss
|
0.00%
0/90 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
0.00%
0/86 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
1.1%
1/90 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
|
Cardiac disorders
Coronary artery stenosis
|
0.00%
0/90 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
1.2%
1/86 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
0.00%
0/90 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
|
Cardiac disorders
Myocardial infarction
|
0.00%
0/90 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
1.2%
1/86 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
0.00%
0/90 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
|
Cardiac disorders
Angina unstable
|
1.1%
1/90 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
0.00%
0/86 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
0.00%
0/90 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
|
Gastrointestinal disorders
Duodenal ulcer
|
0.00%
0/90 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
1.2%
1/86 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
0.00%
0/90 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
|
Gastrointestinal disorders
Large intestine polyp
|
1.1%
1/90 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
0.00%
0/86 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
1.1%
1/90 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
|
Hepatobiliary disorders
Cholecystitis
|
0.00%
0/90 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
0.00%
0/86 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
1.1%
1/90 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
|
Hepatobiliary disorders
Cholelithiasis
|
1.1%
1/90 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
0.00%
0/86 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
0.00%
0/90 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.00%
0/90 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
1.2%
1/86 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
0.00%
0/90 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
|
Musculoskeletal and connective tissue disorders
Lumbar spinal stenosis
|
0.00%
0/90 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
0.00%
0/86 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
1.1%
1/90 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/90 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
0.00%
0/86 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
1.1%
1/90 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
|
Injury, poisoning and procedural complications
Femur fracture
|
1.1%
1/90 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
0.00%
0/86 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
0.00%
0/90 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
|
Injury, poisoning and procedural complications
Lumbar vertebral fracture
|
1.1%
1/90 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
0.00%
0/86 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
0.00%
0/90 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
|
Injury, poisoning and procedural complications
Radius fracture
|
1.1%
1/90 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
0.00%
0/86 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
0.00%
0/90 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
|
Injury, poisoning and procedural complications
Spinal compression fracture
|
0.00%
0/90 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
0.00%
0/86 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
1.1%
1/90 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
|
Injury, poisoning and procedural complications
Subdural haematoma
|
1.1%
1/90 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
0.00%
0/86 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
0.00%
0/90 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
Other adverse events
| Measure |
Placebo
n=90 participants at risk
Patients were orally administered Placebo matching Empagliflozin 10 milligram (mg) or 25 mg once daily for 52 weeks of double-blind treatment period
|
Empagliflozin 10 mg
n=86 participants at risk
Patients were orally administered Empagliflozin 10 mg film-coated tablet once daily for 52 weeks of double-blind treatment period
|
Empagliflozin 25 mg
n=90 participants at risk
Patients were orally administered Empagliflozin 25 mg film-coated tablet once daily for 52 weeks of double-blind treatment period
|
|---|---|---|---|
|
Infections and infestations
Nasopharyngitis
|
31.1%
28/90 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
34.9%
30/86 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
26.7%
24/90 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
|
Infections and infestations
Asymptomatic bacteriuria
|
8.9%
8/90 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
3.5%
3/86 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
5.6%
5/90 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
21.1%
19/90 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
27.9%
24/86 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
27.8%
25/90 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
|
Skin and subcutaneous tissue disorders
Eczema
|
5.6%
5/90 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
5.8%
5/86 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
2.2%
2/90 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
3.3%
3/90 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
5.8%
5/86 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
6.7%
6/90 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
|
Renal and urinary disorders
Pollakiuria
|
2.2%
2/90 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
10.5%
9/86 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
10.0%
9/90 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
|
Investigations
Blood ketone body increased
|
1.1%
1/90 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
5.8%
5/86 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
2.2%
2/90 • From 1st intake of study drug to last intake of study drug + 7 days; up to 53 weeks
|
Additional Information
Boehringer Ingelheim, Call Center
Boehringer Ingelheim
Phone: 1-800-243-0127
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER