Trial Outcomes & Findings for Efficacy and Safety of Empagliflozin (BI 10773) in Type 2 Diabetes Patients on a Background of Pioglitazone Alone or With Metformin (NCT NCT01210001)

NCT ID: NCT01210001

Last Updated: 2014-06-17

Results Overview

Change From Baseline in HbA1c after 24 weeks. Note that adjusted means are provided.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

499 participants

Primary outcome timeframe

Baseline and 24 weeks

Results posted on

2014-06-17

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo A placebo tablet, matching the empagliflozin 10mg and 25mg tablets, taken once daily for 24 weeks	Empa 10mg Single oral dose of empagliflozin (empa) 10mg taken once daily for 24 weeks	Empa 25mg Single oral dose of empagliflozin (empa) 25mg taken once daily for 24 weeks
Overall Study STARTED	166	165	168
Overall Study COMPLETED	147	154	156
Overall Study NOT COMPLETED	19	11	12

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo A placebo tablet, matching the empagliflozin 10mg and 25mg tablets, taken once daily for 24 weeks	Empa 10mg Single oral dose of empagliflozin (empa) 10mg taken once daily for 24 weeks	Empa 25mg Single oral dose of empagliflozin (empa) 25mg taken once daily for 24 weeks
Overall Study Not treated	1	0	0
Overall Study Adverse Event	4	2	5
Overall Study Non compliant with protocol	2	2	3
Overall Study Lost to Follow-up	4	3	2
Overall Study Patient refusal to continue,not due toAE	6	2	1
Overall Study Other reason not defined above	2	2	1

Baseline Characteristics

Efficacy and Safety of Empagliflozin (BI 10773) in Type 2 Diabetes Patients on a Background of Pioglitazone Alone or With Metformin

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=165 Participants A placebo tablet, matching the empagliflozin 10mg and 25mg tablets, taken once daily for 24 weeks	Empa 10mg n=165 Participants Single oral dose of empagliflozin (empa) 10mg taken once daily for 24 weeks	Empa 25mg n=168 Participants Single oral dose of empagliflozin (empa) 25mg taken once daily for 24 weeks	Total n=498 Participants Total of all reporting groups
Age, Continuous	54.6 years STANDARD_DEVIATION 10.5 • n=99 Participants	54.7 years STANDARD_DEVIATION 9.9 • n=107 Participants	54.2 years STANDARD_DEVIATION 8.9 • n=206 Participants	54.5 years STANDARD_DEVIATION 9.8 • n=157 Participants
Sex: Female, Male Female	92 Participants n=99 Participants	82 Participants n=107 Participants	83 Participants n=206 Participants	257 Participants n=157 Participants
Sex: Female, Male Male	73 Participants n=99 Participants	83 Participants n=107 Participants	85 Participants n=206 Participants	241 Participants n=157 Participants

PRIMARY outcome

Timeframe: Baseline and 24 weeks

Population: Full analysis set (FAS) which included all randomised and treated patients who had a baseline HbA1c value. Values after start of antidiabetic rescue therapy were set to missing and last observation carried forward (LOCF) was used for imputation of missing values.

Change From Baseline in HbA1c after 24 weeks. Note that adjusted means are provided.

Outcome measures

Outcome measures
Measure	Placebo n=165 Participants A placebo tablet, matching the empagliflozin 10mg and 25mg tablets, taken once daily for 24 weeks	Empa 10mg n=165 Participants Single oral dose of empagliflozin (empa) 10mg taken once daily for 24 weeks	Empa 25mg n=168 Participants Single oral dose of empagliflozin (empa) 25mg taken once daily for 24 weeks
HbA1c Change From Baseline	-0.11 percentage of HbA1c Standard Error 0.07	-0.59 percentage of HbA1c Standard Error 0.07	-0.72 percentage of HbA1c Standard Error 0.07

PRIMARY outcome

Timeframe: Baseline and 24 weeks

Population: Full analysis set (FAS) which included all randomised and treated patients who had a baseline HbA1c value for patients on pioglitazone and metformin background medication. Values after start of antidiabetic rescue therapy were set to missing and last observation carried forward (LOCF) was used for imputation of missing values.

Change From Baseline in HbA1c after 24 weeks for patients with pioglitazone (pio) and metformin (met) background medication only. Note that adjusted means are provided.

Outcome measures

Outcome measures
Measure	Placebo n=124 Participants A placebo tablet, matching the empagliflozin 10mg and 25mg tablets, taken once daily for 24 weeks	Empa 10mg n=125 Participants Single oral dose of empagliflozin (empa) 10mg taken once daily for 24 weeks	Empa 25mg n=127 Participants Single oral dose of empagliflozin (empa) 25mg taken once daily for 24 weeks
HbA1c Change From Baseline for Pio and Met Background Medication Patients	-0.11 percentage of HbA1c Standard Error 0.08	-0.55 percentage of HbA1c Standard Error 0.08	-0.70 percentage of HbA1c Standard Error 0.07

SECONDARY outcome

Timeframe: Baseline and 24 weeks

Change from baseline in fasting plasma glucose (FPG) after 24 weeks of treatment. Note that adjusted means are provided.

Outcome measures

Outcome measures
Measure	Placebo n=165 Participants A placebo tablet, matching the empagliflozin 10mg and 25mg tablets, taken once daily for 24 weeks	Empa 10mg n=163 Participants Single oral dose of empagliflozin (empa) 10mg taken once daily for 24 weeks	Empa 25mg n=168 Participants Single oral dose of empagliflozin (empa) 25mg taken once daily for 24 weeks
Fasting Plasma Glucose (FPG) Change From Baseline	6.47 mg/dL Standard Error 2.61	-17.00 mg/dL Standard Error 2.63	-21.99 mg/dL Standard Error 2.59

SECONDARY outcome

Timeframe: Baseline and 24 weeks

Change from baseline in body weight after 24 weeks. Note that adjusted means are provided.

Outcome measures

Outcome measures
Measure	Placebo n=165 Participants A placebo tablet, matching the empagliflozin 10mg and 25mg tablets, taken once daily for 24 weeks	Empa 10mg n=165 Participants Single oral dose of empagliflozin (empa) 10mg taken once daily for 24 weeks	Empa 25mg n=168 Participants Single oral dose of empagliflozin (empa) 25mg taken once daily for 24 weeks
Body Weight Change From Baseline	0.34 kg Standard Error 0.21	-1.62 kg Standard Error 0.21	-1.47 kg Standard Error 0.21

OTHER_PRE_SPECIFIED outcome

Timeframe: From first drug administration until 7 days after last intake of study drug, up to 256 days

Population: Treated set which included all patients treated with at least one dose of randomised study medication

Number of patients with hypoglycaemic events, as reported as adverse events.

Outcome measures

Outcome measures
Measure	Placebo n=165 Participants A placebo tablet, matching the empagliflozin 10mg and 25mg tablets, taken once daily for 24 weeks	Empa 10mg n=165 Participants Single oral dose of empagliflozin (empa) 10mg taken once daily for 24 weeks	Empa 25mg n=168 Participants Single oral dose of empagliflozin (empa) 25mg taken once daily for 24 weeks
Hypoglycaemic Events	1.8 percentage of participants	1.2 percentage of participants	2.4 percentage of participants

Adverse Events

Placebo

Serious events: 7 serious events

Other events: 56 other events

Deaths: 0 deaths

Empa 10mg

Serious events: 7 serious events

Other events: 50 other events

Deaths: 0 deaths

Empa 25mg

Serious events: 6 serious events

Other events: 34 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo n=165 participants at risk A placebo tablet, matching the empagliflozin 10mg and 25mg tablets, taken once daily for 24 weeks	Empa 10mg n=165 participants at risk Single oral dose of empagliflozin (empa) 10mg taken once daily for 24 weeks	Empa 25mg n=168 participants at risk Single oral dose of empagliflozin (empa) 25mg taken once daily for 24 weeks
Infections and infestations Urinary tract infection	10.9% 18/165 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days	14.5% 24/165 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days	10.7% 18/168 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days
Metabolism and nutrition disorders Dyslipidaemia	10.3% 17/165 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days	10.9% 18/165 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days	7.1% 12/168 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days
Metabolism and nutrition disorders Hyperglycaemia	15.8% 26/165 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days	4.8% 8/165 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days	2.4% 4/168 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days
Vascular disorders Hypertension	5.5% 9/165 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days	1.8% 3/165 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days	1.2% 2/168 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days

Additional Information

Boehringer Ingelheim Call Center

Boehringer Ingelheim Pharmaceuticals

Phone: 1-800-243-0127

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Any publication of the result of this trial must be consistent with the Boehringer Ingelheim publication policy. The rights of the investigator and of the sponsor with regard to publication of the results of this trial are described in the investigator contract.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo n=165 participants at risk A placebo tablet, matching the empagliflozin 10mg and 25mg tablets, taken once daily for 24 weeks	Empa 10mg n=165 participants at risk Single oral dose of empagliflozin (empa) 10mg taken once daily for 24 weeks	Empa 25mg n=168 participants at risk Single oral dose of empagliflozin (empa) 25mg taken once daily for 24 weeks
Cardiac disorders Atrial fibrillation	0.00% 0/165 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days	0.00% 0/165 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days	0.60% 1/168 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days
Cardiac disorders Atrial flutter	0.00% 0/165 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days	0.00% 0/165 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days	0.60% 1/168 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days
Cardiac disorders Cardio-respiratory arrest	0.00% 0/165 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days	0.00% 0/165 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days	0.60% 1/168 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days
Cardiac disorders Myocardial ischaemia	0.61% 1/165 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days	0.00% 0/165 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days	0.60% 1/168 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days
Eye disorders Diabetic retinopathy	0.00% 0/165 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days	0.61% 1/165 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days	0.00% 0/168 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days
Gastrointestinal disorders Anal fissure	0.61% 1/165 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days	0.00% 0/165 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days	0.00% 0/168 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days
Gastrointestinal disorders Constipation	0.61% 1/165 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days	0.00% 0/165 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days	0.00% 0/168 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days
Gastrointestinal disorders Oesophageal rupture	0.00% 0/165 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days	0.00% 0/165 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days	0.60% 1/168 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days
Hepatobiliary disorders Cholecystitis	0.00% 0/165 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days	0.61% 1/165 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days	0.00% 0/168 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days
Hepatobiliary disorders Cholecystitis acute	0.61% 1/165 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days	0.00% 0/165 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days	0.00% 0/168 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days
Infections and infestations Amoebic colitis	0.00% 0/165 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days	0.61% 1/165 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days	0.00% 0/168 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days
Infections and infestations Cellulitis	0.00% 0/165 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days	0.61% 1/165 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days	0.60% 1/168 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days
Infections and infestations Dengue fever	0.00% 0/165 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days	0.00% 0/165 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days	0.60% 1/168 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days
Infections and infestations Pseudomonas infection	0.00% 0/165 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days	0.00% 0/165 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days	0.60% 1/168 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days
Infections and infestations Pyelonephritis acute	0.61% 1/165 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days	0.00% 0/165 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days	0.00% 0/168 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days
Infections and infestations Septic shock	0.00% 0/165 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days	0.00% 0/165 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days	0.60% 1/168 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days
Infections and infestations Urosepsis	0.00% 0/165 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days	0.61% 1/165 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days	0.00% 0/168 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days
Injury, poisoning and procedural complications Hand fracture	0.61% 1/165 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days	0.00% 0/165 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days	0.00% 0/168 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days
Injury, poisoning and procedural complications Humerus fracture	0.61% 1/165 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days	0.00% 0/165 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days	0.00% 0/168 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days
Injury, poisoning and procedural complications Road traffic accident	0.61% 1/165 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days	0.00% 0/165 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days	0.00% 0/168 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days
Injury, poisoning and procedural complications Traumatic fracture	0.61% 1/165 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days	0.00% 0/165 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days	0.00% 0/168 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days
Investigations Haemoglobin decreased	0.61% 1/165 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days	0.00% 0/165 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days	0.60% 1/168 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/165 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days	0.61% 1/165 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days	0.00% 0/168 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days
Musculoskeletal and connective tissue disorders Joint swelling	0.00% 0/165 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days	0.61% 1/165 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days	0.00% 0/168 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/165 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days	0.61% 1/165 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days	0.00% 0/168 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.00% 0/165 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days	0.00% 0/165 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days	0.60% 1/168 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days
Nervous system disorders Brain stem infarction	0.00% 0/165 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days	0.00% 0/165 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days	0.60% 1/168 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days
Skin and subcutaneous tissue disorders Skin ulcer	0.61% 1/165 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days	0.00% 0/165 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days	0.00% 0/168 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days
Vascular disorders Haematoma	0.00% 0/165 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days	0.00% 0/165 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days	0.60% 1/168 • From first dose of randomised study medication until 7 days after the last dose, up to 256 days