Trial Outcomes & Findings for Efficacy and Safety of BI 10773 in Combination With Insulin in Patients With Type 2 Diabetes (NCT NCT01011868)

NCT ID: NCT01011868

Last Updated: 2014-09-30

Results Overview

Change from baseline in Glycosylated haemoglobin A1c (HbA1c) after 18 weeks of treatment

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

494 participants

Primary outcome timeframe

Baseline and 18 weeks

Results posted on

2014-09-30

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo Oral Placebo	Empagliflozin 10 mg Empagliflozin 10 mg orally once daily	Empagliflozin 25 mg Empagliflozin 25 mg orally once daily
After Week 18 Follow-up STARTED	170	169	155
After Week 18 Follow-up COMPLETED	147	153	129
After Week 18 Follow-up NOT COMPLETED	23	16	26
After Week 78 Follow-up STARTED	170	169	155
After Week 78 Follow-up COMPLETED	118	131	111
After Week 78 Follow-up NOT COMPLETED	52	38	44

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Oral Placebo	Empagliflozin 10 mg Empagliflozin 10 mg orally once daily	Empagliflozin 25 mg Empagliflozin 25 mg orally once daily
After Week 18 Follow-up Adverse Event	8	6	13
After Week 18 Follow-up Lack of Efficacy	1	0	0
After Week 18 Follow-up Protocol Violation	1	1	1
After Week 18 Follow-up Lost to Follow-up	5	3	0
After Week 18 Follow-up Withdrawal by Subject	6	3	0
After Week 18 Follow-up Other reason not defined above	2	3	12
After Week 78 Follow-up Adverse Event	14	18	21
After Week 78 Follow-up Lack of Efficacy	4	0	0
After Week 78 Follow-up Protocol Violation	9	1	2
After Week 78 Follow-up Lost to Follow-up	11	6	4
After Week 78 Follow-up Withdrawal by Subject	9	8	1
After Week 78 Follow-up Other reason not defined above	5	5	16

Baseline Characteristics

Efficacy and Safety of BI 10773 in Combination With Insulin in Patients With Type 2 Diabetes

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=170 Participants Oral Placebo	Empagliflozin 10 mg n=169 Participants Empagliflozin 10 mg orally once daily	Empagliflozin 25 mg n=155 Participants Empagliflozin 25 mg orally once daily	Total n=494 Participants Total of all reporting groups
Age, Continuous	58.1 years STANDARD_DEVIATION 9.4 • n=5 Participants	58.6 years STANDARD_DEVIATION 9.8 • n=7 Participants	59.9 years STANDARD_DEVIATION 10.5 • n=5 Participants	58.8 years STANDARD_DEVIATION 9.9 • n=4 Participants
Sex: Female, Male Female	80 Participants n=5 Participants	76 Participants n=7 Participants	62 Participants n=5 Participants	218 Participants n=4 Participants
Sex: Female, Male Male	90 Participants n=5 Participants	93 Participants n=7 Participants	93 Participants n=5 Participants	276 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline and 18 weeks

Population: FAS18-completers-included FAS patients not prematurely discontinue prior to Week 18, completed required minimum treatment duration, and had an on treatment HbA1c value within Week 18 time window. Values after start of antidiabetic rescue therapy were set to missing and last observation carried forward (LOCF-18) was used for imputation. (LOCF-18)

Change from baseline in Glycosylated haemoglobin A1c (HbA1c) after 18 weeks of treatment

Outcome measures

Outcome measures
Measure	Placebo n=125 Participants Oral Placebo	Empagliflozin 10 mg n=132 Participants Empagliflozin 10 mg orally once daily	Empagliflozin 25 mg n=117 Participants Empagliflozin 25 mg orally once daily
Change From Baseline in Glycosylated Haemoglobin A1c (HbA1c) After 18 Weeks of Treatment	0.03 percentage of HbA1c Standard Error 0.07	-0.58 percentage of HbA1c Standard Error 0.07	-0.75 percentage of HbA1c Standard Error 0.08

SECONDARY outcome

Timeframe: Baseline and 18, 54 and 78 weeks

Population: FAS with non-completers considered failure (NCF)

Patients that had a reduction in HbA1c of at least 0.5% from baseline to 18, 54 and 78 weeks of treatment

Outcome measures

Outcome measures
Measure	Placebo n=170 Participants Oral Placebo	Empagliflozin 10 mg n=169 Participants Empagliflozin 10 mg orally once daily	Empagliflozin 25 mg n=155 Participants Empagliflozin 25 mg orally once daily
Occurrence of Relative Efficacy Response (HbA1c Lowering by at Least 0.5%) After 18, 54 and 78 Weeks of Treatment 18 weeks	27 participants	85 participants	73 participants
Occurrence of Relative Efficacy Response (HbA1c Lowering by at Least 0.5%) After 18, 54 and 78 Weeks of Treatment 54 weeks	30 participants	72 participants	69 participants
Occurrence of Relative Efficacy Response (HbA1c Lowering by at Least 0.5%) After 18, 54 and 78 Weeks of Treatment 78 weeks	27 participants	59 participants	61 participants

SECONDARY outcome

Timeframe: Baseline, 18, 54 and 78 weeks

Population: FAS observed cases (OC)

Change from baseline in fasting plasma glucose (FPG) after 18, 54 and 78 weeks of treatment

Outcome measures

Outcome measures
Measure	Placebo n=135 Participants Oral Placebo	Empagliflozin 10 mg n=138 Participants Empagliflozin 10 mg orally once daily	Empagliflozin 25 mg n=120 Participants Empagliflozin 25 mg orally once daily
Change From Baseline in Fasting Plasma Glucose (FPG) After 18, 54 and 78 Weeks of Treatment week 18 Change from BL	9.81 mg/dL Standard Error 5.48	-14.79 mg/dL Standard Error 3.93	-27.03 mg/dL Standard Error 3.92
Change From Baseline in Fasting Plasma Glucose (FPG) After 18, 54 and 78 Weeks of Treatment week 54 Change from BL (N=103,111,99)	0.91 mg/dL Standard Error 5.08	-9.59 mg/dL Standard Error 4.69	-23.75 mg/dL Standard Error 4.62
Change From Baseline in Fasting Plasma Glucose (FPG) After 18, 54 and 78 Weeks of Treatment week 78 Change from BL (N=92,104,92)	-5.53 mg/dL Standard Error 4.95	-7.75 mg/dL Standard Error 4.66	-21.62 mg/dL Standard Error 5.13

SECONDARY outcome

Timeframe: Baseline, 18, 54 and 78 weeks

Population: FAS (OC)

Percent change from baseline in fasting plasma glucose (FPG) after 18, 54 and 78 weeks of treatment

Outcome measures

Outcome measures
Measure	Placebo n=135 Participants Oral Placebo	Empagliflozin 10 mg n=138 Participants Empagliflozin 10 mg orally once daily	Empagliflozin 25 mg n=120 Participants Empagliflozin 25 mg orally once daily
Percent Change From Baseline in Fasting Plasma Glucose (FPG) After 18, 54 and 78 Weeks of Treatment week 18 % CHG	19.02 percentage of Change from BL in FPG Standard Error 6.32	-2.80 percentage of Change from BL in FPG Standard Error 3.17	-13.43 percentage of Change from BL in FPG Standard Error 2.39
Percent Change From Baseline in Fasting Plasma Glucose (FPG) After 18, 54 and 78 Weeks of Treatment week 54 % CHG (N=103,111,99)	9.67 percentage of Change from BL in FPG Standard Error 5.58	0.67 percentage of Change from BL in FPG Standard Error 4.05	-11.59 percentage of Change from BL in FPG Standard Error 3.04
Percent Change From Baseline in Fasting Plasma Glucose (FPG) After 18, 54 and 78 Weeks of Treatment week 78 % CHG (N=92,104,92)	4.75 percentage of Change from BL in FPG Standard Error 5.67	2.43 percentage of Change from BL in FPG Standard Error 4.18	-9.52 percentage of Change from BL in FPG Standard Error 3.40

SECONDARY outcome

Timeframe: Baseline, 54 and 78 weeks

Population: FAS (OC-78) for week 54 FAS78-completers (LOCF-78) for week 78 - Values after start of antidiabetic rescue therapy except changes in basal insulin dose were set to missing and last observation carried forward (LOCF) was used for imputation of missing values

Change from baseline in basal insulin dose/day after 54 and 78 weeks of treatment

Outcome measures

Outcome measures
Measure	Placebo n=112 Participants Oral Placebo	Empagliflozin 10 mg n=127 Participants Empagliflozin 10 mg orally once daily	Empagliflozin 25 mg n=110 Participants Empagliflozin 25 mg orally once daily
Change From Baseline in Basal Insulin Dose/Day After 54 and 78 Weeks of Treatment week 54 (N=112,122,104)	5.39 IU Standard Error 1.60	-1.20 IU Standard Error 1.40	-1.12 IU Standard Error 1.27
Change From Baseline in Basal Insulin Dose/Day After 54 and 78 Weeks of Treatment week 78	4.79 IU Standard Error 2.06	-0.70 IU Standard Error 1.85	-0.39 IU Standard Error 1.06

SECONDARY outcome

Timeframe: Baseline, 18, 54, 78 weeks

Population: FAS (OC)

Change from baseline in body weight after 18, 54 and 78 weeks of treatment

Outcome measures

Outcome measures
Measure	Placebo n=141 Participants Oral Placebo	Empagliflozin 10 mg n=148 Participants Empagliflozin 10 mg orally once daily	Empagliflozin 25 mg n=125 Participants Empagliflozin 25 mg orally once daily
Change From Baseline in Body Weight After 18, 54 and 78 Weeks of Treatment 54 weeks (N=114,120,106)	-0.52 kg Standard Error 0.32	-2.28 kg Standard Error 0.33	-2.23 kg Standard Error 0.35
Change From Baseline in Body Weight After 18, 54 and 78 Weeks of Treatment 18 weeks	-0.04 kg Standard Error 0.21	-2.06 kg Standard Error 0.22	-0.91 kg Standard Error 1.27
Change From Baseline in Body Weight After 18, 54 and 78 Weeks of Treatment 78 weeks (N=100,113,96)	1.12 kg Standard Error 1.28	-2.61 kg Standard Error 0.31	-1.99 kg Standard Error 0.32

SECONDARY outcome

Timeframe: Baseline and 82 weeks

Population: FAS-FU (OR)

Change from baseline in body weight at follow up (82 weeks)

Outcome measures

Outcome measures
Measure	Placebo n=111 Participants Oral Placebo	Empagliflozin 10 mg n=119 Participants Empagliflozin 10 mg orally once daily	Empagliflozin 25 mg n=112 Participants Empagliflozin 25 mg orally once daily
Change From Baseline in Body Weight at Follow-up Follow-up	90.56 kg Standard Deviation 25.87	90.44 kg Standard Deviation 19.35	93.98 kg Standard Deviation 20.87
Change From Baseline in Body Weight at Follow-up Follow-up change from baseline	0.92 kg Standard Deviation 12.20	-2.02 kg Standard Deviation 4.04	-1.05 kg Standard Deviation 3.96
Change From Baseline in Body Weight at Follow-up Change from last value on treatment N=111,118,109	-0.23 kg Standard Deviation 16.84	0.62 kg Standard Deviation 2.11	1.34 kg Standard Deviation 1.90

SECONDARY outcome

Timeframe: Baseline, 54 and 78 weeks

Population: Week 54 - FAS (OC-78) Week 78 - FAS78-completers (LOCF-78)

Change from baseline in HbA1c after 54 and 78 weeks of treatment

Outcome measures

Outcome measures
Measure	Placebo n=113 Participants Oral Placebo	Empagliflozin 10 mg n=127 Participants Empagliflozin 10 mg orally once daily	Empagliflozin 25 mg n=110 Participants Empagliflozin 25 mg orally once daily
Change From Baseline in HbA1c After 54 and 78 Weeks of Treatment Week 54 (N=113,121,107)	-0.06 percentage of HbA1c Standard Error 0.08	-0.59 percentage of HbA1c Standard Error 0.08	-0.84 percentage of HbA1c Standard Error 0.09
Change From Baseline in HbA1c After 54 and 78 Weeks of Treatment Week 78 (N=112,127,110)	-0.05 percentage of HbA1c Standard Error 0.10	-0.51 percentage of HbA1c Standard Error 0.09	-0.68 percentage of HbA1c Standard Error 0.09

SECONDARY outcome

Timeframe: Baseline, 18, 54 and 78 weeks

Population: FAS (NCF)

The occurrence of treat to target efficacy response, that is an HbA1c under treatment of \<7.0% After 18, 54, and 78 weeks of treatment

Outcome measures

Outcome measures
Measure	Placebo n=165 Participants Oral Placebo	Empagliflozin 10 mg n=167 Participants Empagliflozin 10 mg orally once daily	Empagliflozin 25 mg n=154 Participants Empagliflozin 25 mg orally once daily
The Occurrence of Treat to Target Efficacy Response, That is an HbA1c Under Treatment of <7.0% After 18, 54, and 78 Weeks of Treatment 18 weeks	9 participants	30 participants	30 participants
The Occurrence of Treat to Target Efficacy Response, That is an HbA1c Under Treatment of <7.0% After 18, 54, and 78 Weeks of Treatment 54 weeks	14 participants	23 participants	27 participants
The Occurrence of Treat to Target Efficacy Response, That is an HbA1c Under Treatment of <7.0% After 18, 54, and 78 Weeks of Treatment 78 weeks	11 participants	20 participants	27 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: During the course of the study (82 weeks)

Population: Treated set (TS). Treatment assignment as first medication taken.

Confirmed hypoglycemic events refer to all hypoglycemic events that had a glucose value ≤70 ml/dL or where assistance was required. Symptomatic hypoglycemic events were to be reported as adverse events. Investigator-defined hypoglycaemia adverse events include all events that investigator marked as 'Hypoglycaemic event' in CRFs, regardless of the reported term or blood glucose value. It may include hypoglycemia itself as reported term or any other symptoms that that investigator may have attributed to hypoglycemia (e.g. dizziness, hyperhidrosis, and asthenia).

Outcome measures

Outcome measures
Measure	Placebo n=170 Participants Oral Placebo	Empagliflozin 10 mg n=169 Participants Empagliflozin 10 mg orally once daily	Empagliflozin 25 mg n=155 Participants Empagliflozin 25 mg orally once daily
Confirmed Hypoglycemic Events	60 participants	61 participants	56 participants

Adverse Events

Placebo

Serious events: 28 serious events

Other events: 115 other events

Deaths: 0 deaths

Empagliflozin 10 mg

Serious events: 28 serious events

Other events: 110 other events

Deaths: 0 deaths

Empagliflozin 25 mg

Serious events: 28 serious events

Other events: 95 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

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=170 participants at risk Oral Placebo	Empagliflozin 10 mg n=169 participants at risk Empagliflozin 10 mg orally once daily	Empagliflozin 25 mg n=155 participants at risk Empagliflozin 25 mg orally once daily
Infections and infestations Nasopharyngitis	12.9% 22/170 • During the course of the study (82 weeks)	11.8% 20/169 • During the course of the study (82 weeks)	11.0% 17/155 • During the course of the study (82 weeks)
Infections and infestations Urinary tract infection	7.6% 13/170 • During the course of the study (82 weeks)	12.4% 21/169 • During the course of the study (82 weeks)	10.3% 16/155 • During the course of the study (82 weeks)
Infections and infestations Upper respiratory tract infection	5.9% 10/170 • During the course of the study (82 weeks)	10.7% 18/169 • During the course of the study (82 weeks)	8.4% 13/155 • During the course of the study (82 weeks)
Metabolism and nutrition disorders Hypoglycaemia	32.9% 56/170 • During the course of the study (82 weeks)	33.1% 56/169 • During the course of the study (82 weeks)	35.5% 55/155 • During the course of the study (82 weeks)
Metabolism and nutrition disorders Hyperglycaemia	10.0% 17/170 • During the course of the study (82 weeks)	9.5% 16/169 • During the course of the study (82 weeks)	9.7% 15/155 • During the course of the study (82 weeks)
Psychiatric disorders Depression	1.8% 3/170 • During the course of the study (82 weeks)	5.9% 10/169 • During the course of the study (82 weeks)	1.3% 2/155 • During the course of the study (82 weeks)
Nervous system disorders Dizziness	7.1% 12/170 • During the course of the study (82 weeks)	10.7% 18/169 • During the course of the study (82 weeks)	4.5% 7/155 • During the course of the study (82 weeks)
Nervous system disorders Headache	2.9% 5/170 • During the course of the study (82 weeks)	3.0% 5/169 • During the course of the study (82 weeks)	5.2% 8/155 • During the course of the study (82 weeks)
Vascular disorders Hypertension	7.1% 12/170 • During the course of the study (82 weeks)	0.59% 1/169 • During the course of the study (82 weeks)	1.9% 3/155 • During the course of the study (82 weeks)
Respiratory, thoracic and mediastinal disorders Cough	5.3% 9/170 • During the course of the study (82 weeks)	3.6% 6/169 • During the course of the study (82 weeks)	2.6% 4/155 • During the course of the study (82 weeks)
Gastrointestinal disorders Diarrhoea	7.6% 13/170 • During the course of the study (82 weeks)	5.9% 10/169 • During the course of the study (82 weeks)	7.1% 11/155 • During the course of the study (82 weeks)
Gastrointestinal disorders Nausea	7.1% 12/170 • During the course of the study (82 weeks)	5.3% 9/169 • During the course of the study (82 weeks)	5.2% 8/155 • During the course of the study (82 weeks)
Gastrointestinal disorders Vomiting	2.9% 5/170 • During the course of the study (82 weeks)	2.4% 4/169 • During the course of the study (82 weeks)	5.2% 8/155 • During the course of the study (82 weeks)
Musculoskeletal and connective tissue disorders Back pain	7.6% 13/170 • During the course of the study (82 weeks)	6.5% 11/169 • During the course of the study (82 weeks)	8.4% 13/155 • During the course of the study (82 weeks)
Musculoskeletal and connective tissue disorders Arthralgia	5.3% 9/170 • During the course of the study (82 weeks)	3.6% 6/169 • During the course of the study (82 weeks)	5.2% 8/155 • During the course of the study (82 weeks)
General disorders Fatigue	1.2% 2/170 • During the course of the study (82 weeks)	5.9% 10/169 • During the course of the study (82 weeks)	2.6% 4/155 • During the course of the study (82 weeks)