Linagliptin as Add on Therapy to Empagliflozin 10 mg or 2... | NCT01778049

NCT01778049

ID	Type	Description	Link
2012-002271-34	EudraCT Number	EudraCT

Status Module

Name	Class
Eli Lilly and Company	INDUSTRY

Description Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Empagliflozin 10 mg dose	Experimental	Empagliflozin open label treatment period	Drug: BI 10773
Placebo add on 10 mg dose	Experimental	Empagliflozin / Linagliptin 10/5 mg Dose FDC placebo add on run-in	Drug: BI 10773 / BI 1356 Placebo Drug: BI 10773
Empagliflozin/Linagliptin 25/5 mg Dose	Experimental	Empagliflozin / Linagliptin 25/5 mg Dose FDC active	Drug: BI 10773 / BI 1356 Drug: BI 10773 Placebo
Empagliflozin/Linagliptin 10/5 mg Dose.	Experimental	Empagliflozin / Linagliptin 10/5 mg Dose FDC placebo	Drug: BI 10773 / BI 1356 Placebo Drug: BI 10773
Empagliflozin/Linagliptin 10/5 mg Dose	Experimental	Empagliflozin / Linagliptin 10/5 mg Dose FDC active	Drug: BI 10773 Placebo Drug: BI 10773 / BI 1356
Empagliflozin 25 mg dose

Name	Type	Description	Arm Group Labels	Other Names
BI 10773	Drug	Empagliflozin active	Placebo add on 25 mg dose
BI 10773 Placebo

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline of HbA1c After 24 Weeks of Treatment.	Change from baseline in Glycated haemoglobin (HbA1c) [%] after 24 weeks of treatment with double-blind trial medication, i.e. HbA1c change from baseline at Week 24. The term "baseline" was not used to refer to measurements prior to the administration of open-label medication. Such measurements were referred to as "pre-treatment". Analyses of change from pre-treatment used the last value before first administration of open-label medication as point of reference. Observed Case (OC): This method analyse only available data that were observed while patients were on treatment, i.e., excluding the missing data. All values measured after rescue medication taken were set to missing. Full Analysis Set (FAS): Includes all patients in the Treated set who had a baseline HbA1c assessment and at least 1 on-treatment HbA1c assessment during the double-blind part of the trial.	Baseline and 24 weeks

Secondary Outcomes

Measure	Description	Time Frame
Fasting Plasma Glucose (FPG) Change From Baseline at 24 Weeks.	Change from baseline FPG (mmol/L) after 24 weeks of treatment with double-blind trial medication, i.e. FPG change from baseline at Week 24.	Baseline and 24 weeks

Eligibility Module

Contacts/Locations Module

Name	Affiliation	Role
Boehringer Ingelheim	Boehringer Ingelheim	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
1275.10.01019 Boehringer Ingelheim Investigational Site		Chino	California		United States
1275.10.01008 Boehringer Ingelheim Investigational Site

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
27762093	Derived	Tinahones FJ, Gallwitz B, Nordaby M, Gotz S, Maldonado-Lutomirsky M, Woerle HJ, Broedl UC. Linagliptin as add-on to empagliflozin and metformin in patients with type 2 diabetes: Two 24-week randomized, double-blind, double-dummy, parallel-group trials. Diabetes Obes Metab. 2017 Feb;19(2):266-274. doi: 10.1111/dom.12814. Epub 2016 Nov 24.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Empa 10 mg OL	Subjects were orally administered once daily empa 10 mg film-coated tablet for 16 wk during OL treatment period, thereafter patients received once daily fixed dose combination (FDC) placebo tablet matching to FDC empa 10 mg/lina 5 mg in addition to empa 10 mg for 1 week during open label placebo add-on treatment period.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Empa 10 mg OL	Subjects were orally administered once daily empa 10 mg film-coated tablet for 16 wk during OL treatment period, thereafter patients received once daily fixed dose combination (FDC) placebo tablet matching to FDC empa 10 mg/lina 5 mg in addition to empa 10 mg for 1 week during open label placebo add-on treatment period.
BG001	Empa 25 mg OL	Subjects were orally administered once daily empa 25 mg film-coated tablet for 16 week during OL treatment period, thereafter patients received once daily FDC Plc tablet matching to FDC empa 25 mg/lina 5 mg in addition to empa 25 mg for 1 wk during open label placebo add-on treatment period.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

Years

Title

Denominators

Categories

Title	Measurements
	OG000-0.53± 0.07 OG001-0.21± 0.07 OG002-0.58± 0.07 OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Superiority of lina5 (E10) vs. Plc (E10): change in HbA1c using a restricted maximum likelihood (REML)- based mixed model repeated measures (MMRM) approach. The model includes baseline HbA1c as linear covariates & baseline estimated glomerula filtration rate (eGFR), geographical region, treatment, visit, visit by treatment interaction as fixed effects.	Mixed Model Repeated Measure (MMRM)	The unstructured covariance structure has been used to fit the mixed model.	0.0013		Mean Difference (Final Values)	-0.32	Standard Error of the Mean	0.10		95	-0.52	-0.13			Mean Difference (Final Values) is actually the adjusted mean difference calculated as lina5 (E10) minus Plc (E10) value.

Secondary

Fasting Plasma Glucose (FPG) Change From Baseline at 24 Weeks.

Change from baseline FPG (mmol/L) after 24 weeks of treatment with double-blind trial medication, i.e. FPG change from baseline at Week 24.

FAS (OC)

Posted

Least Squares Mean

Standard Error

mmol/L

Baseline and 24 weeks

ID	Title	Description
OG000	Lina5 (E10)	Subjects were orally administered FDC empa 10 mg/lina 5 mg and placebo matching to empa 10 mg for 24 wk during the double-blind treatment period.
OG001	Plc (E10)	Subjects were orally administered empa 10 mg and matching placebo to FDC empa 10 mg/lina 5 mg for 24 wk during the double-blind treatment period.
OG002	Lina5 (E25)	Subjects were orally administered FDC empa 25 mg/lina 5 mg and placebo matching to empa 25 mg for 24 wk during the double-blind treatment period.
OG003	Plc (E25)	Subjects were orally administered empa 25 mg and matching placebo to FDC empa 25 mg/lina 5 mg for 24 wk during the double-blind treatment period.

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Empa 10 mg OL	Subjects were orally administered once daily empa 10 mg film-coated tablet for 16 wk during OL treatment period, thereafter patients received once daily fixed dose combination (FDC) placebo tablet matching to FDC empa 10 mg/lina 5 mg in addition to empa 10 mg for 1 week during open label placebo add-on treatment period.	12	352	47	352
EG001	Empa 25 mg OL	Subjects were orally administered once daily empa 25 mg film-coated tablet for 16 week during OL treatment period, thereafter patients received once daily FDC Plc tablet matching to FDC empa 25 mg/lina 5 mg in addition to empa 25 mg for 1 wk during open label placebo add-on treatment period.	12	354	38	354
EG002	Lina5 (E10)	Subjects were orally administered FDC empa 10 mg/lina 5 mg and placebo matching to empa 10 mg for 24 wk during the double-blind treatment period.	4	126	22	126
EG003	Plc (E10)	Subjects were orally administered empa 10 mg and matching placebo to FDC empa 10 mg/lina 5 mg for 24 wk during the double-blind treatment period.	5	128	10	128
EG004	Lina5 (E25)	Subjects were orally administered FDC empa 25 mg/lina 5 mg and placebo matching to empa 25 mg for 24 wk during the double-blind treatment period.	3	112	18	112
EG005	Plc (E25)	Subjects were orally administered empa 25 mg and matching placebo to FDC empa 25 mg/lina 5 mg for 24 wk during the double-blind treatment period.	4	112	21	112

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Pancytopenia	Blood and lymphatic system disorders	MedDRA 17.1	Systematic Assessment	EG0000 affected352 at risk EG0011 affected354 at risk EG0020 affected126 at risk EG0030 affected128 at risk EG0040 affected112 at risk EG0050 affected112 at risk
Angina unstable	Cardiac disorders	MedDRA 17.1	Systematic Assessment	EG0001 affected352 at risk EG0010 affected354 at risk EG0020 affected126 at risk EG003
Atrial fibrillation	Cardiac disorders	MedDRA 17.1	Systematic Assessment	EG0001 affected352 at risk EG0010 affected354 at risk EG0020 affected126 at risk EG003
Atrial flutter	Cardiac disorders	MedDRA 17.1	Systematic Assessment	EG0000 affected352 at risk EG0010 affected354 at risk EG0020 affected126 at risk EG003
Coronary artery disease	Cardiac disorders	MedDRA 17.1	Systematic Assessment	EG0000 affected352 at risk EG0010 affected354 at risk EG0020 affected126 at risk EG003
Myocardial infarction	Cardiac disorders	MedDRA 17.1	Systematic Assessment	EG0001 affected352 at risk EG0010 affected354 at risk EG0020 affected126 at risk EG003
Myocardial ischaemia	Cardiac disorders	MedDRA 17.1	Systematic Assessment	EG0001 affected352 at risk EG0010 affected354 at risk EG0020 affected126 at risk EG003
Tachycardia	Cardiac disorders	MedDRA 17.1	Systematic Assessment	EG0000 affected352 at risk EG0010 affected354 at risk EG0020 affected126 at risk EG003
Diverticulum intestinal	Gastrointestinal disorders	MedDRA 17.1	Systematic Assessment	EG0000 affected352 at risk EG0011 affected354 at risk EG0020 affected126 at risk EG003
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 17.1	Systematic Assessment	EG0000 affected352 at risk EG0011 affected354 at risk EG0020 affected126 at risk EG003
Intestinal polyp	Gastrointestinal disorders	MedDRA 17.1	Systematic Assessment	EG0000 affected352 at risk EG0010 affected354 at risk EG0020 affected126 at risk EG003
Pancreatitis acute	Gastrointestinal disorders	MedDRA 17.1	Systematic Assessment	EG0002 affected352 at risk EG0010 affected354 at risk EG0021 affected126 at risk EG003
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 17.1	Systematic Assessment	EG0000 affected352 at risk EG0011 affected354 at risk EG0020 affected126 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 17.1	Systematic Assessment	EG0000 affected352 at risk EG0010 affected354 at risk EG0021 affected126 at risk EG003
Calcinosis	General disorders	MedDRA 17.1	Systematic Assessment	EG0000 affected352 at risk EG0011 affected354 at risk EG0020 affected126 at risk EG003
Chest pain	General disorders	MedDRA 17.1	Systematic Assessment	EG0001 affected352 at risk EG0010 affected354 at risk EG0020 affected126 at risk EG003
Death	General disorders	MedDRA 17.1	Systematic Assessment	EG0000 affected352 at risk EG0011 affected354 at risk EG0020 affected126 at risk EG003
General physical health deterioration	General disorders	MedDRA 17.1	Systematic Assessment	EG0000 affected352 at risk EG0010 affected354 at risk EG0021 affected126 at risk EG003
Cholecystitis acute	Hepatobiliary disorders	MedDRA 17.1	Systematic Assessment	EG0002 affected352 at risk EG0010 affected354 at risk EG0020 affected126 at risk EG003
Liver injury	Hepatobiliary disorders	MedDRA 17.1	Systematic Assessment	EG0001 affected352 at risk EG0010 affected354 at risk EG0020 affected126 at risk EG003
Abscess limb	Infections and infestations	MedDRA 17.1	Systematic Assessment	EG0000 affected352 at risk EG0011 affected354 at risk EG0020 affected126 at risk EG003
Bronchitis	Infections and infestations	MedDRA 17.1	Systematic Assessment	EG0000 affected352 at risk EG0011 affected354 at risk EG0020 affected126 at risk EG003
Gangrene	Infections and infestations	MedDRA 17.1	Systematic Assessment	EG0000 affected352 at risk EG0011 affected354 at risk EG0020 affected126 at risk EG003
Infectious colitis	Infections and infestations	MedDRA 17.1	Systematic Assessment	EG0000 affected352 at risk EG0011 affected354 at risk EG0020 affected126 at risk EG003
Osteomyelitis	Infections and infestations	MedDRA 17.1	Systematic Assessment	EG0000 affected352 at risk EG0010 affected354 at risk EG0020 affected126 at risk EG003
Pneumonia	Infections and infestations	MedDRA 17.1	Systematic Assessment	EG0000 affected352 at risk EG0010 affected354 at risk EG0021 affected126 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 17.1	Systematic Assessment	EG0001 affected352 at risk EG0010 affected354 at risk EG0020 affected126 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 17.1	Systematic Assessment	EG0000 affected352 at risk EG0010 affected354 at risk EG0021 affected126 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA 17.1	Systematic Assessment	EG0001 affected352 at risk EG0010 affected354 at risk EG0020 affected126 at risk EG003
Skull fractured base	Injury, poisoning and procedural complications	MedDRA 17.1	Systematic Assessment	EG0001 affected352 at risk EG0010 affected354 at risk EG0020 affected126 at risk EG003
Amylase increased	Investigations	MedDRA 17.1	Systematic Assessment	EG0001 affected352 at risk EG0010 affected354 at risk EG0020 affected126 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 17.1	Systematic Assessment	EG0000 affected352 at risk EG0010 affected354 at risk EG0021 affected126 at risk EG003
Haemarthrosis	Musculoskeletal and connective tissue disorders	MedDRA 17.1	Systematic Assessment	EG0000 affected352 at risk EG0010 affected354 at risk EG0020 affected126 at risk EG003
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 17.1	Systematic Assessment	EG0000 affected352 at risk EG0010 affected354 at risk EG0020 affected126 at risk EG003
Rhabdomyolysis	Musculoskeletal and connective tissue disorders	MedDRA 17.1	Systematic Assessment	EG0000 affected352 at risk EG0010 affected354 at risk EG0021 affected126 at risk EG003
Rotator cuff syndrome	Musculoskeletal and connective tissue disorders	MedDRA 17.1	Systematic Assessment	EG0000 affected352 at risk EG0010 affected354 at risk EG0020 affected126 at risk EG003
Pancreatic carcinoma metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 17.1	Systematic Assessment	EG0000 affected352 at risk EG0011 affected354 at risk EG0020 affected126 at risk EG003
Prostatic adenoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 17.1	Systematic Assessment	EG0001 affected352 at risk EG0010 affected354 at risk EG0020 affected126 at risk EG003
Cerebral haematoma	Nervous system disorders	MedDRA 17.1	Systematic Assessment	EG0001 affected352 at risk EG0010 affected354 at risk EG0020 affected126 at risk EG003
Cerebral haemorrhage	Nervous system disorders	MedDRA 17.1	Systematic Assessment	EG0001 affected352 at risk EG0010 affected354 at risk EG0020 affected126 at risk EG003
Cerebrovascular accident	Nervous system disorders	MedDRA 17.1	Systematic Assessment	EG0000 affected352 at risk EG0010 affected354 at risk EG0020 affected126 at risk EG003
Ischaemic stroke	Nervous system disorders	MedDRA 17.1	Systematic Assessment	EG0001 affected352 at risk EG0010 affected354 at risk EG0020 affected126 at risk EG003
Balanoposthitis	Reproductive system and breast disorders	MedDRA 17.1	Systematic Assessment	EG0000 affected352 at risk EG0010 affected354 at risk EG0020 affected126 at risk EG003
Metrorrhagia	Reproductive system and breast disorders	MedDRA 17.1	Systematic Assessment	EG0000 affected352 at risk EG0011 affected354 at risk EG0020 affected126 at risk EG003
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA 17.1	Systematic Assessment	EG0001 affected352 at risk EG0010 affected354 at risk EG0020 affected126 at risk EG003
Nasal septum deviation	Respiratory, thoracic and mediastinal disorders	MedDRA 17.1	Systematic Assessment	EG0000 affected352 at risk EG0011 affected354 at risk EG0020 affected126 at risk EG003
Nasal turbinate hypertrophy	Respiratory, thoracic and mediastinal disorders	MedDRA 17.1	Systematic Assessment	EG0000 affected352 at risk EG0011 affected354 at risk EG0020 affected126 at risk EG003
Pharyngeal lesion	Respiratory, thoracic and mediastinal disorders	MedDRA 17.1	Systematic Assessment	EG0000 affected352 at risk EG0010 affected354 at risk EG0020 affected126 at risk EG003
Dermatitis bullous	Skin and subcutaneous tissue disorders	MedDRA 17.1	Systematic Assessment	EG0000 affected352 at risk EG0010 affected354 at risk EG0020 affected126 at risk EG003
Dyshidrotic eczema	Skin and subcutaneous tissue disorders	MedDRA 17.1	Systematic Assessment	EG0000 affected352 at risk EG0010 affected354 at risk EG0020 affected126 at risk EG003
Extremity necrosis	Vascular disorders	MedDRA 17.1	Systematic Assessment	EG0000 affected352 at risk EG0010 affected354 at risk EG0020 affected126 at risk EG003
Subclavian vein thrombosis	Vascular disorders	MedDRA 17.1	Systematic Assessment	EG0001 affected352 at risk EG0010 affected354 at risk EG0020 affected126 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Nasopharyngitis	Infections and infestations	MedDRA 17.1	Systematic Assessment	EG00017 affected352 at risk EG0015 affected354 at risk EG0028 affected126 at risk EG0033 affected128 at risk EG0042 affected112 at risk EG0058 affected112 at risk
Urinary tract infection	Infections and infestations	MedDRA 17.1	Systematic Assessment	EG00016 affected352 at risk EG00123 affected354 at risk EG00210 affected126 at risk EG003
Lipase increased	Investigations	MedDRA 17.1	Systematic Assessment	EG00015 affected352 at risk EG00110 affected354 at risk EG0024 affected126 at risk EG003

ID	Term
D003920	Diabetes Mellitus
D044882	Glucose Metabolism Disorders
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases
D004700	Endocrine System Diseases

ID	Term
D011687	Purines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds
D011799	Quinazolines