Efficacy and Safety of BI 10773 in Combination With Insul... | NCT01011868

ID	Type	Description	Link
2009-013668-38	EudraCT Number	EudraCT

Official Title

A Phase IIb, Randomized, Double-blind, Placebo-controlled, Parallel Group, Safety and Efficacy Study of BI 10773 (10 mg and 25 mg) Administered Orally, Once Daily Over 78 Weeks in Type 2 Diabetic Patients Receiving Treatment With Basal Insulin (Glargine, Detemir, or NPH Insulin Only) With or Without Concomitant Metformin and/or Sulfonylurea Therapy and Insufficient Glycemic Control

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
BI 10773 low dose	Experimental	Patients receive BI 10773 low dose daily	Drug: BI 10773 low dose
BI 10773 high dose	Experimental	Patients receive BI 10773 high dose daily	Drug: BI 10773 placebo Drug: BI 10773 high dose
placebo	Placebo Comparator	Patients receive placebo to match BI 10773 daily	Drug: BI 10773 placebo

Name	Type	Description	Arm Group Labels	Other Names
BI 10773 placebo	Drug	BI 10773 placebo	BI 10773 high dose
BI 10773 low dose

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline in Glycosylated Haemoglobin A1c (HbA1c) After 18 Weeks of Treatment	Change from baseline in Glycosylated haemoglobin A1c (HbA1c) after 18 weeks of treatment	Baseline and 18 weeks

Secondary Outcomes

Measure	Description	Time Frame
Occurrence of Relative Efficacy Response (HbA1c Lowering by at Least 0.5%) After 18, 54 and 78 Weeks of Treatment	Patients that had a reduction in HbA1c of at least 0.5% from baseline to 18, 54 and 78 weeks of treatment	Baseline and 18, 54 and 78 weeks
Change From Baseline in Fasting Plasma Glucose (FPG) After 18, 54 and 78 Weeks of Treatment

Other Outcomes

Measure	Description	Time Frame
Confirmed Hypoglycemic Events	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).

Eligibility Module

Contacts/Locations Module

Name	Affiliation	Role
Boehringer Ingelheim	Boehringer Ingelheim	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
1245.33.01014 Boehringer Ingelheim Investigational Site		Birmingham	Alabama		United States
1245.33.01047 Boehringer Ingelheim Investigational Site

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
35472672	Derived	Tuttle KR, Levin A, Nangaku M, Kadowaki T, Agarwal R, Hauske SJ, Elsasser A, Ritter I, Steubl D, Wanner C, Wheeler DC. Safety of Empagliflozin in Patients With Type 2 Diabetes and Chronic Kidney Disease: Pooled Analysis of Placebo-Controlled Clinical Trials. Diabetes Care. 2022 Jun 2;45(6):1445-1452. doi: 10.2337/dc21-2034.

Results Section

Participant Flow Module

ID	Title	Description
FG000	Placebo	Oral Placebo
FG001	Empagliflozin 10 mg	Empagliflozin 10 mg orally once daily

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Placebo	Oral Placebo
BG001	Empagliflozin 10 mg	Empagliflozin 10 mg orally once daily
BG002	Empagliflozin 25 mg	Empagliflozin 25 mg orally once daily
BG003	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
	OG0000.03± 0.07 OG001-0.58± 0.07 OG002-0.75± 0.08

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	The null and alternative hypotheses to be tested: H0,1: No difference in change from baseline to Week 18 in HbA1c between empagliflozin 10 mg and placebo H1,1: A difference in change from baseline to Week 18 in HbA1c between empagliflozin 10 mg and placebo	ANCOVA	ANCOVA that included treatment group and geographic region as fixed effects along with baseline HbA1c as covariate.	<0.0001	Hypotheses were tested at significance level of 0.025, which is half of overall alpha of 0.05, split equally between 2 treatment comparisons. This maintained the overall type-I (alpha) at 5%. There was no a priori assumption on testing order.	Adjusted mean difference	-0.56	Standard Error of the Mean	0.10	2-Sided	97.5	-0.78	-0.33

Secondary

Occurrence of Relative Efficacy Response (HbA1c Lowering by at Least 0.5%) After 18, 54 and 78 Weeks of Treatment

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

FAS with non-completers considered failure (NCF)

Number

participants

Baseline and 18, 54 and 78 weeks

ID	Title	Description
OG000	Placebo	Oral Placebo
OG001	Empagliflozin 10 mg	Empagliflozin 10 mg orally once daily
OG002	Empagliflozin 25 mg	Empagliflozin 25 mg orally once daily

Units	Counts
Participants	OG000

Secondary

Change From Baseline in Fasting Plasma Glucose (FPG) After 18, 54 and 78 Weeks of Treatment

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

FAS observed cases (OC)

Mean

Standard Error

mg/dL

Baseline, 18, 54 and 78 weeks

ID	Title	Description
OG000	Placebo	Oral Placebo
OG001	Empagliflozin 10 mg	Empagliflozin 10 mg orally once daily
OG002	Empagliflozin 25 mg	Empagliflozin 25 mg orally once daily

Units	Counts
Participants	OG000

Secondary

Percent Change From Baseline in Fasting Plasma Glucose (FPG) After 18, 54 and 78 Weeks of Treatment

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

FAS (OC)

Mean

Standard Error

percentage of Change from BL in FPG

Baseline, 18, 54 and 78 weeks

ID	Title	Description
OG000	Placebo	Oral Placebo
OG001	Empagliflozin 10 mg	Empagliflozin 10 mg orally once daily
OG002	Empagliflozin 25 mg	Empagliflozin 25 mg orally once daily

Units	Counts
Participants	OG000

Secondary

Change From Baseline in Basal Insulin Dose/Day After 54 and 78 Weeks of Treatment

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

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

Mean

Standard Error

Baseline, 54 and 78 weeks

ID	Title	Description
OG000	Placebo	Oral Placebo
OG001	Empagliflozin 10 mg	Empagliflozin 10 mg orally once daily
OG002	Empagliflozin 25 mg	Empagliflozin 25 mg orally once daily

Units	Counts
Participants	OG000

Secondary

Change From Baseline in Body Weight After 18, 54 and 78 Weeks of Treatment

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

FAS (OC)

Mean

Standard Error

Baseline, 18, 54, 78 weeks

ID	Title	Description
OG000	Placebo	Oral Placebo
OG001	Empagliflozin 10 mg	Empagliflozin 10 mg orally once daily
OG002	Empagliflozin 25 mg	Empagliflozin 25 mg orally once daily

Units	Counts
Participants	OG000

Secondary

Change From Baseline in Body Weight at Follow-up

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

FAS-FU (OR)

Mean

Standard Deviation

Baseline and 82 weeks

ID	Title	Description
OG000	Placebo	Oral Placebo
OG001	Empagliflozin 10 mg	Empagliflozin 10 mg orally once daily
OG002	Empagliflozin 25 mg	Empagliflozin 25 mg orally once daily

Units	Counts
Participants	OG000

Secondary

Change From Baseline in HbA1c After 54 and 78 Weeks of Treatment

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

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

Mean

Standard Error

percentage of HbA1c

Baseline, 54 and 78 weeks

ID	Title	Description
OG000	Placebo	Oral Placebo
OG001	Empagliflozin 10 mg	Empagliflozin 10 mg orally once daily
OG002	Empagliflozin 25 mg	Empagliflozin 25 mg orally once daily

Units	Counts
Participants	OG000

Other Pre-specified

Confirmed Hypoglycemic Events

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).

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

Number

participants

During the course of the study (82 weeks)

ID	Title	Description
OG000	Placebo	Oral Placebo
OG001	Empagliflozin 10 mg	Empagliflozin 10 mg orally once daily
OG002	Empagliflozin 25 mg	Empagliflozin 25 mg orally once daily

Units	Counts

Secondary

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

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

FAS (NCF)

Number

participants

Baseline, 18, 54 and 78 weeks

ID	Title	Description
OG000	Placebo	Oral Placebo
OG001	Empagliflozin 10 mg	Empagliflozin 10 mg orally once daily
OG002	Empagliflozin 25 mg	Empagliflozin 25 mg orally once daily

Units	Counts
Participants	OG000

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Oral Placebo	28	170	115	170
EG001	Empagliflozin 10 mg	Empagliflozin 10 mg orally once daily	28	169	110	169
EG002	Empagliflozin 25 mg	Empagliflozin 25 mg orally once daily	28	155	95	155

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Cystitis	Infections and infestations	MEDDRA 15.0	Systematic Assessment	EG0001 affected170 at risk EG0010 affected169 at risk EG0020 affected155 at risk
Diverticulitis	Infections and infestations	MEDDRA 15.0	Systematic Assessment	EG0000 affected170 at risk EG0011 affected169 at risk EG0020 affected155 at risk
Enterocolitis infectious	Infections and infestations	MEDDRA 15.0	Systematic Assessment	EG0001 affected170 at risk EG0010 affected169 at risk EG0020 affected155 at risk
Osteomyelitis	Infections and infestations	MEDDRA 15.0	Systematic Assessment	EG0001 affected170 at risk EG0010 affected169 at risk EG0020 affected155 at risk
Pneumonia	Infections and infestations	MEDDRA 15.0	Systematic Assessment	EG0000 affected170 at risk EG0010 affected169 at risk EG0021 affected155 at risk
Pyelonephritis	Infections and infestations	MEDDRA 15.0	Systematic Assessment	EG0000 affected170 at risk EG0010 affected169 at risk EG0021 affected155 at risk
Scrotal abscess	Infections and infestations	MEDDRA 15.0	Systematic Assessment	EG0000 affected170 at risk EG0011 affected169 at risk EG0020 affected155 at risk
Sepsis	Infections and infestations	MEDDRA 15.0	Systematic Assessment	EG0001 affected170 at risk EG0010 affected169 at risk EG0020 affected155 at risk
Sinusitis	Infections and infestations	MEDDRA 15.0	Systematic Assessment	EG0000 affected170 at risk EG0010 affected169 at risk EG0021 affected155 at risk
Urinary tract infection	Infections and infestations	MEDDRA 15.0	Systematic Assessment	EG0000 affected170 at risk EG0011 affected169 at risk EG0020 affected155 at risk
Thyroid cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MEDDRA 15.0	Systematic Assessment	EG0000 affected170 at risk EG0010 affected169 at risk EG0022 affected155 at risk
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MEDDRA 15.0	Systematic Assessment	EG0002 affected170 at risk EG0010 affected169 at risk EG0020 affected155 at risk
Bladder cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MEDDRA 15.0	Systematic Assessment	EG0000 affected170 at risk EG0011 affected169 at risk EG0020 affected155 at risk
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MEDDRA 15.0	Systematic Assessment	EG0001 affected170 at risk EG0011 affected169 at risk EG0020 affected155 at risk
Colon cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MEDDRA 15.0	Systematic Assessment	EG0001 affected170 at risk EG0010 affected169 at risk EG0020 affected155 at risk
Gastric cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MEDDRA 15.0	Systematic Assessment	EG0000 affected170 at risk EG0010 affected169 at risk EG0021 affected155 at risk
Lung neoplasm malignant	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MEDDRA 15.0	Systematic Assessment	EG0000 affected170 at risk EG0011 affected169 at risk EG0020 affected155 at risk
Malignant fibrous histiocytoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MEDDRA 15.0	Systematic Assessment	EG0000 affected170 at risk EG0010 affected169 at risk EG0021 affected155 at risk
Mycosis fungoides	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MEDDRA 15.0	Systematic Assessment	EG0000 affected170 at risk EG0010 affected169 at risk EG0021 affected155 at risk
Pancreatic carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MEDDRA 15.0	Systematic Assessment	EG0000 affected170 at risk EG0010 affected169 at risk EG0021 affected155 at risk
Prostatic adenoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MEDDRA 15.0	Systematic Assessment	EG0000 affected170 at risk EG0010 affected169 at risk EG0021 affected155 at risk
Squamous cell carcinoma of the cervix	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MEDDRA 15.0	Systematic Assessment	EG0000 affected170 at risk EG0010 affected169 at risk EG0021 affected155 at risk
Dehydration	Metabolism and nutrition disorders	MEDDRA 15.0	Systematic Assessment	EG0001 affected170 at risk EG0011 affected169 at risk EG0020 affected155 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MEDDRA 15.0	Systematic Assessment	EG0000 affected170 at risk EG0010 affected169 at risk EG0021 affected155 at risk
Hypovolaemia	Metabolism and nutrition disorders	MEDDRA 15.0	Systematic Assessment	EG0000 affected170 at risk EG0010 affected169 at risk EG0021 affected155 at risk
Depression	Psychiatric disorders	MEDDRA 15.0	Systematic Assessment	EG0001 affected170 at risk EG0011 affected169 at risk EG0020 affected155 at risk
Syncope	Nervous system disorders	MEDDRA 15.0	Systematic Assessment	EG0000 affected170 at risk EG0012 affected169 at risk EG0020 affected155 at risk
Carotid artery occlusion	Nervous system disorders	MEDDRA 15.0	Systematic Assessment	EG0000 affected170 at risk EG0010 affected169 at risk EG0021 affected155 at risk
Carotid artery stenosis	Nervous system disorders	MEDDRA 15.0	Systematic Assessment	EG0001 affected170 at risk EG0010 affected169 at risk EG0020 affected155 at risk
Cerebral haemorrhage	Nervous system disorders	MEDDRA 15.0	Systematic Assessment	EG0000 affected170 at risk EG0011 affected169 at risk EG0020 affected155 at risk
Cerebral infarction	Nervous system disorders	MEDDRA 15.0	Systematic Assessment	EG0000 affected170 at risk EG0010 affected169 at risk EG0021 affected155 at risk
Cerebrovascular accident	Nervous system disorders	MEDDRA 15.0	Systematic Assessment	EG0000 affected170 at risk EG0011 affected169 at risk EG0021 affected155 at risk
Convulsion	Nervous system disorders	MEDDRA 15.0	Systematic Assessment	EG0001 affected170 at risk EG0010 affected169 at risk EG0020 affected155 at risk
Haemorrhagic stroke	Nervous system disorders	MEDDRA 15.0	Systematic Assessment	EG0001 affected170 at risk EG0010 affected169 at risk EG0020 affected155 at risk
Sciatica	Nervous system disorders	MEDDRA 15.0	Systematic Assessment	EG0000 affected170 at risk EG0010 affected169 at risk EG0021 affected155 at risk
Transient ischaemic attack	Nervous system disorders	MEDDRA 15.0	Systematic Assessment	EG0000 affected170 at risk EG0010 affected169 at risk EG0021 affected155 at risk
Macular fibrosis	Eye disorders	MEDDRA 15.0	Systematic Assessment	EG0000 affected170 at risk EG0011 affected169 at risk EG0020 affected155 at risk
Retinal detachment	Eye disorders	MEDDRA 15.0	Systematic Assessment	EG0000 affected170 at risk EG0011 affected169 at risk EG0020 affected155 at risk
Vitreous haemorrhage	Eye disorders	MEDDRA 15.0	Systematic Assessment	EG0001 affected170 at risk EG0010 affected169 at risk EG0020 affected155 at risk
Vertigo	Ear and labyrinth disorders	MEDDRA 15.0	Systematic Assessment	EG0000 affected170 at risk EG0010 affected169 at risk EG0021 affected155 at risk
Bradycardia	Cardiac disorders	MEDDRA 15.0	Systematic Assessment	EG0000 affected170 at risk EG0012 affected169 at risk EG0020 affected155 at risk
Coronary artery disease	Cardiac disorders	MEDDRA 15.0	Systematic Assessment	EG0002 affected170 at risk EG0012 affected169 at risk EG0020 affected155 at risk
Acute myocardial infarction	Cardiac disorders	MEDDRA 15.0	Systematic Assessment	EG0000 affected170 at risk EG0010 affected169 at risk EG0021 affected155 at risk
Angina pectoris	Cardiac disorders	MEDDRA 15.0	Systematic Assessment	EG0001 affected170 at risk EG0011 affected169 at risk EG0020 affected155 at risk
Angina unstable	Cardiac disorders	MEDDRA 15.0	Systematic Assessment	EG0001 affected170 at risk EG0010 affected169 at risk EG0020 affected155 at risk
Atrial fibrillation	Cardiac disorders	MEDDRA 15.0	Systematic Assessment	EG0000 affected170 at risk EG0011 affected169 at risk EG0020 affected155 at risk
Atrial flutter	Cardiac disorders	MEDDRA 15.0	Systematic Assessment	EG0000 affected170 at risk EG0011 affected169 at risk EG0020 affected155 at risk
Cardiac arrest	Cardiac disorders	MEDDRA 15.0	Systematic Assessment	EG0000 affected170 at risk EG0010 affected169 at risk EG0021 affected155 at risk
Coronary artery occlusion	Cardiac disorders	MEDDRA 15.0	Systematic Assessment	EG0000 affected170 at risk EG0011 affected169 at risk EG0020 affected155 at risk
Myocardial infarction	Cardiac disorders	MEDDRA 15.0	Systematic Assessment	EG0000 affected170 at risk EG0011 affected169 at risk EG0021 affected155 at risk
Myocardial ischaemia	Cardiac disorders	MEDDRA 15.0	Systematic Assessment	EG0000 affected170 at risk EG0010 affected169 at risk EG0021 affected155 at risk
Right ventricular failure	Cardiac disorders	MEDDRA 15.0	Systematic Assessment	EG0000 affected170 at risk EG0011 affected169 at risk EG0020 affected155 at risk
Femoral arterial stenosis	Vascular disorders	MEDDRA 15.0	Systematic Assessment	EG0000 affected170 at risk EG0010 affected169 at risk EG0021 affected155 at risk
Orthostatic hypotension	Vascular disorders	MEDDRA 15.0	Systematic Assessment	EG0001 affected170 at risk EG0010 affected169 at risk EG0020 affected155 at risk
Peripheral vascular disorder	Vascular disorders	MEDDRA 15.0	Systematic Assessment	EG0001 affected170 at risk EG0010 affected169 at risk EG0020 affected155 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MEDDRA 15.0	Systematic Assessment	EG0001 affected170 at risk EG0010 affected169 at risk EG0020 affected155 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MEDDRA 15.0	Systematic Assessment	EG0000 affected170 at risk EG0010 affected169 at risk EG0021 affected155 at risk
Vocal cord polyp	Respiratory, thoracic and mediastinal disorders	MEDDRA 15.0	Systematic Assessment	EG0000 affected170 at risk EG0011 affected169 at risk EG0020 affected155 at risk
Abdominal distension	Gastrointestinal disorders	MEDDRA 15.0	Systematic Assessment	EG0000 affected170 at risk EG0011 affected169 at risk EG0020 affected155 at risk
Constipation	Gastrointestinal disorders	MEDDRA 15.0	Systematic Assessment	EG0000 affected170 at risk EG0011 affected169 at risk EG0020 affected155 at risk
Enterocutaneous fistula	Gastrointestinal disorders	MEDDRA 15.0	Systematic Assessment	EG0000 affected170 at risk EG0010 affected169 at risk EG0021 affected155 at risk
Gastric ulcer haemorrhage	Gastrointestinal disorders	MEDDRA 15.0	Systematic Assessment	EG0000 affected170 at risk EG0010 affected169 at risk EG0021 affected155 at risk
Haematochezia	Gastrointestinal disorders	MEDDRA 15.0	Systematic Assessment	EG0001 affected170 at risk EG0010 affected169 at risk EG0020 affected155 at risk
Oesophageal ulcer	Gastrointestinal disorders	MEDDRA 15.0	Systematic Assessment	EG0001 affected170 at risk EG0010 affected169 at risk EG0020 affected155 at risk
Oesophagitis	Gastrointestinal disorders	MEDDRA 15.0	Systematic Assessment	EG0000 affected170 at risk EG0011 affected169 at risk EG0020 affected155 at risk
Pancreatitis acute	Gastrointestinal disorders	MEDDRA 15.0	Systematic Assessment	EG0001 affected170 at risk EG0010 affected169 at risk EG0020 affected155 at risk
Rectal haemorrhage	Gastrointestinal disorders	MEDDRA 15.0	Systematic Assessment	EG0001 affected170 at risk EG0010 affected169 at risk EG0020 affected155 at risk
Skin ulcer	Skin and subcutaneous tissue disorders	MEDDRA 15.0	Systematic Assessment	EG0001 affected170 at risk EG0010 affected169 at risk EG0020 affected155 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MEDDRA 15.0	Systematic Assessment	EG0000 affected170 at risk EG0012 affected169 at risk EG0021 affected155 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MEDDRA 15.0	Systematic Assessment	EG0001 affected170 at risk EG0010 affected169 at risk EG0020 affected155 at risk
Costochondritis	Musculoskeletal and connective tissue disorders	MEDDRA 15.0	Systematic Assessment	EG0001 affected170 at risk EG0010 affected169 at risk EG0020 affected155 at risk
Joint contracture	Musculoskeletal and connective tissue disorders	MEDDRA 15.0	Systematic Assessment	EG0000 affected170 at risk EG0010 affected169 at risk EG0021 affected155 at risk
Joint instability	Musculoskeletal and connective tissue disorders	MEDDRA 15.0	Systematic Assessment	EG0001 affected170 at risk EG0010 affected169 at risk EG0020 affected155 at risk
Musculoskeletal stiffness	Musculoskeletal and connective tissue disorders	MEDDRA 15.0	Systematic Assessment	EG0000 affected170 at risk EG0011 affected169 at risk EG0020 affected155 at risk
Rotator cuff syndrome	Musculoskeletal and connective tissue disorders	MEDDRA 15.0	Systematic Assessment	EG0001 affected170 at risk EG0011 affected169 at risk EG0020 affected155 at risk
Nephrolithiasis	Renal and urinary disorders	MEDDRA 15.0	Systematic Assessment	EG0002 affected170 at risk EG0010 affected169 at risk EG0020 affected155 at risk
Nephrotic syndrome	Renal and urinary disorders	MEDDRA 15.0	Systematic Assessment	EG0001 affected170 at risk EG0010 affected169 at risk EG0020 affected155 at risk
Neurogenic bladder	Renal and urinary disorders	MEDDRA 15.0	Systematic Assessment	EG0001 affected170 at risk EG0010 affected169 at risk EG0020 affected155 at risk
Renal failure	Renal and urinary disorders	MEDDRA 15.0	Systematic Assessment	EG0000 affected170 at risk EG0011 affected169 at risk EG0020 affected155 at risk
Renal failure acute	Renal and urinary disorders	MEDDRA 15.0	Systematic Assessment	EG0000 affected170 at risk EG0011 affected169 at risk EG0021 affected155 at risk
Arnold-Chiari malformation	Congenital, familial and genetic disorders	MEDDRA 15.0	Systematic Assessment	EG0000 affected170 at risk EG0011 affected169 at risk EG0020 affected155 at risk
Chest discomfort	General disorders	MEDDRA 15.0	Systematic Assessment	EG0000 affected170 at risk EG0011 affected169 at risk EG0020 affected155 at risk
Chest pain	General disorders	MEDDRA 15.0	Systematic Assessment	EG0000 affected170 at risk EG0010 affected169 at risk EG0021 affected155 at risk
Device failure	General disorders	MEDDRA 15.0	Systematic Assessment	EG0000 affected170 at risk EG0010 affected169 at risk EG0021 affected155 at risk
Non-cardiac chest pain	General disorders	MEDDRA 15.0	Systematic Assessment	EG0000 affected170 at risk EG0010 affected169 at risk EG0021 affected155 at risk
Hepatic enzyme increased	Investigations	MEDDRA 15.0	Systematic Assessment	EG0000 affected170 at risk EG0010 affected169 at risk EG0021 affected155 at risk
Road traffic accident	Injury, poisoning and procedural complications	MEDDRA 15.0	Systematic Assessment	EG0000 affected170 at risk EG0012 affected169 at risk EG0020 affected155 at risk
Accident at home	Injury, poisoning and procedural complications	MEDDRA 15.0	Systematic Assessment	EG0000 affected170 at risk EG0011 affected169 at risk EG0020 affected155 at risk
Accident at work	Injury, poisoning and procedural complications	MEDDRA 15.0	Systematic Assessment	EG0000 affected170 at risk EG0010 affected169 at risk EG0021 affected155 at risk
Concussion	Injury, poisoning and procedural complications	MEDDRA 15.0	Systematic Assessment	EG0000 affected170 at risk EG0011 affected169 at risk EG0020 affected155 at risk
Contusion	Injury, poisoning and procedural complications	MEDDRA 15.0	Systematic Assessment	EG0000 affected170 at risk EG0011 affected169 at risk EG0021 affected155 at risk
Fall	Injury, poisoning and procedural complications	MEDDRA 15.0	Systematic Assessment	EG0000 affected170 at risk EG0011 affected169 at risk EG0020 affected155 at risk
Ligament sprain	Injury, poisoning and procedural complications	MEDDRA 15.0	Systematic Assessment	EG0000 affected170 at risk EG0011 affected169 at risk EG0020 affected155 at risk
Limb crushing injury	Injury, poisoning and procedural complications	MEDDRA 15.0	Systematic Assessment	EG0000 affected170 at risk EG0010 affected169 at risk EG0021 affected155 at risk
Overdose	Injury, poisoning and procedural complications	MEDDRA 15.0	Systematic Assessment	EG0001 affected170 at risk EG0010 affected169 at risk EG0020 affected155 at risk
Radius fracture	Injury, poisoning and procedural complications	MEDDRA 15.0	Systematic Assessment	EG0001 affected170 at risk EG0010 affected169 at risk EG0020 affected155 at risk
Skeletal injury	Injury, poisoning and procedural complications	MEDDRA 15.0	Systematic Assessment	EG0000 affected170 at risk EG0011 affected169 at risk EG0020 affected155 at risk
Wrist fracture	Injury, poisoning and procedural complications	MEDDRA 15.0	Systematic Assessment	EG0000 affected170 at risk EG0010 affected169 at risk EG0021 affected155 at risk
Carotid endarterectomy	Surgical and medical procedures	MEDDRA 15.0	Systematic Assessment	EG0001 affected170 at risk EG0010 affected169 at risk EG0020 affected155 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Nasopharyngitis	Infections and infestations	MEDDRA 15.0	Systematic Assessment	EG00022 affected170 at risk EG00120 affected169 at risk EG00217 affected155 at risk
Urinary tract infection	Infections and infestations	MEDDRA 15.0	Systematic Assessment	EG00013 affected170 at risk EG00121 affected169 at risk EG00216 affected155 at risk
Upper respiratory tract infection	Infections and infestations	MEDDRA 15.0	Systematic Assessment	EG00010 affected170 at risk EG00118 affected169 at risk EG00213 affected155 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MEDDRA 15.0	Systematic Assessment	EG00056 affected170 at risk EG00156 affected169 at risk EG00255 affected155 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MEDDRA 15.0	Systematic Assessment	EG00017 affected170 at risk EG00116 affected169 at risk EG00215 affected155 at risk
Depression	Psychiatric disorders	MEDDRA 15.0	Systematic Assessment	EG0003 affected170 at risk EG00110 affected169 at risk EG0022 affected155 at risk
Dizziness	Nervous system disorders	MEDDRA 15.0	Systematic Assessment	EG00012 affected170 at risk EG00118 affected169 at risk EG0027 affected155 at risk
Headache	Nervous system disorders	MEDDRA 15.0	Systematic Assessment	EG0005 affected170 at risk EG0015 affected169 at risk EG0028 affected155 at risk
Hypertension	Vascular disorders	MEDDRA 15.0	Systematic Assessment	EG00012 affected170 at risk EG0011 affected169 at risk EG0023 affected155 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MEDDRA 15.0	Systematic Assessment	EG0009 affected170 at risk EG0016 affected169 at risk EG0024 affected155 at risk
Diarrhoea	Gastrointestinal disorders	MEDDRA 15.0	Systematic Assessment	EG00013 affected170 at risk EG00110 affected169 at risk EG00211 affected155 at risk
Nausea	Gastrointestinal disorders	MEDDRA 15.0	Systematic Assessment	EG00012 affected170 at risk EG0019 affected169 at risk EG0028 affected155 at risk
Vomiting	Gastrointestinal disorders	MEDDRA 15.0	Systematic Assessment	EG0005 affected170 at risk EG0014 affected169 at risk EG0028 affected155 at risk
Back pain	Musculoskeletal and connective tissue disorders	MEDDRA 15.0	Systematic Assessment	EG00013 affected170 at risk EG00111 affected169 at risk EG00213 affected155 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MEDDRA 15.0	Systematic Assessment	EG0009 affected170 at risk EG0016 affected169 at risk EG0028 affected155 at risk
Fatigue	General disorders	MEDDRA 15.0	Systematic Assessment	EG0002 affected170 at risk EG00110 affected169 at risk EG0024 affected155 at risk

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