Efficacy and Safety Study With Empagliflozin (BI 10773) v... | NCT01159600

NCT01159600

ID	Type	Description	Link
2009-016258-41	EudraCT Number	EudraCT

Status Module

Name	Class
Eli Lilly and Company	INDUSTRY

Label	Type	Description	Intervention Names
BI 10773 Arm 2	Experimental	BI 10773 once daily high dose	Drug: BI 10773 Drug: Placebo identical to BI 10773 low dose
Placebo	Placebo Comparator	Placebo matching BI 10773	Drug: Placebo identical to BI 10773 low dose Drug: Placebo identical to BI 10773 high dose
BI 10773 open-label	Experimental	BI 10773 once daily high dose open label	Drug: BI 10773
BI 10773 Arm 1	Experimental	BI 10773 once daily low dose	Drug: Placebo identical to BI 10773 high dose Drug: BI 10773

Name	Type	Description	Arm Group Labels	Other Names
Placebo identical to BI 10773 high dose	Drug	Placebo tablets matching BI 10773 high dose	BI 10773 Arm 1

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
HbA1c Change From Baseline	Change from baseline in HbA1c after 24 weeks. For open-label groups the descriptive mean is provided, for randomised groups adjusted means are provided. The means are adjusted separately for metformin alone and metformin plus sulphonylurea background medication.	Baseline and 24 weeks

Secondary Outcomes

Measure	Description	Time Frame
Body Weight Change From Baseline	Body weight change from baseline after 24 weeks. For open-label groups the descriptive mean is provided, for randomised groups adjusted means are provided. The means are adjusted separately for metformin alone and metformin plus sulphonylurea background medication.	Baseline and 24 weeks

Other Outcomes

Measure	Description	Time Frame
Confirmed Hypoglycaemic Adverse Events	Number of patients with confirmed hypoglycaemic events, as reported as adverse events.	From first intake of randomised trial medication until 7 days after last trial medication intake, up to 231 days

Eligibility Module

Eligibility Criteria

Inclusion criteria:

Diagnosis of type 2 diabetes mellitus prior to informed consent
Male and female patients on a diet and exercise regimen who are pre-treated with immediate release metformin or immediate release metformin plus sulfonylurea (see below for minimum doses). The treatment regimen has to be unchanged for 12 weeks prior to randomisation.

Minimum dose for metformin: > or = 1500 mg/day or maximum tolerated dose or maximum dose according to local label Minimum dose for sulfonylurea: > or = half of the maximal recommended dose or maximum tolerated dose or maximum dose according to local label
HbA1c of > or = 7.0% and < or = 11% at Visit 1 (screening) in order to be eligible for randomised treatment HbA1c of > 11% at Visit 1 (screening) in order to be eligible for the open-label treatment arm (25 mg BI 10773)
Age> or = 18
Body Mass Index (BM)I < or = 45 kg/m2 (Body Mass Index) at Visit 1 (Screening)
Signed and dated written informed consent by date of Visit 1 in accordance with Good Clinical Practice (GCP) and local legislation

Exclusion criteria:

Uncontrolled hyperglycaemia with a glucose level > 240 mg/dl (>13.3 mmol/L) after an overnight fast during placebo run-in and confirmed by a second measurement (not on the same day)
Any other antidiabetic drug within 12 weeks prior to randomisation except those mentioned in inclusion criterion 2
Myocardial infarction, stroke or transient ischemic attack (TIA) within 3 months prior to informed consent
Indication of liver disease, defined by serum levels of either ALT (SGPT), AST (SGOT), or alkaline phosphatase above 3 x upper limit of normal (ULN) as determined during screening and/or run-in phase
Impaired renal function, defined as eGFR<30 ml/min (severe renal impairment) as determined during screening and/or run-in phase
Bariatric surgery within the past two years and other gastrointestinal surgeries that induce chronic malabsorption
Medical history of cancer (except for basal cell carcinoma) and/or treatment for cancer within the last 5 years
Contraindications to metformin and/or sulfonylurea according to the local label for those patients that enter the study with the respective background therapy
Blood dyscrasias or any disorders causing haemolysis or unstable Red Blood Cell (e.g. malaria, babesiosis, haemolytic anaemia)
Treatment with anti-obesity drugs (e.g. sibutramine, orlistat) 3 months prior to informed consent or any other treatment at the time of screening (i.e. surgery, aggressive diet regimen, etc.) leading to unstable body weight
Current treatment with systemic steroids at time of informed consent or change in dosage of thyroid hormones within 6 weeks prior to informed consent or any other uncontrolled endocrine disorder except Typ 2 Diabetes
Pre-menopausal women (last menstruation ¿ 1 year prior to informed consent) who:
- are nursing or pregnant or
- are of child-bearing potential and are not practicing an acceptable method of birth control, or do not plan to continue using this method throughout the study and do not agree to submit to periodic pregnancy testing during participation in the trial. Acceptable methods of birth control include tubal ligation, transdermal patch, intra uterine devices/systems (IUDs/IUSs), oral, implantable or injectable contraceptives, sexual abstinence (if acceptable by local authorities), double barrier method and vasectomised partner
Alcohol or drug abuse within the 3 months prior to informed consent that would interfere with trial participation or any ongoing condition leading to a decreased compliance to study procedures or study drug intake
Participation in another trial with an investigational drug within 30 days prior to informed consent
Any other clinical condition that would jeopardize patients safety while participating in this clinical trial

Name	Affiliation	Role
Boehringer Ingelheim	Boehringer Ingelheim	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
1245.23.10145 Boehringer Ingelheim Investigational Site		Birmingham	Alabama		United States
1245.23.10046 Boehringer Ingelheim Investigational Site

PubMed Identifier	Type	Citation	Retractions
38770818	Derived	Natale P, Tunnicliffe DJ, Toyama T, Palmer SC, Saglimbene VM, Ruospo M, Gargano L, Stallone G, Gesualdo L, Strippoli GF. Sodium-glucose co-transporter protein 2 (SGLT2) inhibitors for people with chronic kidney disease and diabetes. Cochrane Database Syst Rev. 2024 May 21;5(5):CD015588. doi: 10.1002/14651858.CD015588.pub2.
35472672

ID	Title	Description
FG000	Met: Placebo	A placebo tablet, matching the empagliflozin 10mg and 25mg tablets, taken once daily for 24 weeks in patients with background medication of metformin only.
FG001	Met: Empa 10mg

Arm/Group Information

ID	Title	Description
BG000	Met: Placebo	A placebo tablet, matching the empagliflozin 10mg and 25mg tablets, taken once daily for 24 weeks in patients with background medication of metformin only.
BG001	Met: Empa 10mg	Single oral dose of empagliflozin (empa) 10mg taken once daily for 24 weeks in patients with background medication of metformin only.
BG002	Met: Empa 25mg	Single oral dose of empagliflozin (empa) 25mg taken once daily for 24 weeks in patients with background medication of metformin only.
BG003	Met: Empa 25mg Open Label	Single oral dose of empagliflozin (empa) 25mg taken once daily for 24 weeks in patients with background medication of metformin only.
BG004	Met+SU: Placebo	A placebo tablet, matching the empagliflozin 10mg and 25mg tablets, taken once daily for 24 weeks in patients with background medication of metformin plus sulphonylurea (SU).
BG005	Met+SU: Empa 10mg	Single oral dose of empagliflozin (empa) 10mg taken once daily for 24 weeks in patients with background medication of metformin plus sulphonylurea (SU).
BG006	Met+SU: Empa 25mg	Single oral dose of empagliflozin (empa) 25mg taken once daily for 24 weeks in patients with background medication of metformin plus sulphonylurea (SU).
BG007	Met+SU: Empa 25mg Open Label	Single oral dose of empagliflozin (empa) 25mg taken once daily for 24 weeks in patients with background medication of metformin plus sulphonylurea (SU).
BG008	Total	Total of all reporting groups

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Secondary

Body Weight Change From Baseline

Body weight change from baseline after 24 weeks.

For open-label groups the descriptive mean is provided, for randomised groups adjusted means are provided. The means are adjusted separately for metformin alone and metformin plus sulphonylurea background medication.

Full analysis set. Treatment assignment as randomised.

Open-label analysis: Open-label set which included all patients entered in the empa 25mg open-label treatment arm.

Values after start of antidiabetic rescue therapy were set to missing and last observation carried forward (LOCF) was used for imputation of missing values.

Posted

Mean

Standard Error

Baseline and 24 weeks

ID	Title	Description
OG000	Met: Placebo	A placebo tablet, matching the empagliflozin 10mg and 25mg tablets, taken once daily for 24 weeks in patients with background medication of metformin only.
OG001	Met: Empa 10mg	Single oral dose of empagliflozin (empa) 10mg taken once daily for 24 weeks in patients with background medication of metformin only.
OG002	Met: Empa 25mg	Single oral dose of empagliflozin (empa) 25mg taken once daily for 24 weeks in patients with background medication of metformin only.
OG003	Met: Empa 25mg Open Label	Single oral dose of empagliflozin (empa) 25mg taken once daily for 24 weeks in patients with background medication of metformin only.
OG004	Met+SU: Placebo	A placebo tablet, matching the empagliflozin 10mg and 25mg tablets, taken once daily for 24 weeks in patients with background medication of metformin plus sulphonylurea (SU).
OG005	Met+SU: Empa 10mg	Single oral dose of empagliflozin (empa) 10mg taken once daily for 24 weeks in patients with background medication of metformin plus sulphonylurea (SU).
OG006	Met+SU: Empa 25mg	Single oral dose of empagliflozin (empa) 25mg taken once daily for 24 weeks in patients with background medication of metformin plus sulphonylurea (SU).
OG007	Met+SU: Empa 25mg Open Label	Single oral dose of empagliflozin (empa) 25mg taken once daily for 24 weeks in patients with background medication of metformin plus sulphonylurea (SU).

Units	Counts
Participants	OG000207 OG001217 OG002213 OG003

Title

Denominators

Categories

Title	Measurements
	OG000-0.45± 0.17 OG001-2.08± 0.17 OG002-2.46± 0.17 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	Null hypothesis: No difference in change from baseline to week 24 in body weight between Empagliflozin 10mg and placebo. A hierarchical testing approach was applied to each of the two dose comparisons (10mg vs placebo and 25mg vs placebo) within each background therapy group (metformin and metformin + SU). If for a specific dose the null hypothesis was rejected for the primary endpoint, the same dose was tested against placebo for the change from baseline in body weight.	ANCOVA	ANCOVA with baseline HbA1c and baseline body weight as linear covariates and baseline eGFR, geographical region and treatment as fixed effects	<0.0001	Each of the hypotheses (10mg vs placebo and 25mg vs placebo) were tested (two-sided test) at the significance level of 0.025.	Mean difference	-1.63	Standard Error of the Mean	0.24	2-Sided	97.5	-2.17	-1.08

Secondary

Mean Daily Plasma Glucose (MDG) Change From Baseline

Change from baseline in mean daily glucose (MDG) using the 8-point blood glucose profile, after 24 weeks of treatment.

Full analysis set. Treatment assignment as randomised.

Open-label analysis: Open-label set which included all patients entered in the empa 25mg open-label treatment arm.

Values after start of antidiabetic rescue therapy were set to missing and last observation carried forward (LOCF) was used for imputation of missing values.

Posted

Mean

Standard Error

mg/dL

Baseline and 24 weeks

ID	Title	Description
OG000	Met: Placebo	A placebo tablet, matching the empagliflozin 10mg and 25mg tablets, taken once daily for 24 weeks in patients with background medication of metformin only.
OG001	Met: Empa 10mg	Single oral dose of empagliflozin (empa) 10mg taken once daily for 24 weeks in patients with background medication of metformin only.
OG002	Met: Empa 25mg	Single oral dose of empagliflozin (empa) 25mg taken once daily for 24 weeks in patients with background medication of metformin only.

Primary

HbA1c Change From Baseline

Change from baseline in HbA1c after 24 weeks.

Full analysis set. Treatment assignment as randomised.

Open-label analysis: Open-label set which included all patients entered in the empa 25mg open-label treatment arm.

Values after start of antidiabetic rescue therapy were set to missing and last observation carried forward (LOCF) was used for imputation of missing values.

Posted

Mean

Standard Error

percentage of HbA1c

Baseline and 24 weeks

ID	Title	Description
OG000	Met: Placebo	A placebo tablet, matching the empagliflozin 10mg and 25mg tablets, taken once daily for 24 weeks, in patients with background medication of metformin only.
OG001	Met: Empa 10mg	Single oral dose of empagliflozin (empa) 10mg taken once daily for 24 weeks in patients with background medication of metformin only.
OG002	Met: Empa 25mg	Single oral dose of empagliflozin (empa) 25mg taken once daily for 24 weeks in patients with background medication of metformin only.

Other Pre-specified

Confirmed Hypoglycaemic Adverse Events

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

Treated set, which included all patients treated with at least one dose of randomised trial medication. Treatment assignment as first medication taken.

Open label set which included all patients entered into the open-label arm.

Posted

Number

percentage of participants

From first intake of randomised trial medication until 7 days after last trial medication intake, up to 231 days

ID	Title	Description
OG000	Met: Placebo	A placebo tablet, matching the empagliflozin 10mg and 25mg tablets, taken once daily for 24 weeks in patients with background medication of metformin only.
OG001	Met: Empa 10mg	Single oral dose of empagliflozin (empa) 10mg taken once daily for 24 weeks in patients with background medication of metformin only.
OG002	Met: Empa 25mg	Single oral dose of empagliflozin (empa) 25mg taken once daily for 24 weeks in patients with background medication of metformin only.
OG003	Met: Empa 25mg Open Label

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Met: Placebo	A placebo tablet, matching the empagliflozin 10mg and 25mg tablets, taken once daily for 24 weeks in patients with background medication of metformin only.	7	206	56	206
EG001	Met: Empa 10mg	Single oral dose of empagliflozin (empa) 10mg taken once daily for 24 weeks in patients with background medication of metformin only.	7	217	29	217
EG002	Met: Empa 25mg	Single oral dose of empagliflozin (empa) 25mg taken once daily for 24 weeks in patients with background medication of metformin only.	5	214	38	214
EG003	Met: Empa 25mg Open Label	Single oral dose of empagliflozin (empa) 25mg taken once daily for 24 weeks in patients with background medication of metformin only.	1	69	18	69
EG004	Met+SU: Placebo	A placebo tablet, matching the empagliflozin 10mg and 25mg tablets, taken once daily for 24 weeks in patients with background medication of metformin plus sulphonylurea (SU).	14	225	76	225
EG005	Met+SU: Empa 10mg	Single oral dose of empagliflozin (empa) 10mg taken once daily for 24 weeks in patients with background medication of metformin plus sulphonylurea (SU).	11	224	77	224
EG006	Met+SU: Empa 25mg	Single oral dose of empagliflozin (empa) 25mg taken once daily for 24 weeks in patients with background medication of metformin plus sulphonylurea (SU).	1	217	67	217
EG007	Met+SU: Empa 25mg Open Label	Single oral dose of empagliflozin (empa) 25mg taken once daily for 24 weeks in patients with background medication of metformin plus sulphonylurea (SU).	5	101	28	101

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anal abscess	Infections and infestations	MEDDRA 14.1	Systematic Assessment	EG0001 affected206 at risk EG0010 affected217 at risk EG0020 affected214 at risk EG0030 affected69 at risk EG0040 affected225 at risk EG0050 affected224 at risk EG0060 affected217 at risk EG0070 affected101 at risk
Cellulitis	Infections and infestations	MEDDRA 14.1	Systematic Assessment	EG0001 affected206 at risk EG0010 affected217 at risk EG0020 affected214 at risk EG003
Sepsis	Infections and infestations	MEDDRA 14.1	Systematic Assessment	EG0001 affected206 at risk EG0010 affected217 at risk EG0020 affected214 at risk EG003
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MEDDRA 14.1	Systematic Assessment	EG0000 affected206 at risk EG0010 affected217 at risk EG0021 affected214 at risk EG003
Prostatic adenoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MEDDRA 14.1	Systematic Assessment	EG0000 affected206 at risk EG0010 affected217 at risk EG0021 affected214 at risk EG003
Hypersensitivity	Immune system disorders	MEDDRA 14.1	Systematic Assessment	EG0001 affected206 at risk EG0010 affected217 at risk EG0020 affected214 at risk EG003
Lacunar infarction	Nervous system disorders	MEDDRA 14.1	Systematic Assessment	EG0000 affected206 at risk EG0011 affected217 at risk EG0020 affected214 at risk EG003
Trigeminal neuralgia	Nervous system disorders	MEDDRA 14.1	Systematic Assessment	EG0000 affected206 at risk EG0011 affected217 at risk EG0020 affected214 at risk EG003
Angina unstable	Cardiac disorders	MEDDRA 14.1	Systematic Assessment	EG0000 affected206 at risk EG0011 affected217 at risk EG0020 affected214 at risk EG003
Arteriosclerosis coronary artery	Cardiac disorders	MEDDRA 14.1	Systematic Assessment	EG0000 affected206 at risk EG0011 affected217 at risk EG0020 affected214 at risk EG003
Cardiac failure congestive	Cardiac disorders	MEDDRA 14.1	Systematic Assessment	EG0001 affected206 at risk EG0010 affected217 at risk EG0020 affected214 at risk EG003
Myocardial infarction	Cardiac disorders	MEDDRA 14.1	Systematic Assessment	EG0001 affected206 at risk EG0010 affected217 at risk EG0020 affected214 at risk EG003
Peripheral arterial occlusive disease	Vascular disorders	MEDDRA 14.1	Systematic Assessment	EG0000 affected206 at risk EG0010 affected217 at risk EG0021 affected214 at risk EG003
Hepatitis toxic	Hepatobiliary disorders	MEDDRA 14.1	Systematic Assessment	EG0001 affected206 at risk EG0010 affected217 at risk EG0020 affected214 at risk EG003
Foot deformity	Musculoskeletal and connective tissue disorders	MEDDRA 14.1	Systematic Assessment	EG0001 affected206 at risk EG0010 affected217 at risk EG0020 affected214 at risk EG003
Diabetic nephropathy	Renal and urinary disorders	MEDDRA 14.1	Systematic Assessment	EG0000 affected206 at risk EG0010 affected217 at risk EG0021 affected214 at risk EG003
Benign prostatic hyperplasia	Reproductive system and breast disorders	MEDDRA 14.1	Systematic Assessment	EG0000 affected206 at risk EG0011 affected217 at risk EG0020 affected214 at risk EG003
Non-cardiac chest pain	General disorders	MEDDRA 14.1	Systematic Assessment	EG0001 affected206 at risk EG0010 affected217 at risk EG0020 affected214 at risk EG003
Injury	Injury, poisoning and procedural complications	MEDDRA 14.1	Systematic Assessment	EG0000 affected206 at risk EG0010 affected217 at risk EG0020 affected214 at risk EG003
Comminuted fracture	Injury, poisoning and procedural complications	MEDDRA 14.1	Systematic Assessment	EG0000 affected206 at risk EG0011 affected217 at risk EG0020 affected214 at risk EG003
Facial bones fracture	Injury, poisoning and procedural complications	MEDDRA 14.1	Systematic Assessment	EG0000 affected206 at risk EG0011 affected217 at risk EG0020 affected214 at risk EG003
Fall	Injury, poisoning and procedural complications	MEDDRA 14.1	Systematic Assessment	EG0000 affected206 at risk EG0011 affected217 at risk EG0020 affected214 at risk EG003
Ligament rupture	Injury, poisoning and procedural complications	MEDDRA 14.1	Systematic Assessment	EG0000 affected206 at risk EG0010 affected217 at risk EG0021 affected214 at risk EG003
Tendon rupture	Injury, poisoning and procedural complications	MEDDRA 14.1	Systematic Assessment	EG0000 affected206 at risk EG0010 affected217 at risk EG0021 affected214 at risk EG003
Herpes zoster	Infections and infestations	MEDDRA 14.1	Systematic Assessment	EG0000 affected206 at risk EG0010 affected217 at risk EG0020 affected214 at risk EG003
Listeria sepsis	Infections and infestations	MEDDRA 14.1	Systematic Assessment	EG0000 affected206 at risk EG0010 affected217 at risk EG0020 affected214 at risk EG003
Pneumonia	Infections and infestations	MEDDRA 14.1	Systematic Assessment	EG0000 affected206 at risk EG0010 affected217 at risk EG0020 affected214 at risk EG003
Pneumonia primary atypical	Infections and infestations	MEDDRA 14.1	Systematic Assessment	EG0000 affected206 at risk EG0010 affected217 at risk EG0020 affected214 at risk EG003
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MEDDRA 14.1	Systematic Assessment	EG0000 affected206 at risk EG0010 affected217 at risk EG0020 affected214 at risk EG003
Colon cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MEDDRA 14.1	Systematic Assessment	EG0000 affected206 at risk EG0010 affected217 at risk EG0020 affected214 at risk EG003
Goitre	Endocrine disorders	MEDDRA 14.1	Systematic Assessment	EG0000 affected206 at risk EG0010 affected217 at risk EG0020 affected214 at risk EG003
Stress	Psychiatric disorders	MEDDRA 14.1	Systematic Assessment	EG0000 affected206 at risk EG0010 affected217 at risk EG0020 affected214 at risk EG003
Cerebrovascular accident	Nervous system disorders	MEDDRA 14.1	Systematic Assessment	EG0000 affected206 at risk EG0010 affected217 at risk EG0020 affected214 at risk EG003
Dizziness	Nervous system disorders	MEDDRA 14.1	Systematic Assessment	EG0000 affected206 at risk EG0010 affected217 at risk EG0020 affected214 at risk EG003
Intercostal neuralgia	Nervous system disorders	MEDDRA 14.1	Systematic Assessment	EG0000 affected206 at risk EG0010 affected217 at risk EG0020 affected214 at risk EG003
Syringomyelia	Nervous system disorders	MEDDRA 14.1	Systematic Assessment	EG0000 affected206 at risk EG0010 affected217 at risk EG0020 affected214 at risk EG003
Acute myocardial infarction	Cardiac disorders	MEDDRA 14.1	Systematic Assessment	EG0000 affected206 at risk EG0010 affected217 at risk EG0020 affected214 at risk EG003
Angina pectoris	Cardiac disorders	MEDDRA 14.1	Systematic Assessment	EG0000 affected206 at risk EG0010 affected217 at risk EG0020 affected214 at risk EG003
Aortic valve stenosis	Cardiac disorders	MEDDRA 14.1	Systematic Assessment	EG0000 affected206 at risk EG0010 affected217 at risk EG0020 affected214 at risk EG003
Gastritis	Gastrointestinal disorders	MEDDRA 14.1	Systematic Assessment	EG0000 affected206 at risk EG0010 affected217 at risk EG0020 affected214 at risk EG003
Abdominal hernia	Gastrointestinal disorders	MEDDRA 14.1	Systematic Assessment	EG0000 affected206 at risk EG0010 affected217 at risk EG0020 affected214 at risk EG003
Duodenal ulcer	Gastrointestinal disorders	MEDDRA 14.1	Systematic Assessment	EG0000 affected206 at risk EG0010 affected217 at risk EG0020 affected214 at risk EG003
Faecaloma	Gastrointestinal disorders	MEDDRA 14.1	Systematic Assessment	EG0000 affected206 at risk EG0010 affected217 at risk EG0020 affected214 at risk EG003
Osteoarthritis	Musculoskeletal and connective tissue disorders	MEDDRA 14.1	Systematic Assessment	EG0000 affected206 at risk EG0010 affected217 at risk EG0020 affected214 at risk EG003
Cystitis haemorrhagic	Renal and urinary disorders	MEDDRA 14.1	Systematic Assessment	EG0000 affected206 at risk EG0010 affected217 at risk EG0020 affected214 at risk EG003
Hydrocele	Congenital, familial and genetic disorders	MEDDRA 14.1	Systematic Assessment	EG0000 affected206 at risk EG0010 affected217 at risk EG0020 affected214 at risk EG003
Phimosis	Congenital, familial and genetic disorders	MEDDRA 14.1	Systematic Assessment	EG0000 affected206 at risk EG0010 affected217 at risk EG0020 affected214 at risk EG003
Chest pain	General disorders	MEDDRA 14.1	Systematic Assessment	EG0000 affected206 at risk EG0010 affected217 at risk EG0020 affected214 at risk EG003
Blood creatinine increased	Investigations	MEDDRA 14.1	Systematic Assessment	EG0000 affected206 at risk EG0010 affected217 at risk EG0020 affected214 at risk EG003
Lumbar vertebral fracture	Injury, poisoning and procedural complications	MEDDRA 14.1	Systematic Assessment	EG0000 affected206 at risk EG0010 affected217 at risk EG0020 affected214 at risk EG003
Femoral neck fracture	Injury, poisoning and procedural complications	MEDDRA 14.1	Systematic Assessment	EG0000 affected206 at risk EG0010 affected217 at risk EG0020 affected214 at risk EG003
Neck injury	Injury, poisoning and procedural complications	MEDDRA 14.1	Systematic Assessment	EG0000 affected206 at risk EG0010 affected217 at risk EG0020 affected214 at risk EG003
Post-traumatic neck syndrome	Injury, poisoning and procedural complications	MEDDRA 14.1	Systematic Assessment	EG0000 affected206 at risk EG0010 affected217 at risk EG0020 affected214 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Nasopharyngitis	Infections and infestations	MEDDRA 14.1	Systematic Assessment	EG00016 affected206 at risk EG00112 affected217 at risk EG00215 affected214 at risk EG0035 affected69 at risk EG00411 affected225 at risk EG00518 affected224 at risk EG00613 affected217 at risk EG0075 affected101 at risk
Urinary tract infection	Infections and infestations	MEDDRA 14.1	Systematic Assessment	EG0008 affected206 at risk EG0019 affected217 at risk EG0029 affected214 at risk EG003
Upper respiratory tract infections	Infections and infestations	MEDDRA 14.1	Systematic Assessment	EG0009 affected206 at risk EG0012 affected217 at risk EG0029 affected214 at risk EG003
Hypoglycaemia	Metabolism and nutrition disorders	MEDDRA 14.1	Systematic Assessment	EG0000 affected206 at risk EG0010 affected217 at risk EG0020 affected214 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MEDDRA 14.1	Systematic Assessment	EG00023 affected206 at risk EG0015 affected217 at risk EG0022 affected214 at risk EG003
Diarrhoea	Gastrointestinal disorders	MEDDRA 14.1	Systematic Assessment	EG0007 affected206 at risk EG0014 affected217 at risk EG0023 affected214 at risk EG003
Dizziness	Nervous system disorders	MEDDRA 14.1	Systematic Assessment	EG0000 affected206 at risk EG0010 affected217 at risk EG0020 affected214 at risk EG003

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