Patient Preference and Satisfaction With Insulin Glargine... | NCT01226043

ID	Type	Description	Link
U1111-1116-3054	Other Identifier	UTN

Description Module

Brief Summary

Primary Objective:

To assess patient preference for Lantus SoloSTAR pen versus Lantus vial and syringe at the end of Crossover Phase (Week 4) in patients with type 2 diabetes mellitus (T2DM)

Secondary Objectives:

To compare Lantus SoloSTAR pen versus Lantus vial and syringe with regard to the following parameters:

Randomization/Crossover phase:

Healthcare professional's (HCP) recommendation for Lantus SoloSTAR pen versus Lantus vial and syringe

Re-randomization phase:

Change in Fasting Plasma Glucose (FPG) from week 4 to week 10
Percentage of patients achieving FPG<110 mg/dL at week 10
Change in Lantus dose injected per day (U) from week 4 to week 10

Observational phase:

Percentage of patients achieving glycosylated hemoglobin (HbA1c) goal (<7%) at week 40
Time to first observation of HbA1c<7% during the observational phase
Percentage of patients who discontinue Investigational Product (IP) during the observational phase due to dissatisfaction with their current device

All phases:

Percentage of patients who discontinue IP during each phase of the study
Safety assessment such as occurrence of hypoglycemic events (HE) and adverse events (AE)

Label	Type	Description	Intervention Names
Lantus (insulin glargine) vial & syringe	Experimental	10 mL vial, 1000 U per vial for subcutaneous administration once a day. Starting dose will be 0.2 Unit per kilogram of body weight.	Drug: Insulin Glargine
Lantus (insulin glargine) SoloSTAR pen	Experimental	3 mL SoloSTAR pre-filled disposable insulin delivery device (pen), 300 U per device for subcutaneous administration once a day. Starting dose will be 0.2 Unit per kilogram of body weight.	Drug: Insulin Glargine

Name	Type	Description	Arm Group Labels	Other Names
Insulin Glargine	Drug	Pharmaceutical form: solution for injection Route of administration: subcutaneous	Lantus (insulin glargine) SoloSTAR pen Lantus (insulin glargine) vial & syringe

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Patient Overall Preference	The patient preference was assessed in terms of the difference in scores obtained from the overall preference question 14d "Overall, what is your level of preference for each of the insulin delivery systems?" 5 points scale: from 1=Not preferred to 5= Always preferred	At week 4 (end of crossover phase)

Secondary Outcomes

Measure	Description	Time Frame
Patient Preference Composite Score	The patient preference composite score was the sum of the scores of the 3 following individual preference questions from the Patient preference Questionnaire: Question 14a: How strongly do you prefer each of these insulin delivery systems to control blood sugar? Question 14b: If using insulin for the first time, how strongly would you prefer using each of these delivery systems to overcome reluctance to use insulin? Question 14c: How strongly would you prefer each insulin delivery system for long-term use? Each individual question scored from 1 to 5. The lowest score 1 indicated 'Not Preferred' and the highest score 5 indicated 'Always Preferred'. Therefore the total range of the composite score was 3 to 15.

Other Outcomes

Measure	Description	Time Frame
Number of Patients With Hypoglycemic Events	The hypoglycemic event was to be recorded on the electronic case report form hypoglycemia page and had to fit in one of the following categories: Mild-to-moderate hypoglycemia (36 mg/dL ≤ Self Monitored Blood Glucose (SMBG) <70mg/dL), Severe hypoglycemia (assistance of another person is required, and either a recorded SMBG <36 mg/dL, or treatment with oral carbohydrates, intravenous glucose or glucagon with prompt response) or Hypoglycemia symptoms with or without SMBG values with a documented SMBG >70 mg/dL, or no recorded SMBG value. Only hypoglycemia events associated with coma, loss of consciousness or seizure were considered serious adverse event (SAEs).

Eligibility Module

Eligibility Criteria

Inclusion criteria:

Patients with a confirmed diagnosis of type 2 diabetes mellitus who were treated with any combination of 2 or 3 oral antidiabetic drugs (OADs) at a stable dose for the preceding 3 months, including but not limited to:

Metformin + sulfonylurea + thiazolidinedione (Pioglitazone)
Metformin + sulfonylurea
Metformin + thiazolidinedione (Pioglitazone)
Metformin + dipeptidyl peptidase (DPPIV)

And for whom the Investigator/treating physician had decided that basal insulin was appropriate.

Patients who had signed an Informed Consent Form and Health Insurance Portability and Accountability Act (HIPAA) Authorization Form

Exclusion criteria:

Patients less than 18 years or greater than 85 years of age (ie, have not reached the age of 86 at the screening visit)
Patients with a confirmed diagnosis of type 1 diabetes mellitus
Patients who were treated with insulin or who had been treated with insulin in the preceding 12 months with the exception of insulin treatment during hospitalization (ie, patients who received insulin while hospitalized could be included)
Patients whose screening HbA1c is <7% or >10%
Patients with current addiction or current alcohol / drug abuse
Patients with cardiac status New York Heart Association III-IV
Patients with stroke, myocardial infarction, coronary artery bypass graft, percutaneous transluminal coronary angioplasty, or unstable angina pectoris within the 12 months prior to screening
Patients with a diagnosis of dementia, severe visual or dexterity impairment
Patients with any malignancy within the last 5 years, with the exception of adequately treated basal or squamous cell carcinoma of the skin or adequately treated cervical carcinoma in situ
Patients with concomitant disease or concomitant medication that could interfere with treatment or ability to answer questionnaires
Patients who were unable to self-inject
Patients who were taking or had been treated with Byetta® (exenatide) or other Glucagon-Like Peptide-1 agonists within 3 months before screening:
Patients who were pregnant or breastfeeding
Women of childbearing potential not protected by a highly effective contraceptive method of birth control (as defined for contraception in the Informed Consent Form and /or in a local protocol addendum) and/or who were unwilling or unable to be tested for pregnancy
Patients with impaired renal function as shown by serum creatinine ≥1.5 mg/dL for males or ≥1.4 mg/dL for females at screening
Patients with clinical evidence of active liver disease, or serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) 2.5 times the upper limit of the normal range (ULN)
Patients unlikely to comply with the protocol requirements (eg, illiterate, uncooperative, unable to return for scheduled visits, unlikely to complete the study)

Name	Affiliation	Role
Clinical Sciences & Operations	Sanofi	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Sanofi-Aventis Administrative Office		Bridgewater	New Jersey	08807	United States

ID	Title	Description
FG000	Pen (Period 1) / Vial & Syringe (Period 2)	Crossover phase: patients randomized to the sequence: Lantus SoloSTAR® pen in Period 1 and Lantus vial and syringe in Period 2.
FG001	Vial &Syringe (Period 1) / Pen (Period 2)

ID	Title	Description
BG000	Crossover Phase: Pen / Vial & Syringe	Patients randomized to the sequence: Lantus SoloSTAR pen in Period 1 and Lantus vial and syringe in Period 2 for the 4-week crossover phase.
BG001	Crossover Phase: Vial & Syringe / Pen	Patients randomized to the sequence: Lantus vial and syringe in Period 1 and Lantus SoloSTAR pen in Period 2 for the 4-week crossover phase.
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG000202 BG001203 BG002405

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

Primary

Patient Overall Preference

The patient preference was assessed in terms of the difference in scores obtained from the overall preference question 14d "Overall, what is your level of preference for each of the insulin delivery systems?"

5 points scale: from 1=Not preferred to 5= Always preferred

The modified intent-to-treat (mITT) population for the Patient Preference Questionnaire analysis consisted of all randomized patients who received at least one dose of Lantus via both insulin delivery systems and completed the questionnaire at Week 4. This analysis included patients who answered question 14d.

Posted

Least Squares Mean

95% Confidence Interval

units on a scale

At week 4 (end of crossover phase)

ID	Title	Description
OG000	SoloSTAR® Pen	Patients using the SoloSTAR® Pen during the crossover phase either at period 1 or at period 2 depending on the sequence allocated by randomization.
OG001	Vial and Syringe	Patients using the Vial and Syringe during the crossover phase either at period 1 or at period 2 depending on the sequence allocated by randomization.

Units	Counts
Participants	OG000388 OG001388

Title

Denominators

Categories

Title	Measurements
	OG0004.75± 4.75(4.65 to 4.85) OG0012.45(2.35 to 2.56)

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 hypothesis was to determine whether patients have higher preference score for Lantus® SoloSTAR® pen compared to Lantus® vial/syringe. Differences of patient preference score greater than 0.5 were considered clinically meaningful. The power for detecting a true difference of 0.5 considering a standard deviation from 1.6 to 2.5, assuming 130 evaluable patients per arm and a two-sided test at 0.05 significance level ranged from 89% to more than 99%.	ANOVA	The last observation carried forward (LOCF) method was applied to impute missing Week 4 overall patient preference values for ANOVA analysis.	<0.0001		Mean Difference (Net)	2.3			2-Sided	95	2.15	2.44				No

Secondary

Patient Preference Composite Score

The patient preference composite score was the sum of the scores of the 3 following individual preference questions from the Patient preference Questionnaire:

Question 14a: How strongly do you prefer each of these insulin delivery systems to control blood sugar?
Question 14b: If using insulin for the first time, how strongly would you prefer using each of these delivery systems to overcome reluctance to use insulin?
Question 14c: How strongly would you prefer each insulin delivery system for long-term use?

Each individual question scored from 1 to 5. The lowest score 1 indicated 'Not Preferred' and the highest score 5 indicated 'Always Preferred'. Therefore the total range of the composite score was 3 to 15.

Posted

Least Squares Mean

95% Confidence Interval

units on a scale

At week 4 (end of crossover phase)

ID	Title	Description
OG000	SoloSTAR® Pen	Patients using the SoloSTAR® Pen during the crossover phase either at period 1 or at period 2 depending on the sequence allocated by randomization.
OG001	Vial and Syringe	Patients using the Vial and Syringe during the crossover phase either at period 1 or at period 2 depending on the sequence allocated by randomization.

Secondary

Healthcare Professional's (HCP) Recommendation

The overall recommendation score was obtained from the question 20d of the Healthcare Professional Questionnaire: "Overall, how strongly would you recommend each of the insulin delivery systems for your patients?"

5 points scale: from 1= Not Recommended to 5= Recommended

The HCP Questionnaire analysis population consisted of HCPs:

who treated at least 1 randomized patient during the crossover phase and this(these) patient(s) received at least one dose of Lantus via both insulin delivery systems during the crossover phase
who completed the HCP Questionnaire.

Posted

Median

Full Range

units on a scale

At week 4 (end of crossover phase)

ID	Title	Description
OG000	SoloSTAR® Pen	SoloSTAR® Pen used during the crossover phase either at period 1 or at period 2
OG001	Vial and Syringe	Vial and Syringe used during the crossover phase either at period 1 or at period 2

Units	Counts
Participants

Secondary

Change in Fasting Plasma Glucose (FPG)

The mITT population for Re-randomization and Observational Phases consisted of all patients who were re-randomized, received at least one dose of Lantus after re-randomization, and had both a re-randomization baseline assessment and at least one post re-randomization assessment of FPG measured during the on-treatment period.

Posted

Least Squares Mean

Standard Error

mg/dL

From week 4 (baseline for re-randomization phase) to week 10 (end of re-randomization phase)

ID	Title	Description
OG000	SoloSTAR® Pen	Patients randomized to SoloSTAR® Pen during the Re-randomization period (Week 4 to Week 10)
OG001	Vial and Syringe	Patients randomized to Vial and Syringe during the Re-randomization period (Week 4 to Week 10)

Units	Counts
Participants	OG000

Secondary

Percentage of Patients Achieving Fasting Plasma Glucose (FPG) <110 mg/dL

The mITT population for Re-randomization and Observational Phases consisted of all patients who were re-randomized, received at least one dose of Lantus after re-randomization, and had a re-randomization baseline assessment FPG > or = 110 (week 4) and at least one post re-randomization assessment of FPG.

Posted

Number

percentage of patients

At week 10 (end of re-randomization phase)

ID	Title	Description
OG000	SoloSTAR® Pen	Patients randomized to SoloSTAR® Pen during the Re-randomization period (Week 4 to Week 10)
OG001	Vial and Syringe	Patients randomized to Vial and Syringe during the Re-randomization period (Week 4 to Week 10)

Units	Counts
Participants	OG000

Secondary

Change in Lantus Dose Injected Per Day

Posted

Least Squares Mean

Standard Error

U (insulin unit)

From week 4 (baseline for re-randomization phase) to week 10 (end of re-randomization phase)

ID	Title	Description
OG000	SoloSTAR® Pen	Patients randomized to SoloSTAR® Pen during the Re-randomization period (Week 4 to Week 10)
OG001	Vial and Syringe	Patients randomized to Vial and Syringe during the Re-randomization period (Week 4 to Week 10)

Units	Counts
Participants	OG000

Secondary

Percentage of Patients Achieving HbA1c Goal

Percentage of patients achieving HbA1c < 7% at Week 40 (end of the observational phase)

Patients from the mITT population for Re-randomization and Observational Phases who had at least one post re-randomization assessment of HbA1c.

Posted

Number

percentage of patients

measured at week 40 or at study discontinuation

ID	Title	Description
OG000	SoloSTAR® Pen	Patients randomized to SoloSTAR® Pen during the Re-randomization phase (from Week 4 to Week 10) and the Observational phase (from Week 10 to Week 40).
OG001	Vial and Syringe	Patients randomized to Vial and Syringe during the Re-randomization phase (from Week 4 to Week 10) and the Observational phase (from Week 10 to Week 40).

Units	Counts
Participants	OG000

Secondary

Time to First Observation of HbA1c <7%

Posted

Median

95% Confidence Interval

Days since Re-randomization (week 4)

From week 10 to week 40 (observational phase)

ID	Title	Description
OG000	SoloSTAR® Pen	Patients randomized to SoloSTAR® Pen during the Re-randomization phase (from Week 4 to Week 10) and the Observational phase (from Week 10 to Week 40).
OG001	Vial and Syringe	Patients randomized to Vial and Syringe during the Re-randomization phase (from Week 4 to Week 10) and the Observational phase (from Week 10 to Week 40).

Units	Counts
Participants	OG000

Secondary

Percentage of Patients Who Discontinued Investigational Product (IP) During the Crossover Phase

Randomized population (crossover phase) exposed to at least one dose of the IP

Posted

Number

percentage of patients

From baseline to week 4 (crossover phase)

ID	Title	Description
OG000	SoloSTAR® Pen (Period 1)	Patients using SoloSTAR® pen during period 1 of the crossover phase.
OG001	Vial and Syringe (Period 2)	Patients using Vial and Syringe during period 2 of the crossover phase.
OG002	SoloSTAR® Pen (Period 2)	Patients using SoloSTAR® pen during period 2 of the crossover phase.
OG003	Vial and Syringe (Period 1)	Patients using Vial and Syringe during period 1 of the crossover phase.

Units	Counts

Secondary

Percentage of Patients Who Discontinued Investigational Product During the Re-randomization Phase

Re-randomized population at week 4 exposed to at least one dose of the IP

Posted

Number

percentage of patients

From week 4 to week 10 (re-randomization phase)

ID	Title	Description
OG000	SoloSTAR® Pen	Patients using SoloSTAR® pen during the re-randomization phase.
OG001	Vial and Syringe	Patients using Vial and Syringe during the re-randomization phase.

Units	Counts
Participants	OG000

Secondary

Percentage of Patients Who Discontinued Investigational Product During the Observational Phase

Re-randomized population at week 4 and included in the observational phase at week 10 and exposed to at least one dose of the IP

Posted

Number

percentage of patients

From week 10 to week 40 (observational phase)

ID	Title	Description
OG000	SoloSTAR® Pen	Patients using SoloSTAR® pen during the observational phase.
OG001	Vial and Syringe	Patients using Vial and Syringe during the observational phase.

Units	Counts
Participants	OG000

Other Pre-specified

Number of Patients With Hypoglycemic Events

The hypoglycemic event was to be recorded on the electronic case report form hypoglycemia page and had to fit in one of the following categories: Mild-to-moderate hypoglycemia (36 mg/dL ≤ Self Monitored Blood Glucose (SMBG) <70mg/dL), Severe hypoglycemia (assistance of another person is required, and either a recorded SMBG <36 mg/dL, or treatment with oral carbohydrates, intravenous glucose or glucagon with prompt response) or Hypoglycemia symptoms with or without SMBG values with a documented SMBG >70 mg/dL, or no recorded SMBG value. Only hypoglycemia events associated with coma, loss of consciousness or seizure were considered serious adverse event (SAEs).

The safety population for each phase (crossover, re-randomization, observational) was the total treated population defined as all the patients who were randomized and exposed to at least one dose of Lantus during that phase.

Posted

Number

participants having reported the event

each study phase (crossover, re-randomization, observational) up to 40 weeks

ID	Title	Description
OG000	Crossover Phase: SoloSTAR® Pen	Patients using the SoloSTAR® Pen during the crossover phase either at period 1 or at period 2 depending on the sequence allocated by randomization.
OG001	Crossover Phase: Vial and Syringe	Patients using Vial and Syringe during the crossover phase either at period 1 or at period 2 depending on the sequence allocated by randomization.

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Crossover Phase: SoloSTAR® Pen	Patients using the SoloSTAR® Pen during the crossover phase either at period 1 or at period 2 depending on the sequence allocated by randomization.	4	396	18	396
EG001	Crossover Phase: Vial and Syringe	Patients using Vial and Syringe during the crossover phase either at period 1 or at period 2 depending on the sequence allocated by randomization.	1	399	5	399
EG002	Re-randomization Phase: SoloSTAR® Pen	Patients randomized to SoloSTAR® Pen during the Re-randomization period (Week 4 to Week 10)	1	165	12	165
EG003	Re-randomization Phase: Vial and Syringe	Patients randomized to Vial and Syringe during the Re-randomization period (Week 4 to Week 10)	0	165	14	165
EG004	Observational Phase: SoloSTAR® Pen	Patients using SoloSTAR® Pen during the Observational phase (from Week 10 to Week 40)	16	159	35	159
EG005	Observational Phase: Vial and Syringe	Patients using Vial and Syringe during the Observational phase (from Week 10 to Week 40)	14	153	34	153

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal pain lower	Gastrointestinal disorders	MedDRA 15.0	Non-systematic Assessment	EG0000 affected396 at risk EG0010 affected399 at risk EG0020 affected165 at risk EG0030 affected165 at risk EG0041 affected159 at risk EG0050 affected153 at risk
Angina pectoris	Cardiac disorders	MedDRA 15.0	Non-systematic Assessment	EG0000 affected396 at risk EG0010 affected399 at risk EG0020 affected165 at risk EG003
Angina unstable	Cardiac disorders	MedDRA 15.0	Non-systematic Assessment	EG0000 affected396 at risk EG0010 affected399 at risk EG0020 affected165 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 15.0	Non-systematic Assessment	EG0000 affected396 at risk EG0010 affected399 at risk EG0020 affected165 at risk EG003
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 15.0	Non-systematic Assessment	EG0001 affected396 at risk EG0010 affected399 at risk EG0020 affected165 at risk EG003
Atrial fibrillation	Cardiac disorders	MedDRA 15.0	Non-systematic Assessment	EG0000 affected396 at risk EG0010 affected399 at risk EG0020 affected165 at risk EG003
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.0	Non-systematic Assessment	EG0000 affected396 at risk EG0010 affected399 at risk EG0020 affected165 at risk EG003
Bipolar I disorder	Psychiatric disorders	MedDRA 15.0	Non-systematic Assessment	EG0000 affected396 at risk EG0010 affected399 at risk EG0020 affected165 at risk EG003
Breast calcifications	Reproductive system and breast disorders	MedDRA 15.0	Non-systematic Assessment	EG0000 affected396 at risk EG0010 affected399 at risk EG0020 affected165 at risk EG003
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.0	Non-systematic Assessment	EG0000 affected396 at risk EG0010 affected399 at risk EG0020 affected165 at risk EG003
Calculus ureteric	Renal and urinary disorders	MedDRA 15.0	Non-systematic Assessment	EG0000 affected396 at risk EG0010 affected399 at risk EG0020 affected165 at risk EG003
Cardiac failure congestive	Cardiac disorders	MedDRA 15.0	Non-systematic Assessment	EG0000 affected396 at risk EG0010 affected399 at risk EG0020 affected165 at risk EG003
Cauda equina syndrome	Cardiac disorders	MedDRA 15.0	Non-systematic Assessment	EG0000 affected396 at risk EG0010 affected399 at risk EG0021 affected165 at risk EG003
Cellulitis	Cardiac disorders	MedDRA 15.0	Non-systematic Assessment	EG0000 affected396 at risk EG0010 affected399 at risk EG0020 affected165 at risk EG003
Cerebrovascular accident	Cardiac disorders	MedDRA 15.0	Non-systematic Assessment	EG0000 affected396 at risk EG0010 affected399 at risk EG0020 affected165 at risk EG003
Chest pain	Cardiac disorders	MedDRA 15.0	Non-systematic Assessment	EG0000 affected396 at risk EG0010 affected399 at risk EG0020 affected165 at risk EG003
Chronic obstructive pulmonary disease	Cardiac disorders	MedDRA 15.0	Non-systematic Assessment	EG0001 affected396 at risk EG0010 affected399 at risk EG0020 affected165 at risk EG003
Colon neoplasm	Cardiac disorders	MedDRA 15.0	Non-systematic Assessment	EG0000 affected396 at risk EG0010 affected399 at risk EG0020 affected165 at risk EG003
Diarrhoea	Cardiac disorders	MedDRA 15.0	Non-systematic Assessment	EG0000 affected396 at risk EG0010 affected399 at risk EG0020 affected165 at risk EG003
Duodenal ulcer	Cardiac disorders	MedDRA 15.0	Non-systematic Assessment	EG0000 affected396 at risk EG0010 affected399 at risk EG0020 affected165 at risk EG003
Duodenal ulcer haemorrhage	Cardiac disorders	MedDRA 15.0	Non-systematic Assessment	EG0000 affected396 at risk EG0010 affected399 at risk EG0020 affected165 at risk EG003
Dyspnoea	Cardiac disorders	MedDRA 15.0	Non-systematic Assessment	EG0000 affected396 at risk EG0010 affected399 at risk EG0020 affected165 at risk EG003
Hypercalcaemia	General disorders	MedDRA 15.0	Non-systematic Assessment	EG0000 affected396 at risk EG0010 affected399 at risk EG0020 affected165 at risk EG003
Intracranial aneurysm	Injury, poisoning and procedural complications	MedDRA 15.0	Non-systematic Assessment	EG0000 affected396 at risk EG0010 affected399 at risk EG0020 affected165 at risk EG003
Ligament rupture	Injury, poisoning and procedural complications	MedDRA 15.0	Non-systematic Assessment	EG0000 affected396 at risk EG0010 affected399 at risk EG0020 affected165 at risk EG003
Myocardial infarction	Musculoskeletal and connective tissue disorders	MedDRA 15.0	Non-systematic Assessment	EG0000 affected396 at risk EG0010 affected399 at risk EG0020 affected165 at risk EG003
Myocardial ischaemia	Musculoskeletal and connective tissue disorders	MedDRA 15.0	Non-systematic Assessment	EG0000 affected396 at risk EG0010 affected399 at risk EG0020 affected165 at risk EG003
Nephrolithiasis	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.0	Non-systematic Assessment	EG0000 affected396 at risk EG0010 affected399 at risk EG0020 affected165 at risk EG003
Non-cardiac chest pain	Nervous system disorders	MedDRA 15.0	Non-systematic Assessment	EG0000 affected396 at risk EG0010 affected399 at risk EG0020 affected165 at risk EG003
Osteomyelitis	Nervous system disorders	MedDRA 15.0	Non-systematic Assessment	EG0001 affected396 at risk EG0010 affected399 at risk EG0020 affected165 at risk EG003
Pancreatic mass	Nervous system disorders	MedDRA 15.0	Non-systematic Assessment	EG0000 affected396 at risk EG0011 affected399 at risk EG0020 affected165 at risk EG003
Pneumonia	Nervous system disorders	MedDRA 15.0	Non-systematic Assessment	EG0000 affected396 at risk EG0010 affected399 at risk EG0020 affected165 at risk EG003
Post procedural complication	Nervous system disorders	MedDRA 15.0	Non-systematic Assessment	EG0000 affected396 at risk EG0010 affected399 at risk EG0021 affected165 at risk EG003
Renal failure	Renal and urinary disorders	MedDRA 15.0	Non-systematic Assessment	EG0000 affected396 at risk EG0010 affected399 at risk EG0020 affected165 at risk EG003
Road traffic accident	Respiratory, thoracic and mediastinal disorders	MedDRA 15.0	Non-systematic Assessment	EG0000 affected396 at risk EG0010 affected399 at risk EG0020 affected165 at risk EG003
Staphylococcal infection	Respiratory, thoracic and mediastinal disorders	MedDRA 15.0	Non-systematic Assessment	EG0000 affected396 at risk EG0010 affected399 at risk EG0020 affected165 at risk EG003
Syncope	Surgical and medical procedures	MedDRA 15.0	Non-systematic Assessment	EG0001 affected396 at risk EG0010 affected399 at risk EG0020 affected165 at risk EG003
Transurethral bladder resection	Surgical and medical procedures	MedDRA 15.0	Non-systematic Assessment	EG0000 affected396 at risk EG0010 affected399 at risk EG0020 affected165 at risk EG003
Urethral obstruction	Surgical and medical procedures	MedDRA 15.0	Non-systematic Assessment	EG0000 affected396 at risk EG0010 affected399 at risk EG0020 affected165 at risk EG003
Uterine haemorrhage	Surgical and medical procedures	MedDRA 15.0	Non-systematic Assessment	EG0000 affected396 at risk EG0010 affected399 at risk EG0020 affected165 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
D049528	Insulin, Long-Acting
D061385	Insulins
D010187	Pancreatic Hormones
D036361	Peptide Hormones
D006728	Hormones
D006730	Hormones, Hormone Substitutes, and Hormone Antagonists
D010455	Peptides
D000602	Amino Acids, Peptides, and Proteins

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Nasopharyngitis	Infections and infestations	MedDRA 15.0	Non-systematic Assessment	EG0005 affected396 at risk EG0010 affected399 at risk EG0026 affected165 at risk EG0034 affected165 at risk EG0047 affected159 at risk EG00513 affected153 at risk
Sinusitis	Infections and infestations	MedDRA 15.0	Non-systematic Assessment	EG0004 affected396 at risk EG0011 affected399 at risk EG0022 affected165 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 15.0	Non-systematic Assessment	EG0007 affected396 at risk EG0012 affected399 at risk EG0024 affected165 at risk EG003
Oedema peripheral	General disorders	MedDRA 15.0	Non-systematic Assessment	EG0002 affected396 at risk EG0012 affected399 at risk EG0020 affected165 at risk EG003