Comparison of the Safety and Efficacy of HOE901-U300 With Lantus in Older Patients With Type2 Diabetes Insufficiently Controlled on Their Current Antidiabetic Medications (SENIOR)

• ClinicalTrials.gov Identifier: NCT02320721
• Recruitment Status: Completed
• First Posted: December 19, 2014
• Results First Posted: July 11, 2017
• Last Update Posted: July 11, 2017
• Sponsor: Sanofi
• Information provided by (Responsible Party): Sanofi

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Type 2 Diabetes Mellitus
• Interventions: Drug: Insulin Glargine (HOE901 - U300); Drug: Insulin Glargine (HOE901 - U100); Drug: Background therapy
• Enrollment: 1014

Participant Flow

Recruitment Details	The study was conducted at 162 study centers across 18 countries. A total of 1515 participants were screened between 16 January 2015 and 14 October 2015, of whom 501 were screen failures.
Pre-assignment Details	A total of 1014 participants were randomized in 1:1 ratio to either HOE901-U300 or Lantus, stratified by screening hemoglobin A1c (HbA1c) values (<8% or ≥8%); previous use of insulin (insulin-naïve versus pre-treated); and use of sulfonylurea or meglitinides at screening (’yes’ versus ‘no’).

Arm/Group Title	HOE901-U300	Lantus
Arm/Group Description	HOE901-U300 (Insulin glargine, 300 U/mL) subcutaneous (SC) injection once daily up to Week 26 on top of stable non-insulin antihyperglycemic therapy.	Lantus (Insulin glargine, 100 U/mL) SC injection once daily up to Week 26 on top of stable non-insulin antihyperglycemic therapy.
Period Title: Overall Study
Started	508	506
Treated (Safety Population)	508	505
Completed	481	472
Not Completed	27	34
Reason Not Completed
Adverse Event	6	6
Lack of Efficacy	2	0
Poor compliance to protocol	3	7
Randomized but not treated	0	1
Hypoglycemia	1	0
Other than specified above	15	20

Baseline Characteristics

Arm/Group Title		HOE901-U300	Lantus	Total
Arm/Group Description		HOE901-U300 (Insulin glargine, 300 U/mL) SC injection once daily up to Week 26 on top of stable non-insulin antihyperglycemic therapy.	Lantus (Insulin glargine, 100 U/mL) SC injection once daily up to Week 26 on top of stable non-insulin antihyperglycemic therapy.	Total of all reporting groups
Overall Number of Baseline Participants		508	506	1014
Baseline Analysis Population Description		Baseline population included all randomized participants.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	508 participants	506 participants	1014 participants
		71.1 (4.9)	70.8 (4.8)	71.0 (4.9)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	508 participants	506 participants	1014 participants
	Female	258 50.8%	229 45.3%	487 48.0%
	Male	250 49.2%	277 54.7%	527 52.0%
Body Mass Index (BMI) [1]; Mean (Standard Deviation); Unit of measure: Kg/m^2
	Number Analyzed	508 participants	505 participants	1013 participants
		30.9 (5.5)	31.2 (5.7)	31.1 (5.6)
		[1] Measure Analysis Population Description: Number of participants analyzed = participants with available data for this baseline measure.
Duration of Type 2 Diabetes; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	508 participants	506 participants	1014 participants
		15.29 (8.17)	15.35 (7.70)	15.32 (7.93)
Baseline Glycated Hemoglobin A1c (HbA1c); Mean (Standard Deviation); Unit of measure: Percentage of HbA1c
	Number Analyzed	508 participants	506 participants	1014 participants
		8.20 (0.91)	8.22 (0.92)	8.21 (0.91)
Randomization strata of insulin; Measure Type: Count of Participants; Unit of measure: Participants
Insulin-naive	Number Analyzed	508 participants	506 participants	1014 participants
		166 32.7%	165 32.6%	331 32.6%
Insulin pre-treated	Number Analyzed	508 participants	506 participants	1014 participants
		342 67.3%	341 67.4%	683 67.4%
Age Group; Measure Type: Count of Participants; Unit of measure: Participants
<75 years of age	Number Analyzed	508 participants	506 participants	1014 participants
		373 73.4%	400 79.1%	773 76.2%
≥75 years of age	Number Analyzed	508 participants	506 participants	1014 participants
		135 26.6%	106 20.9%	241 23.8%

Outcome Measures

1. Primary Outcome

Title	Change in HbA1c From Baseline to Week 26
Description	Adjusted least square (LS) means were obtained from analysis of covariance (ANCOVA) after multiple imputation of missing data including post baseline HbA1c data during the 26-week randomized period.
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population included all randomized participants regardless of whether the treatment kit was used, and analyzed according to the treatment group allocated by randomization.

Arm/Group Title	HOE901-U300	Lantus
Arm/Group Description:	HOE901-U300 (Insulin glargine, 300 U/mL) SC injection once daily up to Week 26 on top of stable non-insulin antihyperglycemic therapy.	Lantus (Insulin glargine, 100 U/mL) SC injection once daily up to Week 26 on top of stable non-insulin antihyperglycemic therapy.
Overall Number of Participants Analyzed	508	506
Least Squares Mean (Standard Error); Unit of Measure: percentage of hemoglobin
	-0.89 (0.038)	-0.91 (0.042)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	HOE901-U300, Lantus
	Comments	Analysis was performed using ANCOVA model including the fixed categorical effects of treatment group, randomization strata, as well as the continuous fixed covariates of baseline value and following multiple imputation procedure for missing data.
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority of HOE901-U300 vs Lantus was demonstrated if the upper bound of the two-sided 95% confidence interval (CI) for the difference between groups was <0.3%.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.02
	Confidence Interval	(2-Sided) 95%; -0.092 to 0.129
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.056
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Percentage of Participants With At Least One Severe and/ or Confirmed (≤3.9 mmol/L [70 mg/dL]) Nocturnal Hypoglycemia (22:00 to 08:59 Hours Next Morning) During 26-Week Randomized Period
Description	Estimated percentages from multiple imputation approach including data from the 26-week randomized period. Severe hypoglycemia was an event that required assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. Confirmed hypoglycemia was an event associated with plasma glucose ≤3.9 mmol/L (70 mg/dL).
Time Frame	Baseline up to Week 26

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	HOE901-U300	Lantus
Arm/Group Description:	HOE901-U300 (Insulin glargine, 300 U/mL) SC injection once daily up to Week 26 on top of stable non-insulin antihyperglycemic therapy.	Lantus (Insulin glargine, 100 U/mL) SC injection once daily up to Week 26 on top of stable non-insulin antihyperglycemic therapy.
Overall Number of Participants Analyzed	508	506
Measure Type: Number; Unit of Measure: percentage of participants
	48.3	47.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	HOE901-U300, Lantus
	Comments	Analysis was done by Cochran-Mantel-Haenszel method with randomization strata (screening HbA1c [<8.0%; ≥8.0%], previous use of insulin [naive, pre-treated], use of sulfonylurea or meglitinides at screening [yes, no]), following multiple imputation procedure for missing data.
	Type of Statistical Test	Superiority or Other
	Comments	A hierarchical testing procedure was used to control type I error and handle multiple endpoint analyses. Testing was then performed sequentially in the order the endpoints are reported. The hierarchical testing sequence continued only if previous endpoint was statistically significant at 0.05 level.
Statistical Test of Hypothesis	P-Value	0.8415
	Comments	Threshold for significance at 0.05 level.
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Relative risk
	Estimated Value	1.01
	Confidence Interval	(2-Sided) 95%; 0.890 to 1.153
	Estimation Comments	[Not Specified]

3. Secondary Outcome

Title	Percentage of Participants With At Least One Severe and/ or Confirmed (≤3.9 mmol/L [70 mg/dL]) Nocturnal Hypoglycemia (00:00 to 05:59 Hours) During 26-Week Randomized Period
Description	Estimated percentages from multiple imputation approach including data from the 26-week randomized period. Severe hypoglycemia was an event that required assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. Confirmed hypoglycemia was an event associated with plasma glucose ≤3.9 mmol/L (70 mg/dL).
Time Frame	Baseline up to Week 26

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	HOE901-U300	Lantus
Arm/Group Description:	HOE901-U300 (Insulin glargine, 300 U/mL) SC injection once daily up to Week 26 on top of stable non-insulin antihyperglycemic therapy.	Lantus (Insulin glargine, 100 U/mL) SC injection once daily up to Week 26 on top of stable non-insulin antihyperglycemic therapy.
Overall Number of Participants Analyzed	508	506
Measure Type: Number; Unit of Measure: percentage of participants
	20.2	22.5

4. Secondary Outcome

Title	Percentage of Participants With At Least One Severe and/ or Confirmed (≤3.9 mmol/L [70 mg/dL]) Hypoglycemia Occurring at Any Time of the Day During 26-Week Randomized Period
Description	Estimated percentages from multiple imputation approach including data from the 26-week randomized period. Severe hypoglycemia was an event that required assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. Confirmed hypoglycemia was an event associated with plasma glucose ≤3.9 mmol/L (70 mg/dL).
Time Frame	Baseline up to Week 26

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	HOE901-U300	Lantus
Arm/Group Description:	HOE901-U300 (Insulin glargine, 300 U/mL) SC injection once daily up to Week 26 on top of stable non-insulin antihyperglycemic therapy.	Lantus (Insulin glargine, 100 U/mL) SC injection once daily up to Week 26 on top of stable non-insulin antihyperglycemic therapy.
Overall Number of Participants Analyzed	508	506
Measure Type: Number; Unit of Measure: percentage of participants
	59.4	62.7

5. Secondary Outcome

Title	Percentage of Participants With HbA1c <7.5% or HbA1c <7% During 26-Week Randomized Period
Description	Participants without any available HbA1c assessment at Week 26 were considered as non-responders in the analyses.
Time Frame	Baseline up to Week 26

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	HOE901-U300	Lantus
Arm/Group Description:	HOE901-U300 (Insulin glargine, 300 U/mL) SC injection once daily up to Week 26 on top of stable non-insulin antihyperglycemic therapy.	Lantus (Insulin glargine, 100 U/mL) SC injection once daily up to Week 26 on top of stable non-insulin antihyperglycemic therapy.
Overall Number of Participants Analyzed	508	506
Measure Type: Number; Unit of Measure: percentage of participants
HbA1c <7.5%	60.6	58.9
HbA1c <7.0%	33.3	35.2

6. Secondary Outcome

Title	Percentage of Participants With HbA1c <7.5% or <7.0% at Week 26 and No Severe and/or Confirmed (≤3.9 mmol/L [70 mg/dL]) Hypoglycemia During 26-Week Randomized Period
Description	Severe hypoglycemia was an event that required assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. Confirmed hypoglycemia was an event associated with plasma glucose ≤3.9 mmol/L (70 mg/dL).
Time Frame	Baseline up to Week 26

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	HOE901-U300	Lantus
Arm/Group Description:	HOE901-U300 (Insulin glargine, 300 U/mL) SC injection once daily up to Week 26 on top of stable non-insulin antihyperglycemic therapy.	Lantus (Insulin glargine, 100 U/mL) SC injection once daily up to Week 26 on top of stable non-insulin antihyperglycemic therapy.
Overall Number of Participants Analyzed	508	506
Measure Type: Number; Unit of Measure: percentage of participants
HbA1c <7.5%	26.4	21.5
HbA1c <7.0%	14.0	12.3

7. Secondary Outcome

Title	Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26
Description	Adjusted LS means from multiple imputation approach including post baseline values during the 26-week randomized period.
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

ITT population. Here 'Overall number of participants analyzed' signifies participants with available data for this outcome measure.

Arm/Group Title	HOE901-U300	Lantus
Arm/Group Description:	HOE901-U300 (Insulin glargine, 300 U/mL) SC injection once daily up to Week 26 on top of stable non-insulin antihyperglycemic therapy.	Lantus (Insulin glargine, 100 U/mL) SC injection once daily up to Week 26 on top of stable non-insulin antihyperglycemic therapy.
Overall Number of Participants Analyzed	484	482
Least Squares Mean (Standard Error); Unit of Measure: mmol/L
	-1.68 (0.122)	-1.77 (0.135)

8. Secondary Outcome

Title	Change in World Health Organization-5 (WHO-5) Well-Being Questionnaire Percentage Score From Baseline to Week 26
Description	WHO-5 well-being index evaluates positive psychological well-being during the past 2 weeks and consists of 5 questions, each rated on a 6-point Likert scale from 0 (not present) to 5 (constantly present). Total raw score was transformed into a percentage score ranging from 0 (worst possible quality of life) to 100 (best possible quality of life).
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

ITT population. Here ‘Overall number of participants analyzed’ signifies participants with available data for this outcome measure.

Arm/Group Title	HOE901-U300	Lantus
Arm/Group Description:	HOE901-U300 (Insulin glargine, 300 U/mL) SC injection once daily up to Week 26 on top of stable non-insulin antihyperglycemic therapy.	Lantus (Insulin glargine, 100 U/mL) SC injection once daily up to Week 26 on top of stable non-insulin antihyperglycemic therapy.
Overall Number of Participants Analyzed	484	476
Least Squares Mean (Standard Error); Unit of Measure: scores on a scale
	-1.16 (0.751)	0.22 (0.758)

9. Secondary Outcome

Title	Percentage of Participants Requiring Rescue Therapy Over the 26 Weeks of Treatment
Description	Routine fasting self-monitored plasma glucose (SMPG) and central laboratory FPG (and HbA1c after Week 14) values were used to determine the requirement of rescue medication. Threshold values at Week 14: FPG >200 mg/dL (11 mmol/L), or HbA1c >8.5%.
Time Frame	Baseline up to Week 26

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	HOE901-U300	Lantus
Arm/Group Description:	HOE901-U300 (Insulin glargine, 300 U/mL) SC injection once daily up to Week 26 on top of stable non-insulin antihyperglycemic therapy.	Lantus (Insulin glargine, 100 U/mL) SC injection once daily up to Week 26 on top of stable non-insulin antihyperglycemic therapy.
Overall Number of Participants Analyzed	508	506
Measure Type: Number; Unit of Measure: percentage of participants
	3.7	2.6

10. Other Pre-specified Outcome

Title	Percentage of Participants With Hypoglycemia (Any Hypoglycemia, Documented Symptomatic Hypoglycemia, Severe and/or Confirmed Hypoglycemia) During the 26 Weeks of Treatment
Description	Hypoglycemia events were hypoglycemia of any category, severe hypoglycemia (an event that required assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions); documented symptomatic hypoglycemia (symptoms of hypoglycemia with plasma glucose ≤3.9 mmol/L [70 mg/dL]); confirmed hypoglycemia (with or without symptoms of hypoglycemia and plasma glucose ≤3.9 mmol/L).
Time Frame	Baseline up to Week 26

Outcome Measure Data

Analysis Population Description

Safety population included all randomized participants who actually received at least 1 dose or part of a dose of investigational medicinal product (IMP) and analyzed according to the treatment actually received.

Arm/Group Title		HOE901-U300	Lantus
Arm/Group Description:		HOE901-U300 (Insulin glargine, 300 U/mL) SC injection once daily up to Week 26 on top of stable non-insulin antihyperglycemic therapy.	Lantus (Insulin glargine, 100 U/mL) SC injection once daily up to Week 26 on top of stable non-insulin antihyperglycemic therapy.
Overall Number of Participants Analyzed		508	505
Measure Type: Number; Unit of Measure: percentage of participants
Any hypoglycemia	Number Analyzed	508 participants	505 participants
		62.6	66.5
Documented symptomatic hypoglycemia	Number Analyzed	508 participants	505 participants
		32.9	34.7
Severe and/or confirmed hypoglycemia	Number Analyzed	508 participants	505 participants
		58.1	60.6
Severe and/or confirmed hypoglycemia:<75 years age	Number Analyzed	373 participants	399 participants
		59.2	60.9
Severe and/or confirmed hypoglycemia:≥75 years age	Number Analyzed	135 participants	106 participants
		54.8	59.4

11. Other Pre-specified Outcome

Title	Hypoglycemia (Any Hypoglycemia, Documented Symptomatic Hypoglycemia, Severe and/or Confirmed Hypoglycemia) Event Rate Per Participant Year During the 26 Weeks of Treatment
Description	Hypoglycemia events were hypoglycemia of any category, severe hypoglycemia (an event that required assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions); documented symptomatic hypoglycemia (symptoms of hypoglycemia with plasma glucose ≤3.9 mmol/L [70 mg/dL]); confirmed hypoglycemia (with or without symptoms of hypoglycemia and plasma glucose ≤3.9 mmol/L).
Time Frame	Baseline up to Week 26

Outcome Measure Data

Analysis Population Description

Safety population.

Arm/Group Title	HOE901-U300	Lantus
Arm/Group Description:	HOE901-U300 (Insulin glargine, 300 U/mL) SC injection once daily up to Week 26 on top of stable non-insulin antihyperglycemic therapy.	Lantus (Insulin glargine, 100 U/mL) SC injection once daily up to Week 26 on top of stable non-insulin antihyperglycemic therapy.
Overall Number of Participants Analyzed	508	505
Measure Type: Number; Unit of Measure: events per participant year
Any hypoglycemia	6.06	7.74
Documented symptomatic hypoglycemia	1.85	2.56
Severe and/or confirmed hypoglycemia	5.17	6.36

12. Post-Hoc Outcome

Title	Hypoglycemia (Any Hypoglycemia, Documented Symptomatic Hypoglycemia, Severe and/or Confirmed Hypoglycemia) Event Rate Per Participant Year: By Age Categorical Data During the 26 Weeks of Treatment
Description	Hypoglycemia events were hypoglycemia of any category, severe hypoglycemia (an event that required assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions); documented symptomatic hypoglycemia (symptoms of hypoglycemia with plasma glucose ≤3.9 mmol/L [70 mg/dL]); confirmed hypoglycemia (with or without symptoms of hypoglycemia and plasma glucose ≤3.9 mmol/L).
Time Frame	Baseline up to Week 26

Outcome Measure Data

Analysis Population Description

Safety population.

Arm/Group Title		HOE901-U300	Lantus
Arm/Group Description:		HOE901-U300 (Insulin glargine, 300 U/mL) SC injection once daily up to Week 26 on top of stable non-insulin antihyperglycemic therapy.	Lantus (Insulin glargine, 100 U/mL) SC injection once daily up to Week 26 on top of stable non-insulin antihyperglycemic therapy.
Overall Number of Participants Analyzed		508	505
Measure Type: Number; Unit of Measure: events per participant year
Any hypoglycemia:<75 years age	Number Analyzed	373 participants	399 participants
		6.44	7.85
Any hypoglycemia:≥75 years age	Number Analyzed	135 participants	106 participants
		5.01	7.32
Documented symptomatic hypoglycemia:<75 years age	Number Analyzed	373 participants	399 participants
		2.11	2.52
Documented symptomatic hypoglycemia:≥75 years age	Number Analyzed	135 participants	106 participants
		1.12	2.71
Severe and/or confirmed hypoglycemia:<75 years age	Number Analyzed	373 participants	399 participants
		5.43	6.37
Severe and/or confirmed hypoglycemia:≥75 years age	Number Analyzed	135 participants	106 participants
		4.46	6.28

Adverse Events

Time Frame	All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 184) regardless of seriousness or relationship to IMP.
Adverse Event Reporting Description	Reported AEs and deaths were treatment emergent that is AEs that developed/worsened and deaths that occurred during 'on treatment period' (from first dose of IMP injection up to 2 days after the last injection of IMP, regardless of introduction of rescue therapy). Analysis was performed using safety population which included all the treated participants.
Arm/Group Title	HOE901-U300	Lantus
Arm/Group Description	HOE901-U300 (Insulin glargine, 300 U/mL) SC injection once daily up to Week 26 on top of stable non-insulin antihyperglycemic therapy.	Lantus (Insulin glargine, 100 U/mL) SC injection once daily up to Week 26 on top of stable non-insulin antihyperglycemic therapy.
All-Cause Mortality
	HOE901-U300	Lantus
	Affected / at Risk (%)	Affected / at Risk (%)
Total	1/508 (0.20%)	0/505 (0.00%)
Serious Adverse Events
	HOE901-U300	Lantus
	Affected / at Risk (%)	Affected / at Risk (%)
Total	41/508 (8.07%)	34/505 (6.73%)
Blood and lymphatic system disorders
Anaemia † 1	0/508 (0.00%)	1/505 (0.20%)
Cardiac disorders
Acute left ventricular failure † 1	0/508 (0.00%)	1/505 (0.20%)
Acute myocardial infarction † 1	2/508 (0.39%)	1/505 (0.20%)
Angina unstable † 1	2/508 (0.39%)	0/505 (0.00%)
Atrial fibrillation † 1	0/508 (0.00%)	2/505 (0.40%)
Atrioventricular block † 1	1/508 (0.20%)	0/505 (0.00%)
Cardiac failure chronic † 1	0/508 (0.00%)	1/505 (0.20%)
Cardiac failure congestive † 1	1/508 (0.20%)	0/505 (0.00%)
Coronary artery disease † 1	2/508 (0.39%)	2/505 (0.40%)
Myocardial ischaemia † 1	0/508 (0.00%)	1/505 (0.20%)
Sinus node dysfunction † 1	1/508 (0.20%)	0/505 (0.00%)
Tachycardia † 1	1/508 (0.20%)	0/505 (0.00%)
Endocrine disorders
Adrenal mass † 1	1/508 (0.20%)	0/505 (0.00%)
Gastrointestinal disorders
Gastric ulcer haemorrhage † 1	1/508 (0.20%)	0/505 (0.00%)
Ileus † 1	0/508 (0.00%)	1/505 (0.20%)
Rectal haemorrhage † 1	1/508 (0.20%)	0/505 (0.00%)
General disorders
Death † 1	1/508 (0.20%)	0/505 (0.00%)
Hepatobiliary disorders
Bile duct stone † 1	1/508 (0.20%)	0/505 (0.00%)
Cholecystitis † 1	1/508 (0.20%)	0/505 (0.00%)
Cholecystitis acute † 1	1/508 (0.20%)	0/505 (0.00%)
Infections and infestations
Arthritis infective † 1	1/508 (0.20%)	0/505 (0.00%)
Bacterial pyelonephritis † 1	0/508 (0.00%)	1/505 (0.20%)
Diverticulitis † 1	0/508 (0.00%)	1/505 (0.20%)
Empyema † 1	0/508 (0.00%)	1/505 (0.20%)
Endocarditis bacterial † 1	1/508 (0.20%)	0/505 (0.00%)
Lung infection † 1	0/508 (0.00%)	1/505 (0.20%)
Osteomyelitis † 1	1/508 (0.20%)	0/505 (0.00%)
Perirectal abscess † 1	1/508 (0.20%)	0/505 (0.00%)
Pneumonia † 1	1/508 (0.20%)	3/505 (0.59%)
Pyelonephritis † 1	0/508 (0.00%)	2/505 (0.40%)
Urosepsis † 1	1/508 (0.20%)	0/505 (0.00%)
Injury, poisoning and procedural complications
Ankle fracture † 1	0/508 (0.00%)	1/505 (0.20%)
Fall † 1	1/508 (0.20%)	0/505 (0.00%)
Femur fracture † 1	0/508 (0.00%)	1/505 (0.20%)
Heart injury † 1	0/508 (0.00%)	1/505 (0.20%)
Investigations
Hepatic enzyme increased † 1	1/508 (0.20%)	0/505 (0.00%)
Metabolism and nutrition disorders
Hyperkalaemia † 1	1/508 (0.20%)	0/505 (0.00%)
Hypoglycaemia † 1	1/508 (0.20%)	1/505 (0.20%)
Hyponatraemia † 1	1/508 (0.20%)	0/505 (0.00%)
Musculoskeletal and connective tissue disorders
Back pain † 1	1/508 (0.20%)	0/505 (0.00%)
Chondrocalcinosis pyrophosphate † 1	1/508 (0.20%)	0/505 (0.00%)
Osteoarthritis † 1	0/508 (0.00%)	1/505 (0.20%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma of colon † 1	1/508 (0.20%)	0/505 (0.00%)
Basal cell carcinoma † 1	1/508 (0.20%)	1/505 (0.20%)
Bladder cancer † 1	0/508 (0.00%)	1/505 (0.20%)
Bowen's disease † 1	1/508 (0.20%)	0/505 (0.00%)
Breast cancer † 1	0/508 (0.00%)	1/505 (0.20%)
Chronic lymphocytic leukaemia † 1	1/508 (0.20%)	0/505 (0.00%)
Endometrial cancer metastatic † 1	1/508 (0.20%)	0/505 (0.00%)
Glioblastoma † 1	0/508 (0.00%)	1/505 (0.20%)
Hepatic neoplasm † 1	0/508 (0.00%)	1/505 (0.20%)
Lung adenocarcinoma † 1	1/508 (0.20%)	0/505 (0.00%)
Lung neoplasm † 1	0/508 (0.00%)	1/505 (0.20%)
Oesophageal adenocarcinoma † 1	0/508 (0.00%)	1/505 (0.20%)
Pancreatic carcinoma † 1	2/508 (0.39%)	0/505 (0.00%)
Prostate cancer † 1	3/508 (0.59%)	1/505 (0.20%)
Rectal cancer † 1	0/508 (0.00%)	1/505 (0.20%)
Squamous cell carcinoma of skin † 1	1/508 (0.20%)	0/505 (0.00%)
Transitional cell carcinoma † 1	0/508 (0.00%)	1/505 (0.20%)
Nervous system disorders
Embolic stroke † 1	1/508 (0.20%)	0/505 (0.00%)
Hypoglycaemic coma † 1	1/508 (0.20%)	0/505 (0.00%)
Hypoglycaemic unconsciousness † 1	1/508 (0.20%)	0/505 (0.00%)
IIIrd nerve paresis † 1	1/508 (0.20%)	0/505 (0.00%)
Ischaemic stroke † 1	2/508 (0.39%)	0/505 (0.00%)
Loss of consciousness † 1	1/508 (0.20%)	0/505 (0.00%)
Neuromyopathy † 1	1/508 (0.20%)	0/505 (0.00%)
Syncope † 1	1/508 (0.20%)	1/505 (0.20%)
Transient ischaemic attack † 1	0/508 (0.00%)	1/505 (0.20%)
Renal and urinary disorders
Acute kidney injury † 1	1/508 (0.20%)	1/505 (0.20%)
Chronic kidney disease † 1	1/508 (0.20%)	0/505 (0.00%)
Renal colic † 1	0/508 (0.00%)	1/505 (0.20%)
Reproductive system and breast disorders
Benign prostatic hyperplasia † 1	1/508 (0.20%)	0/505 (0.00%)
Breast mass † 1	0/508 (0.00%)	1/505 (0.20%)
Respiratory, thoracic and mediastinal disorders
Pleural effusion † 1	1/508 (0.20%)	0/505 (0.00%)
Skin and subcutaneous tissue disorders
Angioedema † 1	1/508 (0.20%)	0/505 (0.00%)
Vascular disorders
Hypertensive crisis † 1	1/508 (0.20%)	2/505 (0.40%)
Peripheral venous disease † 1	1/508 (0.20%)	0/505 (0.00%)
1 Term from vocabulary, MedDRA 19.0; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	HOE901-U300	Lantus
	Affected / at Risk (%)	Affected / at Risk (%)
Total	62/508 (12.20%)	64/505 (12.67%)
Infections and infestations
Nasopharyngitis † 1	37/508 (7.28%)	38/505 (7.52%)
Upper respiratory tract infection † 1	27/508 (5.31%)	28/505 (5.54%)
1 Term from vocabulary, MedDRA 19.0; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

If no publication has occurred within 12 months of the completion of the study, the Investigator shall have the right to publish/present independently the results of the study. The Investigator shall provide the Sponsor with a copy of any such presentation/publication for comment at least 30 days before any presentation/submission for publication. If requested by the Sponsor, any presentation/submission shall be delayed up to 90 days, to allow the Sponsor to preserve its proprietary rights.

Results Point of Contact

• Name/Title: Trial Transparency Team
• Organization: Sanofi
• EMail: Contact-US@sanofi.com

• Responsible Party: Sanofi
• ClinicalTrials.gov Identifier: NCT02320721 History of Changes
• Other Study ID Numbers: EFC13799; 2014-002399-10; U1111-1159-3018 ( Other Identifier: UTN )
• First Submitted: December 16, 2014
• First Posted: December 19, 2014
• Results First Submitted: May 18, 2017
• Results First Posted: July 11, 2017
• Last Update Posted: July 11, 2017