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Comparison of a New Formulation of Insulin Glargine With Lantus in Patients With Type 2 Diabetes Mellitus on Basal Plus Mealtime Insulin (EDITION I)

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ClinicalTrials.gov Identifier: NCT01499082
Recruitment Status : Completed
First Posted : December 26, 2011
Results First Posted : April 23, 2015
Last Update Posted : November 2, 2016
Sponsor:
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: HOE901-U300 (new formulation of insulin glargine)
Drug: Lantus (insulin glargine)
Enrollment 807
Recruitment Details A total of 1177 participants were screened, of whom 370 participants were screen failure and 807 participants were randomized.
Pre-assignment Details Following the main 6 month treatment period, eligible participants previously using HOE901-U300 were randomized (1:1) in a substudy and continued with fixed-dosing (every 24 hours) or started a adaptable-dosing (at intervals of 24 +/- 3 hours) regimen for 3 Months (Month 6 to 9).
Arm/Group Title HOE901-U300 Lantus
Hide Arm/Group Description HOE901­U300 (new insulin glargine 300 units per milliliter [U/mL]) subcutaneous (SC) injection once daily (evening) for 12 months on top of mealtime insulin analogue. Lantus (HOE901-U100, insulin glargine 100 U/mL) SC injection once daily (evening) for 12 months on top of mealtime insulin analogue.
Period Title: Overall Study
Started 404 403
Treated 404 402
Participated in Substudy 109 [1] 0
Modified Intent-to-Treat Population 404 [2] 400 [2]
Completed 359 355
Not Completed 45 48
Reason Not Completed
Randomized but not Treated             0             1
Adverse Event             12             16
Lack of Efficacy             1             1
Protocol Violation             6             8
Diverse Reasons             18             14
Site Closure for Noncompliance             5             2
Hypoglycemia             2             3
Lost to Follow-up             1             3
[1]
56 participants received adaptable dosing regimen and 53 participants received fixed dosing regimen
[2]
Participants who received at least 1 dose of drug, had both baseline, at least 1 post-baseline data
Arm/Group Title HOE901-U300 Lantus Total
Hide Arm/Group Description HOE901-U300 SC injection once daily for 12 months on top of mealtime insulin. Lantus SC injection once daily for 12 months on top of mealtime insulin. Total of all reporting groups
Overall Number of Baseline Participants 404 403 807
Hide Baseline Analysis Population Description
Randomized population: all screened participants (who originally met inclusion criteria and signed informed consent) allocated to a treatment group and recorded in Interactive Voice/Web Response System (IVRS/IWRS) database, regardless of whether treatment was used or not. Participants were analyzed in treatment group to which they were randomized.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 404 participants 403 participants 807 participants
60.1  (8.5) 59.8  (8.7) 60.0  (8.6)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 404 participants 403 participants 807 participants
Female
187
  46.3%
193
  47.9%
380
  47.1%
Male
217
  53.7%
210
  52.1%
427
  52.9%
Body Mass Index (BMI)  
Mean (Standard Deviation)
Unit of measure:  Kilogram per square meter (kg/m^2)
Number Analyzed 404 participants 403 participants 807 participants
36.6  (6.8) 36.6  (6.1) 36.6  (6.4)
Duration of Diabetes  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 404 participants 403 participants 807 participants
15.6  (7.2) 16.1  (7.8) 15.8  (7.5)
Basal Insulin Daily Dose   [1] 
Mean (Standard Deviation)
Unit of measure:  Units per kilogram (U/kg)
Number Analyzed 404 participants 403 participants 807 participants
0.668  (0.263) 0.667  (0.241) 0.668  (0.252)
[1]
Measure Description: Number of participants analyzed for this baseline characteristics = 372 and 361 in HOE901-U300 and Lantus arm, respectively.
Total Insulin Daily Dose   [1] 
Mean (Standard Deviation)
Unit of measure:  U/kg
Number Analyzed 404 participants 403 participants 807 participants
1.194  (0.483) 1.200  (0.448) 1.197  (0.466)
[1]
Measure Description: Number of participants analyzed for this baseline characteristics = 367 and 360 in HOE901-U300 and Lantus arm, respectively
Glycated Hemoglobin A1c (HbA1c)  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 404 participants 403 participants 807 participants
Less Than (<) 8% 144 144 288
Greater Than or Equal to (>=) 8% 260 259 519
1.Primary Outcome
Title Change in HbA1c From Baseline to Month 6 Endpoint
Hide Description [Not Specified]
Time Frame Baseline, Month 6
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Modified Intent-to-Treat population: all randomized participants who received at least (>=)1 dose, had baseline and >=1 post-baseline assessment of any efficacy variable, irrespective of compliance. Number of participants analyzed = participants with baseline and Week 6 HbA1c assessment. Missing data imputed using last observation carried forward.
Arm/Group Title HOE901-U300 Lantus
Hide Arm/Group Description:
HOE901-U300 SC injection once daily for 12 months on top of mealtime insulin.
Lantus SC injection once daily for 12 months on top of mealtime insulin.
Overall Number of Participants Analyzed 391 394
Least Squares Mean (Standard Error)
Unit of Measure: percentage of hemoglobin
-0.83  (0.060) -0.83  (0.061)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection HOE901-U300, Lantus
Comments Analysis was performed using an analysis of covariance (ANCOVA) model with treatment, strata of screening HbA1c (<8.0 and >=8.0%), and country as fixed effects and using the HbA1c baseline value as a covariate.
Type of Statistical Test Non-Inferiority or Equivalence
Comments

Stepwise closed testing approach was used to assess non-inferiority and superiority sequentially:

  1. Non-inferiority of HOE901-U300 vs Lantus: Upper bound of two-sided 95% confidence interval (CI) of difference between HOE901-U300 and Lantus on mITT population is <0.4%.
  2. Superiority (only if non-inferiority has been demonstrated): Upper bound of two-sided 95% CI for difference in mean change in HbA1c from baseline to endpoint between HOE901-U300 and Lantus on mITT population is <0.
Method of Estimation Estimation Parameter Least Squares (LS) Mean Difference
Estimated Value -0.00
Confidence Interval (2-Sided) 95%
-0.112 to 0.107
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 Nocturnal Hypoglycemia From Start of Week 9 to Month 6 Endpoint
Hide Description Nocturnal hypoglycemia was hypoglycemia that occurred between 00:00 and 05:59 hours (clock time), regardless the participant was awake or woke up because of the event. 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 less than or equal to (<=) 3.9 millimoles per liter (mmol/L) (70 milligram per deciliter [mg/dL]).
Time Frame Week 9 Up to Month 6
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Modified intent-to-treat population.
Arm/Group Title HOE901-U300 Lantus
Hide Arm/Group Description:
HOE901-U300 SC injection once daily for 12 months on top of mealtime insulin.
Lantus SC injection once daily for 12 months on top of mealtime insulin.
Overall Number of Participants Analyzed 404 400
Measure Type: Number
Unit of Measure: percentage of participants
36.1 46.0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection HOE901-U300, Lantus
Comments A one-sided test (at alpha=0.025) for superiority of HOE901-U300 over Lantus was to be performed in case the non-inferiority of HOE901-U300 vs Lantus for the primary endpoint was demonstrated. Analysis was performed using Cochran-Mantel-Haenszel (CMH) method with treatment as a factor and stratified on strata of screening HbA1c (<8.0 and >=8.0%).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0045
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.79
Confidence Interval (2-Sided) 95%
0.67 to 0.93
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change in Average Preinjection Self-Monitored Plasma Glucose (SMPG) From Baseline to Month 6 Endpoint
Hide Description Pre-injection SMPG was measured within 30 minutes prior to the injection of the study drug. Average was assessed by the mean of at least 3 SMPG calculated over the 7 days preceding the assessment visit.
Time Frame Baseline, Month 6
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
mITT population. Missing data imputed using last observation carried forward. Number of participants analyzed = participants with baseline and Month 6 pre-injection SMPG assessment.
Arm/Group Title HOE901-U300 Lantus
Hide Arm/Group Description:
HOE901-U300 SC injection once daily for 12 months on top of mealtime insulin.
Lantus SC injection once daily for 12 months on top of mealtime insulin.
Overall Number of Participants Analyzed 365 360
Least Squares Mean (Standard Error)
Unit of Measure: mmol/L
-0.90  (0.182) -0.84  (0.182)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection HOE901-U300, Lantus
Comments Change in pre-injection SMPG was analyzed using an ANCOVA model with treatment, strata of screening HbA1c (<8.0 and >=8.0%), and country as fixed effects and using the pre-injection SMPG baseline value as a covariate. A test for superiority of HOE901-U300 over Lantus was to be performed one-sided at level alpha = 0.025 if previous analysis for nocturnal hypoglycemia was significant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6909
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.06
Confidence Interval (2-Sided) 95%
-0.383 to 0.254
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.162
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change in Variability of Preinjection SMPG From Baseline to Month 6 Endpoint
Hide Description Pre-injection SMPG was measured within 30 minutes prior to the injection of the study drug. Variability was assessed by the mean of coefficient of variation calculated as 100 multiplied by (standard deviation/mean) over at least 3 SMPG measured during the 7 days preceding the assessment visit.
Time Frame Baseline, Month 6
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
mITT population. Missing data imputed using last observation carried forward. Number of participants analyzed = participants with baseline and Month 6 pre-injection SMPG assessment.
Arm/Group Title HOE901-U300 Lantus
Hide Arm/Group Description:
HOE901-U300 SC injection once daily for 12 months on top of mealtime insulin.
Lantus SC injection once daily for 12 months on top of mealtime insulin.
Overall Number of Participants Analyzed 365 360
Least Squares Mean (Standard Error)
Unit of Measure: percentage of mean
-1.10  (1.222) -1.08  (1.222)
5.Secondary Outcome
Title Percentage of Participants With HbA1c <7% at Month 6 Endpoint
Hide Description [Not Specified]
Time Frame Month 6
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
mITT Population. Number of participants analyzed = participants with baseline and Month 6 HbA1c assessment. Missing data imputed using last observation carried forward.
Arm/Group Title HOE901-U300 Lantus
Hide Arm/Group Description:
HOE901-U300 SC injection once daily for 12 months on top of mealtime insulin.
Lantus SC injection once daily for 12 months on top of mealtime insulin.
Overall Number of Participants Analyzed 391 394
Measure Type: Number
Unit of Measure: percentage of participants
39.6 40.9
6.Secondary Outcome
Title Change in Fasting Plasma Glucose (FPG) From Baseline to Month 6 Endpoint
Hide Description [Not Specified]
Time Frame Baseline, Month 6
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
mITT Population. Number of participants analyzed = participants with baseline and Month 6 FPG assessment. Missing data imputed using last observation carried forward.
Arm/Group Title HOE901-U300 Lantus
Hide Arm/Group Description:
HOE901-U300 SC injection once daily for 12 months on top of mealtime insulin.
Lantus SC injection once daily for 12 months on top of mealtime insulin.
Overall Number of Participants Analyzed 376 385
Least Squares Mean (Standard Error)
Unit of Measure: mmol/L
-1.29  (0.191) -1.38  (0.192)
7.Secondary Outcome
Title Percentage of Participants With FPG <5.6 mmol/L (<100 mg/dL) at Month 6 Endpoint
Hide Description [Not Specified]
Time Frame Month 6
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
mITT Population. Number of participants analyzed = participants with Month 6 FPG assessment. Missing data imputed using last observation carried forward.
Arm/Group Title HOE901-U300 Lantus
Hide Arm/Group Description:
HOE901-U300 SC injection once daily for 12 months on top of mealtime insulin.
Lantus SC injection once daily for 12 months on top of mealtime insulin.
Overall Number of Participants Analyzed 389 392
Measure Type: Number
Unit of Measure: percentage of participants
26.5 23.2
8.Secondary Outcome
Title Change in 8-Point SMPG Profiles Per Time Point From Baseline to Month 6 Endpoint
Hide Description Change in each time-point of 8-point SMPG profile: 03:00 hours (clock time) at night; before and 2 hours after breakfast; before and 2 hours after lunch; before and 2 hours after dinner; and at bedtime.
Time Frame Baseline, Month 6
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
mITT Population. Here, n = participants with Baseline and Month 6 8-point SMPG assessment separately for each analysed time point. Missing data imputed using last observation carried forward.
Arm/Group Title HOE901-U300 Lantus
Hide Arm/Group Description:
HOE901-U300 SC injection once daily for 12 months on top of mealtime insulin.
Lantus SC injection once daily for 12 months on top of mealtime insulin.
Overall Number of Participants Analyzed 404 400
Least Squares Mean (Standard Error)
Unit of Measure: mmol/L
03:00 at Night Plasma Glucose (n=333,323) -0.98  (0.248) -1.16  (0.251)
Pre-Breakfast Plasma Glucose (n=343,333) -1.19  (0.189) -1.49  (0.190)
2 Hours After Breakfast Plasma Glucose (n=335,326) -1.60  (0.241) -1.90  (0.243)
Pre-Lunch Plasma Glucose (n=337,331) -1.05  (0.213) -1.23  (0.216)
2 Hours After Lunch Plasma Glucose (n=336,325) -0.64  (0.280) -0.63  (0.282)
Pre-Dinner Plasma Glucose (n=338,333) -0.47  (0.261) -0.37  (0.260)
2 Hours After Dinner Plasma Glucose (n=331,327) -0.96  (0.298) -1.17  (0.298)
Bedtime Plasma Glucose (n=324, 325) -0.88  (0.324) -0.91  (0.326)
9.Secondary Outcome
Title Change in Daily Basal Insulin Dose From Baseline to Month 6 Endpoint
Hide Description [Not Specified]
Time Frame Baseline, Month 6
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
mITT Population. Number of participants analyzed = participants with Baseline and Month 6 basal insulin dose assessment. Missing data imputed using last observation carried forward.
Arm/Group Title HOE901-U300 Lantus
Hide Arm/Group Description:
HOE901-U300 SC injection once daily for 12 months on top of mealtime insulin.
Lantus SC injection once daily for 12 months on top of mealtime insulin.
Overall Number of Participants Analyzed 403 400
Least Squares Mean (Standard Error)
Unit of Measure: U/kg
0.28  (0.017) 0.19  (0.017)
10.Secondary Outcome
Title Change in Treatment Satisfaction Score Using The Diabetes Treatment Satisfaction Questionnaire (DTSQs) From Baseline to Month 6 Endpoint
Hide Description DTSQ is a validated measure to assess how satisfied participants with diabetes are with their treatment and how they perceive hyper- and hypoglycemia. It consists of 8 questions which are answered on a Likert scale from 0 to 6. DTSQ treatment satisfaction score is the sum of question 1 and 4-8 scores and ranges between 0 and 36, where higher scores indicate more treatment satisfaction.
Time Frame Baseline, Month 6
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
mITT Population. Number of participants analyzed = participants with Baseline and Month 6 DTSQ assessment. Missing data imputed using last observation carried forward.
Arm/Group Title HOE901-U300 Lantus
Hide Arm/Group Description:
HOE901-U300 SC injection once daily for 12 months on top of mealtime insulin.
Lantus SC injection once daily for 12 months on top of mealtime insulin.
Overall Number of Participants Analyzed 366 363
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
2.32  (0.310) 2.24  (0.313)
11.Secondary Outcome
Title Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline up to Month 12
Hide Description Hypoglycemia events were Severe hypoglycemia (an event that required assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions); Documented symptomatic hypoglycemia (typical symptoms of hypoglycemia with plasma glucose level of <=3.9 mmol/L [70 mg/dL]); Asymptomatic hypoglycemia (no typical symptoms of hypoglycemia but plasma glucose level <=3.9 mmol/L); Probable symptomatic hypoglycemia (an event during which symptoms of hypoglycemia were not accompanied by a plasma glucose determination, but was presumably caused by a plasma glucose level <=3.9 mmol/L, symptoms treated with oral carbohydrate without a test of plasma glucose); Relative hypoglycemia (an event during which the person with diabetes reported any of the typical symptoms of hypoglycemia, and interpreted the symptoms as indicative of hypoglycemia, but plasma glucose level >3.9 mmol/L); Severe and/or confirmed a hypoglycemia (plasma glucose <=3.9 mmol/L).
Time Frame Up to Month 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety population: all participants randomized and exposed to at least one dose of study drug, regardless of the amount of treatment administered. In the event of participants having received treatments different from those assigned according to the randomization schedule, safety analyses were conducted according to treatment received.
Arm/Group Title HOE901-U300 Lantus
Hide Arm/Group Description:
HOE901-U300 SC injection once daily for 12 months on top of mealtime insulin.
Lantus SC injection once daily for 12 months on top of mealtime insulin.
Overall Number of Participants Analyzed 404 402
Measure Type: Number
Unit of Measure: percentage of participants
Any Hypoglycemia Event: All Hypoglycemia 87.4 92.0
Severe Hypoglycemia: All Hypoglycemia 6.7 7.5
Documented Symptomatic: All Hypoglycemia 74.8 82.8
Asymptomatic: All Hypoglycemia 70.5 73.4
Probable Symptomatic: All Hypoglycemia 5.7 8.5
Relative: All Hypoglycemia 15.8 21.1
Severe and/or Confirmed: All Hypoglycemia 85.9 91.5
Any Hypoglycemia Event: Nocturnal Hypoglycemia 55.4 66.2
Severe Hypoglycemia: Nocturnal 2.5 3.2
Documented Symptomatic: Nocturnal Hypoglycemia 44.6 57.2
Asymptomatic: Nocturnal Hypoglycemia 29.2 31.1
Probable Symptomatic: Nocturnal Hypoglycemia 2.2 2.7
Relative: Nocturnal Hypoglycemia 5.0 10.0
Severe and/or Confirmed: Nocturnal Hypoglycemia 54.5 64.7
12.Other Pre-specified Outcome
Title Change in HbA1c From Month 6 to Month 9
Hide Description Substudy comparing fixed dosing regimen (every 24 hours) vs. adaptive dosing regimen (every 24 +/- 3 hours) in a subset of participants randomized to HOE901-U300 and treated for 6 months.
Time Frame Month 6 Up to Month 9
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
mITT substudy population. Number of participants analyzed = participants with Month 6 and Month 9 HbA1c assessment. Analysis was planned to be performed for participants enrolled in the substudy and who were receiving HOE901-U300 (Adaptable dosing intervals or Fixed dosing intervals).
Arm/Group Title HOE901-U300: Adaptable Dosing Intervals HOE901-U300: Fixed Dosing Intervals
Hide Arm/Group Description:
HOE901-U300 SC injection once daily for 6 months on top of mealtime insulin. From Month 6 to Month 9 participants received HOE901-U300 once daily at intervals of 24 +/- 3 hours.
HOE901-U300 SC injection once daily for 6 months on top of mealtime insulin. From Month 6 up to Month 9 participants received HOE901-U300 once daily every 24 hours.
Overall Number of Participants Analyzed 55 51
Least Squares Mean (Standard Error)
Unit of Measure: percentage of hemoglobin
0.21  (0.111) 0.15  (0.120)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection HOE901-U300: Adaptable Dosing Intervals, HOE901-U300: Fixed Dosing Intervals
Comments Analysis was performed using Analysis of covariance (ANCOVA) model with treatment regimen and country as fixed effects and baseline HbA1c value as a covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.05
Confidence Interval (2-Sided) 95%
-0.189 to 0.298
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.123
Estimation Comments [Not Specified]
Time Frame All Adverse Events (AE) were collected from signature of the informed consent form up to 12 months regardless of seriousness or relationship to investigational product.
Adverse Event Reporting Description Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the ‘on treatment period’ (time from the first injection of study drug up to 2 days (1 day for FPG, SMPG; 0 day for insulin glargine dose) after the last injection of study drug). Analysis was done on safety population.
 
Arm/Group Title HOE901-U300 Lantus
Hide Arm/Group Description HOE901-U300 SC injection once daily for 12 months on top of mealtime insulin. Lantus SC injection once daily for 12 months on top of mealtime insulin.
All-Cause Mortality
HOE901-U300 Lantus
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
HOE901-U300 Lantus
Affected / at Risk (%) Affected / at Risk (%)
Total   53/404 (13.12%)   62/402 (15.42%) 
Blood and lymphatic system disorders     
Anaemia  1  1/404 (0.25%)  0/402 (0.00%) 
Cardiac disorders     
Acute coronary syndrome  1  1/404 (0.25%)  0/402 (0.00%) 
Angina pectoris  1  0/404 (0.00%)  2/402 (0.50%) 
Angina unstable  1  0/404 (0.00%)  1/402 (0.25%) 
Aortic valve stenosis  1  0/404 (0.00%)  1/402 (0.25%) 
Atrial fibrillation  1  2/404 (0.50%)  3/402 (0.75%) 
Bundle branch block left  1  0/404 (0.00%)  1/402 (0.25%) 
Cardiac failure  1  1/404 (0.25%)  1/402 (0.25%) 
Cardiac failure chronic  1  0/404 (0.00%)  1/402 (0.25%) 
Cardiac failure congestive  1  1/404 (0.25%)  1/402 (0.25%) 
Cardio-respiratory arrest  1  0/404 (0.00%)  1/402 (0.25%) 
Coronary artery disease  1  3/404 (0.74%)  1/402 (0.25%) 
Myocardial infarction  1  1/404 (0.25%)  1/402 (0.25%) 
Myocardial ischaemia  1  1/404 (0.25%)  1/402 (0.25%) 
Palpitations  1  1/404 (0.25%)  0/402 (0.00%) 
Pulseless electrical activity  1  0/404 (0.00%)  1/402 (0.25%) 
Ventricular tachycardia  1  1/404 (0.25%)  0/402 (0.00%) 
Ear and labyrinth disorders     
Vertigo  1  0/404 (0.00%)  1/402 (0.25%) 
Gastrointestinal disorders     
Diverticulitis intestinal haemorrhagic  1  0/404 (0.00%)  1/402 (0.25%) 
Ileus  1  1/404 (0.25%)  1/402 (0.25%) 
General disorders     
Non-cardiac chest pain  1  1/404 (0.25%)  1/402 (0.25%) 
Hepatobiliary disorders     
Bile duct stone  1  1/404 (0.25%)  0/402 (0.00%) 
Cholecystitis acute  1  0/404 (0.00%)  1/402 (0.25%) 
Cholelithiasis  1  0/404 (0.00%)  1/402 (0.25%) 
Immune system disorders     
Anaphylactic reaction  1  0/404 (0.00%)  1/402 (0.25%) 
Infections and infestations     
Bronchitis  1  2/404 (0.50%)  0/402 (0.00%) 
Bronchopneumonia  1  2/404 (0.50%)  0/402 (0.00%) 
Cellulitis  1  3/404 (0.74%)  1/402 (0.25%) 
Diverticulitis  1  0/404 (0.00%)  1/402 (0.25%) 
Endocarditis  1  1/404 (0.25%)  0/402 (0.00%) 
Erysipelas  1  1/404 (0.25%)  1/402 (0.25%) 
Gastroenteritis  1  0/404 (0.00%)  2/402 (0.50%) 
Groin abscess  1  1/404 (0.25%)  0/402 (0.00%) 
Infected skin ulcer  1  1/404 (0.25%)  0/402 (0.00%) 
Lyme disease  1  0/404 (0.00%)  1/402 (0.25%) 
Osteomyelitis  1  3/404 (0.74%)  2/402 (0.50%) 
Pneumonia  1  0/404 (0.00%)  3/402 (0.75%) 
Pneumonia mycoplasmal  1  0/404 (0.00%)  1/402 (0.25%) 
Postoperative wound infection  1  1/404 (0.25%)  0/402 (0.00%) 
Pyelonephritis  1  0/404 (0.00%)  1/402 (0.25%) 
Pyelonephritis acute  1  0/404 (0.00%)  1/402 (0.25%) 
Sepsis  1  1/404 (0.25%)  1/402 (0.25%) 
Septic embolus  1  1/404 (0.25%)  0/402 (0.00%) 
Tracheobronchitis  1  0/404 (0.00%)  1/402 (0.25%) 
Injury, poisoning and procedural complications     
Abdominal wound dehiscence  1  1/404 (0.25%)  0/402 (0.00%) 
Airway complication of anaesthesia  1  0/404 (0.00%)  1/402 (0.25%) 
Ankle fracture  1  1/404 (0.25%)  0/402 (0.00%) 
Concussion  1  0/404 (0.00%)  1/402 (0.25%) 
Fall  1  1/404 (0.25%)  1/402 (0.25%) 
Femoral neck fracture  1  1/404 (0.25%)  0/402 (0.00%) 
Head injury  1  0/404 (0.00%)  1/402 (0.25%) 
Humerus fracture  1  1/404 (0.25%)  0/402 (0.00%) 
Meniscus injury  1  1/404 (0.25%)  0/402 (0.00%) 
Procedural pain  1  2/404 (0.50%)  0/402 (0.00%) 
Subdural haematoma  1  0/404 (0.00%)  1/402 (0.25%) 
Tendon rupture  1  0/404 (0.00%)  1/402 (0.25%) 
Toxicity to various agents  1  0/404 (0.00%)  1/402 (0.25%) 
Metabolism and nutrition disorders     
Diabetes mellitus inadequate control  1  0/404 (0.00%)  1/402 (0.25%) 
Hyperkalaemia  1  0/404 (0.00%)  1/402 (0.25%) 
Hypoglycaemia  1  1/404 (0.25%)  2/402 (0.50%) 
Lactose intolerance  1  0/404 (0.00%)  1/402 (0.25%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  0/404 (0.00%)  1/402 (0.25%) 
Arthritis  1  1/404 (0.25%)  0/402 (0.00%) 
Musculoskeletal chest pain  1  0/404 (0.00%)  1/402 (0.25%) 
Osteoarthritis  1  1/404 (0.25%)  1/402 (0.25%) 
Pain in extremity  1  1/404 (0.25%)  0/402 (0.00%) 
Rhabdomyolysis  1  2/404 (0.50%)  0/402 (0.00%) 
Spondylitis  1  1/404 (0.25%)  1/402 (0.25%) 
Synovial cyst  1  1/404 (0.25%)  1/402 (0.25%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
B-cell small lymphocytic lymphoma  1  0/404 (0.00%)  1/402 (0.25%) 
Basal cell carcinoma  1  0/404 (0.00%)  1/402 (0.25%) 
Bladder cancer  1  1/404 (0.25%)  0/402 (0.00%) 
Breast angiosarcoma  1  1/404 (0.25%)  0/402 (0.00%) 
Breast cancer  1  2/404 (0.50%)  0/402 (0.00%) 
Chronic myeloid leukaemia  1  0/404 (0.00%)  1/402 (0.25%) 
Endometrial cancer  1  1/404 (0.25%)  1/402 (0.25%) 
Hepatic cancer  1  0/404 (0.00%)  1/402 (0.25%) 
Meningioma benign  1  1/404 (0.25%)  0/402 (0.00%) 
Metastatic bronchial carcinoma  1  1/404 (0.25%)  0/402 (0.00%) 
Prostate cancer  1  3/404 (0.74%)  1/402 (0.25%) 
Squamous cell carcinoma of skin  1  0/404 (0.00%)  3/402 (0.75%) 
Uterine leiomyoma  1  1/404 (0.25%)  0/402 (0.00%) 
Nervous system disorders     
Altered state of consciousness  1  0/404 (0.00%)  1/402 (0.25%) 
Cerebral infarction  1  1/404 (0.25%)  0/402 (0.00%) 
Cerebrovascular accident  1  0/404 (0.00%)  1/402 (0.25%) 
Cervicobrachial syndrome  1  0/404 (0.00%)  1/402 (0.25%) 
Guillain-Barre syndrome  1  0/404 (0.00%)  1/402 (0.25%) 
Hypoglycaemic unconsciousness  1  2/404 (0.50%)  0/402 (0.00%) 
Syncope  1  0/404 (0.00%)  1/402 (0.25%) 
Transient ischaemic attack  1  1/404 (0.25%)  1/402 (0.25%) 
Psychiatric disorders     
Depression  1  0/404 (0.00%)  1/402 (0.25%) 
Renal and urinary disorders     
Diabetic nephropathy  1  0/404 (0.00%)  1/402 (0.25%) 
Nephrolithiasis  1  0/404 (0.00%)  1/402 (0.25%) 
Renal failure acute  1  1/404 (0.25%)  1/402 (0.25%) 
Renal failure chronic  1  0/404 (0.00%)  3/402 (0.75%) 
Urinary bladder polyp  1  1/404 (0.25%)  0/402 (0.00%) 
Reproductive system and breast disorders     
Metrorrhagia  1  1/404 (0.25%)  0/402 (0.00%) 
Postmenopausal haemorrhage  1  1/404 (0.25%)  1/402 (0.25%) 
Respiratory, thoracic and mediastinal disorders     
Asthma  1  1/404 (0.25%)  1/402 (0.25%) 
Dyspnoea exertional  1  1/404 (0.25%)  0/402 (0.00%) 
Idiopathic pulmonary fibrosis  1  0/404 (0.00%)  1/402 (0.25%) 
Pulmonary embolism  1  1/404 (0.25%)  0/402 (0.00%) 
Skin and subcutaneous tissue disorders     
Diabetic foot  1  1/404 (0.25%)  1/402 (0.25%) 
Skin ulcer haemorrhage  1  0/404 (0.00%)  1/402 (0.25%) 
Vascular disorders     
Accelerated hypertension  1  0/404 (0.00%)  1/402 (0.25%) 
Aortic stenosis  1  0/404 (0.00%)  1/402 (0.25%) 
Extremity necrosis  1  0/404 (0.00%)  1/402 (0.25%) 
Intermittent claudication  1  0/404 (0.00%)  1/402 (0.25%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDra 16.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
HOE901-U300 Lantus
Affected / at Risk (%) Affected / at Risk (%)
Total   131/404 (32.43%)   132/402 (32.84%) 
Gastrointestinal disorders     
Diarrhoea  1  22/404 (5.45%)  21/402 (5.22%) 
Infections and infestations     
Bronchitis  1  23/404 (5.69%)  30/402 (7.46%) 
Influenza  1  22/404 (5.45%)  18/402 (4.48%) 
Nasopharyngitis  1  34/404 (8.42%)  36/402 (8.96%) 
Sinusitis  1  21/404 (5.20%)  15/402 (3.73%) 
Upper respiratory tract infection  1  38/404 (9.41%)  34/402 (8.46%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  13/404 (3.22%)  21/402 (5.22%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDra 16.1
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
Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01499082     History of Changes
Other Study ID Numbers: EFC11628
2010-023769-23 ( EudraCT Number )
First Submitted: December 16, 2011
First Posted: December 26, 2011
Results First Submitted: March 24, 2015
Results First Posted: April 23, 2015
Last Update Posted: November 2, 2016