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A Study Comparing the Efficacy and Safety of the Morning Injection of Toujeo Versus Lantus in Patients With Type 1 Diabetes Mellitus

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ClinicalTrials.gov Identifier: NCT02688933
Recruitment Status : Completed
First Posted : February 23, 2016
Results First Posted : August 20, 2018
Last Update Posted : August 20, 2018
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 1 Diabetes Mellitus
Interventions Drug: HOE901-U300 (Insulin Glargine 300 U/ml)
Drug: Lantus (Insulin Glargine 100 U/ml)
Drug: Mandated back ground therapy
Enrollment 638
Recruitment Details The study was conducted at 100 sites in United States. A total of 980 participants were screened between 5 May 2016 and 16 February 2017, of whom 342 were screen failures. Screen failures were mainly due to exclusion criteria met.
Pre-assignment Details A total of 638 participants were randomized in HOE901-U300 or Lantus, stratified by baseline HbA1c (<8 %,> =8%), frequency of basal insulin injections at Visit 1 (twice vs once daily), current continuous glucose monitoring (CGM) use at Visit 1(yes/no) and mealtime insulin titration algorithm (simple titration vs carbohydrate counting).
Arm/Group Title HOE901-U300 Lantus
Hide Arm/Group Description HOE901-U300 (Insulin glargine, 300 U/mL) subcutaneous (SC) injection once daily up to Week 16 on top of mealtime insulin analogs. Basal insulin doses were individually titrated to reach fasting self-measured plasma glucose (SMPG) levels within the target range of 80 to 100 mg/dL. Lantus (Insulin glargine, 100 U/mL) SC injection once daily up to Week 16 on top of mealtime insulin analogs. Basal insulin doses were individually titrated to reach fasting SMPG levels within the target range of 80 to 100 mg/dL.
Period Title: Overall Study
Started 320 318
Completed 291 281
Not Completed 29 37
Reason Not Completed
Adverse Event             3             1
Lack of Efficacy             2             2
Poor compliance to protocol             7             4
Hypoglycemia             2             0
Other than Specified             14             25
Lost to Follow-up             1             5
Arm/Group Title HOE901-U300 Lantus Total
Hide Arm/Group Description HOE901-U300 (Insulin glargine, 300 U/mL) SC injection once daily up to Week 16 on top of mealtime insulin analogs. Basal insulin doses were individually titrated to reach fasting SMPG levels within the target range of 80 to 100 mg/dL. Lantus (Insulin glargine, 100 U/mL) SC injection once daily up to Week 16 on top of mealtime insulin analogs. Basal insulin doses were individually titrated to reach fasting SMPG levels within the target range of 80 to 100 mg/dL. Total of all reporting groups
Overall Number of Baseline Participants 320 318 638
Hide Baseline Analysis Population Description
Analysis was performed on randomized population that included any participant who had been allocated to a randomized treatment regardless of whether the treatment kit was used or not.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 320 participants 318 participants 638 participants
45.5  (14.0) 45.5  (13.9) 45.5  (13.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 320 participants 318 participants 638 participants
Female
140
  43.8%
138
  43.4%
278
  43.6%
Male
180
  56.3%
180
  56.6%
360
  56.4%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 320 participants 318 participants 638 participants
Hispanic or Latino
43
  13.4%
42
  13.2%
85
  13.3%
Not Hispanic or Latino
277
  86.6%
276
  86.8%
553
  86.7%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 320 participants 318 participants 638 participants
American Indian or Alaska Native
3
   0.9%
0
   0.0%
3
   0.5%
Asian
5
   1.6%
3
   0.9%
8
   1.3%
Native Hawaiian or Other Pacific Islander
1
   0.3%
1
   0.3%
2
   0.3%
Black or African American
24
   7.5%
28
   8.8%
52
   8.2%
White
281
  87.8%
282
  88.7%
563
  88.2%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
6
   1.9%
4
   1.3%
10
   1.6%
Body mass index  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 320 participants 318 participants 638 participants
27.50  (4.88) 27.65  (4.92) 27.57  (4.90)
1.Primary Outcome
Title Percentage of Time of Mean Glucose Concentration Within the Target Range of 70-180 mg/dL as Obtained From CGM
Hide Description The CGM system combined frequent interstitial glucose measurements (every 5 minutes) with ability to analyze glucose levels in real time. Adjusted least square (LS) means and standard error (SE) were obtained from a generalized linear model with identity link including post baseline CGM assessment during Week 15 (and/or Week 16).
Time Frame During Week 15 and/or 16
Hide Outcome Measure Data
Hide Analysis Population Description
Modified intent-to-treat (mITT) population that included all participants who were randomized and had a post-baseline CGM assessment and enough CGM data values to calculate the primary outcome measure, percent of time in range of 70-180 mg/dL during Week 15 (and/or Week 16).
Arm/Group Title HOE901-U300 Lantus
Hide Arm/Group Description:
HOE901-U300 (Insulin glargine, 300 U/mL) SC injection once daily up to Week 16 on top of mealtime insulin analogs. Basal insulin doses were individually titrated to reach fasting SMPG levels within the target range of 80 to 100 mg/dL.
Lantus (Insulin glargine, 100 U/mL) SC injection once daily up to Week 16 on top of mealtime insulin analogs. Basal insulin doses were individually titrated to reach fasting SMPG levels within the target range of 80 to 100 mg/dL.
Overall Number of Participants Analyzed 277 268
Least Squares Mean (Standard Error)
Unit of Measure: percentage of time
55.40  (1.08) 55.18  (1.10)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection HOE901-U300, Lantus
Comments Analysis was performed using generalized linear model with identity link, had percentage of time glucose concentration within target range 70-180 mg/dL as dependent variable, treatment group as an independent variable, adjusting variables including baseline characteristics: duration of diabetes, baseline BMI, age, and randomization strata (HbA1c at screening [<8.0% vs ≥8.0%], frequency of Lantus injection at screening, current CGM use [yes/no], and mealtime insulin titration algorithm).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8494
Comments Threshold for significance at 0.05 level.
Method Generalized linear model
Comments Generalized linear model with identity link
Method of Estimation Estimation Parameter Least Square mean difference
Estimated Value 0.22
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.15
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Percentage of Participants With Documented Symptomatic Nocturnal Hypoglycemia
Hide Description Documented symptomatic nocturnal hypoglycemia was defined as an event with typical symptoms of hypoglycemia accompanied by SMPG <=70 mg/dL that occurred between 00:00 and 05:59 hours as reported on the hypoglycemia electronic case report form (eCRF).
Time Frame Baseline up to Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population.
Arm/Group Title HOE901-U300 Lantus
Hide Arm/Group Description:
HOE901-U300 (Insulin glargine, 300 U/mL) SC injection once daily up to Week 16 on top of mealtime insulin analogs. Basal insulin doses were individually titrated to reach fasting SMPG levels within the target range of 80 to 100 mg/dL.
Lantus (Insulin glargine, 100 U/mL) SC injection once daily up to Week 16 on top of mealtime insulin analogs. Basal insulin doses were individually titrated to reach fasting SMPG levels within the target range of 80 to 100 mg/dL.
Overall Number of Participants Analyzed 277 268
Measure Type: Number
Unit of Measure: percentage of participants
Documented <=70mg/dL 70.8 68.3
Documented <54 mg/dL 50.9 54.1
3.Secondary Outcome
Title Documented Symptomatic Nocturnal Hypoglycemia Event Rate Per Participant-Year
Hide Description Documented symptomatic nocturnal hypoglycemia was defined as an event with typical symptoms of hypoglycemia accompanied by SMPG <=70 mg/dL that occurred between 00:00 and 05:59 hours as reported on the hypoglycemia eCRF.
Time Frame Baseline up to Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population.
Arm/Group Title HOE901-U300 Lantus
Hide Arm/Group Description:
HOE901-U300 (Insulin glargine, 300 U/mL) SC injection once daily up to Week 16 on top of mealtime insulin analogs. Basal insulin doses were individually titrated to reach fasting SMPG levels within the target range of 80 to 100 mg/dL.
Lantus (Insulin glargine, 100 U/mL) SC injection once daily up to Week 16 on top of mealtime insulin analogs. Basal insulin doses were individually titrated to reach fasting SMPG levels within the target range of 80 to 100 mg/dL.
Overall Number of Participants Analyzed 277 268
Measure Type: Number
Unit of Measure: events per participant-year
Documented <=70 mg/dL 11.38 11.39
Documented <54 mg/dL 4.99 5.61
4.Secondary Outcome
Title Mean Change From Baseline in Glucose Level During Last 4 Hours of CGM Data Collection Prior to the Next Day Basal Insulin Injection During Week 15 and/or Week 16
Hide Description Adjusted LS means and SE were obtained from mixed model including post baseline CGM assessment during the last 4 hours prior to the next day’s basal insulin injection during Week 15 (and/or Week 16).
Time Frame Baseline, during Week 15 and/or Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population.
Arm/Group Title HOE901-U300 Lantus
Hide Arm/Group Description:
HOE901-U300 (Insulin glargine, 300 U/mL) SC injection once daily up to Week 16 on top of mealtime insulin analogs. Basal insulin doses were individually titrated to reach fasting SMPG levels within the target range of 80 to 100 mg/dL.
Lantus (Insulin glargine, 100 U/mL) SC injection once daily up to Week 16 on top of mealtime insulin analogs. Basal insulin doses were individually titrated to reach fasting SMPG levels within the target range of 80 to 100 mg/dL.
Overall Number of Participants Analyzed 277 268
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
-1.99  (3.68) 5.67  (3.72)
5.Secondary Outcome
Title Percentage of Time Glucose Concentrations Within the Target Range of 70 to 140 mg/dL During Last 4 Hours of CGM Data Collection Prior to Next Day Basal Insulin Injection
Hide Description Adjusted LS means and SE were obtained from mixed model including post baseline CGM assessment during the last 4 hours prior to the next day’s basal insulin injection during Week 15 (and/or Week 16).
Time Frame During Week 15 and/or Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population
Arm/Group Title HOE901-U300 Lantus
Hide Arm/Group Description:
HOE901-U300 (Insulin glargine, 300 U/mL) SC injection once daily up to Week 16 on top of mealtime insulin analogs. Basal insulin doses were individually titrated to reach fasting SMPG levels within the target range of 80 to 100 mg/dL.
Lantus (Insulin glargine, 100 U/mL) SC injection once daily up to Week 16 on top of mealtime insulin analogs. Basal insulin doses were individually titrated to reach fasting SMPG levels within the target range of 80 to 100 mg/dL.
Overall Number of Participants Analyzed 277 268
Least Squares Mean (Standard Error)
Unit of Measure: percentage of time
36.49  (1.62) 35.07  (1.65)
6.Secondary Outcome
Title Coefficient of Variation (CV%) in Mean CGM Glucose
Hide Description CV% was a measure of spread of variability relative to mean of population. For CGM glucose values over 24 hours, CV% was measure of glycemic variability across 24-hour day and calculated for each period (total, within day and between days) as ratio of standard deviation of glucose values to mean of glucose values.
Time Frame During Week 15 and/or Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population.
Arm/Group Title HOE901-U300 Lantus
Hide Arm/Group Description:
HOE901-U300 (Insulin glargine, 300 U/mL) SC injection once daily up to Week 16 on top of mealtime insulin analogs. Basal insulin doses were individually titrated to reach fasting SMPG levels within the target range of 80 to 100 mg/dL.
Lantus (Insulin glargine, 100 U/mL) SC injection once daily up to Week 16 on top of mealtime insulin analogs. Basal insulin doses were individually titrated to reach fasting SMPG levels within the target range of 80 to 100 mg/dL.
Overall Number of Participants Analyzed 277 268
Least Squares Mean (Standard Error)
Unit of Measure: percent of mean glucose level
Total CV% 41.27  (0.63) 40.72  (0.64)
Within-day CV% 36.99  (0.56) 36.23  (0.56)
Between-days CV% 17.44  (0.59) 17.53  (0.60)
7.Other Pre-specified Outcome
Title Change From Baseline in Daily Insulin Dose at Week 16
Hide Description Change from Baseline at Week 16 for daily basal insulin dose and daily bolus insulin dose was reported.
Time Frame Baseline, Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population: all participants who took at least 1 dose of randomized treatment & analyzed as-treated (as per treatment actually received) also to whom it was unclear whether they took study medication & who received more than 1 study treatment during trial. Here, “number analyzed”: number of participants evaluable for each specified category.
Arm/Group Title HOE901-U300 Lantus
Hide Arm/Group Description:
HOE901-U300 (Insulin glargine, 300 U/mL) SC injection once daily up to Week 16 on top of mealtime insulin analogs. Basal insulin doses were individually titrated to reach fasting SMPG levels within the target range of 80 to 100 mg/dL.
Lantus (Insulin glargine, 100 U/mL) SC injection once daily up to Week 16 on top of mealtime insulin analogs. Basal insulin doses were individually titrated to reach fasting SMPG levels within the target range of 80 to 100 mg/dL.
Overall Number of Participants Analyzed 320 318
Mean (Standard Deviation)
Unit of Measure: International Units
Daily basal Insulin Dose Number Analyzed 295 participants 283 participants
8.8  (11.8) 7.0  (10.1)
Daily bolus Insulin Dose Number Analyzed 218 participants 209 participants
-1.8  (11.8) -3.0  (11.3)
8.Post-Hoc Outcome
Title Change From Baseline in Time (Min) of Mean Glucose Concentration Within the Target Range of 70 to 180 mg/dL, by End of Study hbA1c Levels During Week 15 and/or Week 16
Hide Description Adjusted LS means and SE were obtained from mixed model including post baseline CGM assessments. Data was reported for participants with an end of study HbA1c <7.5 or HbA1c >=7.5% over a 24 hour period.
Time Frame Baseline, during Week 15 and/or Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population. Here, “number analyzed” signifies the number of participants evaluable for each specified category.
Arm/Group Title HOE901-U300 Lantus
Hide Arm/Group Description:
HOE901-U300 (Insulin glargine, 300 U/mL) SC injection once daily up to Week 16 on top of mealtime insulin analogs. Basal insulin doses were individually titrated to reach fasting SMPG levels within the target range of 80 to 100 mg/dL.
Lantus (Insulin glargine, 100 U/mL) SC injection once daily up to Week 16 on top of mealtime insulin analogs. Basal insulin doses were individually titrated to reach fasting SMPG levels within the target range of 80 to 100 mg/dL.
Overall Number of Participants Analyzed 277 268
Least Squares Mean (Standard Error)
Unit of Measure: minutes
End of study HbA1c <7.5% Number Analyzed 136 participants 146 participants
105.84  (25.64) 56.07  (25.40)
End of study HbA1c >=7.5% Number Analyzed 118 participants 107 participants
11.64  (27.26) 31.95  (27.57)
Time Frame All Adverse Events (AE) were collected from signature of informed consent form up to study completion (Week 16) regardless of seriousness or relationship to study drug.
Adverse Event Reporting Description Reported AEs are treatment-emergent AEs developed/worsened during on treatment period (time from first dose of investigational medicinal product [IMP] up to one day after last dose of IMP).
 
Arm/Group Title HOE901-U300 Lantus
Hide Arm/Group Description HOE901-U300 (Insulin glargine, 300 U/mL) SC injection once daily up to Week 16 on top of mealtime insulin analogs. Basal insulin doses were individually titrated to reach fasting SMPG levels within the target range of 80 to 100 mg/dL. Lantus (Insulin glargine, 100 U/mL) SC injection once daily up to Week 16 on top of mealtime insulin analogs. Basal insulin doses were individually titrated to reach fasting SMPG levels within the target range of 80 to 100 mg/dL.
All-Cause Mortality
HOE901-U300 Lantus
Affected / at Risk (%) Affected / at Risk (%)
Total   0/320 (0.00%)   0/318 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
HOE901-U300 Lantus
Affected / at Risk (%) Affected / at Risk (%)
Total   17/320 (5.31%)   14/318 (4.40%) 
Blood and lymphatic system disorders     
Iron deficiency anaemia  1  1/320 (0.31%)  0/318 (0.00%) 
Cardiac disorders     
Cardiac arrest  1  0/320 (0.00%)  1/318 (0.31%) 
Coronary artery disease  1  0/320 (0.00%)  1/318 (0.31%) 
Eye disorders     
Angle closure glaucoma  1  1/320 (0.31%)  0/318 (0.00%) 
General disorders     
Non-cardiac chest pain  1  1/320 (0.31%)  0/318 (0.00%) 
Infections and infestations     
Diabetic foot infection  1  0/320 (0.00%)  1/318 (0.31%) 
Gangrene  1  0/320 (0.00%)  1/318 (0.31%) 
Influenza  1  1/320 (0.31%)  0/318 (0.00%) 
Injury, poisoning and procedural complications     
Accidental overdose  1  0/320 (0.00%)  3/318 (0.94%) 
Fall  1  0/320 (0.00%)  1/318 (0.31%) 
Intentional overdose  1  1/320 (0.31%)  0/318 (0.00%) 
Lower limb fracture  1  1/320 (0.31%)  0/318 (0.00%) 
Rib fracture  1  0/320 (0.00%)  1/318 (0.31%) 
Road traffic accident  1  2/320 (0.63%)  1/318 (0.31%) 
Metabolism and nutrition disorders     
Diabetic ketoacidosis  1  1/320 (0.31%)  0/318 (0.00%) 
Hyperglycaemia  1  2/320 (0.63%)  0/318 (0.00%) 
Hypoglycaemia  1  2/320 (0.63%)  3/318 (0.94%) 
Nervous system disorders     
Hypoglycaemic coma  1  0/320 (0.00%)  1/318 (0.31%) 
Hypoglycaemic encephalopathy  1  0/320 (0.00%)  1/318 (0.31%) 
Hypoglycaemic seizure  1  2/320 (0.63%)  3/318 (0.94%) 
Hypoglycaemic unconsciousness  1  6/320 (1.88%)  3/318 (0.94%) 
Psychiatric disorders     
Depression  1  1/320 (0.31%)  0/318 (0.00%) 
Renal and urinary disorders     
Acute kidney injury  1  2/320 (0.63%)  0/318 (0.00%) 
Renal injury  1  1/320 (0.31%)  0/318 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Pneumonia aspiration  1  0/320 (0.00%)  1/318 (0.31%) 
Pneumothorax  1  0/320 (0.00%)  1/318 (0.31%) 
Skin and subcutaneous tissue disorders     
Skin ulcer  1  0/320 (0.00%)  1/318 (0.31%) 
Subcutaneous emphysema  1  0/320 (0.00%)  1/318 (0.31%) 
1
Term from vocabulary, MedDra 20.0
Indicates events were collected by systematic assessment
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   54/320 (16.88%)   54/318 (16.98%) 
Infections and infestations     
Nasopharyngitis  1  27/320 (8.44%)  27/318 (8.49%) 
Upper respiratory tract infection  1  28/320 (8.75%)  28/318 (8.81%) 
1
Term from vocabulary, MedDra 20.0
Indicates events were collected by systematic assessment
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
Phone: 800-633-1610 ext 1#
Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT02688933     History of Changes
Other Study ID Numbers: LPS14587
U1111-1176-0936 ( Other Identifier: UTN )
First Submitted: February 18, 2016
First Posted: February 23, 2016
Results First Submitted: June 19, 2018
Results First Posted: August 20, 2018
Last Update Posted: August 20, 2018