Type 2 Diabetes Mellitus
Conditions
Brief summary
Primary Objective: * To compare the efficacy of insulin glargine new formulation and Lantus in terms of change in HbA1c from baseline to endpoint (scheduled month 6) in adult participants with type 2 diabetes mellitus Secondary Objectives: * To compare the efficacy of insulin glargine new formulation and Lantus in terms of occurrence of nocturnal Hypoglycemia
Detailed description
The maximum study duration was up to approximately 58 weeks per participant, consisting of: * up to 2 week screening period * 6-month comparative efficacy and safety treatment period * 6-month comparative safety extension period * 4-week safety follow-up period in a subset of participants * a 3-month administration substudy period starting after completion of the 6-month study period for participants willing to in a subset of participants randomized to HOE901-U300
Interventions
HOE901-U300 (new insulin glargine 300 units per milliliter \[U/mL\]) subcutaneous (SC) injection once daily (evening) for 12 months on top of mealtime insulin analogue. Dose titration seeking fasting plasma glucose 4.4-5.6 millimole per liter (mmol/L) (80 - 100 milligram per deciliter \[mg/dL\]). After 6 months participants were proposed to participate to the administration substudy and to receive either HOE901-U300 once daily at intervals of 24 +/- 3 hours (adaptable dosing intervals) or to continue once daily injections of HOE901-U300 every 24 hours (fixed dosing intervals) up to Month 9.
Lantus (HOE901-U100, insulin glargine 100 U/mL) SC injection once daily (evening) for 12 months on top of mealtime insulin analogue. Dose titration seeking fasting plasma glucose 4.4-5.6 mmol/L (80 - 100 mg/dL).
Sponsors
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
: * Participants with type 2 diabetes mellitus * Substudy inclusion criteria: * Completion of the 6-month study period in main study (Visit 10) * Randomized and treated with insulin glargine new formulation during the 6-month treatment period (Baseline - month 6)
Exclusion criteria
* Age less than (\<) 18 years * HbA1c \<7.0% or greater than (\>) 10% at screening * Diabetes other than type 2 diabetes mellitus * Less than 1 year on basal plus mealtime insulin and self-monitoring of blood glucose * Any contraindication to use of insulin glargine as defined in the national product label * Participants using human regular insulin as mealtime insulin in the last 3 months before screening visit * Use of an insulin pump in the last 6 months before screening visit * Initiation of new glucose-lowering agents and/or weight loss drugs in the last 3 months before screening visit * History or presence of significant diabetic retinopathy or macular edema likely to require laser or injectable drugs or surgical treatment during the study period * Pregnant or breast-feeding women or women who intend to become pregnant during the study period * Substudy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in HbA1c From Baseline to Month 6 Endpoint | Baseline, Month 6 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With At Least One Severe and/or Confirmed Nocturnal Hypoglycemia From Start of Week 9 to Month 6 Endpoint | Week 9 Up to Month 6 | 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 \[mg/dL\]). |
| Change in Average Preinjection Self-Monitored Plasma Glucose (SMPG) From Baseline to Month 6 Endpoint | Baseline, Month 6 | 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. |
| Change in Variability of Preinjection SMPG From Baseline to Month 6 Endpoint | Baseline, Month 6 | 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. |
| Percentage of Participants With HbA1c <7% at Month 6 Endpoint | Month 6 | — |
| Change in Fasting Plasma Glucose (FPG) From Baseline to Month 6 Endpoint | Baseline, Month 6 | — |
| Change in 8-Point SMPG Profiles Per Time Point From Baseline to Month 6 Endpoint | Baseline, Month 6 | 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. |
| Change in Daily Basal Insulin Dose From Baseline to Month 6 Endpoint | Baseline, Month 6 | — |
| Change in Treatment Satisfaction Score Using The Diabetes Treatment Satisfaction Questionnaire (DTSQs) From Baseline to Month 6 Endpoint | Baseline, Month 6 | 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. |
| Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline up to Month 12 | Up to Month 12 | 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). |
| Percentage of Participants With FPG <5.6 mmol/L (<100 mg/dL) at Month 6 Endpoint | Month 6 | — |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in HbA1c From Month 6 to Month 9 | Month 6 Up to Month 9 | 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. |
Countries
Canada, Czechia, Estonia, Finland, France, Germany, Hungary, Latvia, Mexico, Netherlands, Romania, South Africa, United States
Participant flow
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).
Participants by arm
| Arm | Count |
|---|---|
| HOE901-U300 HOE901-U300 SC injection once daily for 12 months on top of mealtime insulin. | 404 |
| Lantus Lantus SC injection once daily for 12 months on top of mealtime insulin. | 403 |
| Total | 807 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 12 | 16 |
| Overall Study | Diverse Reasons | 18 | 14 |
| Overall Study | Hypoglycemia | 2 | 3 |
| Overall Study | Lack of Efficacy | 1 | 1 |
| Overall Study | Lost to Follow-up | 1 | 3 |
| Overall Study | Protocol Violation | 6 | 8 |
| Overall Study | Randomized but not Treated | 0 | 1 |
| Overall Study | Site Closure for Noncompliance | 5 | 2 |
Baseline characteristics
| Characteristic | HOE901-U300 | Lantus | Total |
|---|---|---|---|
| Age, Continuous | 60.1 years STANDARD_DEVIATION 8.5 | 59.8 years STANDARD_DEVIATION 8.7 | 60.0 years STANDARD_DEVIATION 8.6 |
| Basal Insulin Daily Dose | 0.668 units per kilogram (U/kg) STANDARD_DEVIATION 0.263 | 0.667 units per kilogram (U/kg) STANDARD_DEVIATION 0.241 | 0.668 units per kilogram (U/kg) STANDARD_DEVIATION 0.252 |
| Body Mass Index (BMI) | 36.6 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 6.8 | 36.6 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 6.1 | 36.6 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 6.4 |
| Duration of Diabetes | 15.6 years STANDARD_DEVIATION 7.2 | 16.1 years STANDARD_DEVIATION 7.8 | 15.8 years STANDARD_DEVIATION 7.5 |
| Glycated Hemoglobin A1c (HbA1c) Greater Than or Equal to (>=) 8% | 260 participants | 259 participants | 519 participants |
| Glycated Hemoglobin A1c (HbA1c) Less Than (<) 8% | 144 participants | 144 participants | 288 participants |
| Sex: Female, Male Female | 187 Participants | 193 Participants | 380 Participants |
| Sex: Female, Male Male | 217 Participants | 210 Participants | 427 Participants |
| Total Insulin Daily Dose | 1.194 U/kg STANDARD_DEVIATION 0.483 | 1.200 U/kg STANDARD_DEVIATION 0.448 | 1.197 U/kg STANDARD_DEVIATION 0.466 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 131 / 404 | 132 / 402 |
| serious Total, serious adverse events | 53 / 404 | 62 / 402 |
Outcome results
Primary
Change in HbA1c From Baseline to Month 6 Endpoint
Time frame: Baseline, Month 6
Population: 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 | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| HOE901-U300 | Change in HbA1c From Baseline to Month 6 Endpoint | -0.83 percentage of hemoglobin | Standard Error 0.06 |
| Lantus | Change in HbA1c From Baseline to Month 6 Endpoint | -0.83 percentage of hemoglobin | Standard Error 0.061 |
Comparison: 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.95% CI: [-0.112, 0.107]
Secondary
Change in 8-Point SMPG Profiles Per Time Point From Baseline to Month 6 Endpoint
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
Population: 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 | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| HOE901-U300 | Change in 8-Point SMPG Profiles Per Time Point From Baseline to Month 6 Endpoint | 03:00 at Night Plasma Glucose (n=333,323) | -0.98 mmol/L | Standard Error 0.248 |
| HOE901-U300 | Change in 8-Point SMPG Profiles Per Time Point From Baseline to Month 6 Endpoint | Pre-Breakfast Plasma Glucose (n=343,333) | -1.19 mmol/L | Standard Error 0.189 |
| HOE901-U300 | Change in 8-Point SMPG Profiles Per Time Point From Baseline to Month 6 Endpoint | 2 Hours After Breakfast Plasma Glucose (n=335,326) | -1.60 mmol/L | Standard Error 0.241 |
| HOE901-U300 | Change in 8-Point SMPG Profiles Per Time Point From Baseline to Month 6 Endpoint | Pre-Lunch Plasma Glucose (n=337,331) | -1.05 mmol/L | Standard Error 0.213 |
| HOE901-U300 | Change in 8-Point SMPG Profiles Per Time Point From Baseline to Month 6 Endpoint | 2 Hours After Lunch Plasma Glucose (n=336,325) | -0.64 mmol/L | Standard Error 0.28 |
| HOE901-U300 | Change in 8-Point SMPG Profiles Per Time Point From Baseline to Month 6 Endpoint | Pre-Dinner Plasma Glucose (n=338,333) | -0.47 mmol/L | Standard Error 0.261 |
| HOE901-U300 | Change in 8-Point SMPG Profiles Per Time Point From Baseline to Month 6 Endpoint | 2 Hours After Dinner Plasma Glucose (n=331,327) | -0.96 mmol/L | Standard Error 0.298 |
| HOE901-U300 | Change in 8-Point SMPG Profiles Per Time Point From Baseline to Month 6 Endpoint | Bedtime Plasma Glucose (n=324, 325) | -0.88 mmol/L | Standard Error 0.324 |
| Lantus | Change in 8-Point SMPG Profiles Per Time Point From Baseline to Month 6 Endpoint | Bedtime Plasma Glucose (n=324, 325) | -0.91 mmol/L | Standard Error 0.326 |
| Lantus | Change in 8-Point SMPG Profiles Per Time Point From Baseline to Month 6 Endpoint | 03:00 at Night Plasma Glucose (n=333,323) | -1.16 mmol/L | Standard Error 0.251 |
| Lantus | Change in 8-Point SMPG Profiles Per Time Point From Baseline to Month 6 Endpoint | 2 Hours After Lunch Plasma Glucose (n=336,325) | -0.63 mmol/L | Standard Error 0.282 |
| Lantus | Change in 8-Point SMPG Profiles Per Time Point From Baseline to Month 6 Endpoint | Pre-Breakfast Plasma Glucose (n=343,333) | -1.49 mmol/L | Standard Error 0.19 |
| Lantus | Change in 8-Point SMPG Profiles Per Time Point From Baseline to Month 6 Endpoint | 2 Hours After Dinner Plasma Glucose (n=331,327) | -1.17 mmol/L | Standard Error 0.298 |
| Lantus | Change in 8-Point SMPG Profiles Per Time Point From Baseline to Month 6 Endpoint | 2 Hours After Breakfast Plasma Glucose (n=335,326) | -1.90 mmol/L | Standard Error 0.243 |
| Lantus | Change in 8-Point SMPG Profiles Per Time Point From Baseline to Month 6 Endpoint | Pre-Dinner Plasma Glucose (n=338,333) | -0.37 mmol/L | Standard Error 0.26 |
| Lantus | Change in 8-Point SMPG Profiles Per Time Point From Baseline to Month 6 Endpoint | Pre-Lunch Plasma Glucose (n=337,331) | -1.23 mmol/L | Standard Error 0.216 |
Secondary
Change in Average Preinjection Self-Monitored Plasma Glucose (SMPG) From Baseline to Month 6 Endpoint
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
Population: 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 | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| HOE901-U300 | Change in Average Preinjection Self-Monitored Plasma Glucose (SMPG) From Baseline to Month 6 Endpoint | -0.90 mmol/L | Standard Error 0.182 |
| Lantus | Change in Average Preinjection Self-Monitored Plasma Glucose (SMPG) From Baseline to Month 6 Endpoint | -0.84 mmol/L | Standard Error 0.182 |
Comparison: 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.p-value: 0.690995% CI: [-0.383, 0.254]ANCOVA
Secondary
Change in Daily Basal Insulin Dose From Baseline to Month 6 Endpoint
Time frame: Baseline, Month 6
Population: 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 | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| HOE901-U300 | Change in Daily Basal Insulin Dose From Baseline to Month 6 Endpoint | 0.28 U/kg | Standard Error 0.017 |
| Lantus | Change in Daily Basal Insulin Dose From Baseline to Month 6 Endpoint | 0.19 U/kg | Standard Error 0.017 |
Secondary
Change in Fasting Plasma Glucose (FPG) From Baseline to Month 6 Endpoint
Time frame: Baseline, Month 6
Population: mITT Population. Number of participants analyzed = participants with baseline and Month 6 FPG assessment. Missing data imputed using last observation carried forward.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| HOE901-U300 | Change in Fasting Plasma Glucose (FPG) From Baseline to Month 6 Endpoint | -1.29 mmol/L | Standard Error 0.191 |
| Lantus | Change in Fasting Plasma Glucose (FPG) From Baseline to Month 6 Endpoint | -1.38 mmol/L | Standard Error 0.192 |
Secondary
Change in Treatment Satisfaction Score Using The Diabetes Treatment Satisfaction Questionnaire (DTSQs) From Baseline to Month 6 Endpoint
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
Population: mITT Population. Number of participants analyzed = participants with Baseline and Month 6 DTSQ assessment. Missing data imputed using last observation carried forward.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| HOE901-U300 | Change in Treatment Satisfaction Score Using The Diabetes Treatment Satisfaction Questionnaire (DTSQs) From Baseline to Month 6 Endpoint | 2.32 units on a scale | Standard Error 0.31 |
| Lantus | Change in Treatment Satisfaction Score Using The Diabetes Treatment Satisfaction Questionnaire (DTSQs) From Baseline to Month 6 Endpoint | 2.24 units on a scale | Standard Error 0.313 |
Secondary
Change in Variability of Preinjection SMPG From Baseline to Month 6 Endpoint
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
Population: 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 | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| HOE901-U300 | Change in Variability of Preinjection SMPG From Baseline to Month 6 Endpoint | -1.10 percentage of mean | Standard Error 1.222 |
| Lantus | Change in Variability of Preinjection SMPG From Baseline to Month 6 Endpoint | -1.08 percentage of mean | Standard Error 1.222 |
Secondary
Percentage of Participants With At Least One Severe and/or Confirmed Nocturnal Hypoglycemia From Start of Week 9 to Month 6 Endpoint
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
Population: Modified intent-to-treat population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HOE901-U300 | Percentage of Participants With At Least One Severe and/or Confirmed Nocturnal Hypoglycemia From Start of Week 9 to Month 6 Endpoint | 36.1 percentage of participants |
| Lantus | Percentage of Participants With At Least One Severe and/or Confirmed Nocturnal Hypoglycemia From Start of Week 9 to Month 6 Endpoint | 46.0 percentage of participants |
Comparison: 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%).p-value: 0.004595% CI: [0.67, 0.93]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With FPG <5.6 mmol/L (<100 mg/dL) at Month 6 Endpoint
Time frame: Month 6
Population: mITT Population. Number of participants analyzed = participants with Month 6 FPG assessment. Missing data imputed using last observation carried forward.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HOE901-U300 | Percentage of Participants With FPG <5.6 mmol/L (<100 mg/dL) at Month 6 Endpoint | 26.5 percentage of participants |
| Lantus | Percentage of Participants With FPG <5.6 mmol/L (<100 mg/dL) at Month 6 Endpoint | 23.2 percentage of participants |
Secondary
Percentage of Participants With HbA1c <7% at Month 6 Endpoint
Time frame: Month 6
Population: mITT Population. Number of participants analyzed = participants with baseline and Month 6 HbA1c assessment. Missing data imputed using last observation carried forward.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HOE901-U300 | Percentage of Participants With HbA1c <7% at Month 6 Endpoint | 39.6 percentage of participants |
| Lantus | Percentage of Participants With HbA1c <7% at Month 6 Endpoint | 40.9 percentage of participants |
Secondary
Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline up to Month 12
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HOE901-U300 | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline up to Month 12 | Any Hypoglycemia Event: All Hypoglycemia | 87.4 percentage of participants |
| HOE901-U300 | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline up to Month 12 | Severe Hypoglycemia: All Hypoglycemia | 6.7 percentage of participants |
| HOE901-U300 | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline up to Month 12 | Documented Symptomatic: All Hypoglycemia | 74.8 percentage of participants |
| HOE901-U300 | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline up to Month 12 | Asymptomatic: All Hypoglycemia | 70.5 percentage of participants |
| HOE901-U300 | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline up to Month 12 | Probable Symptomatic: All Hypoglycemia | 5.7 percentage of participants |
| HOE901-U300 | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline up to Month 12 | Relative: All Hypoglycemia | 15.8 percentage of participants |
| HOE901-U300 | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline up to Month 12 | Severe and/or Confirmed: All Hypoglycemia | 85.9 percentage of participants |
| HOE901-U300 | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline up to Month 12 | Any Hypoglycemia Event: Nocturnal Hypoglycemia | 55.4 percentage of participants |
| HOE901-U300 | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline up to Month 12 | Severe Hypoglycemia: Nocturnal | 2.5 percentage of participants |
| HOE901-U300 | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline up to Month 12 | Documented Symptomatic: Nocturnal Hypoglycemia | 44.6 percentage of participants |
| HOE901-U300 | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline up to Month 12 | Asymptomatic: Nocturnal Hypoglycemia | 29.2 percentage of participants |
| HOE901-U300 | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline up to Month 12 | Probable Symptomatic: Nocturnal Hypoglycemia | 2.2 percentage of participants |
| HOE901-U300 | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline up to Month 12 | Relative: Nocturnal Hypoglycemia | 5.0 percentage of participants |
| HOE901-U300 | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline up to Month 12 | Severe and/or Confirmed: Nocturnal Hypoglycemia | 54.5 percentage of participants |
| Lantus | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline up to Month 12 | Asymptomatic: Nocturnal Hypoglycemia | 31.1 percentage of participants |
| Lantus | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline up to Month 12 | Any Hypoglycemia Event: All Hypoglycemia | 92.0 percentage of participants |
| Lantus | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline up to Month 12 | Any Hypoglycemia Event: Nocturnal Hypoglycemia | 66.2 percentage of participants |
| Lantus | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline up to Month 12 | Severe Hypoglycemia: All Hypoglycemia | 7.5 percentage of participants |
| Lantus | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline up to Month 12 | Relative: Nocturnal Hypoglycemia | 10.0 percentage of participants |
| Lantus | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline up to Month 12 | Documented Symptomatic: All Hypoglycemia | 82.8 percentage of participants |
| Lantus | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline up to Month 12 | Severe Hypoglycemia: Nocturnal | 3.2 percentage of participants |
| Lantus | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline up to Month 12 | Asymptomatic: All Hypoglycemia | 73.4 percentage of participants |
| Lantus | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline up to Month 12 | Probable Symptomatic: Nocturnal Hypoglycemia | 2.7 percentage of participants |
| Lantus | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline up to Month 12 | Probable Symptomatic: All Hypoglycemia | 8.5 percentage of participants |
| Lantus | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline up to Month 12 | Documented Symptomatic: Nocturnal Hypoglycemia | 57.2 percentage of participants |
| Lantus | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline up to Month 12 | Relative: All Hypoglycemia | 21.1 percentage of participants |
| Lantus | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline up to Month 12 | Severe and/or Confirmed: Nocturnal Hypoglycemia | 64.7 percentage of participants |
| Lantus | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline up to Month 12 | Severe and/or Confirmed: All Hypoglycemia | 91.5 percentage of participants |
Other Pre-specified
Change in HbA1c From Month 6 to Month 9
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
Population: 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 | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| HOE901-U300 | Change in HbA1c From Month 6 to Month 9 | 0.21 percentage of hemoglobin | Standard Error 0.111 |
| Lantus | Change in HbA1c From Month 6 to Month 9 | 0.15 percentage of hemoglobin | Standard Error 0.12 |
Comparison: Analysis was performed using Analysis of covariance (ANCOVA) model with treatment regimen and country as fixed effects and baseline HbA1c value as a covariate.95% CI: [-0.189, 0.298]