Type 2 Diabetes Mellitus
Conditions
Brief summary
Primary Objective: To compare the efficacy of a new formulation of insulin glargine and Lantus in terms of change of HbA1c from baseline to endpoint (scheduled at Month 6, Week 26) in participants with type 2 diabetes mellitus Secondary Objectives: To compare a new formulation of insulin glargine and Lantus in terms of: \- occurrence of nocturnal hypoglycemia
Detailed description
The maximum study duration was up to approximately 54 weeks per participant, consisting of: * Up to 2 week screening period; it can be exceptionally extended of up to one additional week * 6-month comparative efficacy and safety treatment period * 6-month comparative safety extension period * 2-day post-treatment safety follow-up period
Interventions
HOE901-U300 (new insulin glargine 300 units per milliliter \[U/mL\]) subcutaneous (SC) injection once daily (evening) for 12 months on top of non-insulin antihyperglycemic drug(s). Dose titration seeking fasting plasma glucose 4.4-5.6 millimole per liter (mmol/L) (80 - 100 milligram per deciliter \[mg/dL\]).
Lantus (HOE901-U100, insulin glargine 100 U/mL) SC injection once daily (evening) for 12 months on top of non-insulin antihyperglycemic drug(s). 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
: * Adult participants with type 2 diabetes mellitus inadequately controlled with non-insulin antihyperglycemic drug(s); * Signed written informed consent.
Exclusion criteria
* HbA1c less than (\<) 7.0% (\< 53 millimole per mole \[mmol/mol\]) or greater than (\>) 11% (\> 97 mmol/mol) * History of type 2 diabetes mellitus for less than 1 year before screening * Less than 6 months before screening with non-insulin antihyperglycemic treatment * Change in dose of non-insulin antihyperglycemic treatment in the last 3 month before screening * Initiation of new glucose-lowering medications and/or weight loss drug in the last 3 months before screening visit and/or initiation of Glucagon-like peptide-1 (GLP-1) receptor agonist in the last 6 months before screening visit * Participants receiving only non-insulin antihyperglycemic drugs not approved for combination with insulin according to local labeling/local treatment guidelines and/or sulfonylurea or glinide (Note: non-insulin antihyperglycemic drugs not approved for combination with insulin, sulfonylurea and glinide are to be discontinued at baseline) * Current or previous insulin use except for a maximum of 8 consecutive days (for example, acute illness, surgery) during the last year prior to screening * Unstable proliferative diabetic retinopathy or any other rapidly progressive diabetic retinopathy or macular edema likely to require treatment (for example, laser, surgical treatment or injectable drugs) during the study period The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in HbA1c From Baseline to Month 6 Endpoint | Baseline, Month 6 | Only HbA1c measurements performed before initiation of rescue therapy were considered in the analysis. Month 6 Endpoint is either the observed value at Month 6 visit or value retrieved according to time windows. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With FPG <5.6 mmol/L (100 mg/dL) at Month 6 | Month 6 | Only FPG measurements performed before initiation of rescue therapy were considered in the analysis. Month 6 value corresponds to the observed value at Month 6 visit. |
| Percentage of Participants With At Least One Severe and/or Confirmed Nocturnal Hypoglycemia From Start of Week 9 to Month 6 | 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 \[mg/dL\]). Only nocturnal hypoglycemia occurring before initiation of rescue therapy were considered in the analysis. Week 9 and Month 6 value correspond to the observed value at Week 9 and Month 6 visit respectively. |
| Change in 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. Except for baseline value average of preinjection SMPG was assessed by the mean of at least 3 SMPG calculated over the 7 days preceding the assessment visit. Only preinjection SMPG measurements performed before initiation of rescue therapy were considered in the analysis. Month 6 Endpoint is either the observed value at Month 6 visit or value retrieved according to time windows. |
| Variability of Preinjection SMPG at Month 6 Endpoint | 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. Only preinjection SMPG measurements performed before initiation of rescue therapy were considered in the analysis. Month 6 Endpoint is either the observed value at Month 6 visit or value retrieved according to time windows. |
| Percentage of Participants With HbA1c <7% at Month 6 | Month 6 | Only HbA1c measurements performed before initiation of rescue therapy were considered in the analysis. Month 6 value corresponds to the observed value at Month 6 visit. |
| Change in Fasting Plasma Glucose (FPG) From Baseline to Month 6 Endpoint | Baseline, Month 6 | Only FPG measurements performed before initiation of rescue therapy were considered in the analysis. Month 6 Endpoint is either the observed value at Month 6 visit or value retrieved according to time windows. |
| Change in 24-hour Average 8-point SMPG Profile From Baseline to Month 6 Endpoint | Baseline, Month 6 | Change in 24-hour average of 8-point SMPG profile. 8-point SMPG was assessed at: 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. Only 24-hour average 8-point SMPG measurements performed before initiation of rescue therapy were considered in the analysis. Month 6 Endpoint is either the observed value at Month 6 visit or value retrieved according to time windows. |
| Change in Variability of 24 Hour Average 8-point SMPG Profiles From Baseline to Month 6 Endpoint | Baseline, Month 6 | Variability is assessed by the mean of coefficient of variation calculated as 100 multiplied by (standard deviation/mean) over at least 5 measurements of the 8-point profiles. Only variability of 24-hour 8-point SMPG measurements performed before initiation of rescue therapy were considered in the analysis. Month 6 Endpoint is either the observed value at Month 6 visit or value retrieved according to time windows. |
| Change in Daily Basal Insulin Dose From Baseline to Month 6 | Baseline, Month 6 | Only insulin dose measurements performed before initiation of rescue therapy were considered in the analysis. Month 6 value corresponds to the observed value at Month 6 visit. |
| Change in Total 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. Only DTSQ total score measurements performed before initiation of rescue therapy were considered in the analysis. Month 6 Endpoint is either the observed value at Month 6 visit or value retrieved according to time windows. |
| Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline up to Month 12 | Up to 12 months | 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). |
| Change in 8-Point SMPG Profiles Per Time Point From Baseline to Month 6 | 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. Only 8-point SMPG profiles measurements performed before initiation of rescue therapy were considered in the analysis. Month 6 value corresponds to the observed value at Month 6 visit. |
Countries
Bulgaria, Canada, Czechia, Denmark, Estonia, Finland, Hungary, Japan, Latvia, Lithuania, Netherlands, Puerto Rico, Romania, Slovakia, Sweden, United States
Participant flow
Recruitment details
A total of 1396 participants were screened, of whom 518 participants were screen failure and 878 participants were randomized.
Participants by arm
| Arm | Count |
|---|---|
| HOE901-U300 HOE901-U300 SC injection once daily for 12 months in combination with non-insulin antihyperglycemic drug(s). | 439 |
| Lantus Lantus SC injection once daily for 12 months in combination with non-insulin antihyperglycemic drug(s). | 439 |
| Total | 878 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 10 | 8 |
| Overall Study | Lack of Efficacy | 2 | 5 |
| Overall Study | Lost to Follow-up | 11 | 18 |
| Overall Study | No More Need of Insulin | 1 | 0 |
| Overall Study | Non Serious Hypoglycemia | 2 | 0 |
| Overall Study | Perceived Lack of Efficacy | 3 | 1 |
| Overall Study | Personal Reason | 34 | 45 |
| Overall Study | Protocol Violation | 11 | 12 |
| Overall Study | Randomized But Not Treated | 4 | 1 |
| Overall Study | Received Rescue Therapy | 14 | 22 |
| Overall Study | Selection Criterion/Protocol Violation | 9 | 9 |
| Overall Study | Site Closure/Site Withdrawal | 1 | 4 |
Baseline characteristics
| Characteristic | HOE901-U300 | Lantus | Total |
|---|---|---|---|
| Age, Continuous | 58.2 years STANDARD_DEVIATION 9.9 | 57.2 years STANDARD_DEVIATION 10.3 | 57.7 years STANDARD_DEVIATION 10.1 |
| Basal Insulin Daily Dose | 0.193 units per kilogram (U/kg) STANDARD_DEVIATION 0.027 | 0.193 units per kilogram (U/kg) STANDARD_DEVIATION 0.034 | 0.193 units per kilogram (U/kg) STANDARD_DEVIATION 0.031 |
| Body Mass Index (BMI) | 32.8 kilogram per square meter STANDARD_DEVIATION 6.9 | 33.2 kilogram per square meter STANDARD_DEVIATION 6.6 | 33.0 kilogram per square meter STANDARD_DEVIATION 6.7 |
| Duration of Diabetes | 10.11 years STANDARD_DEVIATION 6.49 | 9.57 years STANDARD_DEVIATION 6.22 | 9.84 years STANDARD_DEVIATION 6.36 |
| Glycated Hemoglobin A1c (HbA1c) Greater Than or Equal to (>=) 8% | 298 participants | 297 participants | 595 participants |
| Glycated Hemoglobin A1c (HbA1c) Less Than (<) 8% | 141 participants | 142 participants | 283 participants |
| Sex: Female, Male Female | 186 Participants | 185 Participants | 371 Participants |
| Sex: Female, Male Male | 253 Participants | 254 Participants | 507 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 115 / 435 | 107 / 438 |
| serious Total, serious adverse events | 35 / 435 | 39 / 438 |
Outcome results
Primary
Change in HbA1c From Baseline to Month 6 Endpoint
Only HbA1c measurements performed before initiation of rescue therapy were considered in the analysis. Month 6 Endpoint is either the observed value at Month 6 visit or value retrieved according to time windows.
Time frame: Baseline, Month 6
Population: Modified Intent-to-Treat (mITT) population:randomized participants who received at least 1 dose, had baseline and at least 1 post-baseline data of any efficacy variable, irrespective of compliance. Number of participants analyzed=participants included in mITT population with baseline and at least 1 post-baseline HbA1c data (Week 12 and/or Month 6).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| HOE901-U300 | Change in HbA1c From Baseline to Month 6 Endpoint | -1.42 percentage of hemoglobin | Standard Error 0.047 |
| Lantus | Change in HbA1c From Baseline to Month 6 Endpoint | -1.46 percentage of hemoglobin | Standard Error 0.048 |
Comparison: Analysis was performed using mixed model for repeated measurements (MMRM) with treatment groups, strata of screening HbA1c (\<8.0, \>=8.0%), geographical region (Non-Japan; Japan), visit and visit-by-treatment groups interaction as fixed categorical effects; baseline HbA1c and baseline HbA1c-by-visit interaction as continuous fixed covariates.95% CI: [-0.09, 0.174]
Secondary
Change in 24-hour Average 8-point SMPG Profile From Baseline to Month 6 Endpoint
Change in 24-hour average of 8-point SMPG profile. 8-point SMPG was assessed at: 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. Only 24-hour average 8-point SMPG measurements performed before initiation of rescue therapy were considered in the analysis. Month 6 Endpoint is either the observed value at Month 6 visit or value retrieved according to time windows.
Time frame: Baseline, Month 6
Population: mITT Population. Number of participants analyzed = participants included in the mITT population with baseline and at least one post-baseline 24-hour average 8-point SMPG assessment (Week 2, Week 4, Week 8, Week 12, Month 4 and/or Month 6).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| HOE901-U300 | Change in 24-hour Average 8-point SMPG Profile From Baseline to Month 6 Endpoint | -2.72 mmol/L | Standard Error 0.088 |
| Lantus | Change in 24-hour Average 8-point SMPG Profile From Baseline to Month 6 Endpoint | -2.90 mmol/L | Standard Error 0.089 |
Secondary
Change in 8-Point SMPG Profiles Per Time Point From Baseline to 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. Only 8-point SMPG profiles measurements performed before initiation of rescue therapy were considered in the analysis. Month 6 value corresponds to the observed value at Month 6 visit.
Time frame: Baseline, Month 6
Population: mITT Population. Only participants from the mITT population with a value at baseline and at specified timepoint were analyzed (represented by n=X, X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HOE901-U300 | Change in 8-Point SMPG Profiles Per Time Point From Baseline to Month 6 | 03:00 at Night Plasma Glucose (n=281,277) | -2.63 mmol/L | Standard Deviation 3.24 |
| HOE901-U300 | Change in 8-Point SMPG Profiles Per Time Point From Baseline to Month 6 | Pre-Breakfast Plasma Glucose (n=292,286) | -3.28 mmol/L | Standard Deviation 2.72 |
| HOE901-U300 | Change in 8-Point SMPG Profiles Per Time Point From Baseline to Month 6 | 2 Hours After Breakfast Plasma Glucose (n=278,278) | -3.69 mmol/L | Standard Deviation 3.65 |
| HOE901-U300 | Change in 8-Point SMPG Profiles Per Time Point From Baseline to Month 6 | Pre-Lunch Plasma Glucose (n=289,281) | -2.58 mmol/L | Standard Deviation 3.39 |
| HOE901-U300 | Change in 8-Point SMPG Profiles Per Time Point From Baseline to Month 6 | 2 Hours After Lunch Plasma Glucose (n=280,269) | -2.19 mmol/L | Standard Deviation 3.88 |
| HOE901-U300 | Change in 8-Point SMPG Profiles Per Time Point From Baseline to Month 6 | Pre-Dinner Plasma Glucose (n=291,285) | -2.57 mmol/L | Standard Deviation 3.49 |
| HOE901-U300 | Change in 8-Point SMPG Profiles Per Time Point From Baseline to Month 6 | 2 Hours After Dinner Plasma Glucose (n=282,269) | -2.36 mmol/L | Standard Deviation 3.89 |
| HOE901-U300 | Change in 8-Point SMPG Profiles Per Time Point From Baseline to Month 6 | Bedtime Plasma Glucose (n=249,249) | -2.19 mmol/L | Standard Deviation 3.75 |
| Lantus | Change in 8-Point SMPG Profiles Per Time Point From Baseline to Month 6 | Bedtime Plasma Glucose (n=249,249) | -2.26 mmol/L | Standard Deviation 3.66 |
| Lantus | Change in 8-Point SMPG Profiles Per Time Point From Baseline to Month 6 | 03:00 at Night Plasma Glucose (n=281,277) | -3.01 mmol/L | Standard Deviation 3.75 |
| Lantus | Change in 8-Point SMPG Profiles Per Time Point From Baseline to Month 6 | 2 Hours After Lunch Plasma Glucose (n=280,269) | -3.13 mmol/L | Standard Deviation 3.77 |
| Lantus | Change in 8-Point SMPG Profiles Per Time Point From Baseline to Month 6 | Pre-Breakfast Plasma Glucose (n=292,286) | -3.72 mmol/L | Standard Deviation 2.96 |
| Lantus | Change in 8-Point SMPG Profiles Per Time Point From Baseline to Month 6 | 2 Hours After Dinner Plasma Glucose (n=282,269) | -2.33 mmol/L | Standard Deviation 4.03 |
| Lantus | Change in 8-Point SMPG Profiles Per Time Point From Baseline to Month 6 | 2 Hours After Breakfast Plasma Glucose (n=278,278) | -4.08 mmol/L | Standard Deviation 4.03 |
| Lantus | Change in 8-Point SMPG Profiles Per Time Point From Baseline to Month 6 | Pre-Dinner Plasma Glucose (n=291,285) | -2.43 mmol/L | Standard Deviation 3.79 |
| Lantus | Change in 8-Point SMPG Profiles Per Time Point From Baseline to Month 6 | Pre-Lunch Plasma Glucose (n=289,281) | -3.39 mmol/L | Standard Deviation 3.76 |
Secondary
Change in Daily Basal Insulin Dose From Baseline to Month 6
Only insulin dose measurements performed before initiation of rescue therapy were considered in the analysis. Month 6 value corresponds to the observed value at Month 6 visit.
Time frame: Baseline, Month 6
Population: mITT Population. Number of participants analyzed = participants included in the mITT population with Baseline and Month 6 basal insulin dose assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HOE901-U300 | Change in Daily Basal Insulin Dose From Baseline to Month 6 | 0.43 U/kg | Standard Deviation 0.29 |
| Lantus | Change in Daily Basal Insulin Dose From Baseline to Month 6 | 0.34 U/kg | Standard Deviation 0.24 |
Secondary
Change in Fasting Plasma Glucose (FPG) From Baseline to Month 6 Endpoint
Only FPG measurements performed before initiation of rescue therapy were considered in the analysis. Month 6 Endpoint is either the observed value at Month 6 visit or value retrieved according to time windows.
Time frame: Baseline, Month 6
Population: mITT Population. Number of participants analyzed = participants included in the mITT population with baseline and at least one post-baseline FPG assessment (Week 12 and/or Month 6).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| HOE901-U300 | Change in Fasting Plasma Glucose (FPG) From Baseline to Month 6 Endpoint | -3.41 mmol/L | Standard Error 0.103 |
| Lantus | Change in Fasting Plasma Glucose (FPG) From Baseline to Month 6 Endpoint | -3.80 mmol/L | Standard Error 0.105 |
Secondary
Change in 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. Except for baseline value average of preinjection SMPG was assessed by the mean of at least 3 SMPG calculated over the 7 days preceding the assessment visit. Only preinjection SMPG measurements performed before initiation of rescue therapy were considered in the analysis. Month 6 Endpoint is either the observed value at Month 6 visit or value retrieved according to time windows.
Time frame: Baseline, Month 6
Population: mITT population. Number of participants analyzed = participants included in the mITT population with baseline and at least one pre-injection SMPG assessment (Week 2, Week 4, Week 8, Week 12, Month 4 and/or Month 6)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| HOE901-U300 | Change in Preinjection Self-Monitored Plasma Glucose (SMPG) From Baseline to Month 6 Endpoint | -2.16 mmol/L | Standard Error 0.162 |
| Lantus | Change in Preinjection Self-Monitored Plasma Glucose (SMPG) From Baseline to Month 6 Endpoint | -2.33 mmol/L | Standard Error 0.156 |
Comparison: Change in pre-injection SMPG was analyzed using MMRM model with treatment groups, strata of screening HbA1c (\<8.0, \>=8.0%), geographical region (Non-Japan; Japan), visit and visit-by-treatment groups interaction as fixed categorical effects; baseline preinjection SMPG value and baseline preinjection SMPG value-by-visit interaction as continuous fixed covariates.95% CI: [-0.275, 0.605]
Secondary
Change in Total 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. Only DTSQ total score measurements performed before initiation of rescue therapy were considered in the analysis. Month 6 Endpoint is either the observed value at Month 6 visit or value retrieved according to time windows.
Time frame: Baseline, Month 6
Population: mITT Population. Number of participants analyzed = participants included in the mITT population with Baseline and at least one post-baseline DTSQ assessment (Week 12 and/or Month 6).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| HOE901-U300 | Change in Total Treatment Satisfaction Score Using The Diabetes Treatment Satisfaction Questionnaire (DTSQs) From Baseline to Month 6 Endpoint | 4.89 units on a scale | Standard Error 0.246 |
| Lantus | Change in Total Treatment Satisfaction Score Using The Diabetes Treatment Satisfaction Questionnaire (DTSQs) From Baseline to Month 6 Endpoint | 5.12 units on a scale | Standard Error 0.251 |
Secondary
Change in Variability of 24 Hour Average 8-point SMPG Profiles From Baseline to Month 6 Endpoint
Variability is assessed by the mean of coefficient of variation calculated as 100 multiplied by (standard deviation/mean) over at least 5 measurements of the 8-point profiles. Only variability of 24-hour 8-point SMPG measurements performed before initiation of rescue therapy were considered in the analysis. Month 6 Endpoint is either the observed value at Month 6 visit or value retrieved according to time windows.
Time frame: Baseline, Month 6
Population: mITT Population. Number of participants analyzed = participants included in the mITT population with baseline and at least one post-baseline variability of 24-hour average 8-point SMPG assessment (Week 2, Week 4, Week 8, Week 12, Month 4 and/or Month 6).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| HOE901-U300 | Change in Variability of 24 Hour Average 8-point SMPG Profiles From Baseline to Month 6 Endpoint | 1.53 percentage of mean | Standard Error 0.643 |
| Lantus | Change in Variability of 24 Hour Average 8-point SMPG Profiles From Baseline to Month 6 Endpoint | 1.41 percentage of mean | Standard Error 0.647 |
Secondary
Percentage of Participants With At Least One Severe and/or Confirmed Nocturnal Hypoglycemia From Start of Week 9 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 \[mg/dL\]). Only nocturnal hypoglycemia occurring before initiation of rescue therapy were considered in the analysis. Week 9 and Month 6 value correspond to the observed value at Week 9 and Month 6 visit respectively.
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 | 15.5 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 | 17.4 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 stratified by randomization strata of screening HbA1c (\<8.0, \>=8.0%), randomization strata of geographical region (Non-Japan; Japan).p-value: 0.453695% CI: [0.66, 1.2]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With FPG <5.6 mmol/L (100 mg/dL) at Month 6
Only FPG measurements performed before initiation of rescue therapy were considered in the analysis. Month 6 value corresponds to the observed value at Month 6 visit.
Time frame: Month 6
Population: mITT Population. Participants without any available FPG assessment at Month 6 were considered as failures (non-responders).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HOE901-U300 | Percentage of Participants With FPG <5.6 mmol/L (100 mg/dL) at Month 6 | 26.2 percentage of participants |
| Lantus | Percentage of Participants With FPG <5.6 mmol/L (100 mg/dL) at Month 6 | 29.5 percentage of participants |
Secondary
Percentage of Participants With HbA1c <7% at Month 6
Only HbA1c measurements performed before initiation of rescue therapy were considered in the analysis. Month 6 value corresponds to the observed value at Month 6 visit.
Time frame: Month 6
Population: mITT Population. Participants without any available Month 6 HbA1C assessment were considered as failures (non-responders).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HOE901-U300 | Percentage of Participants With HbA1c <7% at Month 6 | 43.1 percentage of participants |
| Lantus | Percentage of Participants With HbA1c <7% at Month 6 | 42.1 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 12 months
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 | 58.9 percentage of participants |
| HOE901-U300 | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline up to Month 12 | Severe Hypoglycemia: All Hypoglycemia | 1.4 percentage of participants |
| HOE901-U300 | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline up to Month 12 | Documented Symptomatic: All Hypoglycemia | 39.1 percentage of participants |
| HOE901-U300 | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline up to Month 12 | Asymptomatic: All Hypoglycemia | 41.6 percentage of participants |
| HOE901-U300 | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline up to Month 12 | Probable Symptomatic: All Hypoglycemia | 3.2 percentage of participants |
| HOE901-U300 | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline up to Month 12 | Relative: All Hypoglycemia | 10.6 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 | 56.3 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 | 27.6 percentage of participants |
| HOE901-U300 | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline up to Month 12 | Severe Hypoglycemia: Nocturnal Hypoglycemia | 0.0 percentage of participants |
| HOE901-U300 | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline up to Month 12 | Documented Symptomatic: Nocturnal Hypoglycemia | 18.6 percentage of participants |
| HOE901-U300 | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline up to Month 12 | Asymptomatic: Nocturnal Hypoglycemia | 13.3 percentage of participants |
| HOE901-U300 | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline up to Month 12 | Probable Symptomatic: Nocturnal Hypoglycemia | 0.7 percentage of participants |
| HOE901-U300 | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline up to Month 12 | Relative: Nocturnal Hypoglycemia | 4.4 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 | 25.3 percentage of participants |
| Lantus | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline up to Month 12 | Asymptomatic: Nocturnal Hypoglycemia | 16.0 percentage of participants |
| Lantus | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline up to Month 12 | Any Hypoglycemia Event: All Hypoglycemia | 63.2 percentage of participants |
| Lantus | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline up to Month 12 | Any Hypoglycemia Event: Nocturnal Hypoglycemia | 30.1 percentage of participants |
| Lantus | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline up to Month 12 | Severe Hypoglycemia: All Hypoglycemia | 2.1 percentage of participants |
| Lantus | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline up to Month 12 | Relative: Nocturnal Hypoglycemia | 3.2 percentage of participants |
| Lantus | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline up to Month 12 | Documented Symptomatic: All Hypoglycemia | 44.1 percentage of participants |
| Lantus | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline up to Month 12 | Severe Hypoglycemia: Nocturnal Hypoglycemia | 0.7 percentage of participants |
| Lantus | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline up to Month 12 | Asymptomatic: All Hypoglycemia | 46.8 percentage of participants |
| Lantus | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline up to Month 12 | Probable Symptomatic: Nocturnal Hypoglycemia | 0.0 percentage of participants |
| Lantus | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline up to Month 12 | Probable Symptomatic: All Hypoglycemia | 3.0 percentage of participants |
| Lantus | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline up to Month 12 | Documented Symptomatic: Nocturnal Hypoglycemia | 20.8 percentage of participants |
| Lantus | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline up to Month 12 | Relative: All Hypoglycemia | 11.6 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 | 29.5 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 | 61.2 percentage of participants |
Secondary
Variability of Preinjection SMPG at 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. Only preinjection SMPG measurements performed before initiation of rescue therapy were considered in the analysis. Month 6 Endpoint is either the observed value at Month 6 visit or value retrieved according to time windows.
Time frame: Month 6
Population: mITT population. Number of participants analyzed = participants included in the mITT Population with at least one pre-injection SMPG variability assessment (Week 2, Week 4, Week 8, Week 12, Month 4 and/or Month 6).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| HOE901-U300 | Variability of Preinjection SMPG at Month 6 Endpoint | 18.70 percentage of mean | Standard Error 0.502 |
| Lantus | Variability of Preinjection SMPG at Month 6 Endpoint | 18.33 percentage of mean | Standard Error 0.521 |