Type 1 Diabetes Mellitus
Conditions
Brief summary
Primary Objective: To compare the efficacy of a new formulation of insulin glargine (HOE901-U300) to Lantus in terms of change of HbA1c from baseline to endpoint (month 6) in children and adolescents with type 1 diabetes mellitus. . Secondary Objectives: To compare HOE901-U300 and Lantus in terms of: * Percentage of participants reaching target HbA1c and fasting plasma glucose (FPG). * To assess the safety of HOE901-U300 including analysis of events of hypoglycemia, events of hyperglycemia with ketosis, and development of anti-insulin-antibodies.
Detailed description
The study duration per participant was approximately 58 weeks that consisted of a 2 week screening period, a main 6-month comparative efficacy and safety treatment period, a 6-month comparative safety extension period, and a 4-week post treatment follow up period.
Interventions
DRUGInsulin glargine,300 U/mL
Subcutaneous injection in the morning or evening using a prefilled pen. Dose titration to achieve fasting self-monitored plasma glucose (SMPG) from 90 to 130 milligram/deciliter (mg/dL) (5.0 to 7.2 millimol per liter \[mmol/L\])
DRUGInsulin glargine (100 units /mL)
Subcutaneous injection in the morning or evening using a prefilled pen. Dose titration to achieve fasting SMPG from 90 to 130 mg/dL (5.0 to 7.2 mmol/L)
Fast-acting mealtime insulin analogs
Sponsors
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
: * Children and adolescents with type 1 diabetes mellitus (T1DM) for at least 1 year confirmed by typical symptoms at diagnosis and/or by antibody testing \[presence of anti-GAD (glutamic acid decarboxylase) or anti-IA2 (islet antigen 2/tyrosine phosphatase) or anti-islet cell antibodies\] and/or clinical features (eg, history of ketoacidosis)\]. * Signed written informed consent obtained from parent(s)/legal guardian and written or oral assent obtained from participant.
Exclusion criteria
* Age \<6 years and \>=18 years at randomization. * Less than 1 year on insulin treatment prior to screening visit. * Less than 6 months on basal plus mealtime insulin and self-monitoring of blood glucose prior to screening visit. * Participants using premix insulins in the last 3 months before screening visit or 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 or plans to switch to pump within the next 6 months after screening visit. * Any contraindication to use of insulin glargine as defined in the national product label. * No willingness to inject insulin glargine (Lantus or HOE901-U300) once daily. * HbA1c \<7.5% or \>11% at screening. * Initiation of any glucose-lowering medications in the last 3 months before screening visit. * Hospitalization or care in the emergency ward for diabetic ketoacidosis or history of severe hypoglycemia (as defined by need for glucagon or IV glucose) and accompanied by seizure and/or unconsciousness and/or coma in the last 3 months prior to screening visit. * Postmenarchal girls not protected by highly-effective method(s) of birth control and/or who were unwilling or unable to be tested for pregnancy. Abstinence from sexual intercourse was considered as an acceptable form of birth control. * Pregnant or breast-feeding adolescents, or adolescents who intended to become pregnant during the study period, or who were at risk of getting pregnant due to any psychosocial reason 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 From Baseline in HbA1c to Month 6 | Baseline to Month 6 | Change in HbA1c was calculated by subtracting baseline value from Month 6 value. Adjusted least-square (LS) means and standard errors (SE) were obtained using analysis of covariance (ANCOVA) after multiple imputations of missing data using post-baseline HbA1c data available on the main 6-month randomized period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With HbA1c Values of <7.5% at Month 6 | Month 6 | Participants without any available HbA1c assessment at month 6 and/or with a premature study discontinuation during the main 6-month randomized period were considered as a failure (non-responders) in the analysis. Analysis was performed using Cochran-Mantel-Haenszel (CMH) method with randomization strata of screening HbA1c (\<8.5%; \>=8.5%) and randomization strata of age at screening (\<12 years, \>=12 years). |
| Percentage of Participants With HbA1c Values of <7.5% Without Any Episode of Severe and/or Documented Self-Monitored Plasma Glucose ([SMPG] <54 mg/dL [3.0 mmol/L]) Symptomatic Hypoglycemia During the Last 3 Months of the Main 6-month Randomized Period | upto Month 6 | Participants without any available HbA1c assessment at month 6 and/or with a premature study discontinuation during the main 6-month randomized period were considered as a failure (non-responders) in the analysis. Analysis was performed using Cochran-Mantel-Haenszel (CMH) method with randomization strata of screening HbA1c (\<8.5%; \>=8.5%) and randomization strata of age at screening (\<12 years, \>=12 years). |
| Percentage of Participants With FPG of <=130 mg/dL (7.2 mmol/L) at Month 6 | Month 6 | Participants without any available FPG assessment at month 6 and/or with a premature study discontinuation during the main 6-month randomized period were considered as a failure (non-responders) in the analysis. Analysis was performed using Cochran-Mantel-Haenszel (CMH) method with randomization strata of screening HbA1c (\<8.5%; \>=8.5%) and randomization strata of age at screening (\<12 years, \>=12 years). |
| Percentage of Participants With FPG of <=130 mg/dL (7.2 mmol/L) Without Any Episode of Severe and/or Documented (SMPG <54 mg/dL [3.0 mmol/L]) Symptomatic Hypoglycemia During the Last 3 Months of the Main 6-month Randomized Period | upto Month 6 | Participants without any available HbA1c assessment at month 6 and/or with a premature study discontinuation during the main 6-month randomized period were considered as a failure (non-responders) in the analysis. Analysis was performed using Cochran-Mantel-Haenszel (CMH) method with randomization strata of screening HbA1c (\<8.5%; \>=8.5%) and randomization strata of age at screening (\<12 years, \>=12 years). |
| Change From Baseline in Fasting Plasma Glucose (FPG) to Month 6 | Baseline to Month 6 | Change in FPG was calculated by subtracting baseline value from Month 6 value. Adjusted LS means and SE were obtained using ANCOVA after multiple imputation to address missing data in the main 6 month randomized period. |
| Change From Baseline in Variability of 24-Hour Mean Plasma Glucose Based on 8-point SMPG Profiles at Month 6 | Baseline, Month 6 | 8-point SMPG profiles were measured at the following 8 points: between 01:00 and 04:00 (clock time) at night, pre-breakfast, 2 hours after breakfast, pre-lunch, 2 hours after lunch, pre-dinner, 2 hours after dinner, and bedtime. Variability was assessed by the coefficient of variation (standard deviation divided by mean) calculated over the 8-point SMPG. Analysis was performed using a ANCOVA model including the fixed categorical effects of treatment group, randomization strata of screening HbA1c (\<8.5%; \>=8.5%) and randomization strata of age at screening (\<12 years, \>=12 years). |
| Change From Baseline to Month 6 in 8-Point SMPG Profile Per Time Point | Baseline to Month 6 | 8-point SMPG profiles were measured for following 8 time points at Baseline and Month 6: between 01:00 and 04:00 (clock time) at night, pre-breakfast, 2 hours after breakfast, pre-lunch, 2 hours after lunch, pre-dinner, 2 hours after dinner, and bedtime. |
| Percentage of Participants With at Least One Hypoglycemic Events (Any Hypoglycemia, Severe Hypoglycemia, Documented Symptomatic, Probable Symptomatic, Asymptomatic Hypoglycemia, Pseudo-hypoglycemia and Severe and/or Confirmed Hypoglycemia) at Month 12 | Month 12 | Severe hypoglycemia: an event in which the child/adolescent having altered mental status and cannot assist in their care, is semiconscious or unconscious, or in coma ± convulsions and may require parenteral therapy (glucagon or glucose). Documented symptomatic hypoglycemia: an event during which typical symptoms of hypoglycemia were accompanied by a measured plasma glucose concentration of \<=70 mg/dL (3.9 mmol/L). Asymptomatic hypoglycemia: an event not accompanied by typical symptoms of hypoglycemia but with a measured plasma glucose concentration \<=70 mg/dL. Probable symptomatic hypoglycemia: an event during which symptoms of hypoglycemia were not accompanied by plasma glucose determination but was presumably caused by a plasma glucose concentration \<=70 mg/dL. Pseudo-hypoglycemia:an event with any of the typical symptoms of hypoglycaemia with plasma glucose concentration \>70 mg/dL. |
| Percentage of Participants With Any Hyperglycemia With Ketosis at Month 12 | Month 12 | Hyperglycemia with ketosis was defined as SMPG \>=252 mg/dL (14 mmol/L) with accompanying self-measured blood ketones \>=1.5 mmol/L. |
| Change From Baseline in 24-Hour Mean Plasma Glucose Based on 8-point SMPG Profiles to Month 6 | Baseline to Month 6 | 8-point SMPG profiles were measured at the following 8 points: between 01:00 and 04:00 (clock time) at night, pre-breakfast, 2 hours after breakfast, pre-lunch, 2 hours after lunch, pre-dinner, 2 hours after dinner, and bedtime. Analysis was performed using a ANCOVA model including the fixed categorical effects of treatment group, randomization strata of screening HbA1c (\<8.5%; \>=8.5%), randomization strata of age at screening (\<12 years, \>=12 years) and the baseline 24-hour average 8-point profile SMPG. |
Countries
Argentina, Brazil, Bulgaria, Canada, Chile, Czechia, Denmark, France, Germany, Hungary, Israel, Italy, Japan, Latvia, Mexico, North Macedonia, Poland, Romania, Russia, Serbia, Spain, Sweden, United Kingdom, United States
Participant flow
Recruitment details
The study was conducted at 105 centers in 24 countries. A total of 616 participants were screened between 14 April 2016 and 31 October 2017, of which 153 were screen failures. Screen failures were mainly due to glycated hemoglobin (HbA1c) level outside of defined ranges per eligibility criteria.
Pre-assignment details
A total of 463 participants were randomized in the study. Randomization was stratified by age group (\<12 years and \>=12 years) and by HbA1c (\<8.5% and \>=8.5%). Assignment to arms was done centrally using interactive voice system in 1:1 ratio.
Participants by arm
| Arm | Count |
|---|---|
| HOE901-U300 Insulin glargine 300 U/mL SC injection once daily in the morning or evening for 12 months. | 233 |
| Lantus Insulin glargine 100 U/mL SC injection once daily in the morning or evening for 12 months. | 230 |
| Total | 463 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 3 |
| Overall Study | Lack of Efficacy | 1 | 0 |
| Overall Study | Other, not specified above | 5 | 11 |
| Overall Study | Poor compliance to protocol | 7 | 7 |
| Overall Study | Randomized and not treated | 0 | 2 |
Baseline characteristics
| Characteristic | Lantus | Total | HOE901-U300 |
|---|---|---|---|
| Age, Continuous | 12.9 Years STANDARD_DEVIATION 2.9 | 12.9 Years STANDARD_DEVIATION 2.9 | 12.9 Years STANDARD_DEVIATION 2.9 |
| Body Mass Index (BMI) | 69.13 BMI percentile STANDARD_DEVIATION 26.64 | 68.32 BMI percentile STANDARD_DEVIATION 26.61 | 67.52 BMI percentile STANDARD_DEVIATION 26.62 |
| Hemoglobin A1C (HbA1C) | 8.61 percentage of A1C STANDARD_DEVIATION 0.87 | 8.63 percentage of A1C STANDARD_DEVIATION 0.88 | 8.65 percentage of A1C STANDARD_DEVIATION 0.88 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 17 Participants | 11 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 14 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 211 Participants | 422 Participants | 211 Participants |
| Sex: Female, Male Female | 121 Participants | 226 Participants | 105 Participants |
| Sex: Female, Male Male | 109 Participants | 237 Participants | 128 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 233 | 0 / 228 |
| other Total, other adverse events | 105 / 233 | 118 / 228 |
| serious Total, serious adverse events | 35 / 233 | 31 / 228 |
Outcome results
Primary
Change From Baseline in HbA1c to Month 6
Change in HbA1c was calculated by subtracting baseline value from Month 6 value. Adjusted least-square (LS) means and standard errors (SE) were obtained using analysis of covariance (ANCOVA) after multiple imputations of missing data using post-baseline HbA1c data available on the main 6-month randomized period.
Time frame: Baseline to Month 6
Population: Analysis was performed on intent-to-treat (ITT) population that included all randomized participants, regardless of whether the treatment kit was used, and was analyzed according to the allocated treatment group. Here, 'Overall number of participants analyzed' signified number of participants with available data for the outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| HOE901-U300 | Change From Baseline in HbA1c to Month 6 | -0.399 Percentage of HbA1c | Standard Error 0.063 |
| Lantus | Change From Baseline in HbA1c to Month 6 | -0.402 Percentage of HbA1c | Standard Error 0.064 |
Comparison: Analysis was performed using ANCOVA models which included the treatment group, the randomization stratum of age group at screening visit (\<12 years and \>=12 years), and the continuous fixed covariates of the baseline HbA1c value.95% CI: [-0.172, 0.179]
Comparison: A step-wise closed testing approach was used to control the type I error. Analysis was performed using ANCOVA models which included the treatment group, the randomization stratum of age group at screening visit (\<12 years and \>=12 years), and the continuous fixed covariates of the baseline HbA1c value.p-value: 0.965ANCOVA
Secondary
Change From Baseline in 24-Hour Mean Plasma Glucose Based on 8-point SMPG Profiles to Month 6
8-point SMPG profiles were measured at the following 8 points: between 01:00 and 04:00 (clock time) at night, pre-breakfast, 2 hours after breakfast, pre-lunch, 2 hours after lunch, pre-dinner, 2 hours after dinner, and bedtime. Analysis was performed using a ANCOVA model including the fixed categorical effects of treatment group, randomization strata of screening HbA1c (\<8.5%; \>=8.5%), randomization strata of age at screening (\<12 years, \>=12 years) and the baseline 24-hour average 8-point profile SMPG.
Time frame: Baseline to Month 6
Population: Analysis was performed on ITT population. Here, 'Overall number of participants analyzed' signified number of participants with available data for the outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| HOE901-U300 | Change From Baseline in 24-Hour Mean Plasma Glucose Based on 8-point SMPG Profiles to Month 6 | 0.139 mmol/L | Standard Error 0.249 |
| Lantus | Change From Baseline in 24-Hour Mean Plasma Glucose Based on 8-point SMPG Profiles to Month 6 | -0.266 mmol/L | Standard Error 0.25 |
Secondary
Change From Baseline in Fasting Plasma Glucose (FPG) to Month 6
Change in FPG was calculated by subtracting baseline value from Month 6 value. Adjusted LS means and SE were obtained using ANCOVA after multiple imputation to address missing data in the main 6 month randomized period.
Time frame: Baseline to Month 6
Population: Analysis was performed on ITT population. Here, 'Overall number of participants analyzed' signified number of participants with available data for the outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| HOE901-U300 | Change From Baseline in Fasting Plasma Glucose (FPG) to Month 6 | -0.563 millimole per liter (mmol/L) | Standard Error 0.372 |
| Lantus | Change From Baseline in Fasting Plasma Glucose (FPG) to Month 6 | -0.549 millimole per liter (mmol/L) | Standard Error 0.372 |
Secondary
Change From Baseline in Variability of 24-Hour Mean Plasma Glucose Based on 8-point SMPG Profiles at Month 6
8-point SMPG profiles were measured at the following 8 points: between 01:00 and 04:00 (clock time) at night, pre-breakfast, 2 hours after breakfast, pre-lunch, 2 hours after lunch, pre-dinner, 2 hours after dinner, and bedtime. Variability was assessed by the coefficient of variation (standard deviation divided by mean) calculated over the 8-point SMPG. Analysis was performed using a ANCOVA model including the fixed categorical effects of treatment group, randomization strata of screening HbA1c (\<8.5%; \>=8.5%) and randomization strata of age at screening (\<12 years, \>=12 years).
Time frame: Baseline, Month 6
Population: Analysis was performed on ITT population. Here, 'Overall number of participants analyzed' signified number of participants with available data for the outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| HOE901-U300 | Change From Baseline in Variability of 24-Hour Mean Plasma Glucose Based on 8-point SMPG Profiles at Month 6 | 1.469 percentage of mean variability | Standard Error 1.409 |
| Lantus | Change From Baseline in Variability of 24-Hour Mean Plasma Glucose Based on 8-point SMPG Profiles at Month 6 | 0.789 percentage of mean variability | Standard Error 1.415 |
Secondary
Change From Baseline to Month 6 in 8-Point SMPG Profile Per Time Point
8-point SMPG profiles were measured for following 8 time points at Baseline and Month 6: between 01:00 and 04:00 (clock time) at night, pre-breakfast, 2 hours after breakfast, pre-lunch, 2 hours after lunch, pre-dinner, 2 hours after dinner, and bedtime.
Time frame: Baseline to Month 6
Population: Analysis was performed on ITT population. Here, 'number analyzed' = participants with available data for each specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HOE901-U300 | Change From Baseline to Month 6 in 8-Point SMPG Profile Per Time Point | 2 hours after breakfast | -0.26 mmol/L | Standard Deviation 7.18 |
| HOE901-U300 | Change From Baseline to Month 6 in 8-Point SMPG Profile Per Time Point | Between 01:00 and 04:00 at night | 0.84 mmol/L | Standard Deviation 6.94 |
| HOE901-U300 | Change From Baseline to Month 6 in 8-Point SMPG Profile Per Time Point | Pre-breakfast | -0.41 mmol/L | Standard Deviation 5.48 |
| HOE901-U300 | Change From Baseline to Month 6 in 8-Point SMPG Profile Per Time Point | Pre-lunch | 0.43 mmol/L | Standard Deviation 6.99 |
| HOE901-U300 | Change From Baseline to Month 6 in 8-Point SMPG Profile Per Time Point | 2 hours after lunch | 0.49 mmol/L | Standard Deviation 7.64 |
| HOE901-U300 | Change From Baseline to Month 6 in 8-Point SMPG Profile Per Time Point | Pre-dinner | 0.29 mmol/L | Standard Deviation 8.05 |
| HOE901-U300 | Change From Baseline to Month 6 in 8-Point SMPG Profile Per Time Point | 2 hours after dinner | 0.51 mmol/L | Standard Deviation 8.53 |
| HOE901-U300 | Change From Baseline to Month 6 in 8-Point SMPG Profile Per Time Point | Bedtime | 0.86 mmol/L | Standard Deviation 7.6 |
| Lantus | Change From Baseline to Month 6 in 8-Point SMPG Profile Per Time Point | Bedtime | -0.60 mmol/L | Standard Deviation 7 |
| Lantus | Change From Baseline to Month 6 in 8-Point SMPG Profile Per Time Point | 2 hours after lunch | -0.55 mmol/L | Standard Deviation 7.2 |
| Lantus | Change From Baseline to Month 6 in 8-Point SMPG Profile Per Time Point | Between 01:00 and 04:00 at night | -0.60 mmol/L | Standard Deviation 7.08 |
| Lantus | Change From Baseline to Month 6 in 8-Point SMPG Profile Per Time Point | 2 hours after dinner | 0.60 mmol/L | Standard Deviation 6.86 |
| Lantus | Change From Baseline to Month 6 in 8-Point SMPG Profile Per Time Point | Pre-breakfast | -1.71 mmol/L | Standard Deviation 6.56 |
| Lantus | Change From Baseline to Month 6 in 8-Point SMPG Profile Per Time Point | 2 hours after breakfast | -0.62 mmol/L | Standard Deviation 6.78 |
| Lantus | Change From Baseline to Month 6 in 8-Point SMPG Profile Per Time Point | Pre-dinner | -0.02 mmol/L | Standard Deviation 6.78 |
| Lantus | Change From Baseline to Month 6 in 8-Point SMPG Profile Per Time Point | Pre-lunch | 1.11 mmol/L | Standard Deviation 6.85 |
Secondary
Percentage of Participants With Any Hyperglycemia With Ketosis at Month 12
Hyperglycemia with ketosis was defined as SMPG \>=252 mg/dL (14 mmol/L) with accompanying self-measured blood ketones \>=1.5 mmol/L.
Time frame: Month 12
Population: Analysis was performed on the safety population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HOE901-U300 | Percentage of Participants With Any Hyperglycemia With Ketosis at Month 12 | 9.9 percentage of participants |
| Lantus | Percentage of Participants With Any Hyperglycemia With Ketosis at Month 12 | 13.6 percentage of participants |
Secondary
Percentage of Participants With at Least One Hypoglycemic Events (Any Hypoglycemia, Severe Hypoglycemia, Documented Symptomatic, Probable Symptomatic, Asymptomatic Hypoglycemia, Pseudo-hypoglycemia and Severe and/or Confirmed Hypoglycemia) at Month 12
Severe hypoglycemia: an event in which the child/adolescent having altered mental status and cannot assist in their care, is semiconscious or unconscious, or in coma ± convulsions and may require parenteral therapy (glucagon or glucose). Documented symptomatic hypoglycemia: an event during which typical symptoms of hypoglycemia were accompanied by a measured plasma glucose concentration of \<=70 mg/dL (3.9 mmol/L). Asymptomatic hypoglycemia: an event not accompanied by typical symptoms of hypoglycemia but with a measured plasma glucose concentration \<=70 mg/dL. Probable symptomatic hypoglycemia: an event during which symptoms of hypoglycemia were not accompanied by plasma glucose determination but was presumably caused by a plasma glucose concentration \<=70 mg/dL. Pseudo-hypoglycemia:an event with any of the typical symptoms of hypoglycaemia with plasma glucose concentration \>70 mg/dL.
Time frame: Month 12
Population: Analysis was performed on the safety population which included all randomized participants who actually received who received at least 1 dose or part of a dose of IMP, and was analyzed according to treatment received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HOE901-U300 | Percentage of Participants With at Least One Hypoglycemic Events (Any Hypoglycemia, Severe Hypoglycemia, Documented Symptomatic, Probable Symptomatic, Asymptomatic Hypoglycemia, Pseudo-hypoglycemia and Severe and/or Confirmed Hypoglycemia) at Month 12 | Documented Symptomatic Hypoglycemia | 94.8 percentage of participants |
| HOE901-U300 | Percentage of Participants With at Least One Hypoglycemic Events (Any Hypoglycemia, Severe Hypoglycemia, Documented Symptomatic, Probable Symptomatic, Asymptomatic Hypoglycemia, Pseudo-hypoglycemia and Severe and/or Confirmed Hypoglycemia) at Month 12 | Asymptomatic Hypoglycemia | 88.4 percentage of participants |
| HOE901-U300 | Percentage of Participants With at Least One Hypoglycemic Events (Any Hypoglycemia, Severe Hypoglycemia, Documented Symptomatic, Probable Symptomatic, Asymptomatic Hypoglycemia, Pseudo-hypoglycemia and Severe and/or Confirmed Hypoglycemia) at Month 12 | Severe Hypoglycemia | 8.6 percentage of participants |
| HOE901-U300 | Percentage of Participants With at Least One Hypoglycemic Events (Any Hypoglycemia, Severe Hypoglycemia, Documented Symptomatic, Probable Symptomatic, Asymptomatic Hypoglycemia, Pseudo-hypoglycemia and Severe and/or Confirmed Hypoglycemia) at Month 12 | Pseudo-hypoglycemia | 15.9 percentage of participants |
| HOE901-U300 | Percentage of Participants With at Least One Hypoglycemic Events (Any Hypoglycemia, Severe Hypoglycemia, Documented Symptomatic, Probable Symptomatic, Asymptomatic Hypoglycemia, Pseudo-hypoglycemia and Severe and/or Confirmed Hypoglycemia) at Month 12 | Probable Symptomatic Hypoglycemia | 10.3 percentage of participants |
| HOE901-U300 | Percentage of Participants With at Least One Hypoglycemic Events (Any Hypoglycemia, Severe Hypoglycemia, Documented Symptomatic, Probable Symptomatic, Asymptomatic Hypoglycemia, Pseudo-hypoglycemia and Severe and/or Confirmed Hypoglycemia) at Month 12 | Severe and/or documented hypoglycemia | 99.1 percentage of participants |
| HOE901-U300 | Percentage of Participants With at Least One Hypoglycemic Events (Any Hypoglycemia, Severe Hypoglycemia, Documented Symptomatic, Probable Symptomatic, Asymptomatic Hypoglycemia, Pseudo-hypoglycemia and Severe and/or Confirmed Hypoglycemia) at Month 12 | Any hypoglycemia | 99.1 percentage of participants |
| Lantus | Percentage of Participants With at Least One Hypoglycemic Events (Any Hypoglycemia, Severe Hypoglycemia, Documented Symptomatic, Probable Symptomatic, Asymptomatic Hypoglycemia, Pseudo-hypoglycemia and Severe and/or Confirmed Hypoglycemia) at Month 12 | Severe and/or documented hypoglycemia | 98.2 percentage of participants |
| Lantus | Percentage of Participants With at Least One Hypoglycemic Events (Any Hypoglycemia, Severe Hypoglycemia, Documented Symptomatic, Probable Symptomatic, Asymptomatic Hypoglycemia, Pseudo-hypoglycemia and Severe and/or Confirmed Hypoglycemia) at Month 12 | Any hypoglycemia | 98.7 percentage of participants |
| Lantus | Percentage of Participants With at Least One Hypoglycemic Events (Any Hypoglycemia, Severe Hypoglycemia, Documented Symptomatic, Probable Symptomatic, Asymptomatic Hypoglycemia, Pseudo-hypoglycemia and Severe and/or Confirmed Hypoglycemia) at Month 12 | Severe Hypoglycemia | 11.0 percentage of participants |
| Lantus | Percentage of Participants With at Least One Hypoglycemic Events (Any Hypoglycemia, Severe Hypoglycemia, Documented Symptomatic, Probable Symptomatic, Asymptomatic Hypoglycemia, Pseudo-hypoglycemia and Severe and/or Confirmed Hypoglycemia) at Month 12 | Documented Symptomatic Hypoglycemia | 93.9 percentage of participants |
| Lantus | Percentage of Participants With at Least One Hypoglycemic Events (Any Hypoglycemia, Severe Hypoglycemia, Documented Symptomatic, Probable Symptomatic, Asymptomatic Hypoglycemia, Pseudo-hypoglycemia and Severe and/or Confirmed Hypoglycemia) at Month 12 | Probable Symptomatic Hypoglycemia | 13.6 percentage of participants |
| Lantus | Percentage of Participants With at Least One Hypoglycemic Events (Any Hypoglycemia, Severe Hypoglycemia, Documented Symptomatic, Probable Symptomatic, Asymptomatic Hypoglycemia, Pseudo-hypoglycemia and Severe and/or Confirmed Hypoglycemia) at Month 12 | Asymptomatic Hypoglycemia | 89.5 percentage of participants |
| Lantus | Percentage of Participants With at Least One Hypoglycemic Events (Any Hypoglycemia, Severe Hypoglycemia, Documented Symptomatic, Probable Symptomatic, Asymptomatic Hypoglycemia, Pseudo-hypoglycemia and Severe and/or Confirmed Hypoglycemia) at Month 12 | Pseudo-hypoglycemia | 14.5 percentage of participants |
Secondary
Percentage of Participants With FPG of <=130 mg/dL (7.2 mmol/L) at Month 6
Participants without any available FPG assessment at month 6 and/or with a premature study discontinuation during the main 6-month randomized period were considered as a failure (non-responders) in the analysis. Analysis was performed using Cochran-Mantel-Haenszel (CMH) method with randomization strata of screening HbA1c (\<8.5%; \>=8.5%) and randomization strata of age at screening (\<12 years, \>=12 years).
Time frame: Month 6
Population: Analysis was performed on ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HOE901-U300 | Percentage of Participants With FPG of <=130 mg/dL (7.2 mmol/L) at Month 6 | 27.47 percentage of participants |
| Lantus | Percentage of Participants With FPG of <=130 mg/dL (7.2 mmol/L) at Month 6 | 26.52 percentage of participants |
Secondary
Percentage of Participants With FPG of <=130 mg/dL (7.2 mmol/L) Without Any Episode of Severe and/or Documented (SMPG <54 mg/dL [3.0 mmol/L]) Symptomatic Hypoglycemia During the Last 3 Months of the Main 6-month Randomized Period
Participants without any available HbA1c assessment at month 6 and/or with a premature study discontinuation during the main 6-month randomized period were considered as a failure (non-responders) in the analysis. Analysis was performed using Cochran-Mantel-Haenszel (CMH) method with randomization strata of screening HbA1c (\<8.5%; \>=8.5%) and randomization strata of age at screening (\<12 years, \>=12 years).
Time frame: upto Month 6
Population: Analysis was performed on ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HOE901-U300 | Percentage of Participants With FPG of <=130 mg/dL (7.2 mmol/L) Without Any Episode of Severe and/or Documented (SMPG <54 mg/dL [3.0 mmol/L]) Symptomatic Hypoglycemia During the Last 3 Months of the Main 6-month Randomized Period | 9.44 percentage of participants |
| Lantus | Percentage of Participants With FPG of <=130 mg/dL (7.2 mmol/L) Without Any Episode of Severe and/or Documented (SMPG <54 mg/dL [3.0 mmol/L]) Symptomatic Hypoglycemia During the Last 3 Months of the Main 6-month Randomized Period | 7.39 percentage of participants |
Secondary
Percentage of Participants With HbA1c Values of <7.5% at Month 6
Participants without any available HbA1c assessment at month 6 and/or with a premature study discontinuation during the main 6-month randomized period were considered as a failure (non-responders) in the analysis. Analysis was performed using Cochran-Mantel-Haenszel (CMH) method with randomization strata of screening HbA1c (\<8.5%; \>=8.5%) and randomization strata of age at screening (\<12 years, \>=12 years).
Time frame: Month 6
Population: Analysis was performed on ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HOE901-U300 | Percentage of Participants With HbA1c Values of <7.5% at Month 6 | 26.18 percentage of participants |
| Lantus | Percentage of Participants With HbA1c Values of <7.5% at Month 6 | 23.48 percentage of participants |
Secondary
Percentage of Participants With HbA1c Values of <7.5% Without Any Episode of Severe and/or Documented Self-Monitored Plasma Glucose ([SMPG] <54 mg/dL [3.0 mmol/L]) Symptomatic Hypoglycemia During the Last 3 Months of the Main 6-month Randomized Period
Participants without any available HbA1c assessment at month 6 and/or with a premature study discontinuation during the main 6-month randomized period were considered as a failure (non-responders) in the analysis. Analysis was performed using Cochran-Mantel-Haenszel (CMH) method with randomization strata of screening HbA1c (\<8.5%; \>=8.5%) and randomization strata of age at screening (\<12 years, \>=12 years).
Time frame: upto Month 6
Population: Analysis was performed on ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HOE901-U300 | Percentage of Participants With HbA1c Values of <7.5% Without Any Episode of Severe and/or Documented Self-Monitored Plasma Glucose ([SMPG] <54 mg/dL [3.0 mmol/L]) Symptomatic Hypoglycemia During the Last 3 Months of the Main 6-month Randomized Period | 4.29 percentage of participants |
| Lantus | Percentage of Participants With HbA1c Values of <7.5% Without Any Episode of Severe and/or Documented Self-Monitored Plasma Glucose ([SMPG] <54 mg/dL [3.0 mmol/L]) Symptomatic Hypoglycemia During the Last 3 Months of the Main 6-month Randomized Period | 4.78 percentage of participants |