Type 1 Diabetes Mellitus
Conditions
Brief summary
Primary Objective: * To compare the glucose control during treatment with a new formulation of insulin glargine and Lantus in adult participants with type 1 diabetes mellitus Secondary Objectives: * To compare a new formulation of insulin glargine and Lantus given in the morning or in the evening * To compare the incidence and frequency of hypoglycemic episodes * To assess the safety and tolerability of the new formulation of insulin glargine
Detailed description
* Up to 4-week screening period; * 16-week open-label comparative efficacy and safety treatment period; * 4-week post-treatment safety follow-up period.
Interventions
Sponsors
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
: * Participants with Type 1 diabetes mellitus
Exclusion criteria
* HbA1c greater than (\>) 9% (at screening) * Participants receiving \>0.5 U/kg body weight basal insulin in the last 30 days prior to screening visit * Participants not on stable insulin dose (+/- 20% total basal insulin dose) in the last 30 days prior to screening visit * Less than 1 year on any basal plus mealtime insulin * Participants using pre-mix insulins, human regular insulin as mealtime insulin and/or any antidiabetic drugs other than basal insulin and mealtime analogue insulin in the last 3 months before screening visit * Use of an insulin pump in the last 6 months before screening visit; * Any contraindication to use of insulin glargine as defined in the national product label * Not willing to inject insulin glargine as assigned by the randomization process once daily in the morning or evening * Hospitalization for diabetic ketoacidosis or history of severe hypoglycemia (requiring 3rd party assistance) in the last 6 months prior to randomization * Initiation of any glucose-lowering agents in the last 3 months before screening visit * Weight change of greater than equal to (\>=) 5 kg during the last 3 months prior to screening visit * Unstable proliferative diabetic retinopathy or any other rapidly progressive diabetic retinopathy or macular edema likely to require 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 |
|---|---|---|
| Percentage of Time in Target Plasma Glucose Range (4.4-7.8 mmol/L [80-140 mg/dL]) | Up to Week 16 (assessed at Weeks 7-8 in Period A and Weeks 15-16 in Period B) | Percentage of time with glucose within glycemic range (4.4-7.8 mmol/L) was assessed by the total time within glycemic range divided by the length of the assessment interval. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Time Below The Lower Limit of Glycemic Range (<4.4 mmol/L [80 mg/dL]) | Up to Week 16 (assessed at Weeks 7-8 in Period A and Weeks 15-16 in Period B) | Percentage of time with glucose below the lower limit of glycemic range (\<4.4 mmol/L) was assessed by the total time below the lower limit of glycemic range divided by the length of the assessment interval. |
| Evaluation of Diurnal Glucose Exposure, Variability, and Stability | Up to Week 16 (assessed at Weeks 7-8 in Period A and Weeks 15-16 in Period B) | The diurnal glucose exposure is measured as the average diurnal glucose concentration, diurnal glucose variability is measured by interquartile range (IQR), that is, average distance between the 25th and the 75th point-wise percentiles and diurnal glucose stability is assessed in terms of the mean absolute rate of change (mmol/l), that is, the area under the absolute rate of change of the median curve (based on the median point values between two adjacent hourly basket intervals), divided by the length of the assessment interval. |
| Percentage of Time in Target Plasma Glucose Range (4.4-7.8 mmol/L [80-140 mg/dL]) in the Last Four Hours of Each Dosing Interval at Weeks 7 and 8 in Period A and Weeks 15 and 16 in Period B | Weeks 7-8 in Period A and Weeks 15-16 in Period B | Percentage of time with glucose within glycemic range (4.4-7.8 mmol/L) was assessed by the total time within glycemic range divided by the length of the assessment interval. |
| Change in HbA1c From Baseline to Week 8 and 16 | Baseline, Week 8, 16 | — |
| Percentage of Time Above the Upper Limit of Glycemic Range (Greater Than [>] 7.8 mmol/L [(140 mg/dL]) | Up to Week 16 (assessed at Weeks 7-8 in Period A and Weeks 15-16 in Period B) | Percentage of time with glucose above the upper limit of glycemic range (\>7.8 mmol/L) was assessed by the total time above the upper limit of glycemic range divided by the length of the assessment interval. |
| Change in Average 7-Point Self-Monitored Plasma Glucose (SMPG) Profile From Baseline to Week 8 and 16 | Baseline, Week 8, 16 | Change in average of 7-point SMPG. 7-point SMPG was assessed starting with a measurement at before breakfast and 2 hours after breakfast; before and 2 hours after lunch; before and 2 hours after dinner; at bedtime. |
| Change in Basal Insulin Daily Dose From Baseline to Week 8 and 16 | Baseline, Week 8, 16 | — |
| Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline Up to Week 16 | Up to Week 16 | 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 Fasting Plasma Glucose (FPG) From Baseline to Week 8 and 16 | Baseline, Week 8, 16 | — |
Countries
United States
Participant flow
Pre-assignment details
A total of 85 participants were screened, of whom 26 participants were screen failures and 59 participants were randomized. The data for outcome measures was planned to be reported for combined reporting arms (HOE901-U300 Combined and Lantus Combined).
Participants by arm
| Arm | Count |
|---|---|
| HOE901-U300 Morning Then Evening HOE901-U300 SC injection once daily in morning for 8 weeks during treatment period A, followed by once daily in evening for 8 weeks during treatment period B. | 15 |
| HOE901-U300 Evening Then Morning HOE901-U300 SC injection once daily in evening for 8 weeks during treatment period A, followed by once daily in morning for 8 weeks during treatment period B. | 15 |
| Lantus Morning Then Evening Lantus SC injection once daily in morning for 8 weeks during treatment period A, followed by once daily in evening for 8 weeks during treatment period B. | 15 |
| Lantus Evening Then Morning Lantus SC injection once daily in evening for 8 weeks during treatment period A, followed by once daily in morning for 8 weeks during treatment period B. | 14 |
| Total | 59 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Treatment Period A | Adverse Event | 1 | 0 | 0 | 0 |
| Treatment Period A | Other | 0 | 0 | 1 | 1 |
| Treatment Period B | Other | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | HOE901-U300 Morning Then Evening | HOE901-U300 Evening Then Morning | Lantus Morning Then Evening | Lantus Evening Then Morning | Total |
|---|---|---|---|---|---|
| Age, Continuous | 43.6 years STANDARD_DEVIATION 14.6 | 46.2 years STANDARD_DEVIATION 15.9 | 39.7 years STANDARD_DEVIATION 12.5 | 47.6 years STANDARD_DEVIATION 14.1 | 44.2 years STANDARD_DEVIATION 14.3 |
| Basal Insulin Daily Dose | 0.309 units per kilogram (U/kg) STANDARD_DEVIATION 0.086 | 0.283 units per kilogram (U/kg) STANDARD_DEVIATION 0.088 | 0.341 units per kilogram (U/kg) STANDARD_DEVIATION 0.1 | 0.267 units per kilogram (U/kg) STANDARD_DEVIATION 0.055 | 0.301 units per kilogram (U/kg) STANDARD_DEVIATION 0.087 |
| Body Mass Index (BMI) | 27.5 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 4.9 | 27.4 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 5 | 28.3 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 6.2 | 26.1 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 5.1 | 27.3 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 5.3 |
| Duration of Diabetes | 16.8 years | 23.9 years | 20.6 years | 16.7 years | 20.7 years |
| Glycated Hemoglobin (HbA1c) Greater Than or Equal to (>=) 8 | 4 participants | 1 participants | 3 participants | 2 participants | 10 participants |
| Glycated Hemoglobin (HbA1c) Less Than (<) 8 | 11 participants | 14 participants | 12 participants | 12 participants | 49 participants |
| Sex: Female, Male Female | 11 Participants | 2 Participants | 4 Participants | 10 Participants | 27 Participants |
| Sex: Female, Male Male | 4 Participants | 13 Participants | 11 Participants | 4 Participants | 32 Participants |
| Total Insulin Daily Dose | 0.600 U/kg STANDARD_DEVIATION 0.237 | 0.620 U/kg STANDARD_DEVIATION 0.179 | 0.677 U/kg STANDARD_DEVIATION 0.204 | 0.513 U/kg STANDARD_DEVIATION 0.115 | 0.603 U/kg STANDARD_DEVIATION 0.193 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 18 / 30 | 17 / 29 |
| serious Total, serious adverse events | 1 / 30 | 0 / 29 |
Outcome results
Primary
Percentage of Time in Target Plasma Glucose Range (4.4-7.8 mmol/L [80-140 mg/dL])
Percentage of time with glucose within glycemic range (4.4-7.8 mmol/L) was assessed by the total time within glycemic range divided by the length of the assessment interval.
Time frame: Up to Week 16 (assessed at Weeks 7-8 in Period A and Weeks 15-16 in Period B)
Population: Continuous glucose monitoring (CGM) population: All participants who received at least 1 dose, had evaluable post-baseline CGM data, irrespective of compliance. Number of participants analyzed = participants with baseline, Weeks 7-8 (Period A) and/or Weeks 15-16 (Period B) CGM assessment. Missing data imputed using last observation carried forward.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| HOE901-U300 Combined | Percentage of Time in Target Plasma Glucose Range (4.4-7.8 mmol/L [80-140 mg/dL]) | 31.75 percentage of time | Standard Error 1.5 |
| Lantus Combined | Percentage of Time in Target Plasma Glucose Range (4.4-7.8 mmol/L [80-140 mg/dL]) | 30.99 percentage of time | Standard Error 1.58 |
Comparison: Analysis was performed using a linear mixed model with treatment and period as fixed effects, and participant as random effect.p-value: 0.730495% CI: [-3.614, 5.124]Linear Mixed Model
Secondary
Change in Average 7-Point Self-Monitored Plasma Glucose (SMPG) Profile From Baseline to Week 8 and 16
Change in average of 7-point SMPG. 7-point SMPG was assessed starting with a measurement at before breakfast and 2 hours after breakfast; before and 2 hours after lunch; before and 2 hours after dinner; at bedtime.
Time frame: Baseline, Week 8, 16
Population: Modified Intent-to-Treat population. Number of participants analyzed = participants with baseline, Week 8 and/or 16 7-point SMPG assessment, n = participants with 7-point SMPG assessment at specified time. Missing data imputed using LOCF.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HOE901-U300 Combined | Change in Average 7-Point Self-Monitored Plasma Glucose (SMPG) Profile From Baseline to Week 8 and 16 | Week 8 | -0.39 mmol/L | Standard Deviation 1.84 |
| HOE901-U300 Combined | Change in Average 7-Point Self-Monitored Plasma Glucose (SMPG) Profile From Baseline to Week 8 and 16 | Week 16 | -0.47 mmol/L | Standard Deviation 1.31 |
| Lantus Combined | Change in Average 7-Point Self-Monitored Plasma Glucose (SMPG) Profile From Baseline to Week 8 and 16 | Week 8 | 0.39 mmol/L | Standard Deviation 1.54 |
| Lantus Combined | Change in Average 7-Point Self-Monitored Plasma Glucose (SMPG) Profile From Baseline to Week 8 and 16 | Week 16 | 0.58 mmol/L | Standard Deviation 2.13 |
Secondary
Change in Basal Insulin Daily Dose From Baseline to Week 8 and 16
Time frame: Baseline, Week 8, 16
Population: Modified Intent-to-Treat population. Here n = participants with basal insulin dose assessment at specified time-point. Missing data imputed using LOCF.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HOE901-U300 Combined | Change in Basal Insulin Daily Dose From Baseline to Week 8 and 16 | Week 16 (n=29, 27) | 0.05 U/kg | Standard Deviation 0.09 |
| HOE901-U300 Combined | Change in Basal Insulin Daily Dose From Baseline to Week 8 and 16 | Week 8 (n= 30, 29) | 0.06 U/kg | Standard Deviation 0.09 |
| Lantus Combined | Change in Basal Insulin Daily Dose From Baseline to Week 8 and 16 | Week 16 (n=29, 27) | 0.03 U/kg | Standard Deviation 0.08 |
| Lantus Combined | Change in Basal Insulin Daily Dose From Baseline to Week 8 and 16 | Week 8 (n= 30, 29) | 0.03 U/kg | Standard Deviation 0.09 |
Secondary
Change in Fasting Plasma Glucose (FPG) From Baseline to Week 8 and 16
Time frame: Baseline, Week 8, 16
Population: Modified Intent-to-Treat population. Number of participants analyzed = participants with baseline, Week 8 and/or 16 FPG assessment, n = participants with FPG assessment at specified time. Missing data imputed using LOCF.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HOE901-U300 Combined | Change in Fasting Plasma Glucose (FPG) From Baseline to Week 8 and 16 | Week 8 (n=24, 23) | -0.89 mmol/L | Standard Deviation 5.04 |
| HOE901-U300 Combined | Change in Fasting Plasma Glucose (FPG) From Baseline to Week 8 and 16 | Week 16 (n= 24, 22) | -0.99 mmol/L | Standard Deviation 5.27 |
| Lantus Combined | Change in Fasting Plasma Glucose (FPG) From Baseline to Week 8 and 16 | Week 8 (n=24, 23) | -0.10 mmol/L | Standard Deviation 5.81 |
| Lantus Combined | Change in Fasting Plasma Glucose (FPG) From Baseline to Week 8 and 16 | Week 16 (n= 24, 22) | 0.78 mmol/L | Standard Deviation 4.92 |
Secondary
Change in HbA1c From Baseline to Week 8 and 16
Time frame: Baseline, Week 8, 16
Population: Modified Intent-to-Treat population: randomized participants who received at least 1 dose; had baseline, at least 1 post-baseline efficacy assessment; irrespective of compliance. Number of participants analyzed = participants with baseline, Week 8 and/or 16 HbA1c assessment, n = participants with HbA1c assessment at specified time. LOCF applied.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HOE901-U300 Combined | Change in HbA1c From Baseline to Week 8 and 16 | Week 8 (n= 29, 20) | -0.22 percentage of hemoglobin | Standard Deviation 0.48 |
| HOE901-U300 Combined | Change in HbA1c From Baseline to Week 8 and 16 | Week 16 (n= 28, 27) | -0.44 percentage of hemoglobin | Standard Deviation 0.51 |
| Lantus Combined | Change in HbA1c From Baseline to Week 8 and 16 | Week 8 (n= 29, 20) | -0.23 percentage of hemoglobin | Standard Deviation 0.54 |
| Lantus Combined | Change in HbA1c From Baseline to Week 8 and 16 | Week 16 (n= 28, 27) | -0.22 percentage of hemoglobin | Standard Deviation 0.58 |
Secondary
Evaluation of Diurnal Glucose Exposure, Variability, and Stability
The diurnal glucose exposure is measured as the average diurnal glucose concentration, diurnal glucose variability is measured by interquartile range (IQR), that is, average distance between the 25th and the 75th point-wise percentiles and diurnal glucose stability is assessed in terms of the mean absolute rate of change (mmol/l), that is, the area under the absolute rate of change of the median curve (based on the median point values between two adjacent hourly basket intervals), divided by the length of the assessment interval.
Time frame: Up to Week 16 (assessed at Weeks 7-8 in Period A and Weeks 15-16 in Period B)
Population: CGM population. Number of participants analyzed = participants with baseline, Weeks 7, 8 (Period A), and/or Weeks 15, 16 (Period B) CGM assessment. Missing data imputed using LOCF.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| HOE901-U300 Combined | Evaluation of Diurnal Glucose Exposure, Variability, and Stability | Diurnal Glucose Exposure | 8.869 mmol/L | Standard Error 0.24 |
| HOE901-U300 Combined | Evaluation of Diurnal Glucose Exposure, Variability, and Stability | Diurnal Glucose Stability | 0.673 mmol/L | Standard Error 0.03 |
| HOE901-U300 Combined | Evaluation of Diurnal Glucose Exposure, Variability, and Stability | Diurnal Glucose Variability | 4.931 mmol/L | Standard Error 0.22 |
| Lantus Combined | Evaluation of Diurnal Glucose Exposure, Variability, and Stability | Diurnal Glucose Exposure | 8.910 mmol/L | Standard Error 0.26 |
| Lantus Combined | Evaluation of Diurnal Glucose Exposure, Variability, and Stability | Diurnal Glucose Stability | 0.703 mmol/L | Standard Error 0.03 |
| Lantus Combined | Evaluation of Diurnal Glucose Exposure, Variability, and Stability | Diurnal Glucose Variability | 5.279 mmol/L | Standard Error 0.23 |
Secondary
Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline Up to Week 16
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 Week 16
Population: Safety population: all randomized participants who were exposed to at least one dose, regardless of 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 Combined | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline Up to Week 16 | Any Hypoglycemia Event: All Hypoglycemia | 100 percentage of participants |
| HOE901-U300 Combined | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline Up to Week 16 | Severe Hypoglycemia: All Hypoglycemia | 3.3 percentage of participants |
| HOE901-U300 Combined | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline Up to Week 16 | Documented Symptomatic: All Hypoglycemia | 93.3 percentage of participants |
| HOE901-U300 Combined | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline Up to Week 16 | Asymptomatic: All Hypoglycemia | 86.7 percentage of participants |
| HOE901-U300 Combined | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline Up to Week 16 | Probable Symptomatic: All Hypoglycemia | 16.7 percentage of participants |
| HOE901-U300 Combined | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline Up to Week 16 | Relative: All Hypoglycemia | 0.0 percentage of participants |
| HOE901-U300 Combined | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline Up to Week 16 | Severe and/or Confirmed: All Hypoglycemia | 100 percentage of participants |
| HOE901-U300 Combined | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline Up to Week 16 | Any Hypoglycemia Event: Nocturnal Hypoglycemia | 80.0 percentage of participants |
| HOE901-U300 Combined | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline Up to Week 16 | Severe Hypoglycemia: Nocturnal Hypoglycemia | 0.0 percentage of participants |
| HOE901-U300 Combined | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline Up to Week 16 | Documented Symptomatic: Nocturnal Hypoglycemia | 66.7 percentage of participants |
| HOE901-U300 Combined | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline Up to Week 16 | Asymptomatic: Nocturnal Hypoglycemia | 40.0 percentage of participants |
| HOE901-U300 Combined | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline Up to Week 16 | Probable Symptomatic: Nocturnal Hypoglycemia | 3.3 percentage of participants |
| HOE901-U300 Combined | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline Up to Week 16 | Relative: Nocturnal Hypoglycemia | 0.0 percentage of participants |
| HOE901-U300 Combined | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline Up to Week 16 | Severe and/or Confirmed: Nocturnal Hypoglycemia | 80.0 percentage of participants |
| Lantus Combined | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline Up to Week 16 | Asymptomatic: Nocturnal Hypoglycemia | 48.3 percentage of participants |
| Lantus Combined | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline Up to Week 16 | Any Hypoglycemia Event: All Hypoglycemia | 100 percentage of participants |
| Lantus Combined | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline Up to Week 16 | Any Hypoglycemia Event: Nocturnal Hypoglycemia | 93.1 percentage of participants |
| Lantus Combined | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline Up to Week 16 | Severe Hypoglycemia: All Hypoglycemia | 10.3 percentage of participants |
| Lantus Combined | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline Up to Week 16 | Relative: Nocturnal Hypoglycemia | 6.9 percentage of participants |
| Lantus Combined | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline Up to Week 16 | Documented Symptomatic: All Hypoglycemia | 96.6 percentage of participants |
| Lantus Combined | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline Up to Week 16 | Severe Hypoglycemia: Nocturnal Hypoglycemia | 6.9 percentage of participants |
| Lantus Combined | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline Up to Week 16 | Asymptomatic: All Hypoglycemia | 96.6 percentage of participants |
| Lantus Combined | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline Up to Week 16 | Probable Symptomatic: Nocturnal Hypoglycemia | 10.3 percentage of participants |
| Lantus Combined | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline Up to Week 16 | Probable Symptomatic: All Hypoglycemia | 27.6 percentage of participants |
| Lantus Combined | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline Up to Week 16 | Documented Symptomatic: Nocturnal Hypoglycemia | 79.3 percentage of participants |
| Lantus Combined | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline Up to Week 16 | Relative: All Hypoglycemia | 6.9 percentage of participants |
| Lantus Combined | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline Up to Week 16 | Severe and/or Confirmed: Nocturnal Hypoglycemia | 93.1 percentage of participants |
| Lantus Combined | Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline Up to Week 16 | Severe and/or Confirmed: All Hypoglycemia | 100 percentage of participants |
Secondary
Percentage of Time Above the Upper Limit of Glycemic Range (Greater Than [>] 7.8 mmol/L [(140 mg/dL])
Percentage of time with glucose above the upper limit of glycemic range (\>7.8 mmol/L) was assessed by the total time above the upper limit of glycemic range divided by the length of the assessment interval.
Time frame: Up to Week 16 (assessed at Weeks 7-8 in Period A and Weeks 15-16 in Period B)
Population: CGM population. Number of participants analyzed = participants with baseline, Weeks 7, 8 (Period A), and/or Weeks 15, 16 (Period B) CGM assessment. Missing data imputed using last observation carried forward (LOCF).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| HOE901-U300 Combined | Percentage of Time Above the Upper Limit of Glycemic Range (Greater Than [>] 7.8 mmol/L [(140 mg/dL]) | 58.24 percentage of time | Standard Error 2.09 |
| Lantus Combined | Percentage of Time Above the Upper Limit of Glycemic Range (Greater Than [>] 7.8 mmol/L [(140 mg/dL]) | 57.38 percentage of time | Standard Error 2.2 |
Secondary
Percentage of Time Below The Lower Limit of Glycemic Range (<4.4 mmol/L [80 mg/dL])
Percentage of time with glucose below the lower limit of glycemic range (\<4.4 mmol/L) was assessed by the total time below the lower limit of glycemic range divided by the length of the assessment interval.
Time frame: Up to Week 16 (assessed at Weeks 7-8 in Period A and Weeks 15-16 in Period B)
Population: CGM population. Number of participants analyzed = participants with baseline, Weeks 7, 8 (Period A), and/or Weeks 15, 16 (Period B) CGM assessment. Missing data imputed using LOCF.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| HOE901-U300 Combined | Percentage of Time Below The Lower Limit of Glycemic Range (<4.4 mmol/L [80 mg/dL]) | 10.01 percentage of time | Standard Error 1.02 |
| Lantus Combined | Percentage of Time Below The Lower Limit of Glycemic Range (<4.4 mmol/L [80 mg/dL]) | 11.64 percentage of time | Standard Error 1.08 |
Secondary
Percentage of Time in Target Plasma Glucose Range (4.4-7.8 mmol/L [80-140 mg/dL]) in the Last Four Hours of Each Dosing Interval at Weeks 7 and 8 in Period A and Weeks 15 and 16 in Period B
Percentage of time with glucose within glycemic range (4.4-7.8 mmol/L) was assessed by the total time within glycemic range divided by the length of the assessment interval.
Time frame: Weeks 7-8 in Period A and Weeks 15-16 in Period B
Population: CGM population. Number of participants analyzed = participants with baseline, Weeks 7, 8 (Period A), and/or Weeks 15, 16 (Period B) CGM assessment, and n = participants with assessment at specified time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HOE901-U300 Combined | Percentage of Time in Target Plasma Glucose Range (4.4-7.8 mmol/L [80-140 mg/dL]) in the Last Four Hours of Each Dosing Interval at Weeks 7 and 8 in Period A and Weeks 15 and 16 in Period B | Week 7, 8 (n=28, 27) | 32.08 percentage of time | Standard Deviation 14.74 |
| HOE901-U300 Combined | Percentage of Time in Target Plasma Glucose Range (4.4-7.8 mmol/L [80-140 mg/dL]) in the Last Four Hours of Each Dosing Interval at Weeks 7 and 8 in Period A and Weeks 15 and 16 in Period B | Week 15, 16 (n=29, 26) | 33.02 percentage of time | Standard Deviation 13.48 |
| Lantus Combined | Percentage of Time in Target Plasma Glucose Range (4.4-7.8 mmol/L [80-140 mg/dL]) in the Last Four Hours of Each Dosing Interval at Weeks 7 and 8 in Period A and Weeks 15 and 16 in Period B | Week 7, 8 (n=28, 27) | 29.07 percentage of time | Standard Deviation 13.82 |
| Lantus Combined | Percentage of Time in Target Plasma Glucose Range (4.4-7.8 mmol/L [80-140 mg/dL]) in the Last Four Hours of Each Dosing Interval at Weeks 7 and 8 in Period A and Weeks 15 and 16 in Period B | Week 15, 16 (n=29, 26) | 28.70 percentage of time | Standard Deviation 14.57 |