Type 2 Diabetes Mellitus
Conditions
Brief summary
Primary Objective: To demonstrate the non-inferiority of H0E901-U300 to Lantus, in change of glycated hemoglobin A1c (HbA1c). Secondary Objectives: To demonstrate the superiority of H0E901-U300 in comparison with Lantus in: * Percentage of participants with at least one severe and/or confirmed (by plasma glucose ≤70mg/dL \[3.9mmol/L\]) hypoglycemia event from 22:00 to 08:59 next morning * Percentage of participants with at least one nocturnal (from 00:00-05:59) severe and/or confirmed (≤70mg/dL \[3.9mmol/L\]) hypoglycemia event * Percentage of participants with at least one severe and/or confirmed (by plasma glucose ≤70mg/dL \[3.9mmol/L\]) hypoglycemia event occurring at any time of day * HbA1c change
Detailed description
The study consisted of a 4-week screening period, a 26-week treatment period comparing HOE901-U300 to Lantus, and a 2-day safety follow-up period.
Interventions
Self-administered by subcutaneous (SC) injection in the evening using a pre-filled pen. Dose titration to achieve fasting self-monitored plasma glucose (SMPG) from 90 to 130 mg/dL (5.0 to 7.2 mmol/L).
DRUGInsulin Glargine (HOE901 - U100)
Self-administered by SC injection in the evening using a pre-filled pen. Dose titration to achieve fasting SMPG from 90 to 130 mg/dL (5.0 to 7.2 mmol/L).
Non-insulin anti-diabetic drugs with the exception of thiazolidinediones.
Sponsors
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants ≥65 years old with type 2 diabetes mellitus, inadequately controlled on antidiabetic regimens either including no insulin, or with basal insulin as their only insulin. * Signed informed consent.
Exclusion criteria
* HbA1c at screening visit: * \<7.0% or \>10.0% for participants taking basal insulin. * \<7.5% or \>11.0% for insulin-naïve participants. * History of type 2 diabetes mellitus for less than 1 year before screening. * Participants not on stable basal insulin dose (±10% in the last 8 weeks prior to screening visit). * Change in dose of antidiabetic treatment or initiation of new glucose-lowering medications in the last 8 weeks prior to screening. * Chronic (\>10 days continuous use in previous 6 months) use of bolus insulin injections, whether given separately or as part of a combination with basal insulin, e.g. premix insulin; For insulin-naïve individuals: current or previous insulin use except for a maximum of 10 consecutive days (e.g. acute illness, surgery) during the last year prior to screening. * Cognitive disorder and dementia assessed clinically and by Mini-Mental State Examination (MMSE) score \<24, or any neurologic disorder that would likely affect the participant's ability to follow the study procedure. The participant would be eligible despite an MMSE score \<24 if the investigator determined that the low score reflected educational or cultural background and not dementia as long as the participant was otherwise able to meet the study requirements. * Participants who had end-stage renal disease (\<15 mL/min/1.73m\^2, per estimated Glomerular filtration rate (eGFR) measurement by Modification of Diet in Renal Disease (MDRD). The above information was 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 Week 26 | Baseline, Week 26 | Adjusted least square (LS) means were obtained from analysis of covariance (ANCOVA) after multiple imputation of missing data including post baseline HbA1c data during the 26-week randomized period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With At Least One Severe and/ or Confirmed (≤3.9 mmol/L [70 mg/dL]) Nocturnal Hypoglycemia (22:00 to 08:59 Hours Next Morning) During 26-Week Randomized Period | Baseline up to Week 26 | Estimated percentages from multiple imputation approach including data from the 26-week randomized period. 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 ≤3.9 mmol/L (70 mg/dL). |
| Percentage of Participants With At Least One Severe and/ or Confirmed (≤3.9 mmol/L [70 mg/dL]) Nocturnal Hypoglycemia (00:00 to 05:59 Hours) During 26-Week Randomized Period | Baseline up to Week 26 | Estimated percentages from multiple imputation approach including data from the 26-week randomized period. 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 ≤3.9 mmol/L (70 mg/dL). |
| Percentage of Participants With At Least One Severe and/ or Confirmed (≤3.9 mmol/L [70 mg/dL]) Hypoglycemia Occurring at Any Time of the Day During 26-Week Randomized Period | Baseline up to Week 26 | Estimated percentages from multiple imputation approach including data from the 26-week randomized period. 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 ≤3.9 mmol/L (70 mg/dL). |
| Percentage of Participants With HbA1c <7.5% or HbA1c <7% During 26-Week Randomized Period | Baseline up to Week 26 | Participants without any available HbA1c assessment at Week 26 were considered as non-responders in the analyses. |
| Change in World Health Organization-5 (WHO-5) Well-Being Questionnaire Percentage Score From Baseline to Week 26 | Baseline, Week 26 | WHO-5 well-being index evaluates positive psychological well-being during the past 2 weeks and consists of 5 questions, each rated on a 6-point Likert scale from 0 (not present) to 5 (constantly present). Total raw score was transformed into a percentage score ranging from 0 (worst possible quality of life) to 100 (best possible quality of life). |
| Percentage of Participants Requiring Rescue Therapy Over the 26 Weeks of Treatment | Baseline up to Week 26 | Routine fasting self-monitored plasma glucose (SMPG) and central laboratory FPG (and HbA1c after Week 14) values were used to determine the requirement of rescue medication. Threshold values at Week 14: FPG \>200 mg/dL (11 mmol/L), or HbA1c \>8.5%. |
| Percentage of Participants With HbA1c <7.5% or <7.0% at Week 26 and No Severe and/or Confirmed (≤3.9 mmol/L [70 mg/dL]) Hypoglycemia During 26-Week Randomized Period | Baseline up to Week 26 | 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 ≤3.9 mmol/L (70 mg/dL). |
| Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26 | Baseline, Week 26 | Adjusted LS means from multiple imputation approach including post baseline values during the 26-week randomized period. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Hypoglycemia (Any Hypoglycemia, Documented Symptomatic Hypoglycemia, Severe and/or Confirmed Hypoglycemia) During the 26 Weeks of Treatment | Baseline up to Week 26 | Hypoglycemia events were hypoglycemia of any category, severe hypoglycemia (an event that required assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions); documented symptomatic hypoglycemia (symptoms of hypoglycemia with plasma glucose ≤3.9 mmol/L \[70 mg/dL\]); confirmed hypoglycemia (with or without symptoms of hypoglycemia and plasma glucose ≤3.9 mmol/L). |
| Hypoglycemia (Any Hypoglycemia, Documented Symptomatic Hypoglycemia, Severe and/or Confirmed Hypoglycemia) Event Rate Per Participant Year During the 26 Weeks of Treatment | Baseline up to Week 26 | Hypoglycemia events were hypoglycemia of any category, severe hypoglycemia (an event that required assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions); documented symptomatic hypoglycemia (symptoms of hypoglycemia with plasma glucose ≤3.9 mmol/L \[70 mg/dL\]); confirmed hypoglycemia (with or without symptoms of hypoglycemia and plasma glucose ≤3.9 mmol/L). |
Countries
Argentina, Australia, Canada, Colombia, France, Germany, Hungary, Italy, Japan, Mexico, Peru, Poland, Romania, South Korea, Spain, Sweden, United Kingdom, United States
Participant flow
Recruitment details
The study was conducted at 162 study centers across 18 countries. A total of 1515 participants were screened between 16 January 2015 and 14 October 2015, of whom 501 were screen failures.
Pre-assignment details
A total of 1014 participants were randomized in 1:1 ratio to either HOE901-U300 or Lantus, stratified by screening hemoglobin A1c (HbA1c) values (\<8% or ≥8%); previous use of insulin (insulin-naïve versus pre-treated); and use of sulfonylurea or meglitinides at screening ('yes' versus 'no').
Participants by arm
| Arm | Count |
|---|---|
| HOE901-U300 HOE901-U300 (Insulin glargine, 300 U/mL) SC injection once daily up to Week 26 on top of stable non-insulin antihyperglycemic therapy. | 508 |
| Lantus Lantus (Insulin glargine, 100 U/mL) SC injection once daily up to Week 26 on top of stable non-insulin antihyperglycemic therapy. | 506 |
| Total | 1,014 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 6 | 6 |
| Overall Study | Hypoglycemia | 1 | 0 |
| Overall Study | Lack of Efficacy | 2 | 0 |
| Overall Study | Other than specified above | 15 | 20 |
| Overall Study | Poor compliance to protocol | 3 | 7 |
| Overall Study | Randomized but not treated | 0 | 1 |
Baseline characteristics
| Characteristic | Lantus | Total | HOE901-U300 |
|---|---|---|---|
| Age, Continuous | 70.8 years STANDARD_DEVIATION 4.8 | 71.0 years STANDARD_DEVIATION 4.9 | 71.1 years STANDARD_DEVIATION 4.9 |
| Age Group <75 years of age | 400 Participants | 773 Participants | 373 Participants |
| Age Group ≥75 years of age | 106 Participants | 241 Participants | 135 Participants |
| Baseline Glycated Hemoglobin A1c (HbA1c) | 8.22 percentage of HbA1c STANDARD_DEVIATION 0.92 | 8.21 percentage of HbA1c STANDARD_DEVIATION 0.91 | 8.20 percentage of HbA1c STANDARD_DEVIATION 0.91 |
| Body Mass Index (BMI) | 31.2 kg/m^2 STANDARD_DEVIATION 5.7 | 31.1 kg/m^2 STANDARD_DEVIATION 5.6 | 30.9 kg/m^2 STANDARD_DEVIATION 5.5 |
| Duration of Type 2 Diabetes | 15.35 years STANDARD_DEVIATION 7.7 | 15.32 years STANDARD_DEVIATION 7.93 | 15.29 years STANDARD_DEVIATION 8.17 |
| Randomization strata of insulin Insulin-naive | 165 Participants | 331 Participants | 166 Participants |
| Randomization strata of insulin Insulin pre-treated | 341 Participants | 683 Participants | 342 Participants |
| Sex: Female, Male Female | 229 Participants | 487 Participants | 258 Participants |
| Sex: Female, Male Male | 277 Participants | 527 Participants | 250 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 508 | 0 / 505 |
| other Total, other adverse events | 62 / 508 | 64 / 505 |
| serious Total, serious adverse events | 41 / 508 | 34 / 505 |
Outcome results
Primary
Change in HbA1c From Baseline to Week 26
Adjusted least square (LS) means were obtained from analysis of covariance (ANCOVA) after multiple imputation of missing data including post baseline HbA1c data during the 26-week randomized period.
Time frame: Baseline, Week 26
Population: Intent-to-treat (ITT) population included all randomized participants regardless of whether the treatment kit was used, and analyzed according to the treatment group allocated by randomization.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| HOE901-U300 | Change in HbA1c From Baseline to Week 26 | -0.89 percentage of hemoglobin | Standard Error 0.038 |
| Lantus | Change in HbA1c From Baseline to Week 26 | -0.91 percentage of hemoglobin | Standard Error 0.042 |
Comparison: Analysis was performed using ANCOVA model including the fixed categorical effects of treatment group, randomization strata, as well as the continuous fixed covariates of baseline value and following multiple imputation procedure for missing data.95% CI: [-0.092, 0.129]
Secondary
Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26
Adjusted LS means from multiple imputation approach including post baseline values during the 26-week randomized period.
Time frame: Baseline, Week 26
Population: ITT population. Here 'Overall number of participants analyzed' signifies participants with available data for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| HOE901-U300 | Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26 | -1.68 mmol/L | Standard Error 0.122 |
| Lantus | Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26 | -1.77 mmol/L | Standard Error 0.135 |
Secondary
Change in World Health Organization-5 (WHO-5) Well-Being Questionnaire Percentage Score From Baseline to Week 26
WHO-5 well-being index evaluates positive psychological well-being during the past 2 weeks and consists of 5 questions, each rated on a 6-point Likert scale from 0 (not present) to 5 (constantly present). Total raw score was transformed into a percentage score ranging from 0 (worst possible quality of life) to 100 (best possible quality of life).
Time frame: Baseline, Week 26
Population: ITT population. Here 'Overall number of participants analyzed' signifies participants with available data for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| HOE901-U300 | Change in World Health Organization-5 (WHO-5) Well-Being Questionnaire Percentage Score From Baseline to Week 26 | -1.16 scores on a scale | Standard Error 0.751 |
| Lantus | Change in World Health Organization-5 (WHO-5) Well-Being Questionnaire Percentage Score From Baseline to Week 26 | 0.22 scores on a scale | Standard Error 0.758 |
Secondary
Percentage of Participants Requiring Rescue Therapy Over the 26 Weeks of Treatment
Routine fasting self-monitored plasma glucose (SMPG) and central laboratory FPG (and HbA1c after Week 14) values were used to determine the requirement of rescue medication. Threshold values at Week 14: FPG \>200 mg/dL (11 mmol/L), or HbA1c \>8.5%.
Time frame: Baseline up to Week 26
Population: ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HOE901-U300 | Percentage of Participants Requiring Rescue Therapy Over the 26 Weeks of Treatment | 3.7 percentage of participants |
| Lantus | Percentage of Participants Requiring Rescue Therapy Over the 26 Weeks of Treatment | 2.6 percentage of participants |
Secondary
Percentage of Participants With At Least One Severe and/ or Confirmed (≤3.9 mmol/L [70 mg/dL]) Hypoglycemia Occurring at Any Time of the Day During 26-Week Randomized Period
Estimated percentages from multiple imputation approach including data from the 26-week randomized period. 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 ≤3.9 mmol/L (70 mg/dL).
Time frame: Baseline up to Week 26
Population: ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HOE901-U300 | Percentage of Participants With At Least One Severe and/ or Confirmed (≤3.9 mmol/L [70 mg/dL]) Hypoglycemia Occurring at Any Time of the Day During 26-Week Randomized Period | 59.4 percentage of participants |
| Lantus | Percentage of Participants With At Least One Severe and/ or Confirmed (≤3.9 mmol/L [70 mg/dL]) Hypoglycemia Occurring at Any Time of the Day During 26-Week Randomized Period | 62.7 percentage of participants |
Secondary
Percentage of Participants With At Least One Severe and/ or Confirmed (≤3.9 mmol/L [70 mg/dL]) Nocturnal Hypoglycemia (00:00 to 05:59 Hours) During 26-Week Randomized Period
Estimated percentages from multiple imputation approach including data from the 26-week randomized period. 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 ≤3.9 mmol/L (70 mg/dL).
Time frame: Baseline up to Week 26
Population: ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HOE901-U300 | Percentage of Participants With At Least One Severe and/ or Confirmed (≤3.9 mmol/L [70 mg/dL]) Nocturnal Hypoglycemia (00:00 to 05:59 Hours) During 26-Week Randomized Period | 20.2 percentage of participants |
| Lantus | Percentage of Participants With At Least One Severe and/ or Confirmed (≤3.9 mmol/L [70 mg/dL]) Nocturnal Hypoglycemia (00:00 to 05:59 Hours) During 26-Week Randomized Period | 22.5 percentage of participants |
Secondary
Percentage of Participants With At Least One Severe and/ or Confirmed (≤3.9 mmol/L [70 mg/dL]) Nocturnal Hypoglycemia (22:00 to 08:59 Hours Next Morning) During 26-Week Randomized Period
Estimated percentages from multiple imputation approach including data from the 26-week randomized period. 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 ≤3.9 mmol/L (70 mg/dL).
Time frame: Baseline up to Week 26
Population: ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HOE901-U300 | Percentage of Participants With At Least One Severe and/ or Confirmed (≤3.9 mmol/L [70 mg/dL]) Nocturnal Hypoglycemia (22:00 to 08:59 Hours Next Morning) During 26-Week Randomized Period | 48.3 percentage of participants |
| Lantus | Percentage of Participants With At Least One Severe and/ or Confirmed (≤3.9 mmol/L [70 mg/dL]) Nocturnal Hypoglycemia (22:00 to 08:59 Hours Next Morning) During 26-Week Randomized Period | 47.7 percentage of participants |
Comparison: Analysis was done by Cochran-Mantel-Haenszel method with randomization strata (screening HbA1c \[\<8.0%; ≥8.0%\], previous use of insulin \[naive, pre-treated\], use of sulfonylurea or meglitinides at screening \[yes, no\]), following multiple imputation procedure for missing data.p-value: 0.841595% CI: [0.89, 1.153]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With HbA1c <7.5% or <7.0% at Week 26 and No Severe and/or Confirmed (≤3.9 mmol/L [70 mg/dL]) Hypoglycemia During 26-Week Randomized Period
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 ≤3.9 mmol/L (70 mg/dL).
Time frame: Baseline up to Week 26
Population: ITT population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HOE901-U300 | Percentage of Participants With HbA1c <7.5% or <7.0% at Week 26 and No Severe and/or Confirmed (≤3.9 mmol/L [70 mg/dL]) Hypoglycemia During 26-Week Randomized Period | HbA1c <7.5% | 26.4 percentage of participants |
| HOE901-U300 | Percentage of Participants With HbA1c <7.5% or <7.0% at Week 26 and No Severe and/or Confirmed (≤3.9 mmol/L [70 mg/dL]) Hypoglycemia During 26-Week Randomized Period | HbA1c <7.0% | 14.0 percentage of participants |
| Lantus | Percentage of Participants With HbA1c <7.5% or <7.0% at Week 26 and No Severe and/or Confirmed (≤3.9 mmol/L [70 mg/dL]) Hypoglycemia During 26-Week Randomized Period | HbA1c <7.5% | 21.5 percentage of participants |
| Lantus | Percentage of Participants With HbA1c <7.5% or <7.0% at Week 26 and No Severe and/or Confirmed (≤3.9 mmol/L [70 mg/dL]) Hypoglycemia During 26-Week Randomized Period | HbA1c <7.0% | 12.3 percentage of participants |
Secondary
Percentage of Participants With HbA1c <7.5% or HbA1c <7% During 26-Week Randomized Period
Participants without any available HbA1c assessment at Week 26 were considered as non-responders in the analyses.
Time frame: Baseline up to Week 26
Population: ITT population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HOE901-U300 | Percentage of Participants With HbA1c <7.5% or HbA1c <7% During 26-Week Randomized Period | HbA1c <7.5% | 60.6 percentage of participants |
| HOE901-U300 | Percentage of Participants With HbA1c <7.5% or HbA1c <7% During 26-Week Randomized Period | HbA1c <7.0% | 33.3 percentage of participants |
| Lantus | Percentage of Participants With HbA1c <7.5% or HbA1c <7% During 26-Week Randomized Period | HbA1c <7.0% | 35.2 percentage of participants |
| Lantus | Percentage of Participants With HbA1c <7.5% or HbA1c <7% During 26-Week Randomized Period | HbA1c <7.5% | 58.9 percentage of participants |
Post Hoc
Hypoglycemia (Any Hypoglycemia, Documented Symptomatic Hypoglycemia, Severe and/or Confirmed Hypoglycemia) Event Rate Per Participant Year: By Age Categorical Data During the 26 Weeks of Treatment
Hypoglycemia events were hypoglycemia of any category, severe hypoglycemia (an event that required assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions); documented symptomatic hypoglycemia (symptoms of hypoglycemia with plasma glucose ≤3.9 mmol/L \[70 mg/dL\]); confirmed hypoglycemia (with or without symptoms of hypoglycemia and plasma glucose ≤3.9 mmol/L).
Time frame: Baseline up to Week 26
Population: Safety population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HOE901-U300 | Hypoglycemia (Any Hypoglycemia, Documented Symptomatic Hypoglycemia, Severe and/or Confirmed Hypoglycemia) Event Rate Per Participant Year: By Age Categorical Data During the 26 Weeks of Treatment | Any hypoglycemia:<75 years age | 6.44 events per participant year |
| HOE901-U300 | Hypoglycemia (Any Hypoglycemia, Documented Symptomatic Hypoglycemia, Severe and/or Confirmed Hypoglycemia) Event Rate Per Participant Year: By Age Categorical Data During the 26 Weeks of Treatment | Any hypoglycemia:≥75 years age | 5.01 events per participant year |
| HOE901-U300 | Hypoglycemia (Any Hypoglycemia, Documented Symptomatic Hypoglycemia, Severe and/or Confirmed Hypoglycemia) Event Rate Per Participant Year: By Age Categorical Data During the 26 Weeks of Treatment | Documented symptomatic hypoglycemia:<75 years age | 2.11 events per participant year |
| HOE901-U300 | Hypoglycemia (Any Hypoglycemia, Documented Symptomatic Hypoglycemia, Severe and/or Confirmed Hypoglycemia) Event Rate Per Participant Year: By Age Categorical Data During the 26 Weeks of Treatment | Documented symptomatic hypoglycemia:≥75 years age | 1.12 events per participant year |
| HOE901-U300 | Hypoglycemia (Any Hypoglycemia, Documented Symptomatic Hypoglycemia, Severe and/or Confirmed Hypoglycemia) Event Rate Per Participant Year: By Age Categorical Data During the 26 Weeks of Treatment | Severe and/or confirmed hypoglycemia:<75 years age | 5.43 events per participant year |
| HOE901-U300 | Hypoglycemia (Any Hypoglycemia, Documented Symptomatic Hypoglycemia, Severe and/or Confirmed Hypoglycemia) Event Rate Per Participant Year: By Age Categorical Data During the 26 Weeks of Treatment | Severe and/or confirmed hypoglycemia:≥75 years age | 4.46 events per participant year |
| Lantus | Hypoglycemia (Any Hypoglycemia, Documented Symptomatic Hypoglycemia, Severe and/or Confirmed Hypoglycemia) Event Rate Per Participant Year: By Age Categorical Data During the 26 Weeks of Treatment | Severe and/or confirmed hypoglycemia:<75 years age | 6.37 events per participant year |
| Lantus | Hypoglycemia (Any Hypoglycemia, Documented Symptomatic Hypoglycemia, Severe and/or Confirmed Hypoglycemia) Event Rate Per Participant Year: By Age Categorical Data During the 26 Weeks of Treatment | Any hypoglycemia:<75 years age | 7.85 events per participant year |
| Lantus | Hypoglycemia (Any Hypoglycemia, Documented Symptomatic Hypoglycemia, Severe and/or Confirmed Hypoglycemia) Event Rate Per Participant Year: By Age Categorical Data During the 26 Weeks of Treatment | Documented symptomatic hypoglycemia:≥75 years age | 2.71 events per participant year |
| Lantus | Hypoglycemia (Any Hypoglycemia, Documented Symptomatic Hypoglycemia, Severe and/or Confirmed Hypoglycemia) Event Rate Per Participant Year: By Age Categorical Data During the 26 Weeks of Treatment | Any hypoglycemia:≥75 years age | 7.32 events per participant year |
| Lantus | Hypoglycemia (Any Hypoglycemia, Documented Symptomatic Hypoglycemia, Severe and/or Confirmed Hypoglycemia) Event Rate Per Participant Year: By Age Categorical Data During the 26 Weeks of Treatment | Severe and/or confirmed hypoglycemia:≥75 years age | 6.28 events per participant year |
| Lantus | Hypoglycemia (Any Hypoglycemia, Documented Symptomatic Hypoglycemia, Severe and/or Confirmed Hypoglycemia) Event Rate Per Participant Year: By Age Categorical Data During the 26 Weeks of Treatment | Documented symptomatic hypoglycemia:<75 years age | 2.52 events per participant year |
Other Pre-specified
Hypoglycemia (Any Hypoglycemia, Documented Symptomatic Hypoglycemia, Severe and/or Confirmed Hypoglycemia) Event Rate Per Participant Year During the 26 Weeks of Treatment
Hypoglycemia events were hypoglycemia of any category, severe hypoglycemia (an event that required assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions); documented symptomatic hypoglycemia (symptoms of hypoglycemia with plasma glucose ≤3.9 mmol/L \[70 mg/dL\]); confirmed hypoglycemia (with or without symptoms of hypoglycemia and plasma glucose ≤3.9 mmol/L).
Time frame: Baseline up to Week 26
Population: Safety population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HOE901-U300 | Hypoglycemia (Any Hypoglycemia, Documented Symptomatic Hypoglycemia, Severe and/or Confirmed Hypoglycemia) Event Rate Per Participant Year During the 26 Weeks of Treatment | Any hypoglycemia | 6.06 events per participant year |
| HOE901-U300 | Hypoglycemia (Any Hypoglycemia, Documented Symptomatic Hypoglycemia, Severe and/or Confirmed Hypoglycemia) Event Rate Per Participant Year During the 26 Weeks of Treatment | Documented symptomatic hypoglycemia | 1.85 events per participant year |
| HOE901-U300 | Hypoglycemia (Any Hypoglycemia, Documented Symptomatic Hypoglycemia, Severe and/or Confirmed Hypoglycemia) Event Rate Per Participant Year During the 26 Weeks of Treatment | Severe and/or confirmed hypoglycemia | 5.17 events per participant year |
| Lantus | Hypoglycemia (Any Hypoglycemia, Documented Symptomatic Hypoglycemia, Severe and/or Confirmed Hypoglycemia) Event Rate Per Participant Year During the 26 Weeks of Treatment | Any hypoglycemia | 7.74 events per participant year |
| Lantus | Hypoglycemia (Any Hypoglycemia, Documented Symptomatic Hypoglycemia, Severe and/or Confirmed Hypoglycemia) Event Rate Per Participant Year During the 26 Weeks of Treatment | Documented symptomatic hypoglycemia | 2.56 events per participant year |
| Lantus | Hypoglycemia (Any Hypoglycemia, Documented Symptomatic Hypoglycemia, Severe and/or Confirmed Hypoglycemia) Event Rate Per Participant Year During the 26 Weeks of Treatment | Severe and/or confirmed hypoglycemia | 6.36 events per participant year |
Other Pre-specified
Percentage of Participants With Hypoglycemia (Any Hypoglycemia, Documented Symptomatic Hypoglycemia, Severe and/or Confirmed Hypoglycemia) During the 26 Weeks of Treatment
Hypoglycemia events were hypoglycemia of any category, severe hypoglycemia (an event that required assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions); documented symptomatic hypoglycemia (symptoms of hypoglycemia with plasma glucose ≤3.9 mmol/L \[70 mg/dL\]); confirmed hypoglycemia (with or without symptoms of hypoglycemia and plasma glucose ≤3.9 mmol/L).
Time frame: Baseline up to Week 26
Population: Safety population included all randomized participants who actually received at least 1 dose or part of a dose of investigational medicinal product (IMP) and analyzed according to the treatment actually received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HOE901-U300 | Percentage of Participants With Hypoglycemia (Any Hypoglycemia, Documented Symptomatic Hypoglycemia, Severe and/or Confirmed Hypoglycemia) During the 26 Weeks of Treatment | Documented symptomatic hypoglycemia | 32.9 percentage of participants |
| HOE901-U300 | Percentage of Participants With Hypoglycemia (Any Hypoglycemia, Documented Symptomatic Hypoglycemia, Severe and/or Confirmed Hypoglycemia) During the 26 Weeks of Treatment | Severe and/or confirmed hypoglycemia:<75 years age | 59.2 percentage of participants |
| HOE901-U300 | Percentage of Participants With Hypoglycemia (Any Hypoglycemia, Documented Symptomatic Hypoglycemia, Severe and/or Confirmed Hypoglycemia) During the 26 Weeks of Treatment | Severe and/or confirmed hypoglycemia | 58.1 percentage of participants |
| HOE901-U300 | Percentage of Participants With Hypoglycemia (Any Hypoglycemia, Documented Symptomatic Hypoglycemia, Severe and/or Confirmed Hypoglycemia) During the 26 Weeks of Treatment | Severe and/or confirmed hypoglycemia:≥75 years age | 54.8 percentage of participants |
| HOE901-U300 | Percentage of Participants With Hypoglycemia (Any Hypoglycemia, Documented Symptomatic Hypoglycemia, Severe and/or Confirmed Hypoglycemia) During the 26 Weeks of Treatment | Any hypoglycemia | 62.6 percentage of participants |
| Lantus | Percentage of Participants With Hypoglycemia (Any Hypoglycemia, Documented Symptomatic Hypoglycemia, Severe and/or Confirmed Hypoglycemia) During the 26 Weeks of Treatment | Severe and/or confirmed hypoglycemia:≥75 years age | 59.4 percentage of participants |
| Lantus | Percentage of Participants With Hypoglycemia (Any Hypoglycemia, Documented Symptomatic Hypoglycemia, Severe and/or Confirmed Hypoglycemia) During the 26 Weeks of Treatment | Any hypoglycemia | 66.5 percentage of participants |
| Lantus | Percentage of Participants With Hypoglycemia (Any Hypoglycemia, Documented Symptomatic Hypoglycemia, Severe and/or Confirmed Hypoglycemia) During the 26 Weeks of Treatment | Documented symptomatic hypoglycemia | 34.7 percentage of participants |
| Lantus | Percentage of Participants With Hypoglycemia (Any Hypoglycemia, Documented Symptomatic Hypoglycemia, Severe and/or Confirmed Hypoglycemia) During the 26 Weeks of Treatment | Severe and/or confirmed hypoglycemia | 60.6 percentage of participants |
| Lantus | Percentage of Participants With Hypoglycemia (Any Hypoglycemia, Documented Symptomatic Hypoglycemia, Severe and/or Confirmed Hypoglycemia) During the 26 Weeks of Treatment | Severe and/or confirmed hypoglycemia:<75 years age | 60.9 percentage of participants |