Type 2 Diabetes
Conditions
Brief summary
To test whether Mylan's insulin glargine once daily is non-inferior to Lantus® once daily (both administered in combination with other anti-diabetic drugs) based on the change in HbA1c from baseline to 24 weeks
Detailed description
This trial is a multi-center, open-label, randomized, parallel group trial in patients with T2DM comparing the efficacy and safety of Mylan's insulin glargine with that of Lantus®. Patients with an established diagnosis of T2DM per ADA 2014 criteria and who satisfy the selection criteria will be included in the trial. This will be followed by a 24-week randomized, comparative, parallel-assignment treatment period with Mylan's insulin glargine or Lantus® (in addition to other anti-diabetic drugs). After the treatment period, there will be a follow-up visit; 4 weeks after the patient has been put back on approved medications.
Interventions
Patients who are randomized to receive Mylan's insulin glargine during the comparative phase will receive the same dose as the dose of Lantus® received during the screening period. The recommended starting dose of Mylan's insulin glargine or Lantus®, in patients with T2DM who are not currently treated with insulin is 10 units (or 0.2 Units/kg) once daily, which should subsequently be adjusted every week if essential.
DRUGLantus®
For patients who are randomized to receive Lantus® during the comparative phase the dose of Lantus® will be equal to the dose received during the screening period.
Sponsors
Mylan GmbH
Mylan Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Patients with an established diagnosis of T2DM per ADA 2014 criteria who also fulfill the following: * Diagnosis established 1 year prior to screening * Insulin-naïve OR * On Lantus® once daily at stable dose (±15% variation in dose) for at least 3 months prior to screening * Body mass index (BMI) of 18.50 to 40.00 kg/m2 at screening (both values inclusive). * Stable weight, with no more than 5 kg gain or loss, in the 3 months prior to screening; this information will be collected by patient interview during medical history. * Hemoglobin ≥9.0 g/dL at screening * Glycosylated hemoglobin (HbA1c) of \<10.5% or between 7.5 to 10.5% for insulin naïve patients at screening.
Exclusion criteria
* History of hypersensitivity to any of the active or inactive ingredients of the insulin/insulin analog preparations used in the trial, OR history of significant allergic drug reactions. * History of use of animal insulin within the last 3 years, any insulin other than Lantus® within the last 3 months prior to screening, or use of biosimilar insulin glargine at any time prior to screening. * Patients requiring basal-bolus insulin therapy or who in the opinion of the investigator require mealtime insulin in order to achieve glycemic control. * Regular use of immune-modulator therapy in the 1 year prior to screening. * History of ≥2 episodes of severe hypoglycemia within the 6 months before screening or history of hypoglycemia unawareness (a sample questionnaire is provided in Appendix I) as judged by the investigator. * History of ≥1 episode of hyperglycemic hyperosmolar coma or emergency room visits for uncontrolled diabetes leading to hospitalization within the 6 months prior to screening. * Serological evidence of human immunodeficiency virus (HIV), hepatitis B (HbSAg) or hepatitis C (HCVAb) antibodies at screening. * History of drug or alcohol dependence or abuse during the 1 year prior to screening. * Receipt of another investigational drug in the 3 months prior to screening (or as per local regulations), or if the screening visit is within 5 half-lives of another investigational drug (whichever is longer), or scheduled to receive another investigational drug during the current trial period.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in HbA1c From Baseline to 24 Weeks | 24 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hypoglycemia Occurrence | 24 weeks | Overall hypoglycemic incidence during treatment period |
| Change in Total Insulin Antibody Percent Binding for Mylan's Insulin Glargine Assay Over Time | Week 12 and week 24 | Comparison of change from Baseline in Immunogenicity |
| Rate of Hypoglycemic Events Per 30 Days | Baseline and up to 24 weeks | The change from baseline at 12 and 24 weeks is reported |
| Change in Cross-Reactive Insulin Antibody Percent Binding for Mylan's Insulin Glargine Assay Over Time | week 12 and week 24 | Comparison of change from Baseline in Immunogenicity |
| Change in Cross-Reactive Insulin Antibody Percent Binding for Lantus Assay Over Time | Week 12 and week 24 | Comparison of change from Baseline in Immunogenicity |
| Change in Total Insulin Antibody Percent Binding for Lantus Assay Over Time | week 12 and week 24 | Comparison of change from Baseline in Immunogenicity |
Countries
Jordan, Slovakia, South Africa, South Korea, Taiwan, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Mylan's Insulin Glargine receive Mylan's insulin Glargine
Mylan's insulin glargine: Patients who are randomized to receive Mylan's insulin glargine during the comparative phase will receive the same dose as the dose of Lantus® received during the screening period. The recommended starting dose of Mylan's insulin glargine or Lantus®, in patients with T2DM who are not currently treated with insulin is 10 units (or 0.2 Units/kg) once daily, which should subsequently be adjusted every week if essential. | 277 |
| Lantus® receive Lantus®
Lantus®: For patients who are randomized to receive Lantus® during the comparative phase the dose of Lantus® will be equal to the dose received during the screening period. | 283 |
| Total | 560 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 0 |
| Overall Study | Lost to Follow-up | 10 | 10 |
| Overall Study | Other | 1 | 3 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Protocol Violation | 10 | 7 |
| Overall Study | Withdrawal by Subject | 12 | 13 |
Baseline characteristics
| Characteristic | Mylan's Insulin Glargine | Lantus® | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 10 Participants | 16 Participants | 26 Participants |
| Age, Categorical Between 18 and 65 years | 267 Participants | 267 Participants | 534 Participants |
| Age, Continuous | 55 years STANDARD_DEVIATION 7.91 | 55.1 years STANDARD_DEVIATION 7.5 | 55.1 years STANDARD_DEVIATION 7.7 |
| Region of Enrollment Jordan | 2 participants | 3 participants | 5 participants |
| Region of Enrollment Slovakia | 34 participants | 33 participants | 67 participants |
| Region of Enrollment South Africa | 12 participants | 15 participants | 27 participants |
| Region of Enrollment South Korea | 3 participants | 4 participants | 7 participants |
| Region of Enrollment Taiwan | 1 participants | 0 participants | 1 participants |
| Region of Enrollment United States | 225 participants | 228 participants | 453 participants |
| Sex: Female, Male Female | 130 Participants | 118 Participants | 248 Participants |
| Sex: Female, Male Male | 147 Participants | 165 Participants | 312 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 276 | 0 / 282 |
| other Total, other adverse events | 177 / 276 | 164 / 282 |
| serious Total, serious adverse events | 8 / 276 | 9 / 282 |
Outcome results
Primary
Change in HbA1c From Baseline to 24 Weeks
Time frame: 24 weeks
Population: Intent-to-Treat Population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Mylan's Insulin Glargine | Change in HbA1c From Baseline to 24 Weeks | -0.6 percent |
| Lantus® | Change in HbA1c From Baseline to 24 Weeks | -0.66 percent |
95% CI: [-0.098, 0.218]
Secondary
Change in Cross-Reactive Insulin Antibody Percent Binding for Lantus Assay Over Time
Comparison of change from Baseline in Immunogenicity
Time frame: Week 12 and week 24
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mylan's Insulin Glargine | Change in Cross-Reactive Insulin Antibody Percent Binding for Lantus Assay Over Time | week 12 | 1.5994 percentage of SB | Standard Deviation 10.64782 |
| Mylan's Insulin Glargine | Change in Cross-Reactive Insulin Antibody Percent Binding for Lantus Assay Over Time | week 24 | 1.5648 percentage of SB | Standard Deviation 9.04243 |
| Lantus® | Change in Cross-Reactive Insulin Antibody Percent Binding for Lantus Assay Over Time | week 12 | 0.5014 percentage of SB | Standard Deviation 6.72058 |
| Lantus® | Change in Cross-Reactive Insulin Antibody Percent Binding for Lantus Assay Over Time | week 24 | 0.8361 percentage of SB | Standard Deviation 7.96308 |
Secondary
Change in Cross-Reactive Insulin Antibody Percent Binding for Mylan's Insulin Glargine Assay Over Time
Comparison of change from Baseline in Immunogenicity
Time frame: week 12 and week 24
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mylan's Insulin Glargine | Change in Cross-Reactive Insulin Antibody Percent Binding for Mylan's Insulin Glargine Assay Over Time | week 12 | 1.7488 percentage of SB | Standard Deviation 11.68129 |
| Mylan's Insulin Glargine | Change in Cross-Reactive Insulin Antibody Percent Binding for Mylan's Insulin Glargine Assay Over Time | week 24 | 1.6301 percentage of SB | Standard Deviation 9.11098 |
| Lantus® | Change in Cross-Reactive Insulin Antibody Percent Binding for Mylan's Insulin Glargine Assay Over Time | week 12 | 0.5116 percentage of SB | Standard Deviation 7.25175 |
| Lantus® | Change in Cross-Reactive Insulin Antibody Percent Binding for Mylan's Insulin Glargine Assay Over Time | week 24 | 0.7524 percentage of SB | Standard Deviation 7.93317 |
Secondary
Change in Total Insulin Antibody Percent Binding for Lantus Assay Over Time
Comparison of change from Baseline in Immunogenicity
Time frame: week 12 and week 24
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mylan's Insulin Glargine | Change in Total Insulin Antibody Percent Binding for Lantus Assay Over Time | week 12 | 1.787 percentage of SB | Standard Deviation 11.67578 |
| Mylan's Insulin Glargine | Change in Total Insulin Antibody Percent Binding for Lantus Assay Over Time | week 24 | 1.6866 percentage of SB | Standard Deviation 9.57132 |
| Lantus® | Change in Total Insulin Antibody Percent Binding for Lantus Assay Over Time | week 12 | 0.6462 percentage of SB | Standard Deviation 7.56375 |
| Lantus® | Change in Total Insulin Antibody Percent Binding for Lantus Assay Over Time | week 24 | 0.8212 percentage of SB | Standard Deviation 8.1084 |
Secondary
Change in Total Insulin Antibody Percent Binding for Mylan's Insulin Glargine Assay Over Time
Comparison of change from Baseline in Immunogenicity
Time frame: Week 12 and week 24
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mylan's Insulin Glargine | Change in Total Insulin Antibody Percent Binding for Mylan's Insulin Glargine Assay Over Time | week 12 | 1.9238 percentage of specific binding (SB) | Standard Deviation 12.54369 |
| Mylan's Insulin Glargine | Change in Total Insulin Antibody Percent Binding for Mylan's Insulin Glargine Assay Over Time | week 24 | 1.7802 percentage of specific binding (SB) | Standard Deviation 9.64745 |
| Lantus® | Change in Total Insulin Antibody Percent Binding for Mylan's Insulin Glargine Assay Over Time | week 12 | 0.6585 percentage of specific binding (SB) | Standard Deviation 8.05473 |
| Lantus® | Change in Total Insulin Antibody Percent Binding for Mylan's Insulin Glargine Assay Over Time | week 24 | 0.7838 percentage of specific binding (SB) | Standard Deviation 8.15086 |
Secondary
Hypoglycemia Occurrence
Overall hypoglycemic incidence during treatment period
Time frame: 24 weeks
Population: Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Mylan's Insulin Glargine | Hypoglycemia Occurrence | Probable Symptomatic Hypoglycemia | 7 number of events |
| Mylan's Insulin Glargine | Hypoglycemia Occurrence | Unknown | 29 number of events |
| Mylan's Insulin Glargine | Hypoglycemia Occurrence | Relative Hypoglycemia | 20 number of events |
| Mylan's Insulin Glargine | Hypoglycemia Occurrence | Any hypoglycemic event | 130 number of events |
| Mylan's Insulin Glargine | Hypoglycemia Occurrence | Severe Hypoglycemia | 0 number of events |
| Mylan's Insulin Glargine | Hypoglycemia Occurrence | Documented Symptomatic Hypoglycemia | 75 number of events |
| Mylan's Insulin Glargine | Hypoglycemia Occurrence | Asymptomatic Hypoglycemia | 85 number of events |
| Lantus® | Hypoglycemia Occurrence | Probable Symptomatic Hypoglycemia | 4 number of events |
| Lantus® | Hypoglycemia Occurrence | Relative Hypoglycemia | 11 number of events |
| Lantus® | Hypoglycemia Occurrence | Severe Hypoglycemia | 1 number of events |
| Lantus® | Hypoglycemia Occurrence | Unknown | 25 number of events |
| Lantus® | Hypoglycemia Occurrence | Asymptomatic Hypoglycemia | 92 number of events |
| Lantus® | Hypoglycemia Occurrence | Documented Symptomatic Hypoglycemia | 76 number of events |
| Lantus® | Hypoglycemia Occurrence | Any hypoglycemic event | 136 number of events |
Secondary
Rate of Hypoglycemic Events Per 30 Days
The change from baseline at 12 and 24 weeks is reported
Time frame: Baseline and up to 24 weeks
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mylan's Insulin Glargine | Rate of Hypoglycemic Events Per 30 Days | week 12 | 0.341 Episodes/30 Days | Standard Deviation 1.8963 |
| Mylan's Insulin Glargine | Rate of Hypoglycemic Events Per 30 Days | week 24 | -0.057 Episodes/30 Days | Standard Deviation 0.919 |
| Lantus® | Rate of Hypoglycemic Events Per 30 Days | week 12 | 0.24 Episodes/30 Days | Standard Deviation 2.0551 |
| Lantus® | Rate of Hypoglycemic Events Per 30 Days | week 24 | -0.102 Episodes/30 Days | Standard Deviation 1.6791 |