Type 1 Diabetes Mellitus
Conditions
Brief summary
The aim of this extension study is to assess the safety and efficacy of Mylan's insulin glargine and Lantus® in T1DM patients.
Detailed description
This multi-center, open-label, randomized clinical extension study in patients with T1DM will assess safety and efficacy of Mylan's insulin glargine and Lantus®. Patients with an established diagnosis of T1DM per American Diabetes Association 2014 criteria who were randomized to the Lantus® treatment arm of the Mylan Glargine 3001 study, and who have completed the 52-week treatment period on Lantus® will be eligible to be screened for the MYL-1501D-3003 study.
Interventions
DRUGLantus®
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 66 Years
Healthy volunteers
Yes
Inclusion criteria
1. Patients who have completed the 52-week treatment period (irrespective of their age at the completion of MYL-GAI-3001 trial) of the MYL-GAI-3001 trial and were assigned to Lantus® in that study. 2. Patients or their legal representatives must give written and signed informed consent before starting any protocol-specific procedures. 3. The patient is able and willing to comply with the requirements of the extension study protocol including the 8-point self-monitoring blood glucose, completion of patient diary records as instructed and following a recommended diet and exercise plan for the entire duration of the extension study. 4. Female patients complying with the following: * Female patients of childbearing potential must be using oral contraception or two other acceptable methods of contraception, (e.g., intra-uterine device plus condom, spermicidal gel plus condom, diaphragm plus condom, etc.) from the time of randomization throughout the entire study. * Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. * Postmenopausal females must have had no menstrual bleeding for at least 1 year prior to inclusion in MYL-GAI-3001 study. * Female patients who report surgical sterilization must have had the procedure at least 6 months prior to inclusion to MYL-GAI-3001 study. * All female patients of childbearing potential, must have negative pregnancy test results at baseline (week 0) and at each clinic visit as per the SCHEDULE OF ACTIVITIES. * If female patients have male partners who have undergone vasectomy, the vasectomy must have occurred more than 6 months prior to inclusion in MYL-GAI-3001 study.
Exclusion criteria
1. History or presence of a medical condition or disease that in the Investigator's opinion would place the patient at an unacceptable risk from trial participation. 2. History of clinically significant (i.e., significant enough to alter the insulin dose requirement, as per the Investigator) acute bacterial, viral or fungal systemic infections in the 4 weeks prior to inclusion / randomization (recorded while collecting patient history) in to the MYL-1501D-3003 extension study 3. Patients scheduled to receive another investigational drug during the extension study period 4. Any major elective surgery requiring hospitalization planned during the extension study period. 5. Moderate insulin resistance, defined as requiring insulin (Basal + Prandial) of ≥1.5 U/kg/day (Lantus® in U/kg/day or Mylan's insulin glargine in IU/kg/day).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in Hemoglobin A1c (HbA1c) From Baseline | Baseline to 36 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Overall Average of Self-monitoring Blood Glucose (SMBG) Change From Baseline | Baseline to 36 weeks |
| Change From Baseline Total Daily Insulin Dose | Baseline to 36 weeks |
| Local and Systemic Allergic Reactions | Baseline to 40 weeks |
| Hypoglycemic Rate | Baseline to 36 weeks |
| Change From Baseline in Fasting Plasma Glucose | Baseline to 36 weeks |
| Change From Baseline in Total Insulin Antibodies - Mylan Insulin Glargine Assay | Baseline to 36 weeks |
| Change From Baseline in Total Insulin Antibodies - Lantus Assay | Baseline to 36 weeks |
| Change From Baseline in Cross-Reactive Insulin Antibody - Mylan Insulin Glargine Assay | Baseline to 36 weeks |
| Change From Baseline in Cross-Reactive Insulin Antibody - Lantus Assay | Baseline to 36 weeks |
| Hypoglycemic Incidence | Baseline to 36 weeks |
Countries
Canada, Czechia, Estonia, Germany, Hungary, Latvia, Slovakia, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Mylan's Insulin Glargine Patients will be administered either Mylan insulin glargine or Lantus® subcutaneously, once daily in combination with lispro and titrated based on blood glucose readings per standard of care for a total of thirty-six (36) weeks, split into three cycles of twelve (12) weeks each.
Mylan's insulin glargine | 64 |
| Lantus® Patients will be administered either Mylan insulin glargine or Lantus® subcutaneously, once daily in combination with lispro and titrated based on blood glucose readings per standard of care for a total of thirty-six (36) weeks, split into three cycles of twelve (12) weeks each.
Lantus® | 63 |
| Total | 127 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 1 | Adverse Event | 0 | 1 |
| Period 1 | Lost to Follow-up | 1 | 0 |
| Period 2 | Withdrawal by Subject | 1 | 4 |
| Period 3 | Lost to Follow-up | 1 | 0 |
Baseline characteristics
| Characteristic | Mylan's Insulin Glargine | Lantus® | Total |
|---|---|---|---|
| Age, Continuous | 44.8 years STANDARD_DEVIATION 11.43 | 43.2 years STANDARD_DEVIATION 12.69 | 44.0 years STANDARD_DEVIATION 12.05 |
| Baseline fasting plasma glucose | 9.82 mmol/L STANDARD_DEVIATION 3.455 | 9.51 mmol/L STANDARD_DEVIATION 4.099 | 9.67 mmol/L STANDARD_DEVIATION 3.779 |
| Baseline hemoglobin A1c (HbA1c) | 7.64 % STANDARD_DEVIATION 0.997 | 7.87 % STANDARD_DEVIATION 0.913 | 7.75 % STANDARD_DEVIATION 0.959 |
| Baseline hepatitis C antibody (HCVAb) Low positive | 0 participants | 1 participants | 1 participants |
| Baseline hepatitis C antibody (HCVAb) Negative | 64 participants | 62 participants | 126 participants |
| Baseline HIV Status Negative | 64 participants | 62 participants | 126 participants |
| Baseline HIV Status Positive | 0 participants | 1 participants | 1 participants |
| Body mass index | 26.744 kg/m2 STANDARD_DEVIATION 4.1795 | 27.134 kg/m2 STANDARD_DEVIATION 4.4084 | 26.937 kg/m2 STANDARD_DEVIATION 4.282 |
| Dosing Time Evening | 53 participants | 51 participants | 104 participants |
| Dosing Time Morning | 11 participants | 12 participants | 23 participants |
| Duration of diabetes | 21.369 years STANDARD_DEVIATION 12.8879 | 20.212 years STANDARD_DEVIATION 8.9657 | 20.801 years STANDARD_DEVIATION 11.1013 |
| Height | 173.299 centimeters STANDARD_DEVIATION 9.9451 | 174.092 centimeters STANDARD_DEVIATION 8.5502 | 173.692 centimeters STANDARD_DEVIATION 9.2511 |
| Hepatitis B surface antigen (HBsAg) Negative | 64 participants | 63 participants | 127 participants |
| Hepatitis B surface antigen (HBsAg) Positive | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Asian | 2 participants | 0 participants | 2 participants |
| Race/Ethnicity, Customized Black | 2 participants | 2 participants | 4 participants |
| Race/Ethnicity, Customized Hispanic | 1 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized White | 59 participants | 61 participants | 120 participants |
| Region of Enrollment Europe | 30 participants | 27 participants | 57 participants |
| Region of Enrollment North America | 34 participants | 36 participants | 70 participants |
| Sex: Female, Male Female | 23 Participants | 27 Participants | 50 Participants |
| Sex: Female, Male Male | 41 Participants | 36 Participants | 77 Participants |
| Weight | 80.712 kilograms STANDARD_DEVIATION 16.5393 | 82.415 kilograms STANDARD_DEVIATION 15.2942 | 81.557 kilograms STANDARD_DEVIATION 15.8936 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 64 | 0 / 63 |
| other Total, other adverse events | 41 / 64 | 42 / 63 |
| serious Total, serious adverse events | 2 / 64 | 5 / 63 |
Outcome results
Primary
Change in Hemoglobin A1c (HbA1c) From Baseline
Time frame: Baseline to 36 weeks
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Mylan's Insulin Glargine | Change in Hemoglobin A1c (HbA1c) From Baseline | -0.05 percent | Standard Error 0.032 |
| Lantus® | Change in Hemoglobin A1c (HbA1c) From Baseline | -0.06 percent | Standard Error 0.034 |
Secondary
Change From Baseline in Cross-Reactive Insulin Antibody - Lantus Assay
Time frame: Baseline to 36 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mylan's Insulin Glargine | Change From Baseline in Cross-Reactive Insulin Antibody - Lantus Assay | -1.232 percent binding | Standard Deviation 4.8965 |
| Lantus® | Change From Baseline in Cross-Reactive Insulin Antibody - Lantus Assay | -2.192 percent binding | Standard Deviation 5.1741 |
Secondary
Change From Baseline in Cross-Reactive Insulin Antibody - Mylan Insulin Glargine Assay
Time frame: Baseline to 36 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mylan's Insulin Glargine | Change From Baseline in Cross-Reactive Insulin Antibody - Mylan Insulin Glargine Assay | -2.051 percent binding | Standard Deviation 5.3697 |
| Lantus® | Change From Baseline in Cross-Reactive Insulin Antibody - Mylan Insulin Glargine Assay | -2.252 percent binding | Standard Deviation 5.1904 |
Secondary
Change From Baseline in Fasting Plasma Glucose
Time frame: Baseline to 36 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mylan's Insulin Glargine | Change From Baseline in Fasting Plasma Glucose | -0.56 mmol/L | Standard Deviation 3.458 |
| Lantus® | Change From Baseline in Fasting Plasma Glucose | 0.10 mmol/L | Standard Deviation 4.521 |
Secondary
Change From Baseline in Total Insulin Antibodies - Lantus Assay
Time frame: Baseline to 36 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mylan's Insulin Glargine | Change From Baseline in Total Insulin Antibodies - Lantus Assay | -1.288 percent binding | Standard Deviation 4.9617 |
| Lantus® | Change From Baseline in Total Insulin Antibodies - Lantus Assay | -2.351 percent binding | Standard Deviation 5.374 |
Secondary
Change From Baseline in Total Insulin Antibodies - Mylan Insulin Glargine Assay
Time frame: Baseline to 36 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mylan's Insulin Glargine | Change From Baseline in Total Insulin Antibodies - Mylan Insulin Glargine Assay | -2.098 percent binding | Standard Deviation 5.3826 |
| Lantus® | Change From Baseline in Total Insulin Antibodies - Mylan Insulin Glargine Assay | -2.474 percent binding | Standard Deviation 5.2505 |
Secondary
Change From Baseline Total Daily Insulin Dose
Time frame: Baseline to 36 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mylan's Insulin Glargine | Change From Baseline Total Daily Insulin Dose | 0.0016 Units per kilogram | Standard Deviation 0.09239 |
| Lantus® | Change From Baseline Total Daily Insulin Dose | 0.0023 Units per kilogram | Standard Deviation 0.07712 |
Secondary
Hypoglycemic Incidence
Time frame: Baseline to 36 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mylan's Insulin Glargine | Hypoglycemic Incidence | 58 events |
| Lantus® | Hypoglycemic Incidence | 57 events |
Secondary
Hypoglycemic Rate
Time frame: Baseline to 36 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mylan's Insulin Glargine | Hypoglycemic Rate | 0.627 episodes/30 days | Standard Deviation 2.718 |
| Lantus® | Hypoglycemic Rate | 0.410 episodes/30 days | Standard Deviation 4.0911 |
Secondary
Local and Systemic Allergic Reactions
Time frame: Baseline to 40 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Mylan's Insulin Glargine | Local and Systemic Allergic Reactions | Systemic | 1 participants |
| Mylan's Insulin Glargine | Local and Systemic Allergic Reactions | Local | 1 participants |
| Lantus® | Local and Systemic Allergic Reactions | Systemic | 0 participants |
| Lantus® | Local and Systemic Allergic Reactions | Local | 1 participants |
Secondary
Overall Average of Self-monitoring Blood Glucose (SMBG) Change From Baseline
Time frame: Baseline to 36 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mylan's Insulin Glargine | Overall Average of Self-monitoring Blood Glucose (SMBG) Change From Baseline | -0.144 mmol/L | Standard Deviation 1.2569 |
| Lantus® | Overall Average of Self-monitoring Blood Glucose (SMBG) Change From Baseline | -0.426 mmol/L | Standard Deviation 1.1243 |