Trial Outcomes & Findings for Non-inferiority Study to Compare the Efficacy and Safety of Mylan's Insulin Glargine With Lantus® in Type 1 Diabetes Mellitus Patients (INSTRIDE 1) (NCT NCT02227862)

NCT ID: NCT02227862

Last Updated: 2022-03-03

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

558 participants

Primary outcome timeframe

24 weeks

Results posted on

2022-03-03

Participant Flow

Participant milestones

Participant milestones
Measure	Mylan's Insulin Glargine Receive Mylan's Insulin Glargine plus insulin lispro. Mylan's insulin glargine: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period, and will continue on this for the complete trial. During the 6 week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.	Lantus® Receive Lantus® plus insulin lispro Lantus®: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period; and will continue on this for the complete trial. During the 6week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.
Overall Study STARTED	280	278
Overall Study Week 24	269	263
Overall Study COMPLETED	261	256
Overall Study NOT COMPLETED	19	22

Reasons for withdrawal

Reasons for withdrawal
Measure	Mylan's Insulin Glargine Receive Mylan's Insulin Glargine plus insulin lispro. Mylan's insulin glargine: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period, and will continue on this for the complete trial. During the 6 week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.	Lantus® Receive Lantus® plus insulin lispro Lantus®: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period; and will continue on this for the complete trial. During the 6week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.
Overall Study Protocol Violation	7	9
Overall Study Other	0	2
Overall Study Adverse Event	4	3
Overall Study Withdrawal by Subject	7	6
Overall Study Lost to Follow-up	1	2

Baseline Characteristics

Non-inferiority Study to Compare the Efficacy and Safety of Mylan's Insulin Glargine With Lantus® in Type 1 Diabetes Mellitus Patients (INSTRIDE 1)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Mylan's Insulin Glargine n=280 Participants Receive Mylan's Insulin Glargine plus insulin lispro. Mylan's insulin glargine: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period, and will continue on this for the complete trial. During the 6 week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.	Lantus® n=278 Participants Receive Lantus® plus insulin lispro Lantus®: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period; and will continue on this for the complete trial. During the 6week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.	Total n=558 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	275 Participants n=5 Participants	272 Participants n=7 Participants	547 Participants n=5 Participants
Age, Categorical >=65 years	5 Participants n=5 Participants	6 Participants n=7 Participants	11 Participants n=5 Participants
Age, Continuous	42 years STANDARD_DEVIATION 12.03 • n=5 Participants	42.2 years STANDARD_DEVIATION 11.97 • n=7 Participants	42.1 years STANDARD_DEVIATION 11.99 • n=5 Participants
Sex: Female, Male Female	116 Participants n=5 Participants	106 Participants n=7 Participants	222 Participants n=5 Participants
Sex: Female, Male Male	164 Participants n=5 Participants	172 Participants n=7 Participants	336 Participants n=5 Participants
Race/Ethnicity, Customized Asian	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Race/Ethnicity, Customized Black	2 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	263 Participants n=5 Participants	265 Participants n=7 Participants	528 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic	6 Participants n=5 Participants	3 Participants n=7 Participants	9 Participants n=5 Participants
Race/Ethnicity, Customized Other	7 Participants n=5 Participants	3 Participants n=7 Participants	10 Participants n=5 Participants
Region of Enrollment Europe	145 Participants n=5 Participants	145 Participants n=7 Participants	290 Participants n=5 Participants
Region of Enrollment North America	126 Participants n=5 Participants	126 Participants n=7 Participants	252 Participants n=5 Participants
Region of Enrollment South Africa	9 Participants n=5 Participants	7 Participants n=7 Participants	16 Participants n=5 Participants
Insulin History Yes	280 Participants n=5 Participants	277 Participants n=7 Participants	557 Participants n=5 Participants
Insulin History No	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Dosing Time Morning	38 Participants n=5 Participants	40 Participants n=7 Participants	78 Participants n=5 Participants
Dosing Time Evening	242 Participants n=5 Participants	238 Participants n=7 Participants	480 Participants n=5 Participants
Body Mass Index (BMI)	26.435 kg/m2 STANDARD_DEVIATION 3.7058 • n=5 Participants	26.636 kg/m2 STANDARD_DEVIATION 4.2022 • n=7 Participants	26.535 kg/m2 STANDARD_DEVIATION 3.9586 • n=5 Participants
Duration of Diabetes	18.685 years STANDARD_DEVIATION 11.7771 • n=5 Participants	19.697 years STANDARD_DEVIATION 11.2868 • n=7 Participants	19.206 years STANDARD_DEVIATION 11.5411 • n=5 Participants
Baseline fasting plasma glucose	167.4 mg/dL STANDARD_DEVIATION 68.43 • n=5 Participants	163.9 mg/dL STANDARD_DEVIATION 61.61 • n=7 Participants	165.6 mg/dL STANDARD_DEVIATION 65.09 • n=5 Participants
Baseline HbA1c	7.37 percent STANDARD_DEVIATION 0.869 • n=5 Participants	7.39 percent STANDARD_DEVIATION 0.843 • n=7 Participants	7.38 percent STANDARD_DEVIATION 0.855 • n=5 Participants
Baseline fasting C-peptide	0.298 mmol/L STANDARD_DEVIATION 0.2291 • n=5 Participants	0.291 mmol/L STANDARD_DEVIATION 0.2508 • n=7 Participants	0.295 mmol/L STANDARD_DEVIATION 0.2395 • n=5 Participants

PRIMARY outcome

Timeframe: 24 weeks

Outcome measures

Outcome measures
Measure	Mylan's Insulin Glargine n=280 Participants Receive Mylan's Insulin Glargine plus insulin lispro. Mylan's insulin glargine: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period, and will continue on this for the complete trial. During the 6 week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.	Lantus® n=277 Participants Receive Lantus® plus insulin lispro Lantus®: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period; and will continue on this for the complete trial. During the 6week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.
Change in HbA1c From Baseline to 24 Weeks	0.14 percent Standard Error 0.054	0.11 percent Standard Error 0.054

SECONDARY outcome

Timeframe: 24 and 52 weeks

Outcome measures

Outcome measures
Measure	Mylan's Insulin Glargine n=280 Participants Receive Mylan's Insulin Glargine plus insulin lispro. Mylan's insulin glargine: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period, and will continue on this for the complete trial. During the 6 week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.	Lantus® n=277 Participants Receive Lantus® plus insulin lispro Lantus®: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period; and will continue on this for the complete trial. During the 6week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.
Summary of Actual and Change From Baseline in HbA1c week 24	0.12 percent Standard Deviation 0.599	0.09 percent Standard Deviation 0.526
Summary of Actual and Change From Baseline in HbA1c week 52	0.2 percent Standard Deviation 0.633	0.25 percent Standard Deviation 0.595

SECONDARY outcome

Timeframe: 24 and 52 weeks

Outcome measures

Outcome measures
Measure	Mylan's Insulin Glargine n=280 Participants Receive Mylan's Insulin Glargine plus insulin lispro. Mylan's insulin glargine: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period, and will continue on this for the complete trial. During the 6 week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.	Lantus® n=277 Participants Receive Lantus® plus insulin lispro Lantus®: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period; and will continue on this for the complete trial. During the 6week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.
Change From Baseline in FPG Over Time week 24	-0.81 mmol/L Standard Deviation 4.485	0.09 mmol/L Standard Deviation 4.507
Change From Baseline in FPG Over Time week 52	0.23 mmol/L Standard Deviation 4.281	0.43 mmol/L Standard Deviation 4.455

SECONDARY outcome

Timeframe: 24 and 52 weeks

Outcome measures

Outcome measures
Measure	Mylan's Insulin Glargine n=280 Participants Receive Mylan's Insulin Glargine plus insulin lispro. Mylan's insulin glargine: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period, and will continue on this for the complete trial. During the 6 week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.	Lantus® n=277 Participants Receive Lantus® plus insulin lispro Lantus®: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period; and will continue on this for the complete trial. During the 6week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.
Change From Baseline in 8-point SMBG Profile Over Time week 24	0.038 mmol/L Standard Deviation 2.3751	-0.095 mmol/L Standard Deviation 1.5012
Change From Baseline in 8-point SMBG Profile Over Time week 52	-0.082 mmol/L Standard Deviation 1.5032	-0.082 mmol/L Standard Deviation 1.5267

SECONDARY outcome

Timeframe: 24 and 52 weeks

Outcome measures

Outcome measures
Measure	Mylan's Insulin Glargine n=280 Participants Receive Mylan's Insulin Glargine plus insulin lispro. Mylan's insulin glargine: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period, and will continue on this for the complete trial. During the 6 week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.	Lantus® n=277 Participants Receive Lantus® plus insulin lispro Lantus®: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period; and will continue on this for the complete trial. During the 6week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.
Change in Total Daily Insulin Dose Per Unit Body Weight From Baseline Over Time week 24	0.0203 U/Kg Standard Deviation 0.09962	0.0127 U/Kg Standard Deviation 0.10871
Change in Total Daily Insulin Dose Per Unit Body Weight From Baseline Over Time week 52	0.0278 U/Kg Standard Deviation 0.1044	0.0138 U/Kg Standard Deviation 0.11372

SECONDARY outcome

Timeframe: 24 and 52 weeks

Outcome measures

Outcome measures
Measure	Mylan's Insulin Glargine n=280 Participants Receive Mylan's Insulin Glargine plus insulin lispro. Mylan's insulin glargine: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period, and will continue on this for the complete trial. During the 6 week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.	Lantus® n=278 Participants Receive Lantus® plus insulin lispro Lantus®: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period; and will continue on this for the complete trial. During the 6week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.
Rate of Hypoglycemic Events Per 30 Days Over Time week 24	-5.162 Episodes/30 Days Standard Deviation 9.0724	-4.93 Episodes/30 Days Standard Deviation 8.3815
Rate of Hypoglycemic Events Per 30 Days Over Time week 52	-6.241 Episodes/30 Days Standard Deviation 9.214	-5.765 Episodes/30 Days Standard Deviation 8.3658

SECONDARY outcome

Timeframe: 52 weeks

Outcome measures

Outcome measures
Measure	Mylan's Insulin Glargine n=280 Participants Receive Mylan's Insulin Glargine plus insulin lispro. Mylan's insulin glargine: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period, and will continue on this for the complete trial. During the 6 week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.	Lantus® n=278 Participants Receive Lantus® plus insulin lispro Lantus®: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period; and will continue on this for the complete trial. During the 6week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.
Hypoglycemia Occurrence Any hypoglycemic event	273 Number of patients	269 Number of patients
Hypoglycemia Occurrence Severe hypoglycemia	11 Number of patients	13 Number of patients
Hypoglycemia Occurrence Documented symptomatic hypoglycemia	249 Number of patients	249 Number of patients
Hypoglycemia Occurrence Asymptomatic hypoglycemia	246 Number of patients	243 Number of patients
Hypoglycemia Occurrence Probable symptomatic hypoglycemia	37 Number of patients	36 Number of patients
Hypoglycemia Occurrence Relative hypoglycemia	35 Number of patients	44 Number of patients
Hypoglycemia Occurrence Other hypoglycemia	19 Number of patients	19 Number of patients
Hypoglycemia Occurrence Unknown	77 Number of patients	71 Number of patients

SECONDARY outcome

Timeframe: 52 weeks

Outcome measures

Outcome measures
Measure	Mylan's Insulin Glargine n=280 Participants Receive Mylan's Insulin Glargine plus insulin lispro. Mylan's insulin glargine: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period, and will continue on this for the complete trial. During the 6 week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.	Lantus® n=278 Participants Receive Lantus® plus insulin lispro Lantus®: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period; and will continue on this for the complete trial. During the 6week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.
Occurrence of Local and Systematic Reactions Local	3 Number of patients	4 Number of patients
Occurrence of Local and Systematic Reactions Systemic	2 Number of patients	2 Number of patients

SECONDARY outcome

Timeframe: 24 and 52 weeks

Outcome measures

Outcome measures
Measure	Mylan's Insulin Glargine n=280 Participants Receive Mylan's Insulin Glargine plus insulin lispro. Mylan's insulin glargine: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period, and will continue on this for the complete trial. During the 6 week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.	Lantus® n=278 Participants Receive Lantus® plus insulin lispro Lantus®: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period; and will continue on this for the complete trial. During the 6week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.
Change in Total Insulin Antibody Percent Binding for Mylan's Insulin Glargine Assay Over Time week 24	-0.3063 %SB Standard Deviation 7.22075	0.3592 %SB Standard Deviation 7.16624
Change in Total Insulin Antibody Percent Binding for Mylan's Insulin Glargine Assay Over Time week 52	-0.9591 %SB Standard Deviation 8.51754	-1.0634 %SB Standard Deviation 8.42794

SECONDARY outcome

Timeframe: 24 and 52 weeks

Outcome measures

Outcome measures
Measure	Mylan's Insulin Glargine n=280 Participants Receive Mylan's Insulin Glargine plus insulin lispro. Mylan's insulin glargine: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period, and will continue on this for the complete trial. During the 6 week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.	Lantus® n=278 Participants Receive Lantus® plus insulin lispro Lantus®: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period; and will continue on this for the complete trial. During the 6week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.
Change in Total Insulin Antibody Percent Binding for Lantus Assay Over Time week 24	-0.215 %SB Standard Deviation 7.3298	0.157 %SB Standard Deviation 7.411
Change in Total Insulin Antibody Percent Binding for Lantus Assay Over Time week 52	-0.896 %SB Standard Deviation 8.5610	-1.233 %SB Standard Deviation 8.623

SECONDARY outcome

Timeframe: 24 and 52 weeks

Outcome measures

Outcome measures
Measure	Mylan's Insulin Glargine n=280 Participants Receive Mylan's Insulin Glargine plus insulin lispro. Mylan's insulin glargine: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period, and will continue on this for the complete trial. During the 6 week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.	Lantus® n=278 Participants Receive Lantus® plus insulin lispro Lantus®: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period; and will continue on this for the complete trial. During the 6week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.
Change in Cross-reactive Insulin Antibody Percent Binding for Mylan's Insulin Glargine Assay Over Time week 24	-0.363 %SB Standard Deviation 7.1081	0.27 %SB Standard Deviation 7.1204
Change in Cross-reactive Insulin Antibody Percent Binding for Mylan's Insulin Glargine Assay Over Time week 52	-1.132 %SB Standard Deviation 8.3911	-1.21 %SB Standard Deviation 8.4096

SECONDARY outcome

Timeframe: 24 and 52 weeks

Outcome measures

Outcome measures
Measure	Mylan's Insulin Glargine n=280 Participants Receive Mylan's Insulin Glargine plus insulin lispro. Mylan's insulin glargine: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period, and will continue on this for the complete trial. During the 6 week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.	Lantus® n=278 Participants Receive Lantus® plus insulin lispro Lantus®: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period; and will continue on this for the complete trial. During the 6week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.
Change in Cross-reactive Insulin Antibody Percent Binding for Lantus Assay Over Time week 24	-0.265 %SB Standard Deviation 7.2543	0.055 %SB Standard Deviation 7.3985
Change in Cross-reactive Insulin Antibody Percent Binding for Lantus Assay Over Time week 52	-1.060 %SB Standard Deviation 8.4414	-1.367 %SB Standard Deviation 8.6848

SECONDARY outcome

Timeframe: 24 and 52 weeks

Outcome measures

Outcome measures
Measure	Mylan's Insulin Glargine n=280 Participants Receive Mylan's Insulin Glargine plus insulin lispro. Mylan's insulin glargine: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period, and will continue on this for the complete trial. During the 6 week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.	Lantus® n=277 Participants Receive Lantus® plus insulin lispro Lantus®: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period; and will continue on this for the complete trial. During the 6week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.
Proportion of Patients With HbA1c < 7% week 24	73 Participants	84 Participants
Proportion of Patients With HbA1c < 7% week 52	65 Participants	61 Participants

Adverse Events

Mylan's Insulin Glargine

Serious events: 18 serious events

Other events: 225 other events

Deaths: 2 deaths

Lantus®

Serious events: 22 serious events

Other events: 239 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Additional Information

David Gillogly, Head of Global Clinical Operations

Mylan Inc.

Phone: +1 (724) 4856581

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Measure	Mylan's Insulin Glargine n=225 participants at risk；n=280 participants at risk Receive Mylan's Insulin Glargine plus insulin lispro. Mylan's insulin glargine: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period, and will continue on this for the complete trial. During the 6 week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.	Lantus® n=239 participants at risk；n=278 participants at risk Receive Lantus® plus insulin lispro Lantus®: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period; and will continue on this for the complete trial. During the 6week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.
Vascular disorders Hypertension	0.00% 0/280 • 56 Weeks After Week 52, all the patients resumed treatment as per local standard of care. A safety follow up visit was done at Week 56.	0.36% 1/278 • Number of events 1 • 56 Weeks After Week 52, all the patients resumed treatment as per local standard of care. A safety follow up visit was done at Week 56.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant oligodendroglioma	0.00% 0/280 • 56 Weeks After Week 52, all the patients resumed treatment as per local standard of care. A safety follow up visit was done at Week 56.	0.36% 1/278 • Number of events 1 • 56 Weeks After Week 52, all the patients resumed treatment as per local standard of care. A safety follow up visit was done at Week 56.
General disorders Death	0.36% 1/280 • Number of events 1 • 56 Weeks After Week 52, all the patients resumed treatment as per local standard of care. A safety follow up visit was done at Week 56.	0.00% 0/278 • 56 Weeks After Week 52, all the patients resumed treatment as per local standard of care. A safety follow up visit was done at Week 56.
Psychiatric disorders Psychotic disorder	0.00% 0/280 • 56 Weeks After Week 52, all the patients resumed treatment as per local standard of care. A safety follow up visit was done at Week 56.	0.36% 1/278 • Number of events 1 • 56 Weeks After Week 52, all the patients resumed treatment as per local standard of care. A safety follow up visit was done at Week 56.
Injury, poisoning and procedural complications Femoral neck fracture	0.36% 1/280 • Number of events 1 • 56 Weeks After Week 52, all the patients resumed treatment as per local standard of care. A safety follow up visit was done at Week 56.	0.00% 0/278 • 56 Weeks After Week 52, all the patients resumed treatment as per local standard of care. A safety follow up visit was done at Week 56.
Injury, poisoning and procedural complications Femur fracture	0.00% 0/280 • 56 Weeks After Week 52, all the patients resumed treatment as per local standard of care. A safety follow up visit was done at Week 56.	0.36% 1/278 • Number of events 1 • 56 Weeks After Week 52, all the patients resumed treatment as per local standard of care. A safety follow up visit was done at Week 56.
Injury, poisoning and procedural complications Lower limb fracture	0.00% 0/280 • 56 Weeks After Week 52, all the patients resumed treatment as per local standard of care. A safety follow up visit was done at Week 56.	0.36% 1/278 • Number of events 1 • 56 Weeks After Week 52, all the patients resumed treatment as per local standard of care. A safety follow up visit was done at Week 56.
Injury, poisoning and procedural complications Postoperative respiratory distress	0.36% 1/280 • Number of events 1 • 56 Weeks After Week 52, all the patients resumed treatment as per local standard of care. A safety follow up visit was done at Week 56.	0.00% 0/278 • 56 Weeks After Week 52, all the patients resumed treatment as per local standard of care. A safety follow up visit was done at Week 56.
Injury, poisoning and procedural complications Scapula fracture	0.00% 0/280 • 56 Weeks After Week 52, all the patients resumed treatment as per local standard of care. A safety follow up visit was done at Week 56.	0.36% 1/278 • Number of events 1 • 56 Weeks After Week 52, all the patients resumed treatment as per local standard of care. A safety follow up visit was done at Week 56.
Injury, poisoning and procedural complications Upper limb fracture	0.00% 0/280 • 56 Weeks After Week 52, all the patients resumed treatment as per local standard of care. A safety follow up visit was done at Week 56.	0.36% 1/278 • Number of events 1 • 56 Weeks After Week 52, all the patients resumed treatment as per local standard of care. A safety follow up visit was done at Week 56.
Cardiac disorders Atrial fibrillation	0.36% 1/280 • Number of events 1 • 56 Weeks After Week 52, all the patients resumed treatment as per local standard of care. A safety follow up visit was done at Week 56.	0.00% 0/278 • 56 Weeks After Week 52, all the patients resumed treatment as per local standard of care. A safety follow up visit was done at Week 56.
Cardiac disorders Coronary artery disease	0.36% 1/280 • Number of events 1 • 56 Weeks After Week 52, all the patients resumed treatment as per local standard of care. A safety follow up visit was done at Week 56.	0.36% 1/278 • Number of events 1 • 56 Weeks After Week 52, all the patients resumed treatment as per local standard of care. A safety follow up visit was done at Week 56.
Cardiac disorders Myocardial infarction	0.00% 0/280 • 56 Weeks After Week 52, all the patients resumed treatment as per local standard of care. A safety follow up visit was done at Week 56.	0.36% 1/278 • Number of events 1 • 56 Weeks After Week 52, all the patients resumed treatment as per local standard of care. A safety follow up visit was done at Week 56.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.36% 1/280 • Number of events 1 • 56 Weeks After Week 52, all the patients resumed treatment as per local standard of care. A safety follow up visit was done at Week 56.	0.00% 0/278 • 56 Weeks After Week 52, all the patients resumed treatment as per local standard of care. A safety follow up visit was done at Week 56.
Nervous system disorders Epilepsy	0.36% 1/280 • Number of events 1 • 56 Weeks After Week 52, all the patients resumed treatment as per local standard of care. A safety follow up visit was done at Week 56.	0.00% 0/278 • 56 Weeks After Week 52, all the patients resumed treatment as per local standard of care. A safety follow up visit was done at Week 56.
Nervous system disorders Generalized tonic-clonic seizure	0.00% 0/280 • 56 Weeks After Week 52, all the patients resumed treatment as per local standard of care. A safety follow up visit was done at Week 56.	0.72% 2/278 • Number of events 2 • 56 Weeks After Week 52, all the patients resumed treatment as per local standard of care. A safety follow up visit was done at Week 56.
Nervous system disorders Hypoglycaemic seizure	0.36% 1/280 • Number of events 1 • 56 Weeks After Week 52, all the patients resumed treatment as per local standard of care. A safety follow up visit was done at Week 56.	0.00% 0/278 • 56 Weeks After Week 52, all the patients resumed treatment as per local standard of care. A safety follow up visit was done at Week 56.
Nervous system disorders Ischaemic stroke	0.00% 0/280 • 56 Weeks After Week 52, all the patients resumed treatment as per local standard of care. A safety follow up visit was done at Week 56.	0.36% 1/278 • Number of events 1 • 56 Weeks After Week 52, all the patients resumed treatment as per local standard of care. A safety follow up visit was done at Week 56.
Eye disorders Retinal artery occlusion	0.36% 1/280 • Number of events 1 • 56 Weeks After Week 52, all the patients resumed treatment as per local standard of care. A safety follow up visit was done at Week 56.	0.00% 0/278 • 56 Weeks After Week 52, all the patients resumed treatment as per local standard of care. A safety follow up visit was done at Week 56.
Renal and urinary disorders Acute kidney injury	0.71% 2/280 • Number of events 2 • 56 Weeks After Week 52, all the patients resumed treatment as per local standard of care. A safety follow up visit was done at Week 56.	0.00% 0/278 • 56 Weeks After Week 52, all the patients resumed treatment as per local standard of care. A safety follow up visit was done at Week 56.
Renal and urinary disorders Glomerulonephritis minimal lesion	0.36% 1/280 • Number of events 1 • 56 Weeks After Week 52, all the patients resumed treatment as per local standard of care. A safety follow up visit was done at Week 56.	0.00% 0/278 • 56 Weeks After Week 52, all the patients resumed treatment as per local standard of care. A safety follow up visit was done at Week 56.
Skin and subcutaneous tissue disorders Skin ulcer	0.36% 1/280 • Number of events 1 • 56 Weeks After Week 52, all the patients resumed treatment as per local standard of care. A safety follow up visit was done at Week 56.	0.00% 0/278 • 56 Weeks After Week 52, all the patients resumed treatment as per local standard of care. A safety follow up visit was done at Week 56.
Musculoskeletal and connective tissue disorders Cervical spinal stenosis	0.00% 0/280 • 56 Weeks After Week 52, all the patients resumed treatment as per local standard of care. A safety follow up visit was done at Week 56.	0.36% 1/278 • Number of events 1 • 56 Weeks After Week 52, all the patients resumed treatment as per local standard of care. A safety follow up visit was done at Week 56.
Musculoskeletal and connective tissue disorders Osteochondrosis	0.36% 1/280 • Number of events 1 • 56 Weeks After Week 52, all the patients resumed treatment as per local standard of care. A safety follow up visit was done at Week 56.	0.00% 0/278 • 56 Weeks After Week 52, all the patients resumed treatment as per local standard of care. A safety follow up visit was done at Week 56.
Endocrine disorders Goitre	0.00% 0/280 • 56 Weeks After Week 52, all the patients resumed treatment as per local standard of care. A safety follow up visit was done at Week 56.	0.72% 2/278 • Number of events 2 • 56 Weeks After Week 52, all the patients resumed treatment as per local standard of care. A safety follow up visit was done at Week 56.
Endocrine disorders Hypothyroidism	0.00% 0/280 • 56 Weeks After Week 52, all the patients resumed treatment as per local standard of care. A safety follow up visit was done at Week 56.	0.36% 1/278 • Number of events 1 • 56 Weeks After Week 52, all the patients resumed treatment as per local standard of care. A safety follow up visit was done at Week 56.
Metabolism and nutrition disorders Hypoglycaemia	2.5% 7/280 • Number of events 7 • 56 Weeks After Week 52, all the patients resumed treatment as per local standard of care. A safety follow up visit was done at Week 56.	3.6% 10/278 • Number of events 10 • 56 Weeks After Week 52, all the patients resumed treatment as per local standard of care. A safety follow up visit was done at Week 56.
Infections and infestations Cellulitis	0.00% 0/280 • 56 Weeks After Week 52, all the patients resumed treatment as per local standard of care. A safety follow up visit was done at Week 56.	0.36% 1/278 • Number of events 1 • 56 Weeks After Week 52, all the patients resumed treatment as per local standard of care. A safety follow up visit was done at Week 56.
Infections and infestations Diverticulitis	0.36% 1/280 • Number of events 1 • 56 Weeks After Week 52, all the patients resumed treatment as per local standard of care. A safety follow up visit was done at Week 56.	0.00% 0/278 • 56 Weeks After Week 52, all the patients resumed treatment as per local standard of care. A safety follow up visit was done at Week 56.
Infections and infestations Haematoma infection	0.00% 0/280 • 56 Weeks After Week 52, all the patients resumed treatment as per local standard of care. A safety follow up visit was done at Week 56.	0.36% 1/278 • Number of events 1 • 56 Weeks After Week 52, all the patients resumed treatment as per local standard of care. A safety follow up visit was done at Week 56.
Infections and infestations Pharyngitis	0.36% 1/280 • Number of events 1 • 56 Weeks After Week 52, all the patients resumed treatment as per local standard of care. A safety follow up visit was done at Week 56.	0.00% 0/278 • 56 Weeks After Week 52, all the patients resumed treatment as per local standard of care. A safety follow up visit was done at Week 56.
Infections and infestations Pneumonia	0.00% 0/280 • 56 Weeks After Week 52, all the patients resumed treatment as per local standard of care. A safety follow up visit was done at Week 56.	0.36% 1/278 • Number of events 1 • 56 Weeks After Week 52, all the patients resumed treatment as per local standard of care. A safety follow up visit was done at Week 56.
Infections and infestations Pyelonephritis acute	0.36% 1/280 • Number of events 1 • 56 Weeks After Week 52, all the patients resumed treatment as per local standard of care. A safety follow up visit was done at Week 56.	0.00% 0/278 • 56 Weeks After Week 52, all the patients resumed treatment as per local standard of care. A safety follow up visit was done at Week 56.
Infections and infestations Urosepsis	0.36% 1/280 • Number of events 1 • 56 Weeks After Week 52, all the patients resumed treatment as per local standard of care. A safety follow up visit was done at Week 56.	0.00% 0/278 • 56 Weeks After Week 52, all the patients resumed treatment as per local standard of care. A safety follow up visit was done at Week 56.
Infections and infestations Viral rash	0.00% 0/280 • 56 Weeks After Week 52, all the patients resumed treatment as per local standard of care. A safety follow up visit was done at Week 56.	0.36% 1/278 • Number of events 1 • 56 Weeks After Week 52, all the patients resumed treatment as per local standard of care. A safety follow up visit was done at Week 56.
Psychiatric disorders Depression	0.00% 0/280 • 56 Weeks After Week 52, all the patients resumed treatment as per local standard of care. A safety follow up visit was done at Week 56.	0.36% 1/278 • Number of events 1 • 56 Weeks After Week 52, all the patients resumed treatment as per local standard of care. A safety follow up visit was done at Week 56.