Insulin Glargine 300 Vs 100 IU - INSTRIDE 1 - 2 Studies

EDITION 1 Trial:
T2DM Patients on Basal insulin + meal time insulin ± metformin
n = 807
Glargine 300 IU (n = 404) vs Glargine 100 IU (n = 403)
Insulin Dose Requirement
About 10% higher dose required to get the same efficacy

parameter in glargine 300 IU group
Insulin glargine 300 IU: 0.67 units/kg/day to 0.97 units/kg/day (70 IU/ day to 103 IU/day)
Insulin glargine 100 IU: 0.67 units/kg/day to 0.88 units/kg/day (71 IU/day to 94 units/day)
EDITION 2 Trial:
T2DM patients Using Oral Agents and Basal Insulin
n = 811
Pre-breakfast SMPG
In the initial 8 weeks, pre-breakfast SMPG is lower

with Glargine 100 IU compared with glargine 300 IU
Mean pre-breakfast SMPG was lower with Gla-100 than with Gla-300 during the first 8 weeks, and a more gradual
decrease in pre-breakfast SMPG was observed with Gla-300 than with Gla-100
Dose Requirement
About 10% higher dose required to get the same

efficacy parameter in glargine 300 IU group
Insulin glargine 300 IU: 0.64 units/kg/day to 0.92 units/kg/day (63.18 IU/day to 90.8 units/day) (weight: 98.7 kg)
Insulin glargine 100 IU: 0.66 units/kg/day to 0.84 units/kg/day (64.68 IU/day to 82.32 units/day) (weight: 98 kg)
EDITION 3 Trial:
Insulin naïve T2DM
n = 878
Insulin Dose Requirement
About 20% higher dose required to get the same efficacy

parameter in glargine 300 IU group in insulin naïve patients
Insulin glargine 300 IU: 0.67 (0.33) U/kg/day

Insulin glargine 100 IU: 0.56 (0.27) U/kg/day
Hypoglycaemia: Nocturnal
• Annualized rates of nocturnal confirmed or severe hypoglycaemic events were similar in

the both groups
– Glargine 300 IU: 1.33 events/participant-year
– Glargine 100 IU: 1.36 events/participant-year
– RR: 0.98 [95% CI: 0.69 to 1.40]) (Glargine 300 IU vs Glargine 100 IU)
No additional benefit w.r.t hypoglycaemia, where both 100

and 300 IU has similar hypoglycaemic episodes
Important Observations of EDITION
• The 10 to 20 % higher dosage of Glargine 300 IU might be due to a slight decrease in

bioavailability related to a longer subcutaneous residence time with exposure to tissue
peptidases
• In the initial 8 weeks, pre-breakfast SMPG is lower with Glargine 100 IU compared
with glargine 300 IU
• No additional benefit w.r.t hypoglycaemia, where both 100 and 300 IU has similar
hypoglycaemic episodes
Biosimilar Insulin Glargine*:
Global Phase 1 (PK/PD) in T1DM
Comparative Pharmacokinetics and Pharmacodynamics

of a Proposed Biosimilar Insulin Glargine and Reference insulin Glargine
in Patients with Type 1 Diabetes
1019-P
Insulin analogues are co-developed with marketing partners; Products outside of India are sold through various
*
*Biosimilar insulin glargine: Biocon’s glargine marketing partners and different brand names 11
Available at https://ada.apprisor.org/epsView.cfm?sK98%2Fd9GKC1VkENOZUEXF841fgw8rN4j5xjABjpHOH475gYII4rkW%2FTLWiMt7jzo Accessed on 17.06.2017
Phase 1 Study: Overview
• Study objective:
– PK/PD bioequivalence measurement of biosimilar glargine with US
reference glargine (US IG) and European reference glargine (EU IG)
• Study population: 114 T1 DM patients
• Study design:
– Single-center, randomized, double-blind, single-dose, 3-way crossover
– Hyperinsulinaemic euglycaemic clamp study
– Patients received a single SC inj of 0.4 U/kg of each trial drug
Biosimilar glargine: Biocon’s glargine 11

Phase 1 Study: Design
Biosimilar IG Biosimilar IG Biosimilar IG
Single-center, randomized, double-blind, single-dose, 3-way crossover, euglycaemic clamp
Biosimilar IG: Biocon’s glargine

US IG: US reference insulin glargine
EU IG: European reference insulin glargine 13
Phase 1 Study: Pharmacokinetic Comparison
Mean Smoothed Serum Insulin Profiles
Biosimilar IG
Mean serum insulin concentration profiles of three insulin glargine

preparations were similar
Biosimilar IG: Biocon’s glargine, US IG: US reference insulin glargine, EU IG: European reference insulin glargine
16
Phase 1 Study: Pharmacodynamic Comparison
Mean smoothed GIR profile
Biosimilar IG
The GIR profiles were nearly superimposable

19
Phase 1 Study: Conclusion
• Bioequivalence of Biosimilar IG, US IG, and EU IG was demonstrated in patients with

T1DM for both primary PK and PD endpoints
• Biosimilar IG, US IG, and EU IG were generally well tolerated, and no significant safety
issues emerged
21
Global Phase 3 Study in T1DM
Efficacy and Safety of Biosimilar Insulin Glargine Compared with Reference

Insulin Glargine in Patients with Type 1 Diabetes after 52 Weeks:
The INSTRIDE 1 Study
1018-P
*
*Biosimilar insulin glargine: Biocon’s glargine marketing partners and different brand names
Available at https://ada.apprisor.org/epsView.cfm?7JUsS9yPV6NVkENOZUEXF841fgw8rN4j5xjABjpHOH475gYII4rkW%2FTLWiMt7jzo. Accessed on 17.06.2017
INSTRIDE 1: Overview
To determine whether biosimilar insulin glargine once daily is

Objective noninferior to reference insulin glargine once daily when administered
in combination with mealtime insulin lispro in patients with T1DM
Study design Multicenter, open-label, randomized, parallel-group, comparative

phase 3 study
Sample size 558 T1DM patients
T1DM, 18 and 65 years, Treated with once-daily insulin glargine for at

Population
least 3 months, HbA1c ≤9.5% at screening
*Biosimilar insulin glargine: Biocon’s glargine 17

INSTRIDE 1: Study Design
Biosimilar insulin glargine

(52 weeks, N=280)
(52 weeks, N=278)

INSTRIDE 1: Study Endpoints
Primary endpoint Change in HbA1c from baseline to wk 24
Non-inferiority Upper limit of 2-sided 95% CI for difference in mean change from
margin baseline to endpoint for HbA1c was no greater than 0.4% at wk 24
Secondary endpoints
(Efficacy) • HbA1c change from initial administration to wk 52
• Change in FPG
• Change in insulin dose
• SMBG
Secondary endpoints
(Safety) • Hypoglycaemia
• Other adverse events and adverse reactions
• Immunogenicity (E.g. antidrug antibodies)

INSTRIDE 1: Mean Actual HbA1c Over Time
Mean ±SD. BL, baseline
Treatment groups Mean change in HbA1c (%) LS mean difference Non-inferiority margin (Upper
• No statistically significant
(Baseline todifferences
wk 24) in between
actual HbA1c
groups profiles
boundwere
of 95%observed
CI for meanbetween
change)
treatment
Biosimilar groups
glargine over
0.14 (95%time
CI: 0.033, 0.244) 0.03 0.4%
Reference glargine 0.11 (95% CI: 0.007, 0.220) (95% CI: -0.066, 0.117)
• *Biosimilar
Upperinsulin
bound
glargine:of 95%glargine
Biocon’s CI for mean change in HbA1c was within non-inferiority margin of 0.4%
7
INSTRIDE 1: Mean Actual Glargine Dose Over Time
Treatment groups Mean change in daily glargine dose (U/Kg) P value

Biosimilar insulin glargine 0.0128 NS
Reference insulin glargine 0.0043
Mean ±SD. BL, baseline *Biosimilar insulin glargine: Biocon’s glargine 8
INSTRIDE 1: Incidence of Anytime and Nocturnal Hypoglycaemia
Hypoglycaemic event: SMBG ≤70 mg/dL
Anytime & nocturnal hypoglycaemic rates and incidence profiles were

comparable between two treatment groups throughout the study
BL, baseline; SMBG, self-monitored blood glucose. *Biosimilar insulin glargine: Biocon’s glargine 10
INSTRIDE 1: Conclusion
• Upper bound of 95% CI for mean change in HbA1c from baseline to wk 24 was within non-
inferiority margin of 0.4%
 Proves non-inferiority of biosimilar insulin glargine vs reference product
• Changes in HbA1c and FPG levels from baseline to week 52 were similar
• Both basal and bolus Insulin dose levels did not differ between groups
• Rates of hypoglycaemia and other AEs were comparable between two groups
*Biosimilar insulin glargine: Biocon’s glargine

23
Global Phase 3 Study in T2DM
Efficacy and Safety of Biosimilar Insulin Glargine Compared with Reference

Insulin Glargine in Patients with Type 2 Diabetes after 24 Weeks:
The INSTRIDE 2 Study
1017-P
*
*Biosimilar insulin glargine: Biocon’s glargine marketing partners and different brand names
Available at https://ada.apprisor.org/epsView.cfm?A3UqB1xgRfFVkENOZUEXF841fgw8rN4j5xjABjpHOH475gYII4rkW%2FTLWiMt7jzo. Accessed on 17.06.2017
INSTRIDE 2: Overview
To determine whether biosimilar insulin glargine once daily is

Objective noninferior to reference insulin glargine once daily when administered
in combination with OADs in patients with T2DM
Study design Multicenter, open-label, randomized, parallel-group, comparative

phase 3 study in patients with T2DM taking OADs
Sample size 560 T2DM patients
• T2DM for atleast 1 year before screening,

Population • Stable dose of an OAD for 3 months before screening
(either insulin naive or on insulin glargine once daily at a stable dose
for at least 3 months before screening)
INSTRIDE 2: Study Design

(24 weeks, n=277)
(24 weeks, N=283)

INSTRIDE 2: Study Endpoints
Primary endpoint Change in HbA1c from baseline to wk 24

Non-inferiority margin Upper limit of the 2-sided 95% CI for difference in mean change from
baseline to endpoint for HbA1c was no greater than 0.4% at wk 24
Secondary endpoints
(Efficacy) • Change in FPG
• Change in insulin dose
• SMBG
Secondary endpoints
(Safety) • Hypoglycaemia
• Other adverse events and adverse reactions
• Immunogenicity (E.g. antidrug antibodies)

INSTRIDE 2: Mean Actual HbA1c Over Time
Mean ±SD. SC, Screening. BL, baseline
Treatment groups Mean change in HbA1c (%) LS mean difference Non-inferiority margin (Upper
(Baseline to wk 24) between groups bound of 95% CI for mean change)
Biosimilar glargine -0.60 (95% CI: -0.78, -0.41) 0.06% 0.4%

Reference glargine -0.66 (95% CI: -0.84, -0.48) (95% CI: -0.10, 0.22)
Available at https://ada.apprisor.org/epsView.cfm?A3UqB1xgRfFVkENOZUEXF841fgw8rN4j5xjABjpHOH475gYII4rkW%2FTLWiMt7jzo. Accessed on 17.06.2017 17
INSTRIDE 2: Mean Actual Glargine Dose Over Time
Mean ±SD. BL, baseline
Treatment groups Mean (SD) increase in daily glargine dose (U/Kg) P value
All Patients Insulin Naive
Biosimilar insulin glargine 0.124 ± 0.139 0.236 ± 0.119 NS
Reference insulin glargine 0.122 ± 0.142 0.240 ± 0.102
INSTRIDE 2: Incidence of Anytime and Nocturnal Hypoglycaemia
Hypoglycaemic event: SMBG ≤70 mg/dL
No statistically significant differences were observed in hypoglycaemic rate or

incidence between treatment groups at any visit
BL, baseline; SMBG, self-monitored blood glucose. *Biosimilar insulin glargine: Biocon’s glargine 21
INSTRIDE 2: Conclusion
• Mean change in HbA1c was similar in patients with T2DM in both groups
• Results demonstrate that biosimilar insulin glargine is noninferior to reference insulin
glargine in patients with T2DM
• Changes in FPG levels from baseline to week 24 were similar in both groups
• Insulin glargine dose levels did not differ between groups
• Rates of hypoglycaemia and other AEs were comparable between two groups

31

Insulin Glargine 300 Vs 100 IU - INSTRIDE 1 - 2 Studies

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Insulin Glargine 300 Vs 100 IU - INSTRIDE 1 - 2 Studies

Uploaded by

Copyright:

Available Formats

EDITION 1 Trial:

T2DM Patients on Basal insulin + meal time insulin ± metformin

About 10% higher dose required to get the same efficacy

In the initial 8 weeks, pre-breakfast SMPG is lower

About 10% higher dose required to get the same

About 20% higher dose required to get the same efficacy

Insulin glargine 300 IU: 0.67 (0.33) U/kg/day

• Annualized rates of nocturnal confirmed or severe hypoglycaemic events were similar in

No additional benefit w.r.t hypoglycaemia, where both 100

• The 10 to 20 % higher dosage of Glargine 300 IU might be due to a slight decrease in

Comparative Pharmacokinetics and Pharmacodynamics

Biosimilar glargine: Biocon’s glargine 11

Biosimilar IG Biosimilar IG Biosimilar IG

Single-center, randomized, double-blind, single-dose, 3-way crossover, euglycaemic clamp

Biosimilar IG: Biocon’s glargine

Mean serum insulin concentration profiles of three insulin glargine

The GIR profiles were nearly superimposable

• Bioequivalence of Biosimilar IG, US IG, and EU IG was demonstrated in patients with

Efficacy and Safety of Biosimilar Insulin Glargine Compared with Reference

To determine whether biosimilar insulin glargine once daily is

Study design Multicenter, open-label, randomized, parallel-group, comparative

Sample size 558 T1DM patients

T1DM, 18 and 65 years, Treated with once-daily insulin glargine for at

*Biosimilar insulin glargine: Biocon’s glargine 17

Biosimilar insulin glargine

(52 weeks, N=278)

*Biosimilar insulin glargine: Biocon’s glargine 3

*Biosimilar insulin glargine: Biocon’s glargine 19

Mean ±SD. BL, baseline

Biosimilar insulin glargine

Treatment groups Mean change in daily glargine dose (U/Kg) P value

Biosimilar insulin glargine

Hypoglycaemic event: SMBG ≤70 mg/dL

Anytime & nocturnal hypoglycaemic rates and incidence profiles were

 Proves non-inferiority of biosimilar insulin glargine vs reference product

*Biosimilar insulin glargine: Biocon’s glargine

Efficacy and Safety of Biosimilar Insulin Glargine Compared with Reference

To determine whether biosimilar insulin glargine once daily is

Study design Multicenter, open-label, randomized, parallel-group, comparative

Sample size 560 T2DM patients

• T2DM for atleast 1 year before screening,

Biosimilar insulin glargine

(24 weeks, N=283)

*Biosimilar insulin glargine: Biocon’s glargine 14

Primary endpoint Change in HbA1c from baseline to wk 24

*Biosimilar insulin glargine: Biocon’s glargine 27

Biosimilar insulin glargine

Mean ±SD. SC, Screening. BL, baseline

Biosimilar glargine -0.60 (95% CI: -0.78, -0.41) 0.06% 0.4%

Biosimilar insulin glargine

Mean ±SD. BL, baseline

Biosimilar insulin glargine

Hypoglycaemic event: SMBG ≤70 mg/dL

No statistically significant differences were observed in hypoglycaemic rate or

*Biosimilar insulin glargine: Biocon’s glargine

You might also like