臨床研究等提出・公開システム

A 26-week trial comparing the effect and safety of once weekly insulin icodec and once daily insulin glargine 100 units/mL, both in combination with bolus insulin with or without non-insulin anti-diabetic drugs, in subjects with type 2 diabetes on a basal-bolus regimen.(NN1436-4480) (ONWARDS4)

A 26-week trial comparing the effect and safety of once weekly insulin icodec and once daily insulin glargine 100 units/mL, both in combination with bolus insulin with or without non-insulin anti-diabetic drugs, in subjects with type 2 diabetes on a basal-bolus regimen.(NN1436-4480) (ONWARDS4)

582

Of the 582 randomised subjects, 47.8% were female, 63.6% were White, 32.3% were Asian, 3.6% were Black/African American and 18.0% were Hispanic/Latino. Their mean baseline characteristics were, age: 59.79 years, HbA1c: 8.30%, FPG: 9.42 mmol/L (169.82 mg/dL), BMI: 30.26 kg/m2, diabetes duration: 17.15 years.

A total of 582 basal-bolus treated subjects with T2D were randomised, 291 in each arm. A total of 291 subjects (100%) were exposed to insulin icodec and 291 subjects (100%) were exposed to insulin glargine, while 274 (94.2%) and 269 subjects (92.4%), respectively, completed the week 26 visit without permanent discontinuation of trial product.

-Estimated change from baseline to week 26 in body weight was 2.73 kg with insulin icodec and 2.16 kg with insulin glargine. The treatment difference was not statistically significant. ETD 0.57 [-0.39 ; 1.54]95% CI -There were 7 episodes of severe (level 3) hypoglycaemia in 4 subjects with insulin icodec and 3 events in 2 subjects with insulin glargine. The rate of severe (level 3) hypoglycaemia was not statistically significantly different with insulin icodec vs. insulin glargine. ERR 2.19 [0.20 ; 24.44]95% CI -The rate of clinically significant (level 2) hypoglycaemia per 100 PYE (patient years of exposure) was 559.86 with insulin icodec and 560.56 with insulin glargine. The rate of clinically significant (level 2) hypoglycaemia was not statistically significantly different with insulin icodec vs. insulin glargine. ERR 0.99 [0.73 ; 1.34]95% CI -The rate of severe (level 3) or clinically significant (level 2) hypoglycaemia per 100 PYE was 564.05 with insulin icodec and 562.36 with insulin glargine. The rate of severe (level 3) or clinically significant (level 2) hypoglycaemia was not statistically significantly different with insulin icodec vs. insulin glargine. ERR 0.99 [0.73 ; 1.33]95% CI -The rate of nocturnal severe (level 3) or clinically significant (level 2) hypoglycaemia per 100 PYE was 78.27 with insulin icodec and 103.72 with insulin glargine. The rate of nocturnal severe (level 3) or clinically significant (level 2) hypoglycaemia was not statistically significantly different with insulin icodec vs. insulin glargine. ERR 0.73 [0.47 ; 1.14]95% CI -No new safety issues were identified in relation to insulin icodec in this trial. -No specific pattern in the occurrence and frequency of events between treatment arms was observed. -SAEs: -Insulin icodec: 35 SAEs, 2 events were assessed as possibly related to insulin icodec. -Insulin glargine: 33 SAEs, 3 events were assessed as possibly related to insulin glargine. -Fatal events: 2 subjects (4 events) with insulin icodec and 1 subject (1 event) with insulin glargine.

Primary Outcome Measures Estimated change from baseline to week 26 in HbA1c was -1.16%-point with insulin icodec and -1.18%-point with insulin glargine, confirming non-inferiority of insulin icodec vs. insulin glargine. ETD 0.02%-point [-0.11; 0.15]95% CI Secondary Outcome -Time in target range 3.9-10.0 mmol/L from week 22 to week 26 was 66.88% with insulin icodec and 66.44% with insulin glargine. The treatment difference was not statistically significant. ETD 0.29%-point [-2.52; 3.09]95% CI -Time spent <3.0 mmol/L from week 22 to week 26 was 0.73% with insulin icodec and 0.61% with insulin glargine. The treatment ratio was not statistically significant. ETR 1.20 [0.91; 1.58]95% CI -Time spent >10.0 mmol/L from week 22 to week 26 was 30.47% with insulin icodec and 31.30% with insulin glargine. The treatment difference was not statistically significant. ETD -0.60%-point [-3.47; 2.28]95% CI -Estimated proportion of subjects achieving HbA1c<7% after 26 weeks was 40.69% with insulin icodec and 45.48% with insulin glargine. The odds of achieving HbA1c<7% were not statistically significantly different between treatment arms. EOR 0.82 [0.58; 1.17]95% CI -Estimated proportion of subjects achieving HbA1c<=6.5% after 26 weeks was 19.81% with insulin icodec and 21.64% with insulin glargine. The odds of achieving HbA1c<=6.5% were not statistically significantly different between treatment arms. EOR 0.89 [0.60; 1.33]95% CI -Estimated change from baseline to week 26 in FPG was -1.75 mmol/L with insulin icodec and -1.61 mmol/L with insulin glargine. The treatment difference was not statistically significant. ETD -0.14 mmol/L [-0.59; 0.31]95% CI -Estimated mean total weekly insulin dose from week 24 to week 26 was 513.54 U with insulin icodec and 559.05 U with insulin glargine. The dose was statistically significantly lower with insulin icodec vs. insulin glargine. ETR 0.92 [0.85 ; 0.99]95% CI -Estimated mean total weekly basal insulin dose from week 24 to week 26 was 305.06 U with insulin icodec and 279.42 U with insulin glargine. The dose was statistically significantly higher with insulin icodec vs. insulin glargine. ETR 1.09 [1.01 ; 1.18]95% CI -Estimated mean total weekly bolus insulin dose from week 24 to week 26 was 197.45 U with insulin icodec and 255.26 U with insulin glargine. The dose was statistically significantly lower with insulin icodec vs. insulin glargine. ETR 0.77 [0.70 ; 0.86]95% CI

Based on this 26-week trial comparing once-weekly insulin icodec with once daily insulin glargine, in type 2 diabetic subjects previously treated with basal-bolus insulin, change in HbA1c for insulin icodec was non-inferior to insulin glargine. No new safety issues were identified in relation to insulin icodec in this trial.

May. 05, 2023

https://pubmed.ncbi.nlm.nih.gov/37156252/

No

https://jrct.mhlw.go.jp/latest-detail/jRCT2031210076

Nishida Hiroko

Novo Nordisk Pharma Ltd

2-1-1, Marunouchi, Chiyodaku

JPHC_clinical_trials@novonordisk.com

Nishida Hiroko

Novo Nordisk Pharma Ltd.

2-1-1, Marunouchi, Chiyodaku

+81-362661000

JPHC_clinical_trials@novonordisk.com

Complete

May. 14, 2021

Interventional

randomized controlled trial

open(masking not used)

active control

parallel assignment

treatment purpose

1. Male or female aged above or equal to 18 years at the time of signing informed consent.
2. Diagnosed with T2D>= 180 days prior to the day of screening.
3. HbA1c from 7.0-10.0% (53.0 85.8 mmol/mol) both inclusive at screening confirmed by central laboratory analysis.
4. 4. Treated with once daily basal insulin (neutral protamine hagedorn insulin, insulin degludec, insulin detemir, insulin glargine 100 units/mL, or insulin glargine 300 units/mL) and 2-4 daily injections of bolus insulin analog (insulin aspart, faster acting insulin aspart, insulin lispro, insulin glulisine) >= 90 days prior to the day of screening with or without any of the following anti-diabetic drugs/regimens with stable doses>= 90 days prior to screening:
-Metformin
-Sulfonylureas
-Meglitinides (glinides)
-DPP-4 inhibitors
-SGLT2 inhibitors
-Thiazolidinediones
-Alpha-glucosidase inhibitors
-Oral combination products (for the allowed individual oral anti-diabetic drugs)
-Oral or injectable GLP-1-receptor agonists
5. Body mass index (BMI) <= 40.0 kg/m2.

1. Any episodesa of diabetic ketoacidosis within 90 days prior to the day of screening.
2. Myocardial infarction, stroke, hospitalisation for unstable angina pectoris or transient ischaemic attack within 180 days prior to the day of screening.
3. Chronic heart failure classified as being in New York Heart Association Class IV at screening.
4. Anticipated initiation or change in concomitant medications (for more than 14 consecutive days) known to affect weight or glucose metabolism (e.g. treatment with orlistat, thyroid hormones, or corticosteroids).
5. Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed within the past 90 days prior to screening or in the period between screening and randomisation. Pharmacological pupil-dilation is a requirement unless using a digital fundus photography camera specified for non-dilated examination.

Both

type 2 diabetes

-Two arm for insulin icodec and insulin glargine
-The study will consist of 3 periods: a Screening Period, a Treatment Period, and a Follow-Up Period.
-Implementation of blood sampling tests, etc. specified in the protocol.
Etc.

The objective of this trial is to demonstrate the effect on glycaemic control of once weekly insulin icodec in combination with insulin aspart, with or without non-insulin anti-diabetic drugs, in subjects with T2D on a basal-bolus regimen. This includes comparing the difference in change from baseline in HbA1c between insulin icodec and insulin glargine after 26 weeks of treatment to a non-inferiority limit of 0.3%.

+81-42-648-5551

Feb. 05, 2021

Belgium/India/Italy/Mexico/Netherlands/Rumania/Russia/United States