NN1436-4480

Novo Nordisk A/S

Novo Allé, Bagsvaerd, Denmark, 2880

Novo Nordisk A/S, Clinical Reporting Office (2834), clinicaltrials@novonordisk.com

Novo Nordisk A/S, Clinical Reporting Office (2834), clinicaltrials@novonordisk.com

No

No

No

Final

22 Aug 2022

No

Yes

16 Jun 2022

No

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 type 2 diabetes (T2D) on a basalbolus regimen. This includes comparing the difference in change from baseline in glycosylated haemoglobin (HbA1c) between insulin icodec and insulin glargine after 26 weeks of treatment to a non-inferiority limit of 0.3%.

The trial was conducted in accordance with the Declaration of Helsinki (64th World Medical Association (WMA) general Assembly; Oct 2013) and International Council for Harmonisation (ICH) Good Clinical Practice, including archiving of essential documents (Current Step 4 version, Nov 2016), and 21 Code of Federal Regulations (CFR) 312.120.

14 May 2021

No

No

Belgium: 18

India: 93

Italy: 40

Japan: 85

Mexico: 66

Netherlands: 13

Romania: 39

Russian Federation: 95

United States: 133

582

110

0

0

0

0

0

0

373

209

0

Overall study (overall period)

Randomised - controlled

Yes

insulin aspart

Solution for injection

Subcutaneous use

Insulin aspart was administered with meals 2-4 times daily subcutaneously at a dose strength of 100 units/ milliliter (mL).

insulin icodec 700 U/mL PDS290

Solution for injection

Subcutaneous use

Insulin icodec was administered once-weekly subcutaneously at a dose strength of 700 units/ milliliter (mL).

insulin aspart

Solution for injection

Subcutaneous use

Insulin aspart was administered with meals 2-4 times daily subcutaneously at a dose strength of 100 units/ milliliter (mL).

Lantus

Lantus 100 units/mL

Solution for injection

Subcutaneous use

Insulin Glargine was administered once-daily subcutaneously at a dose strength of 100 units/ milliliter (mL).

Insulin Icodec

Insulin Glargine

Insulin Icodec

Insulin Glargine

Change in HbA1c from baseline week 0 (V2) to week 26 (V28) is presented. The endpoint data was evaluated based on the in-trial observation period. In-trial observation period started at randomisation and ended at the date of: The last direct subject-site contact, withdrawal for subjects who withdrew their informed consent, the last subject-investigator contact as defined by the investigator for subjects who were lost to follow-up (i.e., possibly an unscheduled phone visit) and death for subjects who died before any of the above. Full analysis set (FAS) included all randomised subjects.

Primary

From baseline week 0 (V2) to week 26 (V28)

The response and change from baseline in response after 26 weeks were analysed using an analysis of covariance (ANCOVA) model with treatment, region and personal continuous glucose monitoring (CGM) device use as fixed factors, and baseline response as covariate.

Insulin Icodec v Insulin Glargine

582

Pre-specified

0.02

2-sided

Change in FPG from baseline week 0 (V2) to week 26 (V28) is presented. The endpoint data was evaluated based on the in-trial observation period. In-trial observation period started at randomisation and ended at the date of: The last direct subject-site contact, withdrawal for subjects who withdrew their informed consent, the last subject-investigator contact as defined by the investigator for subjects who were lost to follow-up (i.e., possibly an unscheduled phone visit) and death for subjects who died before any of the above. FAS included all randomised subjects. Number of subjects analyzed=subjects with available data for this endpoint.

Secondary

From baseline week 0 (V2) to week 26 (V28)

Number of severe hypoglycaemic episodes (level 3) is presented. Severe hypoglycaemia (level 3) is defined as hypoglycaemia with severe cognitive impairment requiring external assistance for recovery. The endpoint data was evaluated based on the on-treatment observation period. The on-treatment period started at the date of first dose of trial product as recorded on the electronic case report form (eCRF), and ended at the first date of any of the following: The end of trial visit (V30), the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin (corresponding to 5 weeks after the end of the dosing interval for both treatment arms) and the end-date for the in-trial observation period. The on-treatment period represented the time period in which a subject was considered exposed to trial product. Safety analysis set included all subjects who were randomly assigned to trial treatment and who took at least 1 dose of trial product.

Secondary

From baseline week 0 (V2) to week 31 (V30)

Percentage of time in target-range 3.9–10.0 mmol/L (70-180 milligrams per deciliter [mg/dL]) using continuous glucose monitoring (CGM) system from week 22 to week 26 is presented. Time in target range is defined as 100 times the number of recorded measurements in glycaemic target range 3.9-10.0 mmol/L (70-180 mg/dL), both inclusive, divided by the total number of recorded measurements. The endpoint data was evaluated based on the in-trial observation period. In-trial observation period started at randomisation and ended at the date of: The last direct subject-site contact, withdrawal for subjects who withdrew their informed consent, the last subject-investigator contact as defined by the investigator for subjects who were lost to follow-up (i.e., possibly an unscheduled phone visit) and death for subjects who died before any of the above. FAS included all randomised subjects. Number of subjects analyzed=subjects with available data for this endpoint.

Secondary

From week 22 (V24) to week 26 (V28)

Number of clinically significant hypoglycaemic episodes (level 2) (<3.0 millimoles per liter [mmol/L] (54 mg/dL), confirmed by BG meter) is presented. Clinically significant hypoglycaemia (level 2) is defined as plasma glucose value of less than (<) 3.0 mmol/L (54 mg/dL) confirmed by BG meter. The endpoint data was evaluated based on on-treatment observation period. On-treatment period started at the date of first dose of trial product and ended at the first date of any of the following: End of trial visit (V30), Last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin (corresponding to 5 weeks after the end of dosing interval for both treatment arms) and the end-date for in-trial observation period. The on-treatment period represented the time period in which a subject was considered exposed to trial product. Safety analysis set included all subjects who were randomly assigned to trial treatment and who took at least 1 dose of trial product.

Secondary

From baseline week 0 (V2) to week 31 (V30)

Percentage of time spent less than (<) 3.0 mmol/L (54 mg/dL) using CGM system from week 22 to week 26 is presented. The endpoint data was evaluated based on the in-trial observation period. In-trial observation period started at randomisation and ended at the date of: The last direct subject-site contact, withdrawal for subjects who withdrew their informed consent, the last subject-investigator contact as defined by the investigator for subjects who were lost to follow-up (i.e., possibly an unscheduled phone visit) and death for subjects who died before any of the above. Full analysis set included all randomised subjects. Number of subjects analyzed=subjects with available data for this endpoint.

Secondary

From week 22 (V24) to week 26 (V28)

Number of clinically significant hypoglycaemic episodes (level 2) (<3.0 mmol/L (54 mg/dL), confirmed by BG meter) or severe hypoglycaemic episodes (level 3) is presented. Clinically significant hypoglycaemia (level 2) is defined as plasma glucose value of < 3.0 mmol/L (54 mg/dL) confirmed by BG meter. Severe hypoglycaemia (level 3) is defined as hypoglycaemia with severe cognitive impairment requiring external assistance for recovery. The endpoint data was evaluated based on on-treatment observation period. On-treatment period started at the date of first dose of trial product and ended at the first date of any of the following: The end of trial visit (V30), the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin and the end-date for in-trial observation period. Safety analysis set included all subjects who were randomly assigned to trial treatment and who took at least 1 dose of trial product.

Secondary

From baseline week 0 (V2) to week 31 (V30)

Estimated mean weekly insulin dose during the last 2 weeks of treatment (from week 24 to week 26) is presented. The endpoint data was evaluated based on the on-treatment observation period. The on-treatment period started at the date of first dose of trial product as recorded on the electronic case report form (eCRF), and ended at the first date of any of the following: The end of trial visit (V30), the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin (corresponding to 5 weeks after the end of the dosing interval for both treatment arms) and the end-date for the in-trial observation period. The on-treatment period represented the time period in which a subject was considered exposed to trial product. FAS included all randomised subjects. Number of subjects analyzed=subjects with available data for this endpoint.

Secondary

From week 24 (V26) to week 26 (V28)

Percentage of time spent > 10 mmol/L (180 mg/dL) using CGM system from week 22 to week 26 is presented. The endpoint data was evaluated based on the in-trial observation period. In-trial observation period started at randomisation and ended at the date of: The last direct subject-site contact, withdrawal for subjects who withdrew their informed consent, the last subject-investigator contact as defined by the investigator for subjects who were lost to follow-up (i.e., possibly an unscheduled phone visit) and death for subjects who died before any of the above. Full analysis set included all randomised subjects. Number of subjects analyzed = subjects with available data for this endpoint.

Secondary

From week 22 (V24) to week 26 (V28)

Change in body weight from baseline week 0 (V2) to week 26 (V28) is presented. The endpoint data was evaluated based on the in-trial observation period. In-trial observation period started at randomisation and ended at the date of: The last direct subject-site contact, withdrawal for subjects who withdrew their informed consent, the last subject-investigator contact as defined by the investigator for subjects who were lost to follow-up (i.e., possibly an unscheduled phone visit) and death for subjects who died before any of the above. Full analysis set included all randomised subjects.

Secondary

From baseline week 0 (V2) to week 26 (V28)

From baseline week 0 to week 31

All presented AEs are treatment emergent. Treatment emergent adverse events (TEAEs): events that had onset date during on-treatment period, time period in which subjects was considered exposed to trial product. Safety analysis set included all randomised subjects randomly assigned to trial treatment who took at least 1 dose of trial product.

24

Insulin icodec

Insulin Glargine