NN1250-4252

Novo Nordisk A/S

Novo Allé, Bagsvaerd, Denmark, 2880

Clinical Reporting Anchor and Disclosure (1452), Novo Nordisk A/S, clinicaltrials@novonordisk.ccom

Clinical Reporting Anchor and Disclosure (1452), Novo Nordisk A/S, clinicaltrials@novonordisk.ccom

No

No

No

Final

10 Jul 2019

Yes

13 Feb 2019

Yes

04 Mar 2019

No

To compare the effects of insulin degludec once daily and insulin glargine 300 units/mL once daily on hypoglycaemia in subjects with type 2 diabetes mellitus, inadequately treated with basal insulin with or without oral anti-diabetic drugs.

The trial was conducted in accordance with the Declaration of Helsinki (64th WMA General Assembly, October 2013) and ICH Good Clinical Practice, including archiving of essential documents, (June 1996) and 21 CFR 312.120.

13 Mar 2017

No

No

Canada: 87

Germany: 100

Denmark: 32

Estonia: 40

Greece: 58

Hungary: 62

Norway: 20

Poland: 145

Romania: 21

Serbia: 60

United States: 984

1609

478

0

0

0

0

0

0

836

764

9

Overall Study (overall period)

Randomised - controlled

Yes

INSULIN DEGLUDEC

Tresiba® 200 units/ml

Solution for injection in pre-filled pen

Subcutaneous use

Insulin degludec 200 units/mL was administered once daily as subcutaneous injections in the thigh, upper arm or abdomen. The daily basal insulin dose was reduced by 20% from their pre-trial dose. Insulin dose was adjusted once weekly by the investigator, based on the mean of three fasting SMPG values, to reach a SMPG of 4.0-5.0 mmol/L (71-90 mg/dL).

INSULIN GLARGINE

Toujeo® 300 units/ml

Solution for injection in pre-filled pen

Subcutaneous use

Insulin glargine (IGlar) 300 units/mL was administered once daily as subcutaneous injections in the thigh, upper arm or abdomen. The dose of IGlar U300 corresponded to the pre-trial daily basal insulin dose. Insulin dose was adjusted once weekly by the investigator, based on the mean of three fasting SMPG values, to reach a SMPG of 4.0-5.0 mmol/L (71-90 mg/dL).

Insulin degludec U200

Insulin glargine U300

Insulin degludec U200

Insulin glargine U300

Severe or BG confirmed symptomatic hypoglycaemia was evaluated during maintenance 2 (36 weeks) period. Severe or BG confirmed symptomatic hypoglycaemia: An episode that is severe according to the ADA 2013 classification or blood glucose (BG) confirmed by a plasma glucose value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia. The observed rates (number of episodes divided by patient years of exposure multiplied by 100) of severe or BG-confirmed symptomatic hypoglycaemic episodes per patient years of exposure (PYE) is presented in this endpoint results.

Primary

During maintenance 2 (36 weeks)

The number of episodes is analysed using a negative binomial regression model (log link) with the logarithm of the time period in which a hypoglycaemic episode was considered treatment emergent as offset. The model includes treatment, number of OADs, region, sex and dosing time as fixed factors, and age as a covariate. Missing values are imputed through multiple imputation by treatment arm, based on a Poisson model.

Insulin degludec U200 v Insulin glargine U300

1483

Pre-specified

0.88

2-sided

The observed mean daily basal insulin doses was evaluated at the end of trial (88 weeks).

Secondary

At end of treatment (up to 88 weeks)

Nocturnal severe or BG confirmed symptomatic hypoglycaemia was evaluated at the end of trial (88 weeks). The nocturnal period defined as the period between 00:01 and 05:59 a.m. (both inclusive). Severe or BG confirmed symptomatic hypoglycaemia: An episode that is severe according to the ADA 2013 classification or blood glucose (BG) confirmed by a plasma glucose value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia. The observed rates (number of episodes divided by patient years of exposure multiplied by 100) of severe or BG-confirmed symptomatic hypoglycaemic episodes per patient years of exposure (PYE) is presented in this endpoint results.

Secondary

During maintenance 2 (36 weeks)

Severe hypoglycaemia are those episodes positively adjudicated by the event adjudication committee according to the ADA definition of a severe hypoglycaemic episode. This was evaluated for maintenance 2 period. The observed rates (number of episodes divided by patient years of exposure multiplied by 100) of severe hypoglycaemic episodes per patient years of exposure (PYE) is presented in this endpoint results.

Secondary

During maintenance 2 (36 weeks)

Change in glycosylated haemoglobin (HbA1c) was evaluated from baseline to end of treatment period (week 88).

Secondary

From baseline to end of treatment (up to 88 weeks)

Severe or BG confirmed symptomatic hypoglycaemia was evaluated during treatment (up to 88 weeks). Severe or BG confirmed symptomatic hypoglycaemia: An episode that is severe according to the ADA 2013 classification or blood glucose (BG) confirmed by a plasma glucose value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia. The observed rates (number of episodes divided by patient years of exposure multiplied by 100) of severe or BG-confirmed symptomatic hypoglycaemic episodes per patient years of exposure (PYE) is presented in this endpoint results.

Secondary

During treatment (up to 88 weeks)

Nocturnal severe or BG confirmed symptomatic hypoglycaemia was evaluated at the end of trial (88 weeks). The nocturnal period defined as the period between 00:01 and 05:59 a.m. (both inclusive). Severe or BG confirmed symptomatic hypoglycaemia: An episode that is severe according to the ADA 2013 classification or blood glucose (BG) confirmed by a plasma glucose value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia. The observed rates (number of episodes divided by patient years of exposure multiplied by 100) of severe or BG-confirmed symptomatic hypoglycaemic episodes per patient years of exposure (PYE) is presented in this endpoint results.

Secondary

During treatment (up to 88 weeks)

Severe hypoglycaemia are those episodes positively adjudicated by the event adjudication committee according to the ADA definition of a severe hypoglycaemic episode. This was evaluated for the total trial period (88 weeks). The observed rates (number of episodes divided by patient years of exposure multiplied by 100) of severe hypoglycaemic episodes per patient years of exposure (PYE) is presented in this endpoint results.

Secondary

During treatment (up to 88 weeks)

The adverse events presented are treatment emergent. A treatment-emergent AE (TEAE) was defined as an event that had onset date on or after the first day of exposure to randomised treatment and no later than 7 days after the last days of randomised treatment or had onset date before the first day of exposure on randomised treatment and increased in severity during the treatment period and until 7 days after the last date of randomised treatment. Number of adverse events expressed in rates, from randomisation to end of maintenance period 2 (up to 88 weeks) is presented. Rate = number of events divided by patient years of exposure multiplied by 100.

Secondary

During treatment (up to 88 weeks)

From the first trial-related activity after the subject had signed the informed consent until the End of Trial (week 88) + 7 days follow-up period.

A treatment-emergent adverse event was defined as one which had onset date on or after the 1st day of exposure to treatment and no later than 7 days after the last days of treatment or had onset date before the 1st day of exposure to treatment and increased in severity during the treatment period and until 7 days after the last date of treatment.

21

Insulin degludec U200

Insulin Glargine U300