NN1436-4466

Novo Nordisk A/S

Novo Allé, Bagsvaerd, Denmark, 2880

Clinical Reporting Anchor and Disclosure (1452), Clinical Reporting Anchor and Disclosure (1452), +1 866 8677178, clinicaltrials@novonordisk.com

Clinical Reporting Anchor and Disclosure (1452), Novo Nordisk A/S, +1 866 8677178, clinicaltrials@novonordisk.com

No

No

No

Final

01 Jun 2020

Yes

19 Dec 2019

Yes

27 Jan 2020

No

The main objective of the trial was to compare the effect on glycaemic control of treatment with once weekly insulin 287 using two different switch approaches versus once-daily insulin glargine U100 both in combination with metformin ± DPP4i ± SGLT2i in basal insulin analogue treated T2DM subjects.

The trial was conducted in accordance with the Declaration of Helsinki (64th WMA general assembly; Oct 2013) and ICH Good Clinical Practice, including archiving of essential documents, (May 1996) and 21 CFR 312.120.

09 May 2019

No

No

Canada: 36

Czechia: 30

Germany: 32

Italy: 31

United States: 25

154

93

0

0

0

0

0

0

89

65

0

Overall study (overall period)

Randomised - controlled

Yes

NNC0148-0287 C 4200 nmol/mL

Solution for injection

Subcutaneous use

Subjects were to receive once weekly subcutaneous (s.c.) injection of insulin 287 for 16 weeks, using PDS290 prefilled pen-injector at a starting dose of 7 times the pre-trial basal insulin dose of the respective subjects ('unit to unit switch' approach: current daily dose x 7). subjects were to perform once daily pre-breakfast self-monitoring plasma glucose (SMPG). The dose was adjusted based on 3 pre-breakfast SMPG values measured on the 2 previous days and the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 millimoles per litre (mmol/L): dose reduced by 28 U; 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: dose increased by 28 U. If the subject received a twice-daily regimen with any basal insulin analogue or a once-daily regimen with insulin glargine U300 prior to randomisation, the total daily insulin dose prior to randomisation was reduced by 20%.

NNC0148-0287 C 4200 nmol/mL

Solution for injection

Subcutaneous use

Subjects were to receive once weekly s.c. injection of insulin 287 for 16 weeks, using PDS290 prefilled pen-injector at a starting dose of 7 times the pre-trial basal insulin dose of the respective subjects with additional loading dose (‘unit to unit switch with an additional 100% loading dose’ approach: current daily dose x 7 x 2). subjects were to perform once daily pre-breakfast SMPG. The dose was adjusted based on 3 pre-breakfast SMPG values measured on the 2 previous days and the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 millimoles per litre (mmol/L): dose reduced by 28 U; 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: insulin dose increased by 28 U. If the subject received a twice-daily regimen with any basal insulin analogue or a once-daily regimen with insulin glargine U300 prior to randomisation, the total daily insulin dose prior to randomisation was reduced by 20%

Insulin Glargine U100

Solution for injection

Subcutaneous use

Subjects were to receive once daily s.c. injection of insulin glargine U100 for 16 weeks, using SoloSTAR prefilled pen-injector at a starting dose same as the pre-trial basal insulin. subjects were to perform once daily pre-breakfast SMPG. The dose was adjusted based on 3 pre-breakfast SMPG values measured on the 2 previous days and the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 millimoles per litre (mmol/L): dose reduced by 4 U; 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: insulin dose increased by 4 U. If the subject received a twice-daily regimen with any basal insulin analogue or a once-daily regimen with insulin glargine U300 prior to randomisation, the total daily insulin dose prior to randomisation was reduced by 20%.

Insulin 287 (without loading dose)

Insulin 287 (with 100% loading dose)

Insulin Glargine U100

Insulin 287 (without loading dose)

Insulin 287 (with 100% loading dose)

Insulin Glargine U100

The percentage of time spent in glycaemic target range was calculated 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 was evaluated based on the data from the on-treatment without rescue medication observation period, which was the time period when a subject was on treatment with trial product, excluding any period after initiation of a non-randomised insulin treatment (rescue medication). Number of subjects analyzed = Number of subjects who contributed to the analysis.

Primary

During the last 2 weeks of treatment (week 15 and 16)

The response and change from baseline in response during last two weeks of treatment (week 15 and 16) were analysed using an analysis of covariance (ANCOVA) model with treatment, pre-trial insulin treatment and SGLT2i use as fixed factors, and baseline response as covariate. Missing endpoint values were imputed using multiple imputation based on own treatment arm with baseline response as a covariate. Each imputed dataset was analysed separately and estimates were combined using Rubin's rules.

Insulin 287 (without loading dose) v Insulin Glargine U100

99

Pre-specified

1.01

2-sided

The response and change from baseline in response during last two weeks of treatment (week 15 and 16) were analysed using an analysis of covariance (ANCOVA) model with treatment, pre-trial insulin treatment and SGLT2i use as fixed factors, and baseline response as covariate. Missing endpoint values were imputed using multiple imputation based on own treatment arm with baseline response as a covariate. Each imputed dataset was analysed separately and estimates were combined using Rubin's rules.

Insulin 287 (with 100% loading dose) v Insulin Glargine U100

103

Pre-specified

7.88

2-sided

Estimated mean change from baseline (week 0, Visit 2) in glycosylated haemoglobin (HbA1c) at week 16 (Visit 18) is presented. The endpoint was evaluated based on the data from the on-treatment without rescue medication observation period, which was the time period when a subject was on treatment with trial product, excluding any period after initiation of a non-randomised insulin treatment (rescue medication). FAS included all randomised subjects.

Secondary

From baseline week 0 (V2) to week 16 (V18)

Estimated mean change from baseline week 0 (visit 2) in FPG at week 16 (Visit 18) is presented. The endpoint was evaluated based on the data from the on-treatment without rescue medication observation period, which was the time period when a subject was on treatment with trial product, excluding any period after initiation of a non-randomised insulin treatment (rescue medication). FAS included all randomised subjects. Number of subjects analyzed = Number of subjects who contributed to the analysis.

Secondary

From baseline week 0 (V2) to week 16 (V18)

Estimated mean change from baseline (week 0) in body weight at week 16 is presented. The endpoint was evaluated based on the data from the on-treatment without rescue medication observation period, which was the time period when a subject was on treatment with trial product, excluding any period after initiation of a non-randomised insulin treatment (rescue medication). FAS included all randomised subjects.

Secondary

From baseline week 0 (V2) to week 16 (V18)

Estimated mean average weekly insulin dose during the last 2 weeks of treatment is presented. The endpoint was evaluated based on the data from the on-treatment without rescue medication observation period, which was the time period when a subject was on treatment with trial product, excluding any period after initiation of a non-randomised insulin treatment (rescue medication). FAS included all randomised subjects.

Secondary

During the last 2 weeks of treatment (week 15 and 16)

An adverse event(AE) is any untoward medical occurrence in a clinical trial subject administered or using a medicinal product, whether or not considered related to the medicinal product or usage. A TEAE was defined as an event that had onset date (or increase in severity) during the on-treatment observation period. The on-treatment observation period was the time period from first dose of trial product until the follow-up visit or the last date on trial product + 5 weeks for once daily insulin and +6 weeks for once weekly insulin. Safety analysis set (SAS) included all subjects exposed to at least one dose of trial product.

Secondary

From baseline week 0 (V2) to week 21 (V20)

Severe hypoglycaemic episodes (level 3) were defined as episodes that were associated with severe cognitive impairment requiring external assistance for recovery. Number of severe hypoglycaemic episodes that occurred during weeks 0-16 are presented. Safety analysis set (SAS) included all subjects exposed to at least one dose of trial product.

Secondary

From baseline week 0 (V2) to week 16 (V18)

Clinically significant hypoglycaemic episodes (level 2) were defined as episodes that were sufficiently low to indicate serious, clinically important hypoglycaemia with plasma glucose value of <3.0 mmol/L (54 mg/dL). Severe hypoglycaemic episodes (level 3) were defined as episodes that were associated with severe cognitive impairment requiring external assistance for recovery. Number of clinically significant hypoglycaemic episodes (level 2), confirmed by blood glucose (BG)meter or severe hypoglycaemic episodes (level 3) that occured during weeks 0-16 are presented. SAS included all subjects exposed to at least one dose of trial product.

Secondary

From baseline week 0 (V2) to week 16 (V18)

Hypoglycaemia alert value (level 1) was defined as episodes that were sufficiently low for treatment with fast-acting carbohydrate and dose adjustment of glucose-lowering therapy. Number of hypoglycaemic alert episodes (level 1) (equal to or above 3.0 and below 3.9 mmol/L (equal to or above 54 and below 70 mg/dL), confirmed by BG meter) that occured during weeks 0-16 are presented. SAS included all subjects exposed to at least one dose of trial product.

Secondary

From baseline week 0 (V2) to week 16 (V18)

Weeks 0-21

Results are based on the safety analysis set which included all participants exposed to at least one dose of trial product. All presented adverse events are TEAEs. TEAE was defined as an event that had onset date (or increase in severity) during the on-treatment observation period.

22

Insulin 287 (without loading dose)

Insulin Glargine U100

Insulin 287 (with 100% loading dose)