NN1218-4049

Novo Nordisk A/S

Novo Allé, Bagsvaerd, Denmark, 2880

Global Clinical Registry (GCR, 1452), Novo Nordisk A/S, clinicaltrials@novonordisk.com

Global Clinical Registry (GCR, 1452), Novo Nordisk A/S, clinicaltrials@novonordisk.com

No

No

No

Final

09 Jul 2015

Yes

17 Nov 2014

Yes

17 Nov 2014

No

To confirm superiority of meal-time faster-acting insulin aspart (FIAsp)/faster aspart in a full basal-bolus regimen versus basal insulin therapy, both in combination with metformin, in terms of glycaemic control after 18-weeks of randomised treatment.

The trial was conducted in accordance with the Declaration of Helsinki and ICH Good Clinical Practice and 21 CFR 312.120

23 Sep 2013

No

No

Argentina: 44

India: 61

Mexico: 31

Romania: 28

Slovenia: 32

United States: 40

236

60

0

0

0

0

0

0

177

59

0

Overall Study (overall period)

Randomised - controlled

Not applicable

Yes

Faster aspart

Solution for injection

Subcutaneous use

Faster aspart was used for bolus insulin administration at each main meal (i.e., breakfast, lunch and main evening meal) and was to be injected subcutaneously into the abdomen. Injection sites were to be rotated within the same area. The bolus insulin injection was to be given 0–2 minutes before each main meal.

Insulin detemir

Levemir®

Solution for injection

Subcutaneous use

Insulin detemir was used for basal insulin administration and was to be injected subcutaneously into the thigh or upper arm (deltoid area). The basal insulin injection was to be given OD, in the evening, at approximately the same time each day. Changing the frequency (e.g., from OD to twice daily [BID]) of basal insulin dosing during the trial was not allowed.

NPH insulin

Insulatard®, Protaphane®, Novolin N™

Suspension for injection

Subcutaneous use

NPH insulin was used for basal insulin administration and was to be injected subcutaneously into the thigh or upper arm (deltoid area). The basal insulin injection was to be given OD, in the evening, at approximately the same time each day. Changing the frequency (e.g., from OD to BID) of basal insulin dosing during the trial was not allowed.

Insulin glargine

Lantus®

Solution for injection

Subcutaneous use

Insulin glargine was used for basal insulin administration and was to be injected subcutaneously into the thigh or upper arm (deltoid area). The basal insulin injection was to be given OD, in the evening, at approximately the same time each day. Changing the frequency (e.g., from OD to BID) of basal insulin dosing during the trial was not allowed.

Insulin detemir

Levemir®

Solution for injection

Subcutaneous use

Insulin detemir was used for basal insulin administration and was to be injected subcutaneously into the thigh or upper arm (deltoid area). The basal insulin injection was to be given OD, in the evening, at approximately the same time each day. Changing the frequency (e.g., from OD to BID) of basal insulin dosing during the trial was not allowed.

NPH insulin

Insulatard®, Protaphane®, Novolin N™

Suspension for injection

Subcutaneous use

NPH insulin was used for basal insulin administration and was to be injected subcutaneously into the thigh or upper arm (deltoid area). The basal insulin injection was to be given OD, in the evening, at approximately the same time each day. Changing the frequency (e.g., from OD to BID) of basal insulin dosing during the trial was not allowed.

Insulin glargine

Lantus®

Solution for injection

Subcutaneous use

Insulin glargine was used for basal insulin administration and was to be injected subcutaneously into the thigh or upper arm (deltoid area). The basal insulin injection was to be given OD, in the evening, at approximately the same time each day. Changing the frequency (e.g., from OD to BID) of basal insulin dosing during the trial was not allowed.

Faster aspart + Basal

Basal

Faster aspart + Basal

Basal

For this endpoint, baseline (week 0) and week 18 have been presented, where week 18 data are the “end of trial” data containing last available measurements. Analysis population: Full analysis set (FAS); the FAS included all randomised subjects. n = treatment wise number of subjects analysed for individual time-point.

Primary

After 18 weeks of randomised treatment

Change from baseline in HbA1c after 18 weeks of treatment was analysed using a mixed-effect model for repeated measurements (MMRM) where all calculated changes in HbA1c from baseline at visits 16, 22 and 28 were included in the analysis. This model included treatment, region and strata as fixed factors, subject as random effect, baseline HbA1c as covariate and interaction between all fixed effects and visit, and between the covariate and visit.

Faster aspart + Basal v Basal

236

Pre-specified

-0.94

2-sided

For this endpoint the "end of trial" data containing last available measurements are presented. PPG measurements were recorded by the subjects at 2 hours after each meal (breakfast, lunch and main evening meal) as part of three 7-point profiles (SMPG) prior to the visits. Individual mean meal PPG (post-breakfast, post-lunch, post-main evening meal) was derived from the three measurements. Overall mean PPG was derived from the individual derived meal time mean PPG values. Analysis population: FAS; the FAS included all randomised subjects. n = treatment wise number of subjects analysed for individual time-point.

Secondary

After 18 weeks of randomised treatment

For this endpoint the "end of trial" data containing last available measurements are presented. Prandial PG increment for each meal (breakfast, lunch, main evening meal) was derived from the 7-point profiles (SMPG) as the difference between the PPG value 2 hours after each meal and the PG value before each meal. Individual mean meal PPG (post-breakfast, post-lunch, post-main evening meal) was derived from the three measurements. Overall mean PPG was derived from the individual derived meal time mean PPG values. Analysis population: FAS; the FAS included all randomised subjects. n = treatment wise number of subjects analysed for individual time-point.

Secondary

After 18 weeks of randomised treatment

For this endpoint, baseline (week 0) and week 18 have been presented, where week 18 data are the “end of trial” data containing last available measurements. Analysis population: FAS; the FAS included all randomised subjects. n = treatment wise number of subjects analysed for individual time-point.

Secondary

After 18 weeks of randomised treatment

Plasma glucose (PG) was always to be measured and recorded when a hypoglycaemic episode was suspected. All PG values ≤3.9 mmol/L (70 mg/dL) or >3.9 mmol/L (70 mg/dL) when they occurred in conjunction with hypoglycaemic symptoms were to be recorded by the subject. Numbers of treatment emergent hypoglycaemic episodes were recorded during 18 weeks of treatment. Analysis population: Safety Analysis Set (SAS); the SAS included all subjects receiving at least one dose of the investigational product or its comparator.

Secondary

During 18 weeks of randomised treatment

All adverse events (AEs) described here refer to treatment emergent adverse events (TEAE). A 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 day of randomised treatment, week 18. Analysis population: SAS; the SAS included all subjects receiving at least one dose of the investigational product or its comparator.

Secondary

During 18 weeks of randomised treatment period.

During 18 weeks of randomised treatment period + 7 days of follow-up period.

All AEs described here refer to TEAE. Analysis population: SAS - included all subjects receiving at least one dose of the investigational product or its comparator. Number of deaths causally related to treatment is the data considered to present under "total number of deaths resulting from adverse events".

17

Faster aspart + Basal

Basal