NN8022-4272

Novo Nordisk A/S

Novo Allé, Bagsvaerd, Denmark, 2880

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

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

No

No

No

Final

04 Mar 2019

Yes

10 Sep 2018

Yes

25 Sep 2018

No

To confirm superiority of liraglutide 3.0 mg vs. placebo, as an adjunct to a reduced-calorie diet and increased physical activity, on weight loss effectiveness in subjects with overweight or obesity and T2DM treated with a basal insulin and up to 2 OAD medications (metformin, glitazone, SGLT-2 inhibitor, alpha glucosidase inhibitor, glinide or sulphonylurea).

The trial was conducted in accordance with the Declaration of Helsinki, ICH GCP and FDA 21 CFR 312.120. In addition, the 21 Code of Federal Regulations, parts 312, 50, and 56 were followed.

06 Feb 2017

No

No

Canada: 44

Germany: 52

Israel: 22

Italy: 31

Mexico: 44

Turkey: 51

United States: 152

396

83

0

0

0

0

0

0

293

103

0

Overall Study (overall period)

Randomised - controlled

Liraglutide and placebo were visually identical in order to ensure double-blinding in the trial.

Yes

Liraglutide

Saxenda®

Solution for injection

Subcutaneous use

Liraglutide was administered once daily by subcutaneous injection irrespective of the timing of meals for 56 weeks. Subjects received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the maintenance dose of 3.0 mg was reached after 4 weeks.

Placebo

Solution for injection

Subcutaneous use

Matching placebo was administered once daily by subcutaneous injection irrespective of the timing of meals for 56 weeks. Dose escalation for placebo matched that of liraglutide.

Liraglutide 3.0 mg

Placebo

Liraglutide 3.0 mg

Placebo

Change in body weight from baseline (week 0) to week 56 was evaluated based on full analysis set (FAS) in-trial data and on-drug data. FAS includes all randomised subjects. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact. On-drug observation period: includes all time intervals in which subjects are considered to be on treatment from the date of first trial product administration to 7 days (or 14 days for adverse events [AEs]) after the final trial product administration, excluding potential off-treatment time intervals triggered by at least 7 consecutive missed doses (or 14 consecutive missed doses for AEs). 'n' is the number of subjects (subjects with available data) analysed for the respective reporting group.

Primary

From baseline to week 56

Analysis of in-trial data with missing observations imputed from placebo arm based on jump to reference multiple (x100) imputation approach. Week 56 responses were analysed using an analysis of covariance model with treatment, body mass index (BMI) groups and sex as factors and baseline body weight as covariate. The treatment policy estimand evaluated treatment effect (liraglutide 3.0 mg vs placebo) at week 56 for all randomised subjects regardless of premature discontinuation of trial product.

Placebo v Liraglutide 3.0 mg

396

Pre-specified

-4.32

2-sided

Standard error of the mean

0.59

Analysis of on-drug before first drug discontinuation date using a mixed model for repeated measurements with treatment, BMI groups and sex as factors and baseline body weight as covariate, all nested within visit. The hypothetical estimand evaluated the treatment effect (liraglutide 3.0 mg vs placebo) for all randomised subjects assuming that all subjects remained on trial product (on-treatment principle).

Liraglutide 3.0 mg v Placebo

396

Pre-specified

-5.1

2-sided

Standard error of the mean

0.61

The estimated percentage of subjects losing at least 5% of baseline (week 0) body weight at week 56 was presented based on FAS in-trial data and on-drug data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact. On-drug observation period: includes all time intervals in which participants are considered to be on treatment from the date of first trial product administration to 7 days (or 14 days for adverse events [AEs]) after the final trial product administration, excluding potential off-treatment time intervals triggered by at least 7 consecutive missed doses (or 14 consecutive missed doses for AEs). 'n' is the number of subjects (subjects with available data) analysed for the respective reporting group.

Primary

Week 56

Analysis of in-trial data with missing observations imputed from the placebo arm based on a jump to reference multiple (x100) imputation approach. Week 56 responses were analysed using a logistic regression model with treatment, BMI groups and sex as factors and baseline body weight as covariate.

Liraglutide 3.0 mg v Placebo

396

Pre-specified

3.41

2-sided

Analysis of on-drug before first drug discontinuation date using a mixed model for repeated measurements with treatment, BMI groups and sex as factors and baseline body weight as covariate, all nested within visit. The MMRM was used to classify responders and analysed with a logistic regression with treatment as the only factor.

Liraglutide 3.0 mg v Placebo

396

Pre-specified

4.73

2-sided

The estimated percentage of subjects losing more than 10% of baseline (week 0) body weight at week 56 was presented based on FAS in-trial data and on-drug data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact. On-drug observation period: includes all time intervals in which participants are considered to be on treatment from the date of first trial product administration to 7 days (or 14 days for adverse events [AEs]) after the final trial product administration, excluding potential off-treatment time intervals triggered by at least 7 consecutive missed doses (or 14 consecutive missed doses for AEs). 'n' is the number of subjects (subjects with available data) analysed for the respective reporting group.

Secondary

Week 56

Change in waist circumference from baseline (week 0) to week 56 was presented based on FAS in-trial data and on-drug data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact. On-drug observation period: includes all time intervals in which subjects are considered to be on treatment from the date of first trial product administration to 7 days (or 14 days for AEs) after the final trial product administration, excluding potential off-treatment time intervals triggered by at least 7 consecutive missed doses (or 14 consecutive missed doses for AEs). 'n' is the number of subjects (subjects with available data) analysed for the respective reporting group.

Secondary

From baseline to week 56

Change in glycosylated haemoglobin (HbA1c) from baseline (week 0) to week 56 was presented based on FAS in-trial data and on-drug data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact. On-drug observation period: includes all time intervals in which subjects are considered to be on treatment from the date of first trial product administration to 7 days (or 14 days for AEs) after the final trial product administration, excluding potential off-treatment time intervals triggered by at least 7 consecutive missed doses (or 14 consecutive missed doses for AEs). 'n' is the number of subjects (subjects with available data) analysed for the respective reporting group.

Secondary

From baseline to week 56

Change from baseline (week 0) in fasting plasma glucose (FPG) was presented based on FAS in-trial data and on-drug data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact. On-drug observation period: includes all time intervals in which subjects are considered to be on treatment from the date of first trial product administration to 7 days (or 14 days for AEs) after the final trial product administration, excluding potential off-treatment time intervals triggered by at least 7 consecutive missed doses (or 14 consecutive missed doses for AEs). 'n' is the number of subjects (subjects with available data) analysed for the respective reporting group.

Secondary

From baseline to week 56

SF-36 is a 36-item patient-reported survey of patient health that measures the subject's overall health-related quality of life (HRQoL). SF-36v2™ questionnaire measured the HRQoL on 8 domains on individual scale ranges. The scores 0-100 (where higher scores indicated a better HRQoL) from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. A norm-based score of 50 corresponds to the mean score and 10 corresponds to the standard deviation of the 2009 U.S. general population. Change from baseline (week 0) in SF-36 physical functioning score was presented based on FAS in-trial data and on-drug data. A positive change score indicates an improvement since baseline. 'n' is the number of subjects (subjects with available data) analysed for the respective reporting group.

Secondary

From baseline to week 56

IWQoL-Lite for CT is a modified version of an instrument designed to assess weight-related quality of life. The scores ranged between 0-100 where higher scores indicated a better quality of life. A positive change score indicates an improvement since baseline. The endpoint was presented based on FAS in-trial data and on-drug data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact. On-drug observation period: includes all time intervals in which subjects are considered to be on treatment from the date of first trial product administration to 7 days (or 14 days for AEs) after the final trial product administration, excluding potential off-treatment time intervals triggered by at least 7 consecutive missed doses (or 14 consecutive missed doses for AEs). 'n' is the number of subjects (subjects with available data) analysed for the respective reporting group.

Secondary

From baseline to week 56

From the date of first dose of trial product (week 0) to end of treatment (week 56) + post treatment follow-up of 30 days.

Evaluation of safety was based on SAS comprised of all randomised subjects who received at least one dose of trial product. AEs with onset during the on-treatment period were considered treatment-emergent. ‘Number of deaths causally related to treatment’ is the data considered to present under ‘total number of deaths resulting from adverse events’.

21

Liraglutide 3.0 mg

Placebo