Effect of Liraglutide on Body Weight in Non-diabetic Obese Subjects or Overweight Subjects With Co-morbidities: SCALE™ - Obesity and Pre-diabetes

Phase 3

Completed

Conditions: Metabolism and Nutrition Disorder
Obesity

Interventions: Drug: placebo
Drug: liraglutide

Registration Number: NCT01272219

Lead Sponsor: Novo Nordisk A/S

Brief Summary: This trial is conducted in Africa, Asia, Europe, Oceania, North America and South America.

The aim of this clinical trial is to evaluate the potential of liraglutide to induce and maintain weight loss over 56 weeks in obese subjects or overweight subjects with co-morbidities. Furthermore, the aim is to investigate the long term potential of liraglutide to delay the onset of type 2 diabetes in subjects diagnosed with pre-diabetes at baseline.

Based on body mass index (BMI) and pre-diabetes status, subjects will be randomised to either 68 weeks (56 weeks of randomised treatment followed by a 12 week re-randomised treatment period) or 160 weeks of treatment (160 week treatment will only be applicable to subjects with pre-diabetes status at baseline).

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 3731

Inclusion Criteria

Informed consent obtained
Body Mass Index (BMI) of 30.0 kg/m^2 or above
Body Mass Index (BMI) of 27 kg/m^2 or above in the presence of co-morbidities of treated or untreated dyslipidemia and/or hypertension
Stable body weight
Preceding failed dietary effort

Exclusion Criteria

Known type 1 or type 2 diabetes
Glycosylated haemoglobin (HbA1c) of 6.5 % or above (Screening visit 1) or FPG of 126 mg/dL (7 mmol/L) or above (Screening visit 2) or 2 hour post-challenge (OGTT) plasma glucose of 200 mg/dL (11.1 mmol/L) or above (Screening visit 2)
Screening calcitonin of 50 ng/L or above
Family or personal history of multiple endocrine neoplasia type 2 (MEN2) or familial medullary thyroid carcinoma (FMTC)
Personal history of non-familial medullary thyroid carcinoma
History of acute or chronic pancreatitis
Obesity induced by drug treatment
Use of approved weight lowering pharmacotherapy
Previous surgical treatment of obesity
History of major depressive disorder or suicide attempt
Uncontrolled hypertension (systolic blood pressure of 160 mmHg or above and/or diastolic blood pressure of 100 mmHg or above)

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Liraglutide Placebo, Pre-diabetes	placebo	-
Liraglutide 3.0mg (week0-56)/Liraglutide Placebo (week56-68)	placebo	-
Liraglutide Placebo, no Pre-diabetes	placebo	-
Liraglutide 3.0mg (week0-56)/Liraglutide 3.0mg (week56-68)	liraglutide	-
Liraglutide 3.0mg, Pre-diabetes	liraglutide	-

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Fasting Body Weight	Week 0, Week 56	The observed mean change from baseline in fasting body weight (%) after 56-weeks of treatment (main treatment period).
Proportion of Subjects Losing at Least 5% of Baseline Fasting Body Weight.	At Week 56	Percentage of subjects losing at least 5% of baseline fasting body weight after 56-weeks of treatment (main treatment period).
Proportion of Subjects Losing More Than 10% of Baseline Fasting Body Weight	At 56 weeks	Percentage of subjects losing \>10% of baseline fasting body weight after 56-weeks of treatment (main treatment period).
Proportion of Subjects With Onset of Type 2 Diabetes	At 160 weeks	Proportion of subjects with onset of Type 2 diabetes mellitus (T2DM) at week 160 (main + extension treatment period) among subjects with pre-diabetes at baseline - evaluated as time to onset of T2DM. Subjects included in FAS, who were stratified to 160-weeks of treatment (i.e., excluding 37 subjects with pre-diabetes who entered the re-randomised period and including 6 subjects without pre-diabetes incorrectly stratified to the 160-week treatment period).

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Waist Circumference (cm)	Week 0, Week 56	The observed mean change from baseline in waist circumference (cm) after 56-weeks of treatment (main treatment period).
Change From Baseline in Waist Circumference (Subjects With Pre-diabetes at Baseline)	Week 0, week 160	The observed mean change from baseline in waist circumference (subjects with pre-diabetes at baseline) after 160 weeks of treatment (main + extension treatment period). Subjects included in FAS, who were stratified to 160-weeks of treatment (i.e., excluding 37 subjects with pre-diabetes who entered the re-randomised period and including 6 subjects without pre-diabetes incorrectly stratified to the 160-week treatment period).
Pre-diabetes Status After 56 Weeks of Treatment	Week 0, Week 56	Observed percentage of subjects with pre-diabetes status after 56 weeks of treatment (main treatment period).
Pre-diabetes Status in Subject With Pre-diabetes at Baseline After 160 Weeks of Treatment	Week 0, week 160	Observed percentage of subjects (subjects with pre-diabetes at baseline) with pre-diabetes status after 160 weeks of treatment (main + extension treatment period). Subjects included in FAS, who were stratified to 160-weeks of treatment (i.e., excluding 37 subjects with pre-diabetes who entered the re-randomised period and including 6 subjects without pre-diabetes incorrectly stratified to the 160-week treatment period).
Mean Change From Baseline in Fasting Body Weight (Subjects With Pre-diabetes at Baseline)	Week 0, week 160	The observed mean change from baseline in fasting body weight (subjects with pre-diabetes at baseline) after 160 weeks of treatment (main + extension treatment period). Subjects included in FAS, who were stratified to 160-weeks of treatment (i.e., excluding 37 subjects with pre-diabetes who entered the re-randomised period and including 6 subjects without pre-diabetes incorrectly stratified to the 160-week treatment period).
Proportion of Subjects Losing at Least 5% and Proportion of Subjects Losing More Than 10% of Baseline Fasting Body Weight (Subjects With Pre-diabetes at Baseline)	At 160 weeks	Percentage of subjects losing \>=5% and percentage of subjects losing \>10% of baseline fasting body weight (pre-diabetic subjects at baseline) after 160-weeks of treatment (main + extension treatment period). Subjects included in FAS, who were stratified to 160-weeks of treatment (i.e., excluding 37 subjects with pre-diabetes who entered the re-randomised period and including 6 subjects without pre-diabetes incorrectly stratified to the 160-week treatment period).
Change From Week 56 in Fasting Body Weight (%) (Re-randomised Subjects With No Pre-diabetes)	Week 56, Week 68	The observed mean change in fasting body weight (%) from week 56 to week 68 in re-randomised subjects (with no pre-diabetes at baseline) after 12-weeks of treatment (re-randomised treatment period).
Change From Baseline in Fasting Body Weight (%) (Re-randomised Subjects With No Pre-diabetes)	Week 0, Week 68	The observed mean change from baseline in fasting body weight (%) in re-randomised subjects (with no pre-diabetes at baseline) after 68 weeks of treatment (main + re-randomised treatment period).