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

Study Overview
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Brief Summary
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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).

Official Title
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Effect of Liraglutide on Body Weight in Non-diabetic Obese Subjects or Overweight Subjects With Co-morbidities: A Randomised, Double-blind, Placebo Controlled, Parallel Group, Multi-centre, Multinational Trial With Stratification of Subject to Either 56 or 160 Weeks of Treatment Based on Pre-diabetes Status at Randomisation

Conditions
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Metabolism and Nutrition Disorder, Obesity

Intervention / Treatment
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* Drug: liraglutide
* Drug: placebo
* Drug: liraglutide
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Liraglutide 3.0mg (week0-56)/Liraglutide 3.0mg (week56-68)<br> | Drug: liraglutide<br>* Subject with no pre-diabetes at screening, receiving liraglutide 3.0 mg subcutaneous (under the skin) injection once daily for 56 weeks. Subjects completing 56 weeks are re-randomised to receive liraglutide 3.0 mg for 12 weeks (until week 68).<br>|
| Experimental: Liraglutide 3.0mg (week0-56)/Liraglutide Placebo (week56-68)<br> | Drug: placebo<br>* Subject with no pre-diabetes at screening, receiving liraglutide 3.0 mg subcutaneous (under the skin) injection once daily for 56 weeks. Subjects completing 56 weeks are re-randomised to receive liraglutide placebo for 12 weeks (until week 68).<br>|
| Placebo Comparator: Liraglutide Placebo, no Pre-diabetes<br> | Drug: placebo<br>* Subject with no pre-diabetes at screening, receiving liraglutide 3.0 mg subcutaneous (under the skin) injection once daily for 56 weeks. Subjects completing 56 weeks are re-randomised to receive liraglutide placebo for 12 weeks (until week 68).<br>|
| Experimental: Liraglutide 3.0mg, Pre-diabetes<br> | Drug: liraglutide<br>* Liraglutide 3.0 mg, subcutaneous (under the skin) injection once daily for 160 weeks.<br>|
| Placebo Comparator: Liraglutide Placebo, Pre-diabetes<br> | Drug: placebo<br>* Liraglutide placebo, subcutaneous (under the skin) injection once daily for 160 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Fasting Body Weight | The observed mean change from baseline in fasting body weight (%) after 56-weeks of treatment (main treatment period). | Week 0, Week 56 | 
| Proportion of Subjects Losing at Least 5% of Baseline Fasting Body Weight. | Percentage of subjects losing at least 5% of baseline fasting body weight after 56-weeks of treatment (main treatment period). | At Week 56 | 
| Proportion of Subjects Losing More Than 10% of Baseline Fasting Body Weight | Percentage of subjects losing >10% of baseline fasting body weight after 56-weeks of treatment (main treatment period). | At 56 weeks | 
| Proportion of Subjects With Onset of Type 2 Diabetes | 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). | At 160 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Waist Circumference (cm) | The observed mean change from baseline in waist circumference (cm) after 56-weeks of treatment (main treatment period). | Week 0, Week 56 | 
| Change From Baseline in Waist Circumference (Subjects With Pre-diabetes at Baseline) | 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). | Week 0, week 160 | 
| Pre-diabetes Status After 56 Weeks of Treatment | Observed percentage of subjects with pre-diabetes status after 56 weeks of treatment (main treatment period). | Week 0, Week 56 | 
| Pre-diabetes Status in Subject With Pre-diabetes at Baseline After 160 Weeks of Treatment | 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). | Week 0, week 160 | 
| Mean Change From Baseline in Fasting Body Weight (Subjects With Pre-diabetes at Baseline) | 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). | Week 0, week 160 | 
| 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) | 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). | At 160 weeks | 
| Change From Week 56 in Fasting Body Weight (%) (Re-randomised Subjects With No Pre-diabetes) | 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). | Week 56, Week 68 | 
| Change From Baseline in Fasting Body Weight (%) (Re-randomised Subjects With No Pre-diabetes) | 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). | Week 0, Week 68 |