Comparison of Liraglutide Versus Placebo in Weight Loss Maintenance in Obese Subjects: SCALE - Maintenance

Study Overview
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Brief Summary
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This trial is conducted in North America. The aim of this clinical trial is to evaluate the potential of liraglutide to maintain long term weight loss in obese non-diabetic subjects, as well as in overweight subjects who have medical problems such as hypertension (high blood pressure) or dyslipidaemia (an abnormal amount of lipids in the blood). Trial has following trial periods: A 12-week run-in period (from week -12 to week 0) followed by a 56-week main trial period (weeks 0-56) and a 12-week follow-up period (weeks 56-68).

Official Title
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Effect of Liraglutide on Long-term Weight Maintenance and Additional Weight Loss Induced by a 4 to 12 Week Low Calorie Diet in Obese Subjects; A 56 Week Randomised, Double-blind, Placebo Controlled, Parallel Group, Multicentre Trial With a 12 Week Follow-up Period

Conditions
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Metabolism and Nutrition Disorder, Obesity

Intervention / Treatment
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* Drug: liraglutide
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body Mass Index (BMI) of either 30 kg/m^2 or more or BMI of less than 30 kg/m^2 to 27 kg/m^2 with presence of co-morbidities Stable body weight during the previous 3 months (less than 5 kg self-reported weight change) Previously undergone dietary weight loss and was not able to maintain reduced weight Exclusion Criteria: Diagnosis of type 1 or type 2 diabetes Previous treatment with GLP-1 (glucagon-like peptide-1) receptor agonists (including liraglutide or exenatide), within the last 3 months Visit 1 thryoid stimulating hormone (TSH) outside of the range of 0.4-6.0 mIU/L History of chronic pancreatitis or idiopathic acute pancreatitis Obesity induced by other endocrinologic disorders (e.g., Cushing Syndrome) Current or history of treatment with medications that may cause significant weight gain for at least 3 months before this trial Current participation in an organized diet reduction program (or within the last 3 months) Currently using or have used within three months before this trial: pramlintide, sibutramine, orlistat, zonisamide, topiramate, phenteremine, or metformin Previous surgical treatment for obesity (excluding liposuction if performed more than one year before trial entry) History of major depressive disorder or a PHQ-9 (Patient Health Questionnaire-9) score of more than 15 within the last 2 years or history of other severe psychiatric disorders or diagnosis of an eating disorder Subjects with a lifetime history of a suicide attempt or history of any suicidal behavior within the past month before entry into the trial

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: Lira 3.0 mg<br>A 12-week run-in period where screened subjects were treated with a low calorie diet. Randomised subjects (those who lost more than or equal to 5% of screening body weight) were treated with liraglutide 3.0 mg, once daily, injected subcutaneously and instructed to follow a standard energy-restricted diet in the 56-week main trial period. Subjects discontinued treatment in the 12-week follow-up period. The starting dose of liraglutide was 0.6 mg, with weekly increments of 0.6 mg every 7 days until the target dose of 3.0 mg was reached | Drug: liraglutide<br>* Liraglutide 3.0 mg per day administered in a 6.0 mg/mL, 3 mL FlexPen® for subcutaneous (under the skin) injection, once daily<br>|
| Placebo Comparator: Placebo<br>A 12-week run-in period where screened subjects were treated with a low calorie diet. Randomised subjects (those who lost more than or equal to 5% of screening body weight) were treated with liraglutide placebo, once daily, injected subcutaneously for 56 weeks and instructed to follow a standard energy-restricted diet in the 56-week main trial period. Subjects discontinued treatment in the 12-week follow-up period | Drug: placebo<br>* Liraglutide placebo 3 mL FlexPen® for subcutaneous (under the skin) injection, once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Percentage Change in Fasting Body Weight From Baseline | Subjects were weighed having fasted (consumed only water) since midnight the night before the visit. | Week 0, week 56 | 
| Percentage of Subjects Who Maintained Their run-in Fasting Weight Loss From Week 0 | Subjects who had a weight regain less than or equal to 0.5% of weight from Week 0 were regarded as maintenance of run-in fasting weight loss. Subjects were weighed having fasted (consumed only water) since midnight the night before the visit. | Week 0, week 56 | 
| Percentage of Subjects Who Lost More Than or Equal to 5% of Fasting Body Weight From Week 0 | Subjects were weighed having fasted (consumed only water) since midnight the night before the visit. | Week 0, week 56 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects Who Lost More Than 10% of Fasting Body Weight From Week 0 | Subjects were weighed having fasted (consumed only water) since midnight the night before the visit. | Week 0, week 56 | 
| Percentage of Subjects With Weight Regain (Fasting) More Than or Equal to 5% From Week 0 | Subjects were weighed having fasted (consumed only water) since midnight the night before the visit. | Week 0, week 56 | 
| Percentage of Subjects With Weight Regain (Fasting) More Than or Equal to 10% From Week 0 | Subjects were weighed having fasted (consumed only water) since midnight the night before the visit. | Week 0, week 56 | 
| Percentage of Subjects With Greater Than 50% of Fasting run-in Weight Loss Maintained From Week 0 | Subjects were weighed having fasted (consumed only water) since midnight the night before the visit. | Week 0, week 56 | 
| Percentage of Subjects With Greater Than 75% of Fasting run-in Weight Loss Maintained From Week 0 | Subjects were weighed having fasted (consumed only water) since midnight the night before the visit. | Week 0, week 56 | 
| Change From Baseline in Fasting Weight | Subjects were weighed having fasted (consumed only water) since midnight the night before the visit. | Week 0, week 56 | 
| Change From Baseline in Fasting Weight for Subjects Completing the Main Trial Period and Entering the Follow-up Period | Subjects were weighed having fasted (consumed only water) since midnight the night before the visit. | Week 0, week 68 | 
| Change From Baseline in Blood Pressure |  | Week 0, week 56 | 
| Change From Baseline in Pulse |  | Week 0, week 56 | 
| Change From Baseline in Fasting Lipid Profile: Triglycerides | Subjects were tested having fasted (consumed only water) since midnight the night before the visit. | Week 0, week 56 | 
| Change From Baseline in Fasting Lipid Profile: Low Density Lipoprotein (LDL) Cholesterol | Subjects were tested having fasted (consumed only water) since midnight the night before the visit. | Week 0, week 56 | 
| Change From Baseline in Fasting Lipid Profile: Total Cholesterol | Subjects were tested having fasted (consumed only water) since midnight the night before the visit. | Week 0, week 56 | 
| Change From Baseline in Cardiovascular Biomarker: High Sensitivity C-reactive Protein (hsCRP) |  | Week 0, week 56 | 
| Percentage of Subjects Meeting Metabolic Syndrome Criteria: ATP (Adult Treatment Panel) III at Week 56 | Metabolic syndrome status required at least 3 of 5 criteria met: Waist circumference (men ≥102cm, women ≥88cm); Triglycerides >1.7mmol/L; High density lipoprotein cholesterol (men <0.9mmol/L, women <1.1mmol/L) or on drug therapy; Blood pressure ≥130mmHg systolic or ≥85mmHg diastolic or on drug therapy; Fasting glucose ≥5.5mmol/L or on drug therapy. | Week 56 | 
| Change From Baseline in Waist Circumference |  | Week 0, week 56 | 
| Change From Baseline in Body Mass Index (BMI) |  | Week 0, week 56 | 
| Change From Baseline in Glycaemic Control Parameter: HOMA-B (Homeostasis Model Assessment - Beta Cell Function) | Change in beta-cell function percent values from Week 0 (X%) to Week 56 (Y%) was calculated [X% - Y%]. Beta-cell function was derived from fasting plasma glucose readings in blood samples using the HOMA method, which is based on the assumption that normal-weight subjects without diabetes aged <35 years have median beta-cell function indexed at 100%. | Week 0, week 56 | 
| Change From Baseline in Glycaemic Control Parameter: HOMA-IR (Homeostasis Model Assessment - Insulin Resistance) | Change in insulin resistance values from Week 0 (X) to Week 56 (Y) was calculated [X - Y]. Insulin resistance was derived from fasting serum insulin levels in blood samples using the HOMA method, which is based on the assumption that normal-weight subjects without diabetes aged <35 years have median insulin resistance indexed at 1.00. | Week 0, week 56 | 
| Change From Baseline in Glycaemic Control Parameter: Fasting Plasma Glucose (FPG) | Subjects were tested having fasted (consumed only water) since midnight the night before the visit. | Week 0, week 56 | 
| Change From Baseline in Glycaemic Control Parameter: Fasting Serum Insulin | Subjects were tested having fasted (consumed only water) since midnight the night before the visit. | Week 0, week 56 | 
| Change From Baseline in Glycaemic Control Parameter: HbA1c (Glycosylated Haemoglobin) | Change in HbA1c percent values from Week 0 (X%) to Week 56 (Y%) was calculated [X% - Y%]. | Week 0, week 56 | 
| Number of Subjects Using Concomitant Medications (Antihypertensive Medications, Lipid Lowering Medications, or Antipsychotic Medications) | Number of subjects using concomitant medications at Week 0 and Week 56, respectively | Week 0 and week 56 | 
| Binge Eating Scale Scores by Week and Severity | Binge Eating Scale (BES) scores are based on responses to the Binge Eating Scale Questionnaire, a 16-item self-reporting diagnostic tool scaled 0-46 (Non-binging: 0-17; Moderate: 17-26; Severe: 27-46) | Week 0, week 50 and week 57 |