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

Phase 3

Completed

Conditions: Obesity
Metabolism and Nutrition Disorder

Interventions: Drug: placebo
Drug: liraglutide

Registration Number: NCT00781937

Lead Sponsor: Novo Nordisk A/S

Brief Summary: 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).

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 422

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	placebo	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
Lira 3.0 mg	liraglutide	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

Primary Outcome Measures

Name	Time	Method
Percentage of Subjects Who Lost More Than or Equal to 5% of Fasting Body Weight From Week 0	Week 0, week 56	Subjects were weighed having fasted (consumed only water) since midnight the night before the visit.
Mean Percentage Change in Fasting Body Weight From Baseline	Week 0, week 56	Subjects were weighed having fasted (consumed only water) since midnight the night before the visit.
Percentage of Subjects Who Maintained Their run-in Fasting Weight Loss From Week 0	Week 0, week 56	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.

Secondary Outcome Measures

Name	Time	Method
Percentage of Subjects Who Lost More Than 10% of Fasting Body Weight From Week 0	Week 0, week 56	Subjects were weighed having fasted (consumed only water) since midnight the night before the visit.
Percentage of Subjects With Weight Regain (Fasting) More Than or Equal to 5% From Week 0	Week 0, week 56	Subjects were weighed having fasted (consumed only water) since midnight the night before the visit.
Percentage of Subjects With Weight Regain (Fasting) More Than or Equal to 10% From Week 0	Week 0, week 56	Subjects were weighed having fasted (consumed only water) since midnight the night before the visit.
Percentage of Subjects With Greater Than 50% of Fasting run-in Weight Loss Maintained From Week 0	Week 0, week 56	Subjects were weighed having fasted (consumed only water) since midnight the night before the visit.
Percentage of Subjects With Greater Than 75% of Fasting run-in Weight Loss Maintained From Week 0	Week 0, week 56	Subjects were weighed having fasted (consumed only water) since midnight the night before the visit.
Change From Baseline in Fasting Weight	Week 0, week 56	Subjects were weighed having fasted (consumed only water) since midnight the night before the visit.
Change From Baseline in Fasting Weight for Subjects Completing the Main Trial Period and Entering the Follow-up Period	Week 0, week 68	Subjects were weighed having fasted (consumed only water) since midnight the night before the visit.
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	Week 0, week 56	Subjects were tested having fasted (consumed only water) since midnight the night before the visit.
Change From Baseline in Fasting Lipid Profile: Low Density Lipoprotein (LDL) Cholesterol	Week 0, week 56	Subjects were tested having fasted (consumed only water) since midnight the night before the visit.
Change From Baseline in Fasting Lipid Profile: Total Cholesterol	Week 0, week 56	Subjects were tested having fasted (consumed only water) since midnight the night before the visit.
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	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.
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)	Week 0, week 56	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%.
Change From Baseline in Glycaemic Control Parameter: HOMA-IR (Homeostasis Model Assessment - Insulin Resistance)	Week 0, week 56	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.
Change From Baseline in Glycaemic Control Parameter: Fasting Plasma Glucose (FPG)	Week 0, week 56	Subjects were tested having fasted (consumed only water) since midnight the night before the visit.
Change From Baseline in Glycaemic Control Parameter: Fasting Serum Insulin	Week 0, week 56	Subjects were tested having fasted (consumed only water) since midnight the night before the visit.
Change From Baseline in Glycaemic Control Parameter: HbA1c (Glycosylated Haemoglobin)	Week 0, week 56	Change in HbA1c percent values from Week 0 (X%) to Week 56 (Y%) was calculated \[X% - Y%\].
Number of Subjects Using Concomitant Medications (Antihypertensive Medications, Lipid Lowering Medications, or Antipsychotic Medications)	Week 0 and week 56	Number of subjects using concomitant medications at Week 0 and Week 56, respectively
Binge Eating Scale Scores by Week and Severity	Week 0, week 50 and week 57	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)