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

Obesity Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00781937
• Other study ID #: NN8022-1923
• Status: Completed
• Phase: Phase 3
• First received: October 28, 2008
• Last updated: September 29, 2017
• Start date: October 30, 2008
• Est. completion date: September 1, 2010

Study information

• Verified date: September 2017
• Source: Novo Nordisk A/S
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 422
• Est. completion date: September 1, 2010
• Est. primary completion date: September 1, 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Metabolism and Nutrition Disorder
• Nutrition Disorders
• Obesity
• Weight Loss

Intervention

Drug:
• liraglutide
Liraglutide 3.0 mg per day administered in a 6.0 mg/mL, 3 mL FlexPen® for subcutaneous (under the skin) injection, once daily
• placebo
Liraglutide placebo 3 mL FlexPen® for subcutaneous (under the skin) injection, once daily

Locations

Country	Name	City	State
Canada	Novo Nordisk Investigational Site	Burlington	Ontario
Canada	Novo Nordisk Investigational Site	Hamilton	Ontario
Canada	Novo Nordisk Investigational Site	Laval	Quebec
Canada	Novo Nordisk Investigational Site	London
Canada	Novo Nordisk Investigational Site	Mirabel	Quebec
Canada	Novo Nordisk Investigational Site	Montreal
Canada	Novo Nordisk Investigational Site	Sarnia	Ontario
Canada	Novo Nordisk Investigational Site	Sherbrooke	Quebec
Canada	Novo Nordisk Investigational Site	Trois Rivières	Quebec
Canada	Novo Nordisk Investigational Site	Winnipeg	Manitoba
United States	Novo Nordisk Investigational Site	Atlanta	Georgia
United States	Novo Nordisk Investigational Site	Butte	Montana
United States	Novo Nordisk Investigational Site	Charleston	South Carolina
United States	Novo Nordisk Investigational Site	Cincinnati	Ohio
United States	Novo Nordisk Investigational Site	Cincinnati	Ohio
United States	Novo Nordisk Investigational Site	Colorado Springs	Colorado
United States	Novo Nordisk Investigational Site	Dallas	Texas
United States	Novo Nordisk Investigational Site	Endwell	New York
United States	Novo Nordisk Investigational Site	Goodyear	Arizona
United States	Novo Nordisk Investigational Site	Hialeah	Florida
United States	Novo Nordisk Investigational Site	Huntington Beach	California
United States	Novo Nordisk Investigational Site	Louisville	Kentucky
United States	Novo Nordisk Investigational Site	Madisonville	Kentucky
United States	Novo Nordisk Investigational Site	Meridian	Idaho
United States	Novo Nordisk Investigational Site	Montclair	California
United States	Novo Nordisk Investigational Site	Nashville	Tennessee
United States	Novo Nordisk Investigational Site	New York	New York
United States	Novo Nordisk Investigational Site	Norfolk	Virginia
United States	Novo Nordisk Investigational Site	Pembroke Pines	Florida
United States	Novo Nordisk Investigational Site	Peoria	Arizona
United States	Novo Nordisk Investigational Site	Philadelphia	Pennsylvania
United States	Novo Nordisk Investigational Site	Philadelphia	Pennsylvania
United States	Novo Nordisk Investigational Site	Round Rock	Texas
United States	Novo Nordisk Investigational Site	Saint Louis	Missouri
United States	Novo Nordisk Investigational Site	Southfield	Michigan
United States	Novo Nordisk Investigational Site	Wilmington	North Carolina
United States	Novo Nordisk Investigational Site	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (7)

Bays H, Pi-Sunyer X, Hemmingsson JU, Claudius B, Jensen CB, Van Gaal L. Liraglutide 3.0 mg for weight management: weight-loss dependent and independent effects. Curr Med Res Opin. 2017 Feb;33(2):225-229. doi: 10.1080/03007995.2016.1251892. Epub 2016 Nov 6 — View Citation

Davies MJ, Aronne LJ, Caterson ID, Thomsen AB, Jacobsen PB, Marso SP; Satiety and Clinical Adiposity - Liraglutide Evidence in individuals with and without diabetes (SCALE) study groups. Liraglutide and cardiovascular outcomes in adults with overweight or — View Citation

McEvoy BW. Missing data in clinical trials for weight management. J Biopharm Stat. 2016;26(1):30-6. doi: 10.1080/10543406.2015.1094814. Review. — View Citation

O'Neil PM, Aroda VR, Astrup A, Kushner R, Lau DCW, Wadden TA, Brett J, Cancino AP, Wilding JPH; Satiety and Clinical Adiposity - Liraglutide Evidence in individuals with and without diabetes (SCALE) study groups. Neuropsychiatric safety with liraglutide 3 — View Citation

O'Neil PM, Garvey WT, Gonzalez-Campoy JM, Mora P, Ortiz RV, Guerrero G, Claudius B, Pi-Sunyer X; Satiety and Clinical Adiposity – Liraglutide Evidence in individuals with and without diabetes (SCALE) study groups. EFFECTS OF LIRAGLUTIDE 3.0 MG ON WEIGHT A — View Citation

Steinberg WM, Rosenstock J, Wadden TA, Donsmark M, Jensen CB, DeVries JH. Impact of Liraglutide on Amylase, Lipase, and Acute Pancreatitis in Participants With Overweight/Obesity and Normoglycemia, Prediabetes, or Type 2 Diabetes: Secondary Analyses of Po — View Citation

Wadden TA, Hollander P, Klein S, Niswender K, Woo V, Hale PM, Aronne L; NN8022-1923 Investigators. Weight maintenance and additional weight loss with liraglutide after low-calorie-diet-induced weight loss: the SCALE Maintenance randomized study. Int J Obe — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Change From Baseline in Blood Pressure		Week 0, week 56
Secondary	Change From Baseline in Pulse		Week 0, week 56
Secondary	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
Secondary	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
Secondary	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
Secondary	Change From Baseline in Cardiovascular Biomarker: High Sensitivity C-reactive Protein (hsCRP)		Week 0, week 56
Secondary	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
Secondary	Change From Baseline in Waist Circumference		Week 0, week 56
Secondary	Change From Baseline in Body Mass Index (BMI)		Week 0, week 56
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

•   Clinical Trials at Novo Nordisk