The Effect of Liraglutide on Body Weight in Obese Subjects Without Diabetes

• ClinicalTrials.gov Identifier: NCT00422058
• Recruitment Status: Completed
• First Posted: January 15, 2007
• Results First Posted: October 28, 2010
• Last Update Posted: November 1, 2017
• Sponsor: Novo Nordisk A/S
• Information provided by (Responsible Party): Novo Nordisk A/S

Study Description

Brief Summary:

This trial is conducted in Europe. The purpose of the 20-week trial is to investigate the efficacy of liraglutide to induce body weight loss and the purpose of the extension is to evaluate the long term safety and tolerability of liraglutide.

Trial has the following trial periods: A 20-week randomised, double-blind, placebo-controlled, six-armed parallel-group, multi-centre, multinational trial with an open label orlistat comparator arm followed by an 84 week extension period.

Condition or disease	Intervention/treatment	Phase
Metabolism and Nutrition Disorder; Obesity	Drug: liraglutide; Drug: orlistat; Drug: placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 564 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Effect of Liraglutide on Body Weight in Obese Subjects Without Diabetes: A 20-week Randomised, Double-blind, Placebo-controlled, Six Armed Parallel Group, Multi-centre, Multinational Trial With an Open Label Orlistat Comparator Arm and With an 84-week Extension Period
• Actual Study Start Date: January 10, 2007
• Actual Primary Completion Date: September 13, 2007
• Actual Study Completion Date: April 30, 2009

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Lira placebo/Lira 2.4 mg/Lira 3.0 mg; Liraglutide placebo once daily, weeks 0-20 (double-blinded), extended to 52 weeks (sponsor was unblinded at 20 weeks). Subjects switched to receive liraglutide 2.4 mg once daily and then liraglutide 3.0 mg once daily in open-label extension period (weeks 52-104)	Drug: placebo; Injected s.c. (under the skin) once daily
Experimental: Lira 1.2 mg/Lira 3.0 mg; Liraglutide 1.2 mg once daily, weeks 0-20 (double-blinded), extended to 52 weeks (sponsor was unblinded at 20 weeks). Subjects switched to receive liraglutide 2.4 mg once daily and then liraglutide 3.0 mg once daily in open-label extension period (weeks 52-104)	Drug: liraglutide; Injected s.c. (under the skin) once daily
Experimental: Lira 1.8 mg/Lira 3.0 mg; Liraglutide 1.8 mg once daily, weeks 0-20 (double-blinded), extended to 52 weeks (sponsor was unblinded at 20 weeks). Subjects switched to receive liraglutide 2.4 mg once daily and then liraglutide 3.0 mg once daily in open-label extension period (weeks 52-104)	Drug: liraglutide; Injected s.c. (under the skin) once daily
Experimental: Lira 2.4 mg/Lira 3.0 mg; Liraglutide 2.4 mg once daily, weeks 0-20 (double-blinded), extended to 52 weeks (sponsor was unblinded at 20 weeks). Subjects switched to receive liraglutide 2.4 mg once daily and then liraglutide 3.0 mg once daily in open-label extension period (weeks 52-104)	Drug: liraglutide; Injected s.c. (under the skin) once daily
Experimental: Liraglutide 3.0 mg; Liraglutide 3.0 mg once daily, weeks 0-20 (double-blinded), extended to 52 weeks (sponsor was unblinded at 20 weeks). Subjects switched to receive liraglutide 2.4 mg once daily and then liraglutide 3.0 mg once daily in open-label extension period (weeks 52-104)	Drug: liraglutide; Injected s.c. (under the skin) once daily; Drug: placebo; Injected s.c. (under the skin) once daily
Active Comparator: Orlistat; Orlistat capsules 3 times daily (3 x 120 mg) in connection with each main meal, weeks 0-20 (open-label) continued to receive Orlistat capsules 3 times daily (3 x 120 mg) in connection with each main meal in open-label extension period (weeks 20-104)	Drug: orlistat; 120 mg capsule. Administered thrice daily

Outcome Measures

Primary Outcome Measures :

1. Mean Change From Baseline in Body Weight at Week 20 [ Time Frame: Week 0, week 20 ]
   Calculated as mean body weight at week 20 - baseline

Secondary Outcome Measures :

1. Mean Change From Baseline in Body Weight at Week 104 [ Time Frame: Week 0, week 104 ]
   Calculated as mean body weight at week 104 - baseline
2. Change From Baseline in Fasting Plasma Glucose at Week 20 [ Time Frame: Week 0, week 20 ]
   Calculated as mean fasting plasma glucose at week 20 - baseline
3. Change From Baseline in Fasting Plasma Glucose at Week 104 [ Time Frame: Week 0, week 104 ]
   Calculated as mean fasting plasma glucose at week 104 - baseline
4. Change From Baseline in Fasting Insulin at Week 20 [ Time Frame: Week 0, week 20 ]
   Calculated as mean fasting insulin at week 20 - baseline
5. Change From Baseline in Fasting Insulin at Week 104 [ Time Frame: Week 0, week 104 ]
   Calculated as mean fasting insulin at week 104 - baseline
6. Change From Baseline in HbA1c (Glycosylated Haemoglobin A1c) at Week 20 [ Time Frame: Week 0, week 20 ]
   Calculated as mean HbA1c (glycosylated haemoglobin A1c) at week 20 - baseline
7. Change From Baseline in HbA1c (Glycosylated Haemoglobin A1c) at Week 104 [ Time Frame: Week 0, week 104 ]
   Calculated as mean HbA1c (glycosylated haemoglobin A1c) at week 104 - baseline
8. Change From Baseline in hsCRP (Highly Sensitive C-reactive Protein) at Week 20 [ Time Frame: Week 0, week 20 ]
   Calculated as mean hsCRP (highly sensitive C-reactive protein) at week 20-baseline. High hsCRP level is associated with greater cardiovascular risk
9. Change From Baseline in hsCRP (Highly Sensitive C-reactive Protein) at Week 104 [ Time Frame: Week 0, week 104 ]
   Calculated as mean hsCRP (highly sensitive C-reactive protein) at week 104- baseline. High hsCRP level is associated with greater cardiovascular risk
10. Change From Baseline in PAI-1 (Plasminogen Activator Inhibitor 1) at Week 20 [ Time Frame: Week 0, week 20 ]
    Calculated as mean PAI-1 (plasminogen activator inhibitor 1) at week 20-baseline. High PAI-1 is associated with greater cardiovascular risk
11. Change From Baseline in PAI-1 (Plasminogen Activator Inhibitor 1) at Week 104 [ Time Frame: Week 0, week 104 ]
    Calculated as mean PAI-1 (plasminogen activator inhibitor 1) at week 104-baseline. High PAI-1 is associated with greater cardiovascular risk
12. Change From Baseline in Fibrinogen at Week 20 [ Time Frame: Week 0, week 20 ]
    Calculated as mean fibrinogen at week 20 - baseline. High fibrinogen is associated with greater cardiovascular risk
13. Change From Baseline in Fibrinogen at Week 104 [ Time Frame: Week 0, week 104 ]
    Calculated as mean fibrinogen at week 104 - baseline. High fibrinogen is associated with greater cardiovascular risk
14. Change From Baseline in Adiponectin at Week 20 [ Time Frame: Week 0, week 20 ]
    Calculated as mean adiponectin at week 20-baseline. A low adiponectin level is associated with greater cardiovascular risk
15. Change From Baseline in Adiponectin at Week 104 [ Time Frame: Week 0, week 104 ]
    Calculated as mean adiponectin at week 104-baseline. A low adiponectin level is associated with greater cardiovascular risk
16. Change From Baseline in Waist Circumference at Week 20 [ Time Frame: Week 0, week 20 ]
    Calculated as mean waist circumference at week 20-baseline.
17. Change From Baseline in Waist Circumference at Week 104 [ Time Frame: Week 0, week 104 ]
    Calculated as mean waist circumference at week 104-baseline.
18. Change From Baseline in Blood Pressure at Week 20 [ Time Frame: Week 0, week 20 ]
    Calculated as mean blood pressure at week 20-baseline.
19. Change From Baseline in Blood Pressure at Week 104 [ Time Frame: Week 0, week 104 ]
    Calculated as mean blood pressure at week 104-baseline.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Body Mass Index (BMI) greater than or equal to 30.0 or lesser than or equal to 40.0 kg/m2
• Stable body weight (less than 5% selfreported change within the last 3 months)

Exclusion Criteria:

• Obesity induced by drug treatment
• Use of approved drugs for weight lowering intervention (e.g. orlistat, sibutramin, rimonabant) within the last 3 months prior to entering trial
• Type 1 or type 2 diabetes

Contacts and Locations

Locations

Belgium

Novo Nordisk Investigational Site

Edegem, Belgium, 2650

Czechia

Novo Nordisk Investigational Site

Praha 1, Czechia, 116 94

Novo Nordisk Investigational Site

Praha 2, Czechia, 128 08

Denmark

Novo Nordisk Investigational Site

Frederiksberg C, Denmark, 1958

Novo Nordisk Investigational Site

Hvidovre, Denmark, 2650

Novo Nordisk Investigational Site

Århus C, Denmark, 8000

Finland

Novo Nordisk Investigational Site

Helsinki, Finland, 00270

Novo Nordisk Investigational Site

Kuopio, Finland, 70210

Novo Nordisk Investigational Site

Oulu, Finland, 90220

Netherlands

Novo Nordisk Investigational Site

Almere, Netherlands, 1311RL

Spain

Novo Nordisk Investigational Site

Barcelona, Spain, 08022

Novo Nordisk Investigational Site

Madrid, Spain, 28006

Novo Nordisk Investigational Site

Madrid, Spain, 28007

Novo Nordisk Investigational Site

Pamplona, Spain, 31008

Sweden

Novo Nordisk Investigational Site

Malmö, Sweden, 205 02

Novo Nordisk Investigational Site

Stockholm, Sweden, 141 86

United Kingdom

Novo Nordisk Investigational Site

Glasgow, United Kingdom, G322ER

Novo Nordisk Investigational Site

Luton, United Kingdom, LU4 0DZ

Novo Nordisk Investigational Site

Norwich, United Kingdom, NR4 7TJ

Sponsors and Collaborators

Novo Nordisk A/S

Investigators

• Study Director: Global Clinical Registry (GCR, 1452); Novo Nordisk A/S

More Information

Additional Information:

Clinical Trials at Novo Nordisk 

Publications of Results:

Astrup A, Carraro R, Finer N, Harper A, Kunesova M, Lean ME, Niskanen L, Rasmussen MF, Rissanen A, Rössner S, Savolainen MJ, Van Gaal L; NN8022-1807 Investigators. Safety, tolerability and sustained weight loss over 2 years with the once-daily human GLP-1 analog, liraglutide. Int J Obes (Lond). 2012 Jun;36(6):843-54. doi: 10.1038/ijo.2011.158. Epub 2011 Aug 16. Erratum in: Int J Obes (Lond). 2012 Jun;36(6):890. Int J Obes (Lond). 2013 Feb;37(2):322.

Astrup A, Rössner S, Van Gaal L, Rissanen A, Niskanen L, Al Hakim M, Madsen J, Rasmussen MF, Lean ME; NN8022-1807 Study Group. Effects of liraglutide in the treatment of obesity: a randomised, double-blind, placebo-controlled study. Lancet. 2009 Nov 7;374(9701):1606-16. doi: 10.1016/S0140-6736(09)61375-1. Epub 2009 Oct 23. Erratum in: Lancet. 2010 Mar 20;375(9719):984.

Lean ME, Carraro R, Finer N, Hartvig H, Lindegaard ML, Rössner S, Van Gaal L, Astrup A; NN8022-1807 Investigators. Tolerability of nausea and vomiting and associations with weight loss in a randomized trial of liraglutide in obese, non-diabetic adults. Int J Obes (Lond). 2014 May;38(5):689-97. doi: 10.1038/ijo.2013.149. Epub 2013 Aug 14.

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 Pooled Data From the SCALE Clinical Development Program. Diabetes Care. 2017 Jul;40(7):839-848. doi: 10.2337/dc16-2684. Epub 2017 May 4. Erratum in: Diabetes Care. 2018 Jul;41(7):1538.

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 3.0 mg for weight management: Results from randomized controlled phase 2 and 3a trials. Diabetes Obes Metab. 2017 Nov;19(11):1529-1536. doi: 10.1111/dom.12963. Epub 2017 Jul 21.

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 obesity: A post hoc analysis from SCALE randomized controlled trials. Diabetes Obes Metab. 2018 Mar;20(3):734-739. doi: 10.1111/dom.13125. Epub 2017 Nov 1.

• Responsible Party: Novo Nordisk A/S
• ClinicalTrials.gov Identifier: NCT00422058
• Obsolete Identifiers: NCT00480909
• Other Study ID Numbers: NN8022-1807; 2006-004481-13 ( EudraCT Number )
• First Posted: January 15, 2007
• Results First Posted: October 28, 2010
• Last Update Posted: November 1, 2017
• Last Verified: September 2017

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Nutrition Disorders; Body Weight; Liraglutide; Orlistat; Hypoglycemic Agents; Physiological Effects of Drugs; Incretins; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Anti-Obesity Agents; Lipid Regulating Agents