1. Multicenter, Placebo-Controlled Trial
of Lorcaserin for Weight Management
Steven R. Smith, M.D., Neil J. Weissman, M.D., Christen M. Anderson, M.D.,Ph.D.,
Matilde Sanchez, Ph.D., Emil Chuang, M.D., Scott Stubbe, M.B.A., Harold Bays, M.D.,
William R. Shanahan, M.D., and the Behavioral Modification and Lorcaserin
for Overweight and Obesity Management (BLOOM) Study Group
N Engl J Med 2010;363:
R1 Chihyeok Oh / Prof. SeungJoon Oh

2. Introduction
Multicenter,Placebo-ControlledTrialofLorcaserinforWeightManagementMulticenter,Placebo-ControlledTrialofLorcaserinforWeightManagementMulticenter,Placebo-ControlledTrialofLorcaserinforW
Activation of the 5-hydroxytryptamine(5-HT, or serotonin) receptor 5-HT2c
Decreases food intake
Through the proopiomelanocortin system of neurons
Lorcaserin
Small-molecule agonist of the serotonin 2C (5-HT2c) receptor
Designed to promote weight loss.

3. The nonselective serotonergic agonists
Fenfluramine and Dexfenfluramine
Weight loss
Increases the risk of serotonin-associated valvulopathy
through 5-HT2b receptors expressed on cardiac valvular interstitial cells
But, Lorcaserin
Selectively activate central 5-HT2c receptors
15 times more than 5-HT2a receptors
100 times more than 5-HT2b receptors
In this report
The Behavioral Modification and Lorcaserin for Overweight and Obesity Management (BLOOM) trial
2-year, randomized, placebo-controlled, double-blind clinical trial
evaluate the efficacy and safety

4. Methods - Study design & Study end points
Multicenter,Placebo-ControlledTrialofLorcaserinforWeightManagementMulticenter,Placebo-ControlledTrialofLorcaserinforWeightManagementMulticenter,Placebo-ControlledTrialofLorcaserinforW
98 academic and private trial sites
From September 11, 2006 ~ February 5, 2009
1st year
A reduction in the baseline body weight of 5% or more
A reduction in the baseline body weight of 10% or more
2nd year
The proportion of patients who had had a reduction in the baseline body weight of 5% or more at the end of year 1 and who maintained this reduction during year 2
Key secondary end points
Lipids, glycemic variables, physical measures, inflammatory markers of cardiovascular risk, the quality of life

5. Methods - Study-group assignments
Multicenter,Placebo-ControlledTrialofLorcaserinforWeightManagementMulticenter,Placebo-ControlledTrialofLorcaserinforWeightManagementMulticenter,Placebo-ControlledTrialofLorcaserinforW
For year 1
1:1 ratio randomly assigned
Lorcaserin(10mg) Vs. placebo (twice daily)
For year 2
Placebo  Placebo
Lorcaserin  2:1 ratio randomly assigned
( Lorcaserin Vs. Placebo)

6. Methods - Patients Inclusion Criteria Exclusion criteria
Multicenter,Placebo-ControlledTrialofLorcaserinforWeightManagementMulticenter,Placebo-ControlledTrialofLorcaserinforWeightManagementMulticenter,Placebo-ControlledTrialofLorcaserinforW
Inclusion Criteria
Age of 18 to 65 years
BMI of 30 to 45
BMI of 27 to 45 with at least 1 coexisting condition
(hypertension, dyslipidemia, cardiovascular disease,
impaired glucose tolerance, or sleep apnea)
Exclusion criteria
Moderate or more severe MR or AR
Diabetes mellitus
sBP > 140 mm Hg or dBP >90 mm Hg
Depression or other major psychiatric disease within 2 years
Pregnancy or Lactation.

7. Methods - Study Procedures
Multicenter,Placebo-ControlledTrialofLorcaserinforWeightManagementMulticenter,Placebo-ControlledTrialofLorcaserinforWeightManagementMulticenter,Placebo-ControlledTrialofLorcaserinforW
Patients returned to the research site 2 and 4 weeks after randomization and then on a monthly basis.
At each visit, a trained counselor at each site administered standardized nutritional and exercise counseling during individual sessions
Patients were instructed to exercise moderately for 30 minutes daily and to reduce the daily calorie intake to 600 kcal below the individual estimate for daily energy requirements.

8. Methods - Statistical Analysis
Multicenter,Placebo-ControlledTrialofLorcaserinforWeightManagementMulticenter,Placebo-ControlledTrialofLorcaserinforWeightManagementMulticenter,Placebo-ControlledTrialofLorcaserinforW
The primary efficacy analyses
the intention-to-treat population and last-observation-carried-forward imputation for missing values.
The three coprimary end points during year 1
were analyzed by means of a closed hierarchical testing procedure.
Logistic regression model : comparison of weight loss
Analysis of covariance models : weight change

9. Results - Patients and Study Completion(1)
Multicenter,Placebo-ControlledTrialofLorcaserinforWeightManagementMulticenter,Placebo-ControlledTrialofLorcaserinforWeightManagementMulticenter,Placebo-ControlledTrialofLorcaserinforW
Total : 3182 Pts.
→ Two group(randomly assigned)
Similar baseline characteristics

10. Results - Patients and Study Completion(2)
Multicenter,Placebo-ControlledTrialofLorcaserinforWeightManagementMulticenter,Placebo-ControlledTrialofLorcaserinforWeightManagementMulticenter,Placebo-ControlledTrialofLorcaserinforW
The rates of completion of year 1
55.4%(in the Lorcarin group) Vs 45.1%(in the placebo group)
Discontinuation
7.1%(in the Lorcarin group) Vs 6.7%(in the placebo group)
d/t adverse event(dizziness, headache)
The rates of completion of year 2
72.6% of patients who completed year 1
25.7% (in the lorcaserin group) Vs 27.3% (in the placebo group)
The rates and reasons for discontinuation during year 2
similar among the three groups

11. Results - Weight Loss(1)
Multicenter,Placebo-ControlledTrialofLorcaserinforWeightManagementMulticenter,Placebo-ControlledTrialofLorcaserinforWeightManagementMulticenter,Placebo-ControlledTrialofLorcaserinforW
47.5%
22.6%
20.3%
7.7%
Figure 1. Effects of the Study Drug on Body Weight, According to Study Group.
The proportions of patients who lost 5% or more or 10%
or more of their baseline body weight at 1 year are shown

12. Results - Weight Loss(2)
Multicenter,Placebo-ControlledTrialofLorcaserinforWeightManagementMulticenter,Placebo-ControlledTrialofLorcaserinforWeightManagementMulticenter,Placebo-ControlledTrialofLorcaserinforW
Average lost of the baseline body weight
5.81±0.16% in the Lorcaserin group Vs
2.16±0.14% in the placebo group
Figure 1. Effects of the Study Drug on Body Weight, According to Study Group.
For the intention-to-treat population (with last-observation-carried-forward imputation),
The mean body weight at each study visit is shown, according to study group, during year 1 among all patients

13. Results - Weight Loss(3)
Multicenter,Placebo-ControlledTrialofLorcaserinforWeightManagementMulticenter,Placebo-ControlledTrialofLorcaserinforWeightManagementMulticenter,Placebo-ControlledTrialofLorcaserinforW
Figure 1. Effects of the Study Drug on Body Weight, According to Study Group.
For the intention-to-treat population (with last-observation-carried-forward imputation),
The mean body weight at each study visit is shown, according to study group,
during years 1 and 2 among only those patients who continued the study past year 1

14. Results - Waist circumference and insulin level
Multicenter,Placebo-ControlledTrialofLorcaserinforWeightManagementMulticenter,Placebo-ControlledTrialofLorcaserinforWeightManagementMulticenter,Placebo-ControlledTrialofLorcaserinforW

15. Results - Markers of cardiovascular risk
Multicenter,Placebo-ControlledTrialofLorcaserinforWeightManagementMulticenter,Placebo-ControlledTrialofLorcaserinforWeightManagementMulticenter,Placebo-ControlledTrialofLorcaserinforW

16. Results - Adverse Events(1)
Multicenter,Placebo-ControlledTrialofLorcaserinforWeightManagementMulticenter,Placebo-ControlledTrialofLorcaserinforWeightManagementMulticenter,Placebo-ControlledTrialofLorcaserinforW

17. Results - Adverse Events(2)
Multicenter,Placebo-ControlledTrialofLorcaserinforWeightManagementMulticenter,Placebo-ControlledTrialofLorcaserinforWeightManagementMulticenter,Placebo-ControlledTrialofLorcaserinforW
Figure 2. Findings on Echocardiography, According to Study Group.

18. Results - Adverse Events(3)
Multicenter,Placebo-ControlledTrialofLorcaserinforWeightManagementMulticenter,Placebo-ControlledTrialofLorcaserinforWeightManagementMulticenter,Placebo-ControlledTrialofLorcaserinforW
Figure 2. Findings on Echocardiography, According to Study Group.

19. Conclusion Lorcaserin ＋ Behavioral Modification Lorcaserin
Multicenter,Placebo-ControlledTrialofLorcaserinforWeightManagementMulticenter,Placebo-ControlledTrialofLorcaserinforWeightManagementMulticenter,Placebo-ControlledTrialofLorcaserinforW
Lorcaserin ＋ Behavioral Modification
Significant weight loss
Improved maintenance of weight loss
Lorcaserin
Improved values for biomarkers
Predictors of future cardiovascular events
Lipid levels
Insulin resistance
Levels of inflammatory markers
Blood pressure