Predictors of Lorcaserin-Induced Weight Loss

In phase 1, at Weeks 1 and 5, participants will take the weight loss drug lorcaserin or
placebo for 7 days. At Week 5 participants will receive whichever treatment they did not
receive at Week 1. At the end of Weeks 1 and 5, participants will have a lumbar puncture
(spinal tap) to collect cerebrospinal fluid (CSF) for neuropeptide and hormone analyses,
including proopiomelanocortin (POMC), Agouti-related protein (AgRP) and cortisol. Blood will
also be obtained for neuropeptide and hormone analyses. Breakfast will be served to
participants who will then complete an eating behavior profile. A laboratory test meal will
be performed 4h after breakfast.

After completing both the 7 day lorcaserin and placebo studies, participants will then
continue on Phase 2 of the study, which includes treatment with lorcaserin for 24 weeks.
Subjects will receive nutritional counseling to reduce their daily caloric intake to 600 kcal
below their calculated caloric requirement and will be encourage to exercise moderately for
30 minutes daily. Participants will visit the clinic monthly during the 24 week study period
for nutritional counseling, review of food diaries, vital signs and safely labs. Blood will
also be obtained for neuropeptide peptide and hormone analyses. At the end of the 24 week
period subjects will come for a final study visit, including a lumbar puncture, blood sample,
breakfast, an eating behavior profile and a test meal.

Inclusion Criteria:

- Body Mass Index (BMI) 28-40

Exclusion Criteria:

- Any clinically significant or relevant medical condition, including:

- Diabetes

- Uncontrolled Hypertension

- Heart disease

- Bleeding disorder

- Kidney or liver dysfunction

- Neurologic disease

- Psychiatric or eating disorders

- Pregnancy or breastfeeding

- Use of tobacco or opiates

- History of alcohol or drug abuse

- Recent weight change +/- 5%

- Medications that affect body weight