A Multicenter Pilot Study of 12-week Duration to Assess the Short-term Safety and Tolerability of Lorcaserin Plus Two Doses of Immediate- Release Phentermine-HCl Compared With Lorcaserin Alone in Overweight and Obese Adults

All subjects will take lorcaserin and phentermine-HCl/placebo once in the morning and again
in the mid-afternoon. The dosing is timed to help reduce potential insomnia due to
phentermine. Subjects in Arm A will take one tablet twice daily of lorcaserin 10 mg in
combination with one capsule twice daily of phentermine placebo. Subjects in Arm B will take
one tablet twice daily of lorcaserin 10 mg, one capsule of phentermine-HCl 15 mg once daily
in the morning, and one capsule of phentermine placebo once daily in the mid-afternoon.
Subjects in Arm C will take one tablet twice daily of lorcaserin 10 mg in combination with
one capsule twice daily of phentermine-HCl 15 mg. Subjects will be instructed to take
lorcaserin tablets and phentermine/placebo capsules concurrently and attempt to remain on a
consistent daily schedule. The study will recruit obese (body mass index [BMI] greater than
or equal to 30 kg/m2) subjects with or without a weight-related comorbid condition (e.g.,
hypertension, dyslipidemia, or sleep apnea) or overweight (BMI greater than or equal to 27
to 29.9 kg/m2) subjects with at least one weight-related co-morbid condition. At least one
third of the subjects will have a BMI of 40 kg/m2 or greater, because there is a high
likelihood that this combination therapy will be used by these subjects in medical practice.

A lifestyle intervention program, using a 12-week adaptation of the Arena Healthy
Lifestyles Program, including diet and exercise counseling, will be implemented for
obesity/overweight.

Blood sampling will be performed to evaluate the pharmacokinetics (PK) of lorcaserin and
phentermine using population PK modeling as well as the potential relationships between
exposure to the lorcaserin/phentermine and measures of safety and change from baseline in
body weight, using population PK/PD (pharmacodynamics) modeling.

Inclusion Criteria

1. BMI is 30 kg/m2 or greater with or without a weight-related comorbid condition (e.g.,
hypertension, dyslipidemia, sleep apnea), or 27 to 29.9 kg/m2 with at least one
weight-related comorbid condition.

2. Ambulatory and able to perform moderate exercise.

3. Male or female subjects between 18 and 60 years at the time of informed consent.

4. Provide written informed consent.

5. Willing and able to comply with all aspects of the protocol.

Exclusion Criteria

1. Recent treatment (within 14 days of the Screening Visit and any time prior to
randomization) with monoamine oxidase inhibitors (MAOIs). MAOIs have been associated
with a risk of hypertensive crisis when used with phentermine.

2. Active or recent history (within 1 month prior to the Screening Visit) of major
depression or other major psychiatric disease requiring treatment (i.e., within 1
month of the Screening Visit and any time prior to randomization or thereafter during
the study) with prescription medication (e.g., SSRIs, SNRIs, tricyclics,
antipsychotics, lithium, Wellbutrin).

3. Use of selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine
reuptake inhibitors (SNRIs) (including bupropion) for reasons other than active
psychiatric indications (e.g., migraine, weight loss, smoking cessation) within 1
month prior to the Screening Visit).

4. Medication history that includes use of one or more of the following:

1. Fenfluramine or related derivatives (i.e., dexfenfluramine, norfenfluramine)

2. Agents that have documented correlation with increased incidence of valvulopathy
and/or primary pulmonary hypertension (e.g., cabergoline, cyproheptadine,
trazodone, nefazodone, amoxapine, mirtazapine, pergolide, ergotamine,
methysergide)

5. Recent treatment (i.e., within 1 month of the Screening Visit and any time prior to
randomization or thereafter during the study) with over-the-counter (OTC) weight loss
products or appetite suppressants (including herbal weight loss agents), or within 6
months and any time prior to randomization or thereafter during the study, with a
prescription weight loss drug (e.g., phentermine, phentermine/topiramate, orlistat).

6. Use of St. John's Wort within 1 month prior to the Screening Visit and for the
duration of the study. St. John's Wort has been associated with serotonin syndrome
when used with another serotonergic drug.

7. Hypersensitivity to sympathomimetic amines or the study drugs.

8. History of stroke, transient ischemic attack, arrhythmias, congestive heart failure,
and/or peripheral vascular disease.

9. Recent history of active cardiovascular disease, including chronic stable angina or
an unstable angina episode or myocardial infarction within the 3 months prior to the
Screening Visit.

10. Uncontrolled hypertension defined as systolic blood pressure greater than or equal to
150 or diastolic blood pressure greater than or equal to 95 on 2 readings taken on
different days. Subjects who have uncontrolled hypertension at screening may be
re-screened greater than 1 month following initiation or adjustment of
antihypertensive therapy.

11. History of or active pulmonary artery hypertension.

12. Severe renal impairment (creatinine clearance less than 30 mL/min, as calculated by
the Cockroft-Gault equation based on ideal body weight) or end stage renal disease.

13. History of valve replacement surgery; clinically significant valvular stenosis;
history of or active clinically significant valvulopathy (defined as aortic
insufficiency of mild, moderate, or severe intensity and/or mitral insufficiency of
moderate or severe intensity).

14. History of or active (confirmed fasting glucose greater than 126 mg/dL or hemoglobin
A1c [HbA1c] greater than ULN [6.5% at central laboratory]) diabetes mellitus (type I,
II or other) and/or currently taking medications for type I or II diabetes. A past
history of gestational diabetes that has resolved is permissible.

15. Glaucoma.

16. Abnormal thyroid stimulating hormone (TSH) laboratory value greater than 1.5 x Upper
Limit of Normal (ULN)

17. Hyperthyroidism, including abnormal screening laboratory values with T3 greater than
ULN and TSH less than Lower Limit of Normal (LLN), and subjects taking methimazole or
propylthiouracil (PTU) and/or beta-blockers for hyperthyroidism.

18. Recent history (within 2 years prior to the Screening Visit) of alcohol or
drug/solvent abuse or a positive screen for drugs of abuse at screening.

19. Significant change is smoking habits or tobacco product use within 3 months prior to
the Screening Visit.

20. Use of tobacco products (i.e., smokes more than one-half pack of cigarettes per day,
or smokes more than 2 cigars per day, or uses 3 or more pinches of smokeless tobacco
per day).

21. Surgical procedure for the treatment of obesity (i.e., gastric bypass, gastric
banding), even if reversed prior to screening.

22. Planned surgery during the study period that may interfere with completion or
compliance with the protocol.

23. A prolonged QT/QTc interval (QTc Bazett's greater than 450 msec) as demonstrated by a
repeated electrocardiogram (ECG).

24. Participation in any clinical study with an investigational drug, biologic, or device
within 1 month prior to screening.

25. Significant change in diet or level of physical activity within 1 month prior to
dosing that in the opinion of the investigator(s) may confound the results of the
study.

26. Change in weight of greater than 5 kg within 3 months of screening.

27. Use of a very-low calorie (less than 800/day) liquid weight loss diet within 6 months
prior to screening and any time prior to randomization.

28. Eligible male and female subjects participating in a conception process (i.e., active
attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization).

29. Females who are lactating or pregnant at Screening or Baseline Visit (as documented
by a negative serum or urine pregnancy test with a minimum sensitivity of 25 IU/L or
equivalent units of beta-human chorionic gonadotropin [B-hCG]). A separate baseline
assessment is required if a negative screening pregnancy test was obtained more than
72 hours before the first dose of study drug.

30. All females will be considered to be of childbearing potential unless they are
postmenopausal (amenorrheic for at least 12 consecutive months, in the appropriate
age group and without other known or suspected cause) or have been sterilized
surgically (i.e., bilateral tubal ligation, total hysterectomy, or bilateral
oophorectomy, all with surgery at least one month before dosing).

31. Females of childbearing potential must not have had unprotected sexual intercourse
within 30 days before study entry and must agree to use a highly effective method of
contraception (e.g., total abstinence, an intrauterine device, a double-barrier
method [such as condom plus diaphragm with spermicide], a contraceptive implant, an
oral contraceptive, or have a vasectomized partner with confirmed azoospermia)
throughout the entire study period and for 30 days after study drug discontinuation.
If currently abstinent, the subject must agree to use a double barrier method as
described above if she becomes sexually active during the study period or for 30 days
after study drug discontinuation. Females who are using hormonal contraceptives must
have been on a stable dose of the same hormonal contraceptive product for at least 4
weeks before dosing and must continue to use the same contraceptive during the study
and for 30 days after study drug discontinuation. Females not meeting these criteria
will be excluded from the study.

32. Any medical or other condition that in the opinion of the investigator(s) would
preclude the subject's participation in a clinical study, such as significantly
abnormal laboratory results or any physical or mental condition that prevents
compliance with the protocol.