A Multicenter, Double-blind, Randomized, Parallel-group, 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
Condition: Chronic Weight Management
MeSH terms: Overweight
Intervention: lorcaserin + phentermine placebo; lorcaserin + phentermine-HCl + phentermine placebo; lorcaserin + phentermine-HCl
Intervention description: lorcaserin 10 mg BID + phentermine placebo BID; lorcaserin 10 mg BID + phentermine-HCl 15 mg QD + phentermine placebo QD; lorcaserin 10 mg BID + phentermine-HCl 15 mg BID
Intervention MeSH terms: Phentermine
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 344.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: No
Keywords: Overweight; Obese; Weight Management

Summary:

      APD356-A001-402 is a multicenter, double-blind, randomized, parallel-group pilot study of
      12-week duration in overweight and obese adults. Approximately 225 subjects will be
      randomized to one of three treatment arms in a ratio 1:1:1 and will receive the combinations
      of lorcaserin 10 mg twice daily (BID) plus immediate-release phentermine-HCl 15 mg BID or 15
      mg once daily (QD), or lorcaserin alone.
    

Eligibility criteria:

        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 buproprion) 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.