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

NCT01987427 | Completed Phase 4 Results

• 1 other identifier: APD356-A001-402
• Study Type: interventional
• Target: 344
• Locations: 1 country
• Sites: 13

Brief 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.

Conditions

Chronic Weight Management

Keywords

Overweight; Obese; Weight Management

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Reporting at Least One of Nine Adverse Events (AEs) of Main Interests That May Related to Serotonergic Reaction

  The nine common serotonergic AEs were headache, dizziness, nausea, fatigue, dry mouth, diarrhea, vomiting, insomnia, and/or anxiety.

  Baseline up to Week 12 (end of treatment)

Secondary Outcomes (7)

• Number of Participants With Treatment Emergent Adverse Event (TEAE), Serious Adverse Event (SAE) and AEs Leading to Study Drug Discontinuation

  Baseline up to Week 16

• Number of Participants With Treatment-Emergent Markedly Abnormal Laboratory Values

  Baseline up to Week 16

• Mean Change From Baseline in Body Weight at Weeks 1, 2, 4, 8, and 12

  Baseline, Weeks 1, 2, 4, 8 and 12

• Percent Change From Baseline in Body Weight at Weeks 1, 2, 4, 8, and 12

  Baseline, Weeks 1, 2, 4, 8 and 12

• Percentage of Participants Who Achieved Greater Than or Equal to (>=) 5 Percent (%) Weight Reduction at Week 12

  Week 12 (end of treatment)

Study Arms (3)

A

EXPERIMENTAL

lorcaserin + phentermine placebo

Drug: lorcaserin + phentermine placebo

B

EXPERIMENTAL

lorcaserin + phentermine-HCl + phentermine placebo

Drug: lorcaserin + phentermine-HCl + phentermine placebo

C

EXPERIMENTAL

lorcaserin + phentermine-HCl

Drug: lorcaserin + phentermine-HCl

Interventions

lorcaserin + phentermine placebo DRUG

lorcaserin 10 mg BID + phentermine placebo BID

A

lorcaserin + phentermine-HCl + phentermine placebo DRUG

lorcaserin 10 mg BID + phentermine-HCl 15 mg QD + phentermine placebo QD

B

lorcaserin + phentermine-HCl DRUG

lorcaserin 10 mg BID + phentermine-HCl 15 mg BID

C

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• Ambulatory and able to perform moderate exercise.
• Male or female subjects between 18 and 60 years at the time of informed consent.
• Provide written informed consent.
• Willing and able to comply with all aspects of the protocol.

You may not qualify if:

• 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.
• 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).
• 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).
• Medication history that includes use of one or more of the following:
• Fenfluramine or related derivatives (i.e., dexfenfluramine, norfenfluramine)
• 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)
• 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).
• 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.
• Hypersensitivity to sympathomimetic amines or the study drugs.
• History of stroke, transient ischemic attack, arrhythmias, congestive heart failure, and/or peripheral vascular disease.
• 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.
• 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.
• History of or active pulmonary artery hypertension.
• 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.
• 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).

Sponsors & Collaborators

• Eisai Inc.: lead

Study Sites (13)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Radiant Research - Arizona

Chandler, Arizona, 85224, United States

Location

Scripps Clinical Research Center

La Jolla, California, 92037, United States

Location

Translational Research Institute for Metabolism and Diabetes

Orlando, Florida, 32804, United States

Location

Pennington Biomedical Research Center

Baton Rouge, Louisiana, 70808, United States

Location

Boston Medical Center

Boston, Massachusetts, United States

Location

Weill Cornell College

New York, New York, 10065, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

Radiant Research - Columbus

Columbus, Ohio, 43212, United States

Location

Radiant Research - South Carolina

Anderson, South Carolina, 29621, United States

Location

Radiant Research - Dallas

Dallas, Texas, 75231, United States

Location

National Clinical Research - Norfolk

Norfolk, Virginia, 23502, United States

Location

National Clinical Research - Richmond

Richmond, Virginia, 23294, United States

Location

Related Publications (2)

• Rebello CJ, Nikonova EV, Zhou S, Aronne LJ, Fujioka K, Garvey WT, Smith SR, Coulter AA, Greenway FL. Effect of Lorcaserin Alone and in Combination with Phentermine on Food Cravings After 12-Week Treatment: A Randomized Substudy. Obesity (Silver Spring). 2018 Feb;26(2):332-339. doi: 10.1002/oby.22094.

  PMID: 29363287 DERIVED

• Smith SR, Garvey WT, Greenway FL, Zhou S, Fain R, Pilson R, Fujioka K, Aronne LJ. Coadministration of lorcaserin and phentermine for weight management: A 12-week, randomized, pilot safety study. Obesity (Silver Spring). 2017 May;25(5):857-865. doi: 10.1002/oby.21811.

  PMID: 28440045 DERIVED

MeSH Terms

Conditions

Overweight; Obesity

Interventions

lorcaserin; Phentermine

Condition Hierarchy (Ancestors)

Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Amphetamines; Phenethylamines; Ethylamines; Amines; Organic Chemicals

Results Point of Contact

• Title: Eisai Medical Services
• Organization: Eisai, Inc.

esi_medinfo@eisai.com

1-888-422-4743

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 12, 2013
• First Posted: November 19, 2013
• Study Start: October 30, 2013
• Primary Completion: August 1, 2014
• Study Completion: September 3, 2014
• Last Updated: September 30, 2019
• Results First Posted: September 30, 2019

Record last verified: 2019-09

Locations

US (13)