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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

Registration Number
NCT01987427
Lead Sponsor
Eisai Inc.
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.

Detailed Description

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
344
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Blorcaserin + phentermine-HCl + phentermine placebolorcaserin + phentermine-HCl + phentermine placebo
Alorcaserin + phentermine placebolorcaserin + phentermine placebo
Clorcaserin + phentermine-HCllorcaserin + phentermine-HCl
Primary Outcome Measures
NameTimeMethod
Percentage of Participants Reporting at Least One of Nine Adverse Events (AEs) of Main Interests That May Related to Serotonergic ReactionBaseline up to Week 12 (end of treatment)

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

Secondary Outcome Measures
NameTimeMethod
Number of Participants With Treatment Emergent Adverse Event (TEAE), Serious Adverse Event (SAE) and AEs Leading to Study Drug DiscontinuationBaseline up to Week 16
Number of Participants With Treatment-Emergent Markedly Abnormal Laboratory ValuesBaseline up to Week 16
Percent Change From Baseline in Body Weight at Weeks 1, 2, 4, 8, and 12Baseline, Weeks 1, 2, 4, 8 and 12
Percentage of Participants Who Achieved Greater Than or Equal to (>=) 5 Percent (%) Weight Reduction at Week 12Week 12 (end of treatment)
Change From Baseline in Waist Circumference and Hip Circumference at Week 12Baseline and Week 12 (end of treatment)
Mean Change From Baseline in Body Weight at Weeks 1, 2, 4, 8, and 12Baseline, Weeks 1, 2, 4, 8 and 12
Change From Baseline in Waist to Hip Circumference Ratio at Week 12Baseline and Week 12 (end of treatment)

Trial Locations

Locations (13)

Scripps Clinical Research Center

🇺🇸

La Jolla, California, United States

Radiant Research - Dallas

🇺🇸

Dallas, Texas, United States

National Clinical Research - Norfolk

🇺🇸

Norfolk, Virginia, United States

University of Alabama at Birmingham

🇺🇸

Birmingham, Alabama, United States

Pennington Biomedical Research Center

🇺🇸

Baton Rouge, Louisiana, United States

Radiant Research - Columbus

🇺🇸

Columbus, Ohio, United States

Weill Cornell College

🇺🇸

New York, New York, United States

Radiant Research - South Carolina

🇺🇸

Anderson, South Carolina, United States

National Clinical Research - Richmond

🇺🇸

Richmond, Virginia, United States

Radiant Research - Arizona

🇺🇸

Chandler, Arizona, United States

Translational Research Institute for Metabolism and Diabetes

🇺🇸

Orlando, Florida, United States

Boston Medical Center

🇺🇸

Boston, Massachusetts, United States

Duke University

🇺🇸

Durham, North Carolina, United States

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