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Chronic Weight ManagementPhase 4NCT01987427

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

A Phase 4 study testing lorcaserin + phentermine-HCl in people with Chronic Weight Management, run by Eisai Inc. at 13 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 to 60 years
Conditions the study is for
Chronic Weight Management
What is being tested?
lorcaserin + phentermine-HCl
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
344 participants
Where
13 sitesUnited States
Study dates
30 Oct 2013to 3 Sep 2014
Phase
Phase 4
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 60 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • 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.

Who cannot join

  • 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)
Show all 34Show fewer
  • 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).
  • 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.
  • Glaucoma.
  • Abnormal thyroid stimulating hormone (TSH) laboratory value greater than 1.5 x Upper Limit of Normal (ULN)
  • 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.
  • 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.
  • Significant change is smoking habits or tobacco product use within 3 months prior to the Screening Visit.
  • 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).
  • Surgical procedure for the treatment of obesity (i.e., gastric bypass, gastric banding), even if reversed prior to screening.
  • Planned surgery during the study period that may interfere with completion or compliance with the protocol.
  • A prolonged QT/QTc interval (QTc Bazett's greater than 450 msec) as demonstrated by a repeated electrocardiogram (ECG).
  • Participation in any clinical study with an investigational drug, biologic, or device within 1 month prior to screening.
  • 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.
  • Change in weight of greater than 5 kg within 3 months of screening.
  • 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.
  • 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).
  • 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.
  • 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).
  • 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.
  • 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.

Trial locations and contacts

13 sites in 1 country.

13 sites in 1 country

United States13 sites

  • Radiant Research - South Carolina

    Anderson, South Carolina, 29621

  • Pennington Biomedical Research Center

    Baton Rouge, Louisiana, 70808

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35294

  • Boston Medical Center

    Boston, Massachusetts

  • Radiant Research - Arizona

    Chandler, Arizona, 85224

  • Radiant Research - Columbus

    Columbus, Ohio, 43212

  • Radiant Research - Dallas

    Dallas, Texas, 75231

  • Duke University

    Durham, North Carolina, 27710

  • Scripps Clinical Research Center

    La Jolla, California, 92037

  • Weill Cornell College

    New York, New York, 10065

  • National Clinical Research - Norfolk

    Norfolk, Virginia, 23502

  • Translational Research Institute for Metabolism and Diabetes

    Orlando, Florida, 32804

  • National Clinical Research - Richmond

    Richmond, Virginia, 23294

Other trials in United States

About this study

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.

Read the 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.

Being tested
lorcaserin + phentermine placebo, lorcaserin + phentermine-HCl + phentermine placebo, lorcaserin + phentermine-HCl
Keywords
Overweight, Obese, Weight Management
Medical subject headings
Overweight, Obesity

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • lorcaserin + phentermine placeboDrug

    lorcaserin 10 mg BID + phentermine placebo BID

  • lorcaserin + phentermine-HCl + phentermine placeboDrug

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

  • lorcaserin + phentermine-HClDrug

    lorcaserin 10 mg BID + phentermine-HCl 15 mg BID

Study groups in NCT01987427
Study groupRoleWhat they receive
AExperimentallorcaserin + phentermine placebo
Receives: Drug: lorcaserin + phentermine placebo
BExperimentallorcaserin + phentermine-HCl + phentermine placebo
Receives: Drug: lorcaserin + phentermine-HCl + phentermine placebo
CExperimentallorcaserin + phentermine-HCl
Receives: Drug: lorcaserin + phentermine-HCl

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Baseline up to Week 12 (end of treatment)

Secondary outcomes (7)

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

    Measured: Baseline up to Week 16

  2. Number of Participants With Treatment-Emergent Markedly Abnormal Laboratory Values

    Measured: Baseline up to Week 16

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

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

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

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

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

    Measured: Week 12 (end of treatment)

  6. Change From Baseline in Waist Circumference and Hip Circumference at Week 12

    Measured: Baseline and Week 12 (end of treatment)

  7. Change From Baseline in Waist to Hip Circumference Ratio at Week 12

    Measured: Baseline and Week 12 (end of treatment)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Nov 2013 (estimated)
  2. Study start30 Oct 2013
  3. Primary completionAug 2014
  4. Study completion3 Sep 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
344 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01987427
Sponsor's protocol ID
APD356-A001-402
Status last verified
Sep 2019
First submitted
12 Nov 2013
Last updated
30 Sep 2019
Data monitoring committee
No

Publications

  • 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.

    PubMed 29363287

  • 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.

    PubMed 28440045

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing lorcaserin + phentermine-HCl in people with Chronic Weight Management, run by Eisai Inc. at 13 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 30 Sep 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants Reporting at Least One of Nine Adverse Events (AEs) of Main Interests That May Related to Serotonergic Reaction (time frame: Baseline up to Week 12 (end of treatment)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01987427, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Sep 2019.

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