A Study to Evaluate the Effect of Long-term Treatment With BELVIQ (Lorcaserin HCl) on the Incidence of Major Adverse Cardiovascular Events and Conversion to Type 2 Diabetes Mellitus in Obese and Overweight Subjects With Cardiovascular Disease or Multiple Cardiovascular Risk Factors - Full Text View

Purpose

This is a multicenter, randomized, double-blind, placebo-controlled, parallel-group study in overweight and obese subjects with CV disease and/or multiple CV risk factors.

Condition	Intervention	Phase
Cardiovascular Disease High Cardiovascular Risk Obesity Overweight Type 2 Diabetes	Drug: APD356-Lorcaserin hydrochloride Drug: Placebo	Phase 4


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
Official Title:	A Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Evaluate the Effect of Long-term Treatment With BELVIQ (Lorcaserin HCl) on the Incidence of Major Adverse Cardiovascular Events and Conversion to Type 2 Diabetes Mellitus in Obese and Overweight Subjects With Cardiovascular Disease or Multiple Cardiovascular Risk Factors

Resource links provided by NLM:

MedlinePlus related topics: Diabetes Type 2

Drug Information available for: Lorcaserin Lorcaserin hydrochloride

U.S. FDA Resources

Further study details as provided by Eisai Inc.:

Primary Outcome Measures:

Time from randomization to first occurrence of Major Adverse Cardiovascular Events (MACE) [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
MACE events include: myocardial infarction, stroke and cardiovascular (CV) death
Time from randomization to conversion to type 2 diabetes mellitus (T2DM) for subjects without any type of diabetes at Baseline [ Time Frame: Baseline, and specified timepoints up to 5 years ] [ Designated as safety issue: No ]
Time from randomization to first occurrence of MACE+ [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
MACE+ events include: myocardial infarction, stroke, CV death, and hospitalization due to unstable angina, heart failure, or any coronary revascularization

Secondary Outcome Measures:

Time from randomization to event of each component of MACE+ [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
Time from randomization to event of all-cause mortality [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
Time from randomization to event of new onset renal impairment or worsening existing renal impairment in subjects with T2DM at Baseline [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
New onset renal impairment or worsening existing renal impairment include the first occurrence of microalbuminuria, macroalbuminuria, worsening of albuminuria, newly developed CKD, or worsening of CKD, doubling of serum creatinine, or any of the following: ESRD, renal transplant, and renal death.
Time from randomization to event of improvement in renal function [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
Change from Baseline in HbA[1c] at 6 months in subjects with T2DM at Baseline [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: No ]
The proportion of subjects who meet FDA-defined valvulopathy in echocardiographically determined heart valve changes [ Time Frame: Baseline and 1 year ] [ Designated as safety issue: Yes ]
Comparison between lorcaserin HCl and placebo will be made at 1 year.
The percent change from Baseline in echocardiographically-determined pulmonary arterial systolic pressure [ Time Frame: Baseline and 1 year ] [ Designated as safety issue: Yes ]
Comparison between lorcaserin HCl and placebo will be made at 1 year.
Time to conversion to normal glucose homeostasis [ Time Frame: Baseline and 1 year ] [ Designated as safety issue: No ]


Enrollment:	12000
Study Start Date:	January 2014
Estimated Study Completion Date:	June 2018
Estimated Primary Completion Date:	May 2018 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: APD356 10 mg APD356 10 mg twice daily	Drug: APD356-Lorcaserin hydrochloride APD356 10 mg twice daily
Placebo Comparator: Placebo Placebo twice daily	Drug: Placebo Placebo twice daily

Detailed Description:

Approximately 12,000 subjects will be randomized to two treatment groups in a ratio of 1:1, stratified by the presence of established CV disease (approximately 80%) or CV risk factors without established CV disease (approximately 20%). Subjects will receive lorcaserin HCl 10 mg BID or placebo BID. The study will consist of 2 phases: Prerandomization and Randomization. The Prerandomization Phase will last up to 30 days and consist of one visit during which subjects will be screened for eligibility. The Randomization Phase will consist of two periods: Treatment and Follow-up. The Treatment Period will last for approximately 5 years with approximately 18 visits and Follow-up period is 30 (+ or - 10 days) from the end of treatment visit.

Eligibility


Ages Eligible for Study:	40 Years and older (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria

BMI greater than or equal to 27 kg/m^2
Subjects able and willing to comply with a reduced-calorie diet and an increased physical activity program
Age greater than or equal to 40 years with established CV disease as defined by one of the following:
1. History of documented MI or ischemic stroke
2. History of peripheral artery disease
3. History of revascularization (coronary, carotid, or peripheral artery)
4. Significant unrevascularized coronary arterial stenosis

OR

Age greater than or equal to 55 years for women or greater than or equal to 50 years for men who have T2DM without established CV disease plus at least one of the following CV risk factors:

Hypertension, or currently receiving therapy for documented hypertension
Dyslipidemia, or currently taking prescription lipid-lowering therapy for documented dyslipidemia
Calculated creatinine clearance greater than or equal to 30 to less than or equal to 60 mL/min per the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation
High hsCRP
Urinary albumin-to-creatinine ratio (ACR) greater than or equal to 30 ug/mg

Subjects with T2DM may have a pre-existing or new diagnosis of T2DM. A new diagnosis of T2DM (ie, discovered at Screening) should be based on the 2013 American Diabetes Association (ADA) guidelines.

All T2DM subjects must have an HbA[1c] less than 10% at Screening. If subjects are being treated, or upon diagnosis need to be treated with antidiabetic agents, the T2DM treatment regimen must be stable for at least 3 months prior to randomization.

Exclusion Criteria

Moderate or greater symptoms of congestive cardiac failure (New York Heart Association [NYHA] class III or IV)
Known left ventricular (LV) ejection fraction less than 20%
Moderate or greater symptoms of pulmonary hypertension (PH)
Known severe valvular disease Moderate renal impairment, severe renal impairment, or end stage renal disease (ESRD) (calculated creatinine clearance less than 30 mL/min per the CKD-EPI equation based on ideal body weight)
Severe hepatic impairment
Use of other products intended for weight loss including prescription drugs, over-the-counter (OTC) drugs, and herbal preparations
Use of more than one other serotonergic drug
Use of drugs known to increase the risk for cardiac valvulopathy prior to Screening including, but not limited to: cyproheptadine, amoxapine, TCAs, mirtazapine, pergolide, ergotamine, methysergide, cabergoline
History or evidence of clinically significant disease (e.g., malignancy, cardiac, respiratory, gastrointestinal, renal or psychiatric disease)
Use of lorcaserin HCl prior to Screening or hypersensitivity to lorcaserin HCl or any of the excipients
Planned bariatric surgery
Females must not be breastfeeding or pregnant

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02019264

Show 394 Study Locations

Sponsors and Collaborators

Eisai Inc.

Thrombolysis In Myocardial Infarction (TIMI) Academic Research Organization

More Information


Responsible Party:	Eisai Inc.
ClinicalTrials.gov Identifier:	NCT02019264 History of Changes
Other Study ID Numbers:	APD356-G000-401 2013-000324-34
Study First Received:	December 18, 2013
Last Updated:	July 15, 2016
Health Authority:	Australia: Department of Health and Ageing Therapeutic Goods Administration Brazil: National Health Surveillance Agency Canada: Health Canada Chile: Comision Nacional de Investigacion Cientifica y Tecnologica Mexico: Federal Commission for Protection Against Health Risks New Zealand: Medsafe Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products United States: Food and Drug Administration

Keywords provided by Eisai Inc.:


Diabetes Cardiovascular Disease Multiple Cardiovascular Risk Factors Obesity	Overweight MACE Conversion to Diabetes

Additional relevant MeSH terms:


Diabetes Mellitus Diabetes Mellitus, Type 2 Cardiovascular Diseases Overweight Glucose Metabolism Disorders	Metabolic Diseases Endocrine System Diseases Body Weight Signs and Symptoms

ClinicalTrials.gov processed this record on September 28, 2016

A Study to Evaluate the Effect of Long-term Treatment With BELVIQ (Lorcaserin HCl) on the Incidence of Major Adverse Cardiovascular Events and Conversion to Type 2 Diabetes Mellitus in Obese and Overweight Subjects With Cardiovascular Disease or Multiple Cardiovascular Risk Factors (CAMELLIA-TIMI)