Overview

This trial is active, not recruiting.

Conditions cardiovascular disease, high cardiovascular risk, obesity, overweight, type 2 diabetes
Treatments apd356-lorcaserin hydrochloride, placebo
Phase phase 4
Sponsor Eisai Inc.
Collaborator Thrombolysis In Myocardial Infarction (TIMI) Academic Research Organization
Start date January 2014
End date May 2018
Trial size 12000 participants
Trial identifier NCT02019264, 2013-000324-34, APD356-G000-401

Summary

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, investigator)
Primary purpose treatment
Arm
(Experimental)
APD356 10 mg twice daily
apd356-lorcaserin hydrochloride
APD356 10 mg twice daily
(Placebo Comparator)
Placebo twice daily
placebo
Placebo twice daily

Primary Outcomes

Measure
Time from randomization to first occurrence of Major Adverse Cardiovascular Events (MACE)
time frame: Up to 5 years
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
Time from randomization to first occurrence of MACE+
time frame: Up to 5 years

Secondary Outcomes

Measure
Time from randomization to event of each component of MACE+
time frame: Up to 5 years
Time from randomization to event of all-cause mortality
time frame: Up to 5 years
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
Time from randomization to event of improvement in renal function
time frame: Up to 5 years
Change from Baseline in HbA[1c] at 6 months in subjects with T2DM at Baseline
time frame: Baseline and 6 months
The proportion of subjects who meet FDA-defined valvulopathy in echocardiographically determined heart valve changes
time frame: Baseline and 1 year
The percent change from Baseline in echocardiographically-determined pulmonary arterial systolic pressure
time frame: Baseline and 1 year
Time to conversion to normal glucose homeostasis
time frame: Baseline and 1 year

Eligibility Criteria

Male or female participants at least 40 years old.

Inclusion Criteria 1. BMI greater than or equal to 27 kg/m^2 2. Subjects able and willing to comply with a reduced-calorie diet and an increased physical activity program 3. 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: 1. Hypertension, or currently receiving therapy for documented hypertension 2. Dyslipidemia, or currently taking prescription lipid-lowering therapy for documented dyslipidemia 3. 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 4. High hsCRP 5. 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 1. Moderate or greater symptoms of congestive cardiac failure (New York Heart Association [NYHA] class III or IV) 2. Known left ventricular (LV) ejection fraction less than 20% 3. Moderate or greater symptoms of pulmonary hypertension (PH) 4. 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) 5. Severe hepatic impairment 6. Use of other products intended for weight loss including prescription drugs, over-the-counter (OTC) drugs, and herbal preparations 7. Use of more than one other serotonergic drug 8. 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 9. History or evidence of clinically significant disease (e.g., malignancy, cardiac, respiratory, gastrointestinal, renal or psychiatric disease) 10. Use of lorcaserin HCl prior to Screening or hypersensitivity to lorcaserin HCl or any of the excipients 11. Planned bariatric surgery 12. Females must not be breastfeeding or pregnant

Additional Information

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
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.
Trial information was received from ClinicalTrials.gov and was last updated in October 2016.
Information provided to ClinicalTrials.gov by Eisai Inc..