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)

Eisai

Status and phase: Completed; Phase 4

Conditions: Overweight; Obesity; Type 2 Diabetes; High Cardiovascular Risk; Cardiovascular Disease

Treatments: Drug: Placebo; Drug: Lorcaserin hydrochloride

Study type: Interventional

Funder types: Industry; Other

Identifiers

NCT02019264

APD356-G000-401

2013-000324-34 (EudraCT Number)

Details and patient eligibility

About

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

Full 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.

Enrollment: 14,673 patients

Sex: All

Ages: 40+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

1. BMI greater than or equal (>=) to 27 kilogram per meter square (kg/m^2)

2. Subjects able and willing to comply with a reduced-calorie diet and an increased physical activity program

3. Age >= 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 >= to 55 years for women or >= to 50 years for men who have type 2 diabetes mellitus (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. Estimated glomerular filtration rate >= to 30 to less than equal (<=) to 60 mililitre per minute per 1.73 meter square (mL/min/1.73 m^) per the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation
4. High high sensitivity C-reactive protein (hsCRP)
5. Urinary albumin-to-creatinine ratio (ACR) >= 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 < than 20%
3. Moderate or greater symptoms of pulmonary hypertension (PH)
4. Known severe valvular disease
5. Moderate renal impairment, severe renal impairment (estimated glomerular filtration rate < 30 mL/min/1.73 m^ per the CKD-EPI equation based on ideal body weight), or end stage renal disease (ESRD)
6. Severe hepatic impairment
7. Use of other products intended for weight loss including prescription drugs, over-the-counter (OTC) drugs, and herbal preparations
8. Use of more than one other serotonergic drug
9. Use of drugs known to increase the risk for cardiac valvulopathy within 6 months prior to Screening including, but not limited to: pergolide, ergotamine, methysergide, cabergoline
10. History or evidence of clinically significant disease (e.g., malignancy, cardiac, respiratory, gastrointestinal, renal or psychiatric disease)
11. Use of lorcaserin HCl prior to Screening or hypersensitivity to lorcaserin HCl or any of the excipients
12. Planned bariatric surgery
13. Females must not be breastfeeding or pregnant

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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14,673 participants in 2 patient groups, including a placebo group

Lorcaserin hydrochloride (HCL)10 mg

Experimental group

Description:

APD356 10 mg twice daily

Treatment:

Drug: Lorcaserin hydrochloride

Placebo

Placebo Comparator group

Description:

Placebo twice daily

Treatment:

Drug: Placebo