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

Phase 4

Completed

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

Interventions: Drug: Placebo
Drug: Lorcaserin hydrochloride

Registration Number: NCT02019264

Lead Sponsor: Eisai Inc.

Brief Summary: 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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 14673

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo twice daily
Lorcaserin hydrochloride (HCL)10 mg	Lorcaserin hydrochloride	APD356 10 mg twice daily

Primary Outcome Measures

Name	Time	Method
Time From Randomization to First Occurrence of Major Adverse Cardiovascular Events (MACE) at Interim Analysis	Baseline up to Month 42	The MACE events involved myocardial infarction (MI), stroke, or cardiovascular (CV) death. The outcome data was assessed using Kaplan-Meier estimate and Greenwood Formula.
Time From Randomization to First Occurrence of MACE+	Baseline up to end of study (Month 56)	The MACE+ events involved MI, stroke, or CV death or hospitalization for unstable angina or heart failure (HF), or any coronary revascularization. The outcome data was assessed using Kaplan-Meier estimate and Greenwood Formula.

Secondary Outcome Measures

Name	Time	Method
Time From Randomization to Conversion to Type 2 Diabetes Mellitus (T2DM) for Participants With Prediabetes at Baseline	Baseline up to end of study (Month 56)	Time from randomization to conversion to T2DM was defined as first occurrence of any component of the 2013 American Diabetes Association (ADA) Diagnostic Criteria (ADA, 2013) in participants with prediabetes at baseline. The diagnostic criteria were met if a participant had unequivocal hyperglycemia (random plasma glucose greater than or equal to (\>=) 200 milligram per deciliter (mg/dL) (11.1 millimole per liter \[mmol/L\]) with classic symptoms of hyperglycemia or hyperglycemic crisis) or any of the following criteria were observed and subsequently confirmed on repeat laboratory testing such as: glycosylated hemoglobin (HbA1c) \>=to 6.5%; fasting plasma glucose (FPG) \>=126 mg/dL (7.0 mmol/L); 2-hour plasma glucose \>=200 mg/dL (11.1 mmol/L) by an oral glucose tolerance test (OGTT). The outcome data was assessed using Kaplan-Meier estimate and Greenwood Formula.
Time From Randomization to First Occurrence of the Individual Components of MACE+	Baseline up to end of study (Month 56)	The MACE+ events involved MI, stroke, or CV death or hospitalization for unstable angina or HF, or any coronary revascularization. The outcome data was assessed using Kaplan-Meier estimate and Greenwood Formula.
Time From Randomization to Event of All-cause Mortality	Baseline up to end of study (Month 56)	The outcome data was assessed using Kaplan-Meier estimate and Greenwood Formula.
Time From Randomization to Conversion to Normal Glucose Homeostasis in Participants With Prediabetes at Baseline	Baseline up to end of study (Month 56)	Normal glucose homeostasis was defined as HbA1c less than or equal to (\<=) 5.6% and FPG \< 100 mg/dL without any antidiabetic treatment. The outcome data was assessed using Kaplan-Meier estimate and Greenwood Formula.
Time From Randomization to Conversion to T2DM for Participants Without Any Type of Diabetes at Baseline	Baseline up to end of study (Month 56)	The outcome data was assessed using Kaplan-Meier estimate and Greenwood Formula.
Change From Baseline in HbA1c at Month 6 in Participants With T2DM at Baseline	Baseline, and Month 6
Time From Randomization to Event of New Onset Renal Impairment or Worsening Existing Renal Impairment in All Participants	Baseline up to end of study (Month 56)	New onset/worsening of existing renal impairment was first occurrence of any events: microalbuminuria and macroalbuminuria (albumin-to-creatinine ratio \[ACR\] \>=30mcg/mg and ACR\>=300 mcg/mg in spot urine), worsening albuminuria (microalbuminuria at Baseline developed macroalbuminuria, ACR increased \>=30% from Baseline during treatment), newly developed chronic kidney disease (CKD) (eGFR \>=90 milliliter per minute per 1.73 \[mL/min/1.73\]body surface area (BSA) and without kidney damage at Baseline changed to CKD Stage 1/higher as per National Kidney Foundation \[NKF\] Guidelines \[2002\]) or worsening of CKD (CKD Stage 1/higher as per NKF Guidelines \[2002\] worsened to higher CKD stages during treatment), or doubling of serum creatinine (creatinine value at least 2 times Baseline value and \>=1.5 mg/dL during treatment.), or any of the following: end-stage renal disease, renal transplant, renal death. The outcome data was assessed using Kaplan-Meier estimate and Greenwood Formula.
Time From Randomization to Event of New Onset Renal Impairment or Worsening Existing Renal Impairment in Participants With T2DM at Baseline	Baseline up to end of study (Month 56)	New onset/worsening of existing renal impairment was first occurrence of any events: microalbuminuria and macroalbuminuria (ACR \>=30 mcg/mg and ACR \>=300 mcg/mg in spot urine), worsening albuminuria (microalbuminuria at baseline developed macroalbuminuria, ACR increased \>=30% from baseline during treatment), CKD (eGFR \>=90 mL/min/1.73 BSA and without kidney damage at baseline changed to CKD Stage 1/higher as per NKF Guidelines \[2002\]) or worsening of CKD (CKD Stage 1/higher as per NKF Guidelines \[2002\] worsened to higher CKD stages during treatment), or doubling of serum creatinine (creatinine value at least 2 times baseline value and \>=1.5 mg/dL during treatment.), or any of the following: end-stage renal disease, renal transplant, renal death. The outcome data was assessed using Kaplan-Meier estimate and Greenwood Formula.
Percentage of Participants With FDA-Defined Valvulopathy at Baseline Who Demonstrated Worsened FDA-Defined Valvulopathy	Months 6 and 12
Time From Randomization to Event of New Onset Renal Impairment or Worsening Existing Renal Impairment in Participants With Prediabetes at Baseline	Baseline up to end of study (Month 56)	New onset/worsening of existing renal impairment was first occurrence of any events: microalbuminuria and macroalbuminuria (ACR \>=30mcg/mg and ACR \>=300 mcg/mg in spot urine), worsening albuminuria (microalbuminuria at baseline developed macroalbuminuria, ACR increased \>=30% from baseline during treatment), CKD (eGFR \>=90 mL/min/1.73 BSA and without kidney damage at baseline changed to CKD Stage 1/higher as per NKF Guidelines \[2002\]) or worsening of CKD (CKD Stage 1/higher as per NKF Guidelines \[2002\] worsened to higher CKD stages during treatment), or doubling of serum creatinine (creatinine value at least 2 times baseline value and \>=1.5 mg/dL during treatment.), or any of the following: end-stage renal disease, renal transplant, renal death. The outcome data was assessed using Kaplan-Meier estimate and Greenwood Formula.
Change From Baseline in Echocardiographically-Determined Pulmonary Arterial Systolic Pressure	Baseline, Month 12
Time From Randomization to Event of Improvement in Renal Function in Participants With T2DM at Baseline	Baseline up to end of study (Month 56)	Improvement in renal function was defined as first occurrence of regression of albuminuria or regression of CKD. Regression of albuminuria was defined as when participants with macroalbuminuria at baseline developed microalbuminuria or nonalbuminuria (ACR \<30 mcg/mg in spot urine), or participants with microalbuminuria at baseline became nonalbuminuric, and ACR value decreased \>= 30% from previous assessment during treatment. Regression of CKD defined as when participants with CKD Stage 1 or higher at baseline improved to normal or lower stages by NKF guidelines (eGFR \>=90 with albuminuria at baseline improved to eGFR \>=90 without albuminuria, or eGFR 60 to 89 at baseline became eGFR \>=90 with or without albuminuria, or eGFR between 30 to 59 at baseline improved to \>60 mL/min/1.73 BSA) during treatment. The outcome data was assessed using Kaplan-Meier estimate and Greenwood Formula.
Percentage of Participants Who Met FDA-Defined Valvulopathy in Echocardiographically Determined Heart Valve Changes	Months 6 and 12

Trial Locations

Locations (478): Advanced Cardiovascular, LLC
🇺🇸
Alexander City, Alabama, United States
North Alabama Research Center, LLC
🇺🇸
Athens, Alabama, United States
UAB Medical Center
🇺🇸
Birmingham, Alabama, United States
Coastal Clinical Research, Inc.
🇺🇸
Mobile, Alabama, United States
Mobile Heart Specialists, PC
🇺🇸
Mobile, Alabama, United States
Alaska Heart Institute
🇺🇸
Anchorage, Alaska, United States
Connect Clinical Research Center, LCC
🇺🇸
Chandler, Arizona, United States
Arrowhead Health Centers
🇺🇸
Glendale, Arizona, United States
Phoenix Heart, PLLC
🇺🇸
Glendale, Arizona, United States
Eclipse Clinical Research
🇺🇸
Tucson, Arizona, United States
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Advanced Cardiovascular, LLC
🇺🇸Alexander City, Alabama, United States