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)

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Eisai Inc.
Sponsor:
Collaborator:
Thrombolysis In Myocardial Infarction (TIMI) Academic Research Organization
Information provided by (Responsible Party):
Eisai Inc.
ClinicalTrials.gov Identifier:
NCT02019264
First received: December 18, 2013
Last updated: May 28, 2014
Last verified: May 2014
  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:


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 ]

Estimated Enrollment: 12000
Study Start Date: January 2014
Estimated Study Completion Date: October 2018
Estimated Primary Completion Date: October 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
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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

Contacts
Contact: Eisai Medical Services 1-888-422-4743

  Show 132 Study Locations
Sponsors and Collaborators
Eisai Inc.
Thrombolysis In Myocardial Infarction (TIMI) Academic Research Organization
  More Information

No publications provided

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: May 28, 2014
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
Brazil: National Health Surveillance Agency
Canada: Health Canada
Chile: Comisión Nacional de Investigación Científica y Tecnológica
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:
Cardiovascular Diseases
Diabetes Mellitus
Diabetes Mellitus, Type 2
Obesity
Overweight
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Overnutrition
Nutrition Disorders
Body Weight
Signs and Symptoms
Pamidronate
Bone Density Conservation Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 23, 2014