World Health Organization site
Skip Navigation Links

Main
Note: This record shows only 21 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: EUCTR
Last refreshed on: 20 August 2018
Main ID:  EUCTR2013-000324-34-PL
Date of registration: 07/07/2014
Prospective Registration: Yes
Primary sponsor: Eisai Limited
Public title: A research study to assess whether lorcaserin HCl affects the risk of developing cardiovascular diseases in obese or overweight men and women at higher risk of developing these diseases
Scientific 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 - CAMELLIA
Date of first enrolment: 10/09/2014
Target sample size: 12000
Recruitment status: Not Recruiting
URL:  https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-000324-34
Study type:  Interventional clinical trial of medicinal product
Study design:  Controlled: yes
Randomised: yes
Open: no
Single blind: no
Double blind: yes
Parallel group: yes
Cross over: no
Other: no
If controlled, specify comparator, Other Medicinial Product: no
Placebo: yes
Other: no
Number of treatment arms in the trial: 2
 
Phase:  Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): yes
Countries of recruitment
Australia Bahamas Canada Chile Mexico New Zealand Poland United States
Contacts
Name: Eisai Medical Information   
Address:  European Knowledge Centre, Mosquito Way AL10 9SN Hatfield United Kingdom
Telephone: +44845676 1400
Email: EUMed_info@eisai.net
Affiliation:  Eisai Limited
Name: Eisai Medical Information   
Address:  European Knowledge Centre, Mosquito Way AL10 9SN Hatfield United Kingdom
Telephone: +44845676 1400
Email: EUMed_info@eisai.net
Affiliation:  Eisai Limited
Key inclusion & exclusion criteria
Inclusion criteria:
1. Body mass index (BMI) =27kg/m2
2. Subjects able and willing to comply with a reduced-calorie diet and an increased physical activity program
3. Age =40 years with established CV disease as defined by one of the following:
a. History of documented MI or ischemic stroke >1 month before randomization
b. History of peripheral artery disease as manifested by symptomatic claudication with an ankle-brachial pressure index of <0.85
c. History of revascularization (coronary, carotid, or peripheral artery)
d. Significant unrevascularized coronary arterial stenosis defined as =50% in two or more coronary arteries
OR
Age =55 years for women or =50 years for men who have T2DM without established CV disease plus at least one of the following CV risk factors:
a. Hypertension, defined as systolic blood pressure (SBP) >140 or diastolic blood pressure (DBP) >90, or currently receiving therapy for documented hypertension
b. Dyslipidemia, defined as low density lipoprotein-cholesterol (LDL-C) >130 mg/dL, or high density lipoprotein-cholesterol (HDL-C) <40 mg/dL, or currently taking prescription lipid-lowering therapy for documented dyslipidemia
c. c. Estimated glomerular filtration rate (eGFR) =30 to =60 mL/min/1.73 m2 per the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation
d. High sensitivity C-reactive protein (hsCRP) > 3 mg/L detected by the central laboratory in the absence of known acute or chronic inflammatory conditions (eg, infection, rheumatologic disease)
e. Urinary albumin-to-creatinine ratio (ACR) =30 µg/mg in spot urine
Subjects with T2DM may have a pre-existing or new diagnosis of T2DM. Subjects with pre-existing T2DM should have prior documentation consistent with the diagnosis and/or be on active pharmacotherapy for T2DM. A new diagnosis of T2DM (ie, discovered at Screening) should be based on the 2013 American Diabetes Association (ADA) guidelines. The diagnostic criteria are met if a subject has unequivocal hyperglycemia (random plasma glucose =200 mg/dL (11.1 mmol/L) with classic symptoms of hyperglycemia or hyperglycemic crisis) OR any of the following criteria are observed and confirmed:
o HbA1c =6.5%
o fasting plasma glucose (FPG) =126 mg/dL (7.0 mmol/L)
o 2-hour plasma glucose =200 mg/dL (11.1mmol/L) by an oral glucose tolerance test (OGTT)
All T2DM subjects must have an HbA1c <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. A single rescreen is allowed following stabilization. Stable control refers to minimal dose changes to existing medications for glycemic control and no medications being initiated for glycemic control in the 3 months before randomization. Minimal changes are defined as a change in insulin dose < 10% of daily dose, without any change in dose frequency, no add-on or discontinuation of other antidiabetic agents, and the subject has not been hospitalized due to hypo- or hyperglycemic events.
4. Provide written informed consent
5. Willing and able to comply with all aspects of the protocol
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 7200
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 4800

Exclusion criteria:
1.Current moderate or greater symptoms of congestive cardiac failure (New York Heart Association [NYHA] class III or IV)
2. Known left ventricular (LV) ejection fraction <20%
3. Current moderate or greater symptoms of pulmonary hypertension (PH) (World Health Organization [WHO] functional Class III and IV)
4. Known severe valvular disease defined by clinical diagnosis and/or most recent echocardiography. History of severe valvular disease is allowed if it has been corrected by valve replacement or repair
5. Severe renal impairment (estimated glomerular filtration rate <30 mL/min/1.73 m2 per the CKD-EPI equation based on ideal body weight), or end-stage renal disease (ESRD)
6. Severe hepatic impairment (Child-Pugh score 10 to 15)
7. Use of other products intended for weight loss including prescription drugs, over-the-counter (OTC) drugs, and herbal preparations within 1 month prior to Screening
8. Use of more than 1 serotonergic drug, within 1 month before Screening, or during the screening window, but not limited to:
a. selective serotonin reuptake inhibitors (SSRIs)
b. serotonin norepinephrine reuptake inhibitors (SNRIs)
c. tricyclic antidepressants (TCAs)
d. bupropion
e. triptans
f. St. John’s Wort and tryptophan
g. Monoamine oxidase inhibitors [MAOIs]
h.linezolid
i.dextromethorphan
j.lithium
k.tramadol
l.antipsychotics or other dopamine antagonists

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 or cabergoline
10. History or evidence of clinically significant disease (e.g., malignancy, cardiac, respiratory, gastrointestinal, renal, or psychiatric disease) that in the opinion of the investigator(s) could affect the subject’s safety, interfere with the study assessments, or result in a life expectancy of less than 1 year
11. Use of lorcaserin HCl within 6 months prior to Screening or hypersensitivity to lorcaserin HCl or any of the excipients
12. History of alcohol dependence or abuse within 2 years prior to Visit 1 (Screening)
13. Recreational drug use within the 2 years prior to Visit 1 (Screening)
14. Currently enrolled in another clinical trial or used any investigational drug or device within 30 days preceding informed consent (the exclusion criterion will not apply if the subjects are no longer in follow- up and have discontinued use of an investigational drug or device for at least 30 days. It will not apply if subjects are enrolled in registries or observational studies)
15. Planned bariatric surgery or bariatric surgery performed within 1 year before screening
16. Subjects considered by the investigator to have insufficient motivation to remain in a long-term clinical trial or who are considered likely to drop out for nonmedical reasons, e.g., social issues
17. Females must not be breastfeeding or pregnant at Visit 1 (Screening) or Visit 2 (Baseline) (as documented by a negative beta-human chorionic gonadotropin [ß-hCG]). A separate Baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of study drug.
18. All females will be considered to be of childbearing potential unless they are postmenopausal (amenorrheic for at least 12 consecutive months, in the appropriate age group and without other known or suspected cause) or have been sterilized surgically (i.e., bilateral tubal ligation, total hysterecto


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes
Health Condition(s) or Problem(s) studied
Obese and overweight patients with cardiovascular (CV) disease and/or multiple CV risk factors
MedDRA version: 20.0 Level: PT Classification code 10029883 Term: Obesity System Organ Class: 10027433 - Metabolism and nutrition disorders
MedDRA version: 20.0 Level: PT Classification code 10033307 Term: Overweight System Organ Class: 10027433 - Metabolism and nutrition disorders
Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]
Intervention(s)

Product Name: Lorcaserin hydrochloride (BELVIQ)
Product Code: APD356
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Lorcaserin
CAS Number: 856681-05-5
Current Sponsor code: APD356
Other descriptive name: lorcaserin hydrochloride hemihydrate (lorcaserin hydrochloride HH; lorcaserin HCl hemihydrate; lorcaserin HCl HH) ; IUPAC: (R)-8-Chloro-1-methyl-2,3,4,5-tetrahydro-1H-3- benzazepine hydrochloride hemihydrate; Other chemical names: (1R)-8-Chloro-1-methyl-2,3,4,5-tetrahydro-1H-3- benzazepine hydrochloride hemihydrate (1R)-8-Chloro-1-methyl-2,3,4,5-tetrahydro-1H-3- benzo[d]azepinium chloride hemihydrate; Laboratory code names: APD356 Hemihydrate (APD356HH) AR226173 hydrochloride hemihydrate
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)
Main Objective: -To demonstrate that, in obese and overweight subjects with cardiovascular (CV) disease and/or multiple CV risk factors, lorcaserin HCl 10 mg administered twice daily (BID) does not increase the incidence of major adverse cardiovascular events (MACE = myocardial infarction [MI], or stroke, or CV death) compared to placebo, with a noninferiority margin for the hazard ratio of 1.4

-To demonstrate that, in obese and overweight subjects with CV disease and/or multiple CV risk factors, lorcaserin HCl 10 mg BID reduces the incidence of MACE+ (MACE or hospitalization for unstable angina or heart failure (HF), or any coronary revascularization) compared to placebo
Primary end point(s): -Time from randomization to first occurrence of MACE (first occurrence of any of the following events: MI, stroke, or CV death)

-Time from randomization to first occurrence of MACE+ (first occurrence of any of the following events: MACE or hospitalization for unstable angina or HF, or any coronary revascularization)
Secondary Objective: Key secondary objective: To confirm that, in subjects with prediabetes at Baseline based on the 2013 ADA guideline, lorcaserin HCl 10 mg BID reduces the incidence of conversion to type 2 diabetes mellitus (T2DM) compared to placebo.
For other Secondary Objectives: MACE and MACE+, Prediabetes, Renal, Safety and exploratory related please refer to the protocol amendment 2 pages 3 and 4.
Timepoint(s) of evaluation of this end point: -Potential MACE/MACE+ events will be recorded throughout the study

Secondary Outcome(s)
Secondary end point(s): Key secondary endpoint:
Time from randomization to conversion to T2DM, defined as first occurrence of any component of the 2013 ADA diagnostic criteria in subjects with prediabetes at Baseline. The diagnostic criteria are met if a subject has unequivocal hyperglycemia (random plasma glucose =200 mg/dL (11.1 mmol/L) with classic symptoms of hyperglycemia or hyperglycemic crisis) OR any of the following criteria are observed and subsequently confirmed on repeat laboratory testing
o HbA1c =6.5%
o FPG=126 mg/dL (7.0 mmol/L)
o 2-hour plasma glucose =200mg/dL (11.1 mmol/L) by an OGTT
Investigators should make every effort to obtain central lab confirmatory testing no later than 6 weeks after meeting any of the above criteria. Abnormalities of any 1 of the above 3 criteria on repeat testing constitutes diagnostic confirmation of diabetes. Subjects who have been started on anti-diabetic medications following abnormalities in preliminary testing do not require confirmatory testing.

Other secondary endpoints:
Other secondary endpoints are detailed on pages 12, 13 and 14 of the protocol amendment 2.
Timepoint(s) of evaluation of this end point: -Potential MACE/MACE+ events recorded throughout the study
-HbA1c, random plasma glucose and fasting plasma glucose will be measured in blood samples collected at Screening, Baseline, and specified timepoints throughout the study
-Glycemic and end-organ benefits in subjects with T2DM at Baseline: HbA1c, random plasma glucose and fasting plasma glucose (FPG) will be measured in blood samples collected at Screening, Baseline, and specified timepoints throughout the study
-Cardiac valve function and pulmonary arterial pressure: Baseline and 1 year
- Exploratory Endpoints: cv risk factors, eGFR,ACR and LFTs baseline, 1 year and yearly thereafter; OAD use at baseline and 6 months;FDAdefined valvulopathy and estimated pulmonary artery systolic pressure baseline, 2 years and yearly thereafter
Secondary ID(s)
APD356-G000-401
Source(s) of Monetary Support
Eisai Inc.
Secondary Sponsor(s)
Results
Results available:
Date Posted:
URL:
Disclaimer: Trials posted on this search portal are not endorsed by WHO, but are provided as a service to our users. In no event shall the World Health Organization be liable for any damages arising from the use of the information linked to in this section. None of the information obtained through use of the search portal should in any way be used in clinical care without consulting a physician or licensed health professional. WHO is not responsible for the accuracy, completeness and/or use made of the content displayed for any trial record.
Copyright - World Health Organization - Version 3.6 - Version history