Please select the eligibility criteria that correspond to the clinical trial below.
Title: Randomized, Multicenter, Double-Blind, Placebo-Controlled, Two-Arm Parallel Group Trial of Rimonabant 20-mg od, for Inhibition of Atherosclerosis Progression Assessed by IVUS (IntraVascular UltraSounds), in Overweight Patients With Clustering Risk Factors
Brief Summary: The purpose of this study is to determine if rimonabant 20 mg once daily (od) administered during 18-20 months will reduce progression of coronary atherosclerosis as assessed by intravascular ultrasound (IVUS) when administered on top of standard behavioral and pharmacological therapy given as needed, in patients with abdominal obesity associated with current smoking and/or metabolic syndrome.


Options:
A: Inclusion Criteria:

* Informed consent
* Body mass index equal to or above 30 kg/m\^2
* Stable body weight (less than 5% self-reported change during the previous 3 months)
* Diagnosis of moderate or severe obstructive sleep apnoea (OSA)
* Unwilling or unable to use continuous positive airway pressure (CPAP) (or other positive airway pressure) treatment. No CPAP (or other positive airway pressure) treatment for at least four weeks prior to screening
* Ability and willingness to comply with all protocol procedures e.g. correct handling of trial product, compliance to visit schedule and dietary advice and complete trial related questionnaires

Exclusion Criteria:

* Treatment with glucagon-like peptide-1 (GLP-1) receptor agonists, dipeptidyl peptidase-4 inhibitors or insulin within the last 3 months prior to screening
* Diagnosis of type 1 or type 2 diabetes per judgement of the investigator
* Glycosylated haemoglobin (HbA1c) equal to or above 6.5%
* Significant craniofacial abnormalities that may cause OSA
* Respiratory and neuromuscular diseases that could interfere with the results of the trial in the opinion of the investigator
* Use of central stimulants, hypnotics, mirtazepine, opioids, trazodone within the previous 3 months prior to screening
* Obesity induced by drug treatment
* Treatment with pramlintide, sibutramine, orlistat, zonisamide, topiramate or phenteremine within the last 3 month prior to screening
* Previous surgical treatment for obesity
* Screening calcitonin equal to or above 50 ng/L
* Familial or personal history of Multiple Endocrine Neoplasia type 2 or familial Medullary Thyroid Carcinoma
* Personal history of non-familial Medullary Thyroid Carcinoma
* History of chronic pancreatitis or idiopathic acute pancreatitis
* History of Major Depressive Disorder or suicide attempts
* Systolic blood pressure equal to or above 160 mmHg and/or diastolic blood pressure equal to or above 100 mmHg
B: Inclusion Criteria:

* Written and signed informed consent
* Indication for coronary angiography
* Abdominal obesity defined by waist circumference \> 88 cm in women or \> 102 cm in men
* At least one of the two following conditions: \*a) Metabolic syndrome as defined by the presence of at least two of the following additional risk factors: 1. Triglyceride level \>= 150 mg/dL (1.69 mmol/L); 2. HDL cholesterol \< 40 mg/dL (1.03 mmol/L) \[men\] or 50 mg/dL (1.28 mmol/L) \[women\]; 3. Fasting glucose \>= 110 mg/dL (6.1 mmol/L); 4. High blood pressure (\>= 140 mmHg systolic and/or \>= 90 mmHg diastolic) at Screening visit, or current treatment by anti-hypertensive medication; \*b) Currently smoking (\> 10 cigarettes /day) and willing to stop
* Angiographic evidence of coronary heart disease as defined by at least 1 lesion in a native coronary artery that has \>= 20% reduction in lumen diameter by angiographic visual estimation
* Presence of at least one coronary artery complying with the definition of "target vessel" for IVUS assessment
* Acceptation of the Baseline IVUS tape by the IVUS Core Laboratory

Exclusion Criteria:

* Age \< 18 years
* Pregnant or breast-feeding women
* History of very low-calorie diet or surgical procedures for weight loss (eg, stomach stapling, bypass) within 6 months prior to screening visit
* Obesity of known endocrine origin
* Uncontrolled diabetes with HBA1c \>10%
* Presence of any severe medical or psychological condition, that in the opinion of the Investigator would compromise the subject's safety or successful participation in the study
* Severe congestive heart failure (New York Heart Association \[NYHA\] Class III or IV)
* Clinically significant heart disease which in the opinion of the Investigator is likely to require coronary artery bypass graft (CABG), percutaneous coronary intervention (PCI), cardiac transplantation, surgical repair and/or replacement during the course of the study
* Angioplasty of a non-qualifying artery which is considered at high risk of acute complication or restenosis, during baseline catheterization
* \>50% reduction in lumen diameter of the left main coronary artery by visual angiographic estimation
* Recent ST-elevation myocardial infarction (MI) \<= 72 hours prior to randomization
C: Inclusion Criteria:

* Female and male subjects, 18 to 65 years of age;
* Have BMI ≥30 and ≤45kg/m² for subjects with uncomplicated obesity, and BMI of ≥27 and ≤45kg/m² for subjects with obesity and controlled hypertension and/or dyslipidemia;
* Normotensive (systolic ≤140 mm Hg; diastolic ≤90 mm Hg). Anti-hypertensive medications are allowed with the exception of alpha-adrenergic blockers and clonidine; medical regimen must be stable for at least 6 weeks prior to randomization;
* Medications for treatment of dyslipidemia are allowed as long as medical regimen has been stable for at least 6 weeks prior to randomization;
* Free of opioid medication for 7 days prior to randomization;
* No clinically significant abnormality of serum albumin, blood urea nitrogen, creatinine, bilirubin, sodium, potassium, chloride, calcium or phosphorus;
* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within 2.5 x upper limit of normal range (ULN);
* No clinically significant abnormality of hematocrit, white blood cell (WBC) count, white cell differential, or platelets;
* Fasting glucose \< 126 mg/dL on no hypoglycemic agents, fasting triglycerides \<400 mg/dL;
* No clinically significant abnormality on urinalysis;
* TSH within normal limits or normal T3, if TSH is below normal limits;
* Negative serum pregnancy test in women of child-bearing potential;
* Negative urine drug screen;
* IDS-SR scores \< 2 on items 5 (sadness), 6 (irritability), 7 (anxiety/tension) and 18 (suicidality), and IDS-SR total score \< 30;
* Women of child bearing potential had to be non-lactating and agree to use effective contraception throughout the study period and 30 days after discontinuation of study drug;
* Able to comply with all required study procedures and schedule;
* Able to speak and read English;
* Willing and able to give written informed consent.

Exclusion Criteria:

* Obesity of known endocrine origin (e.g., untreated hypothyroidism, Cushing's syndrome, established Polycystic Ovary Syndrome);
* Serious medical conditions (including but not limited to ongoing renal or hepatic insufficiency, Class III or IV congestive heart failure; myocardial infarction, history of angina pectoris, claudication, or acute limb ischemia within the previous 6 months; lifetime history of stroke);
* History of malignancy within the previous 5 years with exception of non-melanoma skin cancer or surgically cured cervical cancer;
* A lifetime history of serious psychiatric illness, including lifetime history of bipolar disorder, schizophrenia or other psychosis, bulimia, or anorexia nervosa;
* Current serious psychiatric illness including severe personality disorder, (e.g. borderline or antisocial), current severe major depressive disorder, recent (previous 6 months) suicide attempt, current active suicidal ideation, or recent hospitalization due to psychiatric illness;
* A response to bipolar disorder questions indicating the presence of bipolar disorder;
* In need of medications for the treatment of a psychiatric disorder (with the exception of short-term insomnia) within the previous 6 months prior to randomization;
* History of drug or alcohol abuse or dependence (with the exception of nicotine dependence) within 1 year prior to study initiation;
* Type 1 or Type 2 diabetes mellitus;
* Screening ECG with a corrected QT interval by the method of Bazett (QTcB) \>450 msec (men) and \> 470 millisecond (msec) (women) or the presence of any clinically significant cardiac abnormalities, including but not limited to patterns consistent with myocardial ischemia, electrolyte abnormalities, or atrial or ventricular dysrhythmia or significant conduction abnormalities;
* Excluded concomitant medications: any psychotropic agents (including antipsychotic, antidepressant, anxiolytic, mood stabilizer, anticonvulsant agents or agents for the treatment of Attention Deficit Disorder) with the exception of low dose benzodiazepine or hypnotic agents for the treatment of insomnia (up to 2 mg lorazepam/day or equivalent dose of a benzodiazepine or hypnotic agent); any anorectic or weight loss agents; any over-the-counter dietary supplements or herbs with psychoactive, appetite or weight effects; alpha-adrenergic blockers; dopamine agonists; clonidine; coumadin; theophylline; cimetidine; oral corticosteroids; cholestyramine, cholestypol, Depo Provera®; smoking cessation agents; use of opioid or opioid-like medications, including analgesics and antitussives;
* History of surgical or device (e.g., gastric banding) intervention for obesity;
* History of seizures of any etiology, or of predisposition to seizures (e.g., history of cerebrovascular accident, head trauma with ≥5 minutes loss of consciousness, concussion symptoms lasting ≥15 minutes, brain surgery, skull fracture, subdural hematoma, or febrile seizures);
* History of treatment with bupropion or naltrexone within the preceding 12 months;
* History of hypersensitivity or intolerance to bupropion or naltrexone;
* Initiation or discontinuation of tobacco products including inhaled tobacco (such as cigarettes, cigars, pipes, etc), chewing tobacco or snuff in the 3 months prior to randomization or planned during study participation. Use of nicotine replacement products (nicotine gum, patch) during study participation was not allowed;
* Use of drugs, herbs, or dietary supplements believed to significantly affect body weight or participation in a weight loss management program within one month prior to randomization;
* Loss or gain of more than 4.0 kilograms within 3 months prior to randomization;
* Pregnant or breast-feeding women or planning to become pregnant during the study period or within 30 days of discontinuing study drug;
* Planned surgical procedure that can impact the conduct of the study;
* Use of investigational drug, device or procedure within the previous 30 days;
* Participation in any previous clinical trial sponsored by Orexigen Therapeutics;
* Any condition which in the opinion of the investigator makes the subject unsuitable for inclusion in the study;
* Investigators, study personnel, sponsor representatives and their immediate families.
D: Inclusion Criteria:

1. ≥50 years of age (women) or ≥45 years of age (men)
2. Body mass index (BMI) ≥27 kg/m2 and ≤50 kg/m2
3. Waist circumference ≥88 cm (women) or ≥102 cm (men)
4. At increased risk of adverse cardiovascular outcomes:

   * Cardiovascular disease (confirmed diagnosis or at high likelihood of cardiovascular disease) with at least one of the following:

     * History of documented myocardial infarction \>3 months prior to screening
     * History of coronary revascularization
     * History of carotid or peripheral revascularization
     * Angina with ischemic changes (resting ECG), ECG changes on a graded exercise test (GXT), or positive cardiac imaging study
     * Ankle brachial index \<0.9 (by simple palpation) within prior 2 years
     * ≥50% stenosis of a coronary, carotid, or lower extremity artery within prior 2 years

AND/OR

* Type 2 diabetes mellitus with at least 2 of the following:

  * Hypertension (controlled with or without pharmacotherapy at \<145/95 mm Hg)
  * Dyslipidemia requiring pharmacotherapy
  * Documented low HDL cholesterol (\<50 mg/dL in women or \<40 mg/dL in men) within prior 12 months
  * Current tobacco smoker

Exclusion Criteria:

1. Myocardial infarction within 3 months prior to screening
2. Angina pectoris Grade III or IV as per the Canadian Cardiovascular Society grading scheme
3. Clinical history of cerebrovascular disease (stroke)
4. History of tachyarrhythmia other than sinus tachycardia
5. Planned bariatric surgery, cardiac surgery, or coronary angioplasty
6. History of seizures (including febrile seizures), cranial trauma, or other conditions that predispose the subject to seizures
7. History of mania or current diagnosis of active psychosis, active bulimia or anorexia nervosa (binge eating disorder is not exclusionary)
8. Any condition with life expectancy anticipated to be less than 4 years (e.g., congestive heart failure NYHA Class 3 or 4)

Answer: B