Inclusion Criteria:

• Obese or overweight at screening defined as: BMI greater than or equal to 30 kg/m2 and <50 kg/m2 OR BMI greater than or equal to 27 kg/m2 and <50 kg/m2 in the presence of controlled hypertension and/or treated or untreated dyslipidemia. For subjects receiving antihypertensive and/or hypolipidemic medications, these should have been at a stable dosage for at least 2 months before the start of the run-in period. Controlled hypertension is defined as a diastolic blood pressure <100 mmHg and a systolic blood pressure <160 mmHg, in the presence of antihypertensive drug treatment.For subjects who are not on lipid-lowering drugs, dyslipidemia is defined as LDL-C greater than or equal to 3.4 mmol/L (130 mg/dL), HDL C <1 mmol/L (40 mg/dL) for men or <1.3 mmol/L (50 mg/dL) for women, or triglycerides greater than or equal to 1.7 mmol/L (150 mg/dL)
• A stable weight, i.e., increasing or decreasing not more than 5 kg in the 3 months before the start of the run-in period
• Consumption of breakfast and dinner on a daily basis
• Ability to swallow the intact capsule (17.5 mm in length and 9.1 mm in diameter) with water, as judged by e.g., the subject's history of having no difficulty with swallowing e.g., capsules or intact tablets
• Fasting plasma glucose <7.0 mmol/L (126 mg/dL) at screening
• Women must be postmenopausal or surgically incapable of childbearing or if sexually active, be practicing an effective method of birth control

Exclusion Criteria:

• History of obesity with a known cause (e.g., Cushing's disease)
• History of anorexia nervosa, bulimia, or binge-eating disorder
• An established diagnosis of diabetes mellitus or treatment with glucose lowering prescription drugs at screening
• Prior exposure or known contraindication or hypersensitivity to R256918
• History of weight-reducing diet or receiving any drugs to treat obesity within the 3 months prior to screening
• Treatment with any investigational drug or device within 1 month before the start of the run-in period
• History or evidence of liver or renal impairment
• History of HIV or presence of hepatitis C antibodies or positive hepatitis B serology
• History of clinically significant gastro-intestinal disease
• History of major gastro-intestinal surgery other than appendectomy or uncomplicated cholecystectomy
• Previous gastric restrictive surgery or other surgical procedures to induce weight loss
• Liposuction within the last 3 months before screening
• Pregnant or nursing women, or women who plan to become pregnant during the study
• History of significant cardiovascular disease or hypertension
• Elevated levels of thyroid-stimulating hormone (TSH)
• A significant change in smoking habits within 3 months of the start of the run-in period
• Malignancy or a history of a malignancy within 5 years before the start of the run-in period, other than basal cell carcinomas of the skin or in situ cervical carcinoma
• History of seizures or significant central nervous system-related disorders
• History of significant psychiatric disorder, including, schizophrenia, or psychosis