This is a randomized, double-blind, placebo-controlled, multiple-dose, 2-period, crossover study during which 12 obese subjects will be enrolled, and randomized to one of 2 treatment sequences (melanocortin 4 receptor agonist, RM-493 then placebo;or placebo, then RM-493) over an 8-day study interval. Energy expenditure will be measured in a room calorimeter, and safety and pharmacokinetic data will also be collected. Volunteers meeting all inclusion and none of the exclusion criteria during the screening process will be admitted to the Metabolic Clinical Research Unit (MCRU) for a period of 8 days. Admission should be within 45 days of screening unless a longer period is required for a woman to reach the follicular phase of the menstrual cycle (day 1 through 7). During the 8-day study interval, volunteers will be provided a nutritionally balanced (50% carbohydrate, 30% fat, 20% protein) weight maintenance diet. After baseline evaluation, the subjects will initiate a 3-day treatment period (Period 1) with their first study treatment by continuous SC infusion. During this three day period, subjects will spend 24 hours in the metabolic chamber (from the morning of Day 4 through the morning of Day 5). After the completion of the final assessments on the morning of Day 5, subjects will enter the second 3-day treatment period (Period 2) in which identical evaluations will occur as in Period 1, with the exception that they will receive the alternative treatment. On the morning of Day 8, after completion of the final assessments of Period 2, subjects will complete the study and be discharged.

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