The purpose of this study is to evaluate the effects of RM-493 on mean percent body weight loss, and other weight loss parameters as well as Pharmacokinetic (PK) profile, and ambulatory blood pressure in obese participants. The study is designed to evaluate the efficacy and tolerability of a single dose of RM-493. The study drug (RM-493 and placebo) will be administered subcutaneously in a blinded fashion.

Inclusion Criteria:

1. Be between the age of 18 and 65.
2. Able to provide voluntary, written informed consent with comprehension of all aspects of the protocol, prior to any study procedures.
3. In good general health, without significant medical history, physical examination findings, or clinical laboratory abnormalities.
4. Body Mass Index: 35-50 Kg/m^2, inclusive. It is planned that approximately 20 (but no more than 50% of the total participants enrolled) of these participants will have a BMI ≥ 40 Kg/m^2
5. Stable body weight (+/- 5 Kg) during previous 6 months.
6. Blood pressure (<150/95 mmHg); may include stable dose (≥ 30 days of use) of up to two anti-hypertensive medications to achieve control that are intended to remain on a stable dose during the protocol.
7. Willingness and demonstrates ability to self-administer study medication subcutaneously via an infusion pump during the placebo practice period.
8. Willing to maintain a healthy diet and exercise regime throughout study as recommended by counseling at study start.
9. Females of childbearing potential must agree to be abstinent or else use any two of the following medically acceptable forms of contraception from the Screening Period through the completion of study treatment: hormonal, condom with spermicidal jelly, diaphragm or cervical cap with spermicidal jelly, or intrauterine device (IUD). Hormonal contraception must have started at least 3 months prior to screening. A female whose male partner has had a vasectomy must agree to use one additional form of medically acceptable contraception. Participants must agree to practice the above birth control methods for 30 days after completion of study treatment as a safety precaution.
10. Females of non-childbearing potential, defined as surgically sterile (status post hysterectomy, bilateral oophorectomy, or bilateral tubal ligation) or post-menopausal for at least 12 months (and confirmed with a screening follicle stimulating hormone (FSH) level in the post-menopausal range), do not require contraception during the study.
11. Males with female partners of childbearing potential must agree to use two medically acceptable forms of contraception as described above, with one of the two forms being condom with spermicide, from the Screening Period through 90 days after completion of study treatment. Males with female partners of childbearing potential who themselves are surgically sterile (status post vasectomy) must agree to use condoms with spermicide over the same period of time.

Exclusion Criteria:

1. Fasting blood glucose > than 140 mg/dL.

2. Haemoglobin A1c (HbA1c) ≥6.5%.

3. Thyroid stimulating hormone (TSH) level outside the normal range.

4. Creatinine > 1.5 times the upper limit of normal.

5. Liver function tests > 2 times the upper limit of normal.

6. Active or history of any significant medical condition including renal, hepatic, pulmonary, gastrointestinal, cardiovascular, genitourinary, endocrine, immunologic, metabolic, neurologic or hematological disease.

7. Participants with a history of the following:

   1. Uncontrolled hypertension;
   2. Diabetes requiring medical treatment, presently or in the past;
   3. Major depressive disorder within the last 2 years;
   4. Any lifetime history of a suicide attempt;
   5. Any suicidal behavior in the last month;
   6. Other severe psychiatric disorders (e.g. schizophrenia, bipolar disorder, severe eating disorders including bulimia).

8. A patient health questionnaire - 9 (PHQ-9) score of ≥15.

9. Any suicidal ideation of type 4 or 5 on the columbia suicide severity rating scale (C-SSRS).

10. Prior bariatric surgery.

11. Treated with anorectic agents or drugs with anorexia as a frequent side event.

12. Taking 3 or more anti-hypertensive medications.

13. Acute illness or history of illness, which in the opinion of the Investigator, could pose a threat or harm to the participant or obscure interpretation of laboratory test results or interpretation of study data.

14. History of human immunodeficiency virus (HIV) infection.

15. History of significant drug hypersensitivity or anaphylaxis.

16. History of hypersensitivity to proteins (e.g., allergy shots).

17. Any clinically significant abnormalities on screening laboratories as determined by the Investigator.

18. Abnormal 12-lead electrocardiogram (ECG) at screening or pre-dose (Day 1), except minor deviations deemed to be of no clinical significance by the Investigator. QTc must be < 450 ms.

19. Received any experimental drugs or devices or have participated in a clinical study within 30 days prior to dosing.

20. Hospitalization for surgery within the 3 months prior to screening except for minor outpatient procedures, or any planned hospitalizations during the study period.

21. Poor venous access or inability to tolerate venipuncture.

22. Inability to attend all study visits or comply with protocol requirements including fasting and restrictions on concomitant medication intake.

23. Participation in weight loss programs during the study period, including nutritional supplements/ replacements other than as recommended by nutritional counseling provided at study start.

24. Use of prescription medications on a regular basis with the following exceptions:

    1. Contraceptives (must be on for ≥3 months);
    2. Hormone replacement therapy (must be on stable dose for ≥3 months);
    3. Antihypertensives (<3 medications on a stable dose for ≥ 30 days);
    4. Statins (dose must be ≤ half the maximum dose; must be on a stable dose ≥3 months);
    5. Fibrates (must be on stable dose for ≥3 months);
    6. Niacin (must be on stable dose for ≥3 months);
    7. Thyroxin (stable dose for ≥ 30 days);
    8. The last use of any other prescription medication must have been greater than 5 half-lives for the specific medication or at least 14 days prior to randomization, whichever is longer.

25. Women who are pregnant or are breast feeding.

26. Previously randomized and dosed in this study or previously exposed to RM-493.

27. History of alcohol or drug abuse within 5 years of Screening Visit.

28. Any other reason, which in the opinion of the Investigator would confound proper evaluation of the study.

The Full Analysis Set (FAS) consisted of all randomized participants with both a baseline and at least one post-dose efficacy observation (for at least one efficacy endpoint).

From first dose of study drug (Day 1) until end of study (Up to 184 days)

Safety Population