BNP Pharmacodynamics and Effects on Metabolism in Lean and Obese Subjects

Obesity is major metabolic health concern and the potential beneficial effects of natriuretic
peptides, specifically B-type natriuretic peptide (BNP) on adipocyte biology, energy
expenditure and body weight could be of great significance. This study will provide insight
into the mechanisms of dysregulation of the natriuretic peptides system in obesity and will
contribute to delineate the roles and the clinical importance of BNP in the treatment of
obesity.

Inclusion Criteria:

- Age 18-65 years, inclusive

- Men and women

- Able to provide written, informed consent

- Weight stable (± 3 kg) during the 3 months prior to enrollment

- BMI ≤ 25 kg/m2 for lean subjects or ≥ 30 kg/m2 for obese subjects

Exclusion Criteria:

- 1) Diagnosed with any of the following co-morbidities: a) coronary artery disease,
angina or heart failure, b) diabetes, c) bleeding disorders, d) infections, e)
hepatitis and/or cirrhosis, f) severe asthma or Chronic obstructive pulmonary disease
(COPD), g) renal insufficiency, h) bariatric surgery, i) inflammatory bowel disease or
malabsorption, j) cancer within the last 3 years (except non-melanoma skin cancer or
treated cervical carcinoma in situ), k) psychiatric or eating disorders, l) untreated
or inadequately controlled thyroid or other endocrine disorders, m) active rheumatoid
arthritis or other inflammatory rheumatic disorder

- Pregnant or nursing women

- Presence of clinically significant abnormalities on electrocardiogram;

- Smoking

- Known hypersensitivity to nesiritide or any of its excipients

- Poor intravenous access

- Use of medications: a) nitrates, b) beta-blockers, c) digoxin, d) anti-diabetic
agents, e) oral, injected or chronic topical steroids (inhaled steroids for mild
asthma are acceptable), f) chronic use of aspirin or other non-steroidal
anti-inflammatory drugs, including COX-2 inhibitors, g) other drugs known to affect
immune or metabolic function and h) orlistat, phentermine or other weight loss or
anorectic agents.

- Your blood pressure at your screening visit is less than or equal to 100/60 or greater
than or equal to 160/100.