Study to Evaluate the Efficacy, Safety and Tolerability of N1539

A Randomized Double-Blind, Placebo- and Active-Controlled, Dose-Ranging Study to Evaluate the Analgesic, Efficacy, Safety and Tolerability of Intravenous N1539 in Subjects After Open Abdominal Hysterectomy

To determine the analgesic efficacy, duration of effect, and safety of single doses of N1539 in subjects undergoing open abdominal hysterectomy

Inclusion Criteria:

• moderate to severe pain with VAS of >/= 45 mm
• undergo open abdominal hysterectomy
• ASA I or II
• signed ICF
• BMI >18.5 and < 31.5 kg/m^2

Exclusion Criteria:

• suspected metastatic cervical or endometrial cancer
• prior abdominal surgery with postoperative complications
• active pancreatitis, obstruction of biliary tree or total bilirubin> 2.5 mg/dL
• active GI bleeding, or peptic ulcer disease
• unstable medical condition
• HbA1c >9.5 or uncontrolled diabetes
• SBP >150 mmHg or DBP > 95 mmHg
• personal or familial contraindication to undergoing general anesthesia
• Antihypertensive agents or diabetic regimen that is not stable (4 weeks prior to surgery)
• taking CNS agents for pain
• acetaminophen or NSAIDs not discontinued for at least 5 half-lives prior to planned surgery
• currently taking an opioid or has taken an opioid chronically for pain in past 2 years
• corticosteroid or systemic corticosteroids within 6 weeks of planned surgery
• has a known bleeding disorder or taking agents affecting coagulation
• history of intolerance or allergic reactions to NSAIDs, COX-2 inhibitors, aspirin and other salicylates
• receiving lithium or a combination of furosemide with an ACE inhibitor or angiotensin receptor blocker
• Known to have sleep apnea
• History of hepatitis B or C
• AST or ALT > 2 times the upper limit of normal
• Known or suspected COPD with retention of carbon dioxide
• psychiatric condition that impairs the capability of the subject to report pain