Study to Evaluate the Efficacy, Safety and Tolerability of N1539

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

Official Title
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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

Conditions
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Hysterectomy

Intervention / Treatment
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* Drug: N1539
* Drug: N1539
* Drug: N1539
* Drug: N1539
* Drug: placebo
* Drug: Morphine
* Drug: N1539


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: N1539 5 mg<br> | Drug: N1539<br>* 5 mg IV once per day<br>|
| Experimental: N1539 7.5 mg<br> | Drug: N1539<br>* 7.5 mg IV once per day<br>|
| Experimental: N1539 15 mg<br> | Drug: N1539<br>* 15 mg IV once per day<br>|
| Experimental: N1539 30 mg<br> | Drug: N1539<br>* 30 mg IV once per day<br>|
| Experimental: N1539 60 mg<br> | Drug: N1539<br>* 60 mg IV once per day<br>|
| Placebo Comparator: Placebo<br> | Drug: placebo<br>* IV placebo once per day<br>|
| Active Comparator: morphine<br> | Drug: Morphine<br>* morphine 10-15 mg IV once per day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the analgesic efficacy, duration of effect and safety of single doses of IV N1539 as measured by the SPID (summary of pain intensity) and TOPAR (summary of the time-weighted pain relief scores) from 0-24 hours. | Additionally, to determine the efficacy seen within the first hour after study drug administration, as measured by the SPID 0-60 minutes post-dose. | at 60 minutes post dose and at 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the safety and tolerability of IV N1539 by laboratory data, vital signs, wound site evaluation and Adverse Events |  | 5-7 days post initial dosing |