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

Study Overview

• Status: Completed
• Conditions: Hysterectomy
• Intervention / Treatment: Drug: N1539; Drug: N1539; Drug: N1539; Drug: N1539; Drug: N1539; Drug: placebo; Drug: Morphine

• Study Type: Interventional
• Enrollment (Actual): 486
• Phase: Phase 2

Contacts and Locations

Study Locations

• Georgia
  • Tbilisi, Georgia, 0159
  • Tbilisi, Georgia, 0186
  • Tblisi, Georgia, 0186
• Poland
  • Bialystok, Poland, 15-276
  • Gdansk, Poland, 80-402
  • Lodz, Poland, 94-029
  • Lublin, Poland, 20-081
  • Poznan, Poland, 60-535
  • Ruda Slaska, Poland, 41-703
  • Szczecin, Poland, 70-111
• Serbia
  • Belgrade, Serbia, 11000
  • Kragujevac, Serbia, 34000
  • Novi Sad, Serbia, 21000

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

7

Arms and Interventions

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

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: Alkermes, Inc.

Publications and helpful links

General Publications

• Viscusi ER, Gan TJ, Bergese S, Singla N, Mack RJ, McCallum SW, Du W, Hobson S. Intravenous meloxicam for the treatment of moderate to severe acute pain: a pooled analysis of safety and opioid-reducing effects. Reg Anesth Pain Med. 2019 Mar;44(3):360-368. doi: 10.1136/rapm-2018-100184. Epub 2019 Feb 7.
• Rechberger T, Mack RJ, McCallum SW, Du W, Freyer A. Analgesic Efficacy and Safety of Intravenous Meloxicam in Subjects With Moderate-to-Severe Pain After Open Abdominal Hysterectomy: A Phase 2 Randomized Clinical Trial. Anesth Analg. 2019 Jun;128(6):1309-1318. doi: 10.1213/ANE.0000000000003920.

Study record dates

Study Major Dates

• Study Start: March 1, 2010
• Primary Completion (Actual): January 1, 2011
• Study Completion (Actual): January 1, 2011

Study Registration Dates

• First Submitted: March 5, 2010
• First Submitted That Met QC Criteria: March 9, 2010
• First Posted (Estimate): March 10, 2010

Study Record Updates

• Last Update Posted (Estimate): December 2, 2011
• Last Update Submitted That Met QC Criteria: November 28, 2011
• Last Verified: November 1, 2011

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Morphine
• Other Study ID Numbers: N1539-04