Safety and Efficacy of Multiple Doses of Intranasal Ketorolac in Postoperative Pain Following Major Abdominal Surgery

Postoperative Pain Clinical Trial

Official title:

A Phase 3, Double-Blind, Randomized Study of the Safety, Tolerability, and Analgesic Efficacy of Multiple Doses of Ketorolac Tromethamine Administered Intranasally for Postoperative Pain Following Major Abdominal Surgery

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00266786
• Other study ID #: ROX 2005-01
• Status: Completed
• Phase: Phase 3
• First received: December 16, 2005
• Last updated: February 6, 2017
• Start date: December 2005

Study information

• Verified date: February 2017
• Source: Egalet Ltd
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Ketorolac has been marketed for several years in other forms (tablet and injectable) for the short-term relief of pain. This study will test whether a new dosage form (nasal spray) containing ketorolac is effective at relieving the pain of major abdominal surgery, and will also assess product safety. Previous studies with the nasal spray have suggested that it is similar to the previously approved injectable form in effectiveness for pain relief and in its safety profile.

Patients will be randomized in a 2:1 ratio to receive intranasal ketorolac or placebo when the pain reaches a moderate level (40 on a scale of 100) following surgery. After the first dose, subjects will receive study drug every 6 hours for 48 hours, and then as needed (up to 4 times a day) for a total of 5 days. If pain is not adequately relieved by the study drug, subjects will be given morphine sulfate or other standard analgesics. Follow-up safety evaluations will occur about 1 and 2 weeks after the start of dosing.

Subjects will be asked to answer questions about their pain relief and any possible side effects of the drug during the study, and will be given physical examinations, including nasal evaluations, before and during the clinical trial. A small amount of blood will be drawn for routine clinical laboratory testing.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 321
• Est. primary completion date: February 2007
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 64 Years

Eligibility

Inclusion Criteria:

• Men or women age 18 through 64 years

• Major abdominal surgery

• Body weight = 100 and = 300 pounds

• Negative serum pregnancy test

• Pain intensity score at least 40 (moderate pain) on 100 mm visual analog scale

• Minimum 48 hour hospital stay and 5 day maximum stay

• Able to provide written informed consent

• Willing and able to comply with all testing requirements of the protocol

Exclusion Criteria:

• Allergy or sensitivity to ketorolac or ethylene diamine tetraacetic acid (EDTA)

• Allergy or significant reaction to opioids

• Allergic reaction to aspirin or other nonsteroidal anti-inflammatory drug (NSAIDs)

• Current upper respiratory tract infection or other respiratory tract condition that could interfere with absorption of the nasal spray or adverse event assessment

• Use of any intranasal product in past 24 hours

• Clinically significant abnormality on screening lab tests

• History of cocaine use

• Active peptic ulcer disease or significant history of peptic ulcer disease or gastrointestinal bleeding

• Advanced renal impairment or risk for renal failure

• History of other medical problems that could interfere with the study participation

• Pregnancy or breastfeeding

• Participation in another investigational study within past 30 days

Related Conditions & MeSH terms

• Pain, Postoperative
• Postoperative Pain

Intervention

Drug:
• Intranasal Ketorolac Tromethamine
Intranasal at 30mg
• Intranasal Placebo
Intranasal Placebo

Locations

Country	Name	City	State
New Zealand	Waikato Clinical Research	Hamilton
United States	Methodist Hospital	Arcadia	California
United States	Glendale Adventist Medical Center	Glendale	California
United States	Houston Perinatal Associates	Houston	Texas
United States	Memorial Hermann Healthcare System	Houston	Texas
United States	Clinical Management Services, Inc.	Pasadena	California

Sponsors (1)

Lead Sponsor	Collaborator
Egalet Ltd

Countries where clinical trial is conducted

United States,  New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The Summed Pain Intensity Difference (SPID) on Day 1	Ratings of Pain Intensity (PI) were made using a 100-mm Visual Analog Scale (VAS) on which 0 = no pain and 100 = worst pain possible. The PI values were obtained every hour following the first dose of study medication on Day 1. Pain intensity difference (PID) was calculated by subtracting the posttreatment score from the baseline score, where the baseline score was the PI rating made prior to the first dose of study medication. A summed PID (SPID) on the first postoperative day was calculated at 6 hours.	6 hours after drug administration
Secondary	Pain intensity difference scores	Ratings of Pain Intensity (PI) were made using a 100-mm Visual Analog Scale (VAS) on which 0 = no pain and 100 = worst pain possible. PID was calculated by subtracting the posttreatment score from the baseline score, where the baseline score was the PI rating made prior to the first dose of study medication.	Prior to receiving study drug and at 20, 40, and 60 minutes, and 2, 3, 4, 5, 6, 12, 18, 24, 30, 36, 42, and 48 hours after the first dose, then prior to each dose up to 72 hours
Secondary	Quality of analgesia	Quality of analgesia was assessed on a 5-point categorical scale with 0 = poor, 1 = fair, 2 = good, 3 = very good, and 4 = excellent.	Prior to receiving study drug and at 20, 40, and 60 minutes, and 2, 3, 4, 5, 6, 12, 18, 24, 30, 36, 42, and 48 hours after the first dose, then prior to each dose up to 72 hours
Secondary	Global assessment of pain control	A global evaluation of pain control was conducted once daily at bedtime using a 5-point categorical scale on which 0 = poor, 1 = fair, 2 = good, 3 = very good, and 4 = excellent.	8 hours following first dose of study medication
Secondary	Morphine sulfate consumption at 24, 48, and 72 hours		24, 48, and 72 hours after drug administration