Study of the Safety, Tolerability and Analgesic Efficacy of Multiple Doses of Ketorolac Tromethamine (IN) for Postoperative Pain

A Phase 2, Double-blind, Randomized Study of the Safety, Tolerability and Analgesic Efficacy of Multiple Doses of Ketorolac Tromethamine Administered Intranasally for Postoperative Pain

This was a randomized, double blind, placebo-controlled study in subjects who have undergone major surgery. Each subject's study participation consisted of a screening visit, a 2-day treatment period, and a follow-up visit. Following surgery, subjects were randomly assigned to receive intranasally (IN) ketorolac 10 mg, IN ketorolac 30 mg, or placebo when the pain intensity (PI) rating equaled at least 40 on a 100-mm visual analog scale (VAS). Thereafter, subjects received study drug every 8 hours, with the last dose given at 40 hours. For pain not relieved by the study drug, the subjects had access to morphine sulfate (MS) administered via patient controlled analgesia (PCA).

The primary objective was to evaluate the analgesic efficacy of multiple intranasal (IN) doses of ketorolac over 2 days. The secondary objective was to evaluate the safety and tolerability of this dosing regimen.

Study Overview

• Status: Completed
• Conditions: Postoperative Pain
• Intervention / Treatment: Drug: Placebo; Drug: Ketorolac tromethamine; Drug: Ketorolac tromethamine

• Study Type: Interventional
• Enrollment (Actual): 127
• Phase: Phase 2

Contacts and Locations

Study Locations

• New Zealand
  • Hamilton, New Zealand
    • Waikato Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Men or women, age 18 years or older
• Body weight > or = 100 pounds (45.4 kg) and < or = 300 pounds (136.1 kg)
• Women of childbearing potential must have had a negative serum pregnancy test result prior to entry into the study
• Able to provide written informed consent
• At least moderate pain as determined by a PI score of > or = 40 mm on a 100-mm VAS
• Expected to remain in the hospital for at least 48 hours
• Willing and able to comply with all testing and requirements defined in the protocol
• Willing and able to complete the posttreatment visit

Exclusion Criteria:

• Allergy or sensitivity to ketorolac or ethylene diamine tetraacetic acid (EDTA)
• 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 the absorption of the nasal spray or with the assessment of adverse events
• Use of any IN product within 24 hours prior to study entry
• Clinically significant abnormality on screening laboratory tests
• History of cocaine use resulting in nasal mucosal damage
• Active peptic ulcer disease, recent (defined as within 6 months) gastrointestinal bleeding or perforation, or a history of peptic ulcer disease or gastrointestinal bleeding
• Advanced renal impairment or a risk for renal failure due to volume depletion
• A history of any other clinically significant medical problem, which in the opinion of the investigator would interfere with study participation
• Participation within 30 days of study entry or within 5 times the half-life, whichever is longer, in another investigational drug study
• Allergy or significant reaction to opioids
• Pregnancy or breastfeeding
• Previous participation in this study

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Intranasal
Experimental: Ketorolac tromethamine (5%)	Drug: Ketorolac tromethamine; 10 mg Intranasal (2 x 100 uL of a 5% solution); Drug: Ketorolac tromethamine; 30 mg Intranasal (2 x 100 uL of a 15% solution)
Experimental: Ketorolac tromethamine (15%)	Drug: Ketorolac tromethamine; 10 mg Intranasal (2 x 100 uL of a 5% solution); Drug: Ketorolac tromethamine; 30 mg Intranasal (2 x 100 uL of a 15% solution)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Total Morphine Sulfate (MS) Use in Milligrams by Patient-controlled Analgesia (PCA) Through 24 Hours	8-hour intervals from the start of dosing through 24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total MS Use in Milligrams by PCA From the Start of Dosing Through 48 Hours		8-hour intervals from the start of dosing through 48 hours
Total MS Use in Milligrams by PCA From 24 Hours After the Start of Dosing Through 48 Hours		8-hour intervals from 24 hours after the start of dosing through 48 hours
Pain Intensity Difference (PID) 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.	6 hours after study drug administration

Collaborators and Investigators

• Sponsor: American Regent, Inc.
• Investigators: Study Chair: Lincoln Bynum, MD, ICON Development Solutions

Study record dates

Study Major Dates

• Study Completion (Actual): October 1, 2007

Study Registration Dates

• First Submitted: May 9, 2011
• First Submitted That Met QC Criteria: May 9, 2011
• First Posted (Estimate): May 10, 2011

Study Record Updates

• Last Update Posted (Estimate): October 18, 2012
• Last Update Submitted That Met QC Criteria: September 14, 2012
• Last Verified: September 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Ketorolac; Ketorolac Tromethamine
• Other Study ID Numbers: ROX 2001-03