Safety and Efficacy of Multiple Doses of Ketorolac Tromethamine Administered Intranasally for Postoperative Pain - Full Text View

Purpose

This was a randomized, double-blind, placebo-controlled study in subjects who underwent major surgery. Each subject's study participation consisted of a screening visit and a treatment period of up to 5 days. Following surgery (Day 0), subjects were randomly assigned to receive intranasal ketorolac 30 mg or intranasal placebo when the pain intensity (PI) rating equaled at least 40 mm on a 100-mm visual analog scale (VAS). Subjects received study drug every 8 hours for 48 hours and then 3 times daily for up to 5 calendar days in total; the frequency of dosing could be reduced after 48 hours. Starting at the time of the first dose of study drug and continuing for the first 48 hours after surgery, the subjects had access to morphine sulfate (MS) administered via patient controlled analgesia (PCA). After PCA was no longer required, backup pain relief was provided by another standard nonsteroidal anti-inflammatory drug (non-NSAID) analgesic regimen. If the subjects were discharged before postoperative Day 4, they could self-medicate at home through postoperative Day 4. A safety follow-up evaluation was conducted by telephone approximately 14 days after the end of dosing in a subset of subjects (n = 60).

The primary objective was to evaluate the analgesic efficacy of multiple intranasal doses of ketorolac administered for up to 5 days. The secondary objective was to evaluate the safety and tolerability of this dosing regimen.

Condition	Intervention	Phase
Postoperative Pain	Drug: Ketorolac tromethamine Drug: Placebo	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
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

Resource links provided by NLM:

Drug Information available for: Tromethamine Ketorolac Ketorolac tromethamine

U.S. FDA Resources

Further study details as provided by Luitpold Pharmaceuticals:

Primary Outcome Measures:

The Summed Pain Intensity Difference (SPID) on Day 1 [ Time Frame: 6 hours after drug administration ] [ Designated as safety issue: No ]
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.

Secondary Outcome Measures:

Morphine sulfate consumption at 24 hours and 48 hours [ Time Frame: 24 hours and 48 hours after drug administration ] [ Designated as safety issue: No ]
Hourly Pain Intensity Difference (PID) scores. [ Time Frame: Hourly ] [ Designated as safety issue: No ]
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 during the first 8 hours following the first dose of study medication on Day 1. 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.
Quality of analgesia [ Time Frame: First dose of study medication on Day 1 to the first dose of MS by PCA ] [ Designated as safety issue: No ]
Quality of analgesia was assessed on a 5-point categorical scale with 0 = poor, 1 = fair, 2 = good, 3 = very good, and 4 = excellent.
Global assessment of pain control [ Time Frame: 8 hours following first dose of study medication ] [ Designated as safety issue: No ]
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.
Onset and duration of pain relief [ Time Frame: 8 hours following first dose of study medication ] [ Designated as safety issue: No ]
The onset of pain relief was defined as the time when the stopwatch was stopped to indicate "meaningful" pain relief. Peak PID was calculated. Duration of analgesia was defined as the time from the first dose of study medication on Day 1 to the first dose of MS by PCA.

Enrollment:	300
Study Start Date:	June 2003
Study Completion Date:	June 2007
Primary Completion Date:	June 2005 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Ketorolac tromethamine	Drug: Ketorolac tromethamine 30 mg intranasal post-surgery for up to 5 days total
Placebo Comparator: Placebo	Drug: Placebo Intranasal post-surgery for up to 5 days total

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Men or women, age 18 years or older.
Body weight > or = to 100 pounds and < or = to 300 pounds.
Women of childbearing potential must have a negative serum pregnancy test result.
Able to provide written informed consent.
At least moderate pain as determined by a PI score of > or = to 40 mm on a 100-mm VAS.
Expected to remain in the hospital for at least 48 hours with the possibility of remaining for 5 days.
Willing and able to comply with all testing and requirements defined in the protocol.
Willing and able to complete the post-treatment visit.

Exclusion Criteria:

Allergy or sensitivity to ketorolac or EDTA.
Allergic reaction to aspirin or other 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 intranasal (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) history of peptic ulcer disease or gastrointestinal bleeding considered by the investigator to be clinically significant.
Advanced renal impairment (serum creatinine > 1.5 mg/dL) 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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01347853

Locations

New Zealand
Waikato Clinical Research
Hamilton, New Zealand

Sponsors and Collaborators

Luitpold Pharmaceuticals

More Information

No publications provided

Responsible Party:	David Bregman, M.D., Ph.D., Luitpold Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT01347853 History of Changes
Other Study ID Numbers:	ROX 2003-01
Study First Received:	May 3, 2011
Last Updated:	May 3, 2011
Health Authority:	United States: Food and Drug Administration New Zealand: Medicines and Medical Devices Safety Authority

Additional relevant MeSH terms:

Pain, Postoperative
Postoperative Complications
Pathologic Processes
Pain
Signs and Symptoms
Ketorolac Tromethamine
Ketorolac
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on June 18, 2013