Back to resultsSafety and Efficacy of Multiple Doses of Ketorolac Tromethamine Administered Intranasally for Postoperative Pain
Primary Purpose
Postoperative Pain
Status
Completed
Phase
Phase 3
Locations
New Zealand
Study Type
Interventional
Intervention
Ketorolac tromethamine
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Postoperative Pain
Eligibility 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.
Sites / Locations
- Waikato Clinical Research
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Ketorolac tromethamine
Placebo
Arm Description
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Morphine sulfate consumption at 24 hours and 48 hours
Hourly 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. 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
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
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
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01347853
Brief Title
Safety and Efficacy of Multiple Doses of Ketorolac Tromethamine Administered Intranasally for Postoperative Pain
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
Study Type
Interventional
2. Study Status
Record Verification Date
February 2017
Overall Recruitment Status
Completed
Study Start Date
June 2003 (undefined)
Primary Completion Date
June 2005 (Actual)
Study Completion Date
June 2007 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Egalet Ltd
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Postoperative Pain
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
300 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Ketorolac tromethamine
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Ketorolac tromethamine
Intervention Description
30 mg intranasal post-surgery for up to 5 days total
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Intranasal post-surgery for up to 5 days total
Primary Outcome Measure Information:
Title
The Summed Pain Intensity Difference (SPID) on Day 1
Description
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.
Time Frame
6 hours after drug administration
Secondary Outcome Measure Information:
Title
Morphine sulfate consumption at 24 hours and 48 hours
Time Frame
24 hours and 48 hours after drug administration
Title
Hourly Pain Intensity Difference (PID) scores.
Description
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.
Time Frame
Hourly following the first dose of study medication up to 8 hours
Title
Quality of analgesia
Description
Quality of analgesia was assessed on a 5-point categorical scale with 0 = poor, 1 = fair, 2 = good, 3 = very good, and 4 = excellent.
Time Frame
First dose of study medication on Day 1 to the first dose of MS by PCA
Title
Global assessment of pain control
Description
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.
Time Frame
8 hours following first dose of study medication
Title
Onset and duration of pain relief
Description
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.
Time Frame
8 hours following first dose of study medication
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Facility Information:
Facility Name
Waikato Clinical Research
City
Hamilton
Country
New Zealand
12. IPD Sharing Statement
Learn more about this trial
Safety and Efficacy of Multiple Doses of Ketorolac Tromethamine Administered Intranasally for Postoperative Pain
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