Postoperative Pain
Conditions
Brief summary
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.
Interventions
DRUGKetorolac tromethamine
10 mg Intranasal (2 x 100 uL of a 5% solution)
DRUGPlacebo
Intranasal
Sponsors
American Regent, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | 6 hours after study drug administration | 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. |
Countries
New Zealand
Participant flow
Recruitment details
Recruitment period - October 2001 through August 2002 Locations - Hospitals
Pre-assignment details
Subjects must have been requesting pain medication and have at lease moderate pain defined as a score of at least 40 mm on a 100-mm VAS.
Participants by arm
| Arm | Count |
|---|---|
| Ketorolac IN 10 mg 10 mg Intranasal (2 x 100 uL of a 5% solution) | 43 |
| Ketorolac IN 30 mg 30 mg Intranasal (2 x 100 uL of a 15% solution) | 42 |
| Placebo Vehicle IN Intranasal placebo | 42 |
| Total | 127 |
Baseline characteristics
| Characteristic | Ketorolac IN 30 mg | Placebo Vehicle IN | Ketorolac IN 10 mg | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 13 Participants | 17 Participants | 6 Participants | 36 Participants |
| Age, Categorical Between 18 and 65 years | 29 Participants | 25 Participants | 37 Participants | 91 Participants |
| Age Continuous | 52.8 years STANDARD_DEVIATION 2.5 | 56.7 years STANDARD_DEVIATION 2.5 | 49.7 years STANDARD_DEVIATION 2.1 | 53.0 years STANDARD_DEVIATION 1.4 |
| Region of Enrollment New Zealand | 42 participants | 42 participants | 43 participants | 127 participants |
| Sex: Female, Male Female | 29 Participants | 24 Participants | 32 Participants | 85 Participants |
| Sex: Female, Male Male | 13 Participants | 18 Participants | 11 Participants | 42 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 43 / 43 | 39 / 42 | 41 / 42 |
| serious Total, serious adverse events | 3 / 43 | 5 / 42 | 1 / 42 |
Outcome results
Primary
Total Morphine Sulfate (MS) Use in Milligrams by Patient-controlled Analgesia (PCA) Through 24 Hours
Time frame: 8-hour intervals from the start of dosing through 24 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ketorolac IN 10 mg | Total Morphine Sulfate (MS) Use in Milligrams by Patient-controlled Analgesia (PCA) Through 24 Hours | 54.32 mg | Standard Deviation 6.36 |
| Ketorolac IN 30 mg | Total Morphine Sulfate (MS) Use in Milligrams by Patient-controlled Analgesia (PCA) Through 24 Hours | 37.77 mg | Standard Deviation 4.98 |
| Placebo Vehicle IN | Total Morphine Sulfate (MS) Use in Milligrams by Patient-controlled Analgesia (PCA) Through 24 Hours | 56.45 mg | Standard Deviation 4.82 |
Secondary
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.
Time frame: 6 hours after study drug administration
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ketorolac IN 10 mg | Pain Intensity Difference (PID) Scores | 34.1 units on a scale | Standard Deviation 2.7 |
| Ketorolac IN 30 mg | Pain Intensity Difference (PID) Scores | 38.9 units on a scale | Standard Deviation 2.1 |
| Placebo Vehicle IN | Pain Intensity Difference (PID) Scores | 29.1 units on a scale | Standard Deviation 2.3 |
Secondary
Total MS Use in Milligrams by PCA From 24 Hours After the Start of Dosing Through 48 Hours
Time frame: 8-hour intervals from 24 hours after the start of dosing through 48 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ketorolac IN 10 mg | Total MS Use in Milligrams by PCA From 24 Hours After the Start of Dosing Through 48 Hours | 28.25 mg | Standard Deviation 5.67 |
| Ketorolac IN 30 mg | Total MS Use in Milligrams by PCA From 24 Hours After the Start of Dosing Through 48 Hours | 23.11 mg | Standard Deviation 5.31 |
| Placebo Vehicle IN | Total MS Use in Milligrams by PCA From 24 Hours After the Start of Dosing Through 48 Hours | 32.61 mg | Standard Deviation 4.77 |
Secondary
Total MS Use in Milligrams by PCA From the Start of Dosing Through 48 Hours
Time frame: 8-hour intervals from the start of dosing through 48 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ketorolac IN 10 mg | Total MS Use in Milligrams by PCA From the Start of Dosing Through 48 Hours | 78.66 mg | Standard Deviation 11.2 |
| Ketorolac IN 30 mg | Total MS Use in Milligrams by PCA From the Start of Dosing Through 48 Hours | 61.39 mg | Standard Deviation 10.79 |
| Placebo Vehicle IN | Total MS Use in Milligrams by PCA From the Start of Dosing Through 48 Hours | 87.87 mg | Standard Deviation 9.36 |