Clinical trial NCT01347853: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Postoperative Pain
Lead sponsor: Egalet Ltd
Sponsor class: INDUSTRY
First posted: 2011-05-04
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: The Summed Pain Intensity Difference (SPID) on Day 1
timeFrame: 6 hours after drug administration
Secondary outcomes:
measure: Morphine sulfate consumption at 24 hours and 48 hours
timeFrame: 24 hours and 48 hours after drug administration
measure: Hourly Pain Intensity Difference (PID) scores.
timeFrame: Hourly following the first dose of study medication up to 8 hours
measure: Quality of analgesia
timeFrame: First dose of study medication on Day 1 to the first dose of MS by PCA
measure: Global assessment of pain control
timeFrame: 8 hours following first dose of study medication
measure: Onset and duration of pain relief
timeFrame: 8 hours following first dose of study medication
Other outcomes:
Locations:
city: Hamilton
country: New Zealand
facility: Waikato Clinical Research
Study officials:
References: