Clinical trial NCT01351090: Study of the Safety, Tolerability and Analgesic Efficacy of Multiple Doses of Ketorolac Tromethamine (IN) for Postoperative Pain
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Postoperative Pain
Lead sponsor: American Regent, Inc.
Sponsor class: INDUSTRY
First posted: 2011-05-10
Enrollment: 127
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 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.


Eligibility criteria: 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

Primary outcomes:
measure: Total Morphine Sulfate (MS) Use in Milligrams by Patient-controlled Analgesia (PCA) Through 24 Hours
timeFrame: 8-hour intervals from the start of dosing through 24 hours
Secondary outcomes:
measure: Total MS Use in Milligrams by PCA From the Start of Dosing Through 48 Hours
timeFrame: 8-hour intervals from the start of dosing through 48 hours
measure: Total MS Use in Milligrams by PCA From 24 Hours After the Start of Dosing Through 48 Hours
timeFrame: 8-hour intervals from 24 hours after the start of dosing through 48 hours
measure: Pain Intensity Difference (PID) Scores
timeFrame: 6 hours after study drug administration
Other outcomes:
Locations:
city: Hamilton
country: New Zealand
facility: Waikato Clinical Research
Study officials:
affiliation: ICON Development Solutions
name: Lincoln Bynum, MD
role: STUDY_CHAIR
References: