Safety and Efficacy of Multiple Doses of Intranasal Ketorolac in Postoperative Pain Following Major Abdominal Surgery

• Pain intensity difference scores [ Time Frame: Prior to receiving study drug and at 20, 40, and 60 minutes, and 2, 3, 4, 5, 6, 12, 18, 24, 30, 36, 42, and 48 hours after the first dose, then prior to each dose up to 72 hours ] [ 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. 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: Prior to receiving study drug and at 20, 40, and 60 minutes, and 2, 3, 4, 5, 6, 12, 18, 24, 30, 36, 42, and 48 hours after the first dose, then prior to each dose up to 72 hours ] [ 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.
• Morphine sulfate consumption at 24, 48, and 72 hours [ Time Frame: 24, 48, and 72 hours after drug administration ] [ Designated as safety issue: No ]

• Hourly pain intensity difference scores
• Quality of analgesia
• Global assessment of pain control
• Morphine sulfate consumption at 24, 48, and 72 hours

Ketorolac has been marketed for several years in other forms (tablet and injectable) for the short-term relief of pain. This study will test whether a new dosage form (nasal spray) containing ketorolac is effective at relieving the pain of major abdominal surgery, and will also assess product safety. Previous studies with the nasal spray have suggested that it is similar to the previously approved injectable form in effectiveness for pain relief and in its safety profile.

Patients will be randomized in a 2:1 ratio to receive intranasal ketorolac or placebo when their pain reaches a moderate level (40 on a scale of 100) following surgery. After the first dose, patients will receive study drug every 6 hours for 48 hours, and then as needed (up to 4 times a day) for a total of 5 days. If pain is not adequately relieved by the study drug, patients will be given morphine sulfate or other standard analgesics. Follow-up safety evaluations will occur about 1 and 2 weeks after the start of dosing.

Patients will be asked to answer questions about their pain relief and any possible side effects of the drug during the study, and will be given physical examinations, including nasal evaluations, before and during the clinical trial. A small amount of blood will be drawn for routine clinical laboratory testing.

• Drug: Intranasal Ketorolac Tromethamine
  Intranasal at 30mg
• Drug: Intranasal Placebo
  Intranasal Placebo

• Experimental: Intranasal Ketorolac Tromethamine
  Intervention: Drug: Intranasal Ketorolac Tromethamine
• Placebo Comparator: Intranasal Placebo
  Intervention: Drug: Intranasal Placebo

Inclusion Criteria:

• Men or women age 18 through 64 years
• Major abdominal surgery
• Body weight 100 to 300 pounds
• Negative serum pregnancy test
• Pain intensity score at least 40 on 100 mm visual analog scale
• Possibility of remaining in hospital for 5 days
• Able to provide written informed consent
• Willing and able to comply with all testing requirements of the protocol

Exclusion Criteria:

• Allergy or sensitivity to ketorolac or ethylene diamine tetraacetic acid (EDTA)
• Allergy or significant reaction to opioids
• Past allergic reaction to aspirin or other nonsteroidal anti-inflammatory drug (NSAIDs)
• Current upper respiratory tract infection or other respiratory condition that could interfere with absorption of the nasal spray or adverse event assessment
• Use of any intranasal product in past 24 hours
• Clinically significant abnormality on screening lab tests
• History of cocaine use
• Active peptic ulcer disease or significant history of peptic ulcer disease or gastrointestinal bleeding
• Advanced renal impairment or risk for renal failure
• History of other medical problems that could interfere with the study
• Pregnancy or breastfeeding
• Participation in another investigational study within past 30 days