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
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Egalet Ltd
- 入组人数
- 300
- 试验地点
- 1
- 主要终点
- The Summed Pain Intensity Difference (SPID) on Day 1
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Ketorolac tromethamine
干预措施: Ketorolac tromethamine (Drug)
Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
The Summed Pain Intensity Difference (SPID) on Day 1
时间窗: 6 hours after 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. 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.
次要结局
- Morphine sulfate consumption at 24 hours and 48 hours(24 hours and 48 hours after drug administration)
- Hourly Pain Intensity Difference (PID) scores.(Hourly following the first dose of study medication up to 8 hours)
- Quality of analgesia(First dose of study medication on Day 1 to the first dose of MS by PCA)
- Global assessment of pain control(8 hours following first dose of study medication)
- Onset and duration of pain relief(8 hours following first dose of study medication)