JPWO2019173715A5 - - Google Patents

Description

In one embodiment, the methods disclosed herein can provide peak analgesic action of meloxicam within about 30 minutes to about 60 minutes. That is, administration of a 30 mg/mL bolus IV injection of meloxicam lasts about 30 minutes, about 35 minutes, about 40 minutes, about 45 minutes, about 50 minutes, about 55 minutes, or about 60 minutes, or any time between the above values. can provide a peak analgesic effect with a value or range of In one embodiment, administration of a 30 mg/mL bolus IV injection of meloxicam can provide peak analgesia of approximately 40 minutes.

Meloxicam administration as disclosed herein not only provided a rapid onset of pain relief, but also reached peak analgesic effect earlier than other known IV NSAIDs (ketorolac takes 1-2 hours to reach maximum effect). , has a longer therapeutic window of at least about 24 hours (ketorolac has an analgesic duration of 4-6 hours). See Ketorolac Tromethamine Injection Prescribing Information.

A statistically significant reduction in SPID was also observed up to ₁₂ hours (SPID12; p=0.0434) and up to ₄₈ hours (SPID48; p=0.0040) after Dose 1 compared to placebo. (Table 1). SPIDs evaluated at other post-dose intervals ( _SPID6 , _SPID12 , _SPID48 , and _SPID24-48 ) favored IV meloxicam at all intervals and reached statistical significance at all but the SPID6 interval. (p<0.05). The end of the dosing intervals (SPID _12-24 , SPID _18-24 , SPID _36-48 , and SPID _42-48 ) numerically supported IV meloxicam 30 mg versus placebo at each interval, and SPID _18-24 . All but one reached statistical significance, suggesting that IV meloxicam 30 mg maintains meaningful analgesia throughout the 24 hour dosing interval.

The study was statistically significant for time to perceivable pain relief (p=0.0050), statistically significant number of subjects showing >30% improvement in pain reduction at 24 hours. A difference (p=0.0178), a statistically significant difference (p=0.0275) in the number of times subjects requested rescue analgesia in the first 24 hours and a statistically significant difference (p=0.0275) in the number of times subjects requested rescue analgesia in the 24-48 hour period. Numerous other secondary endpoints were achieved along with statistically significant differences (p=0.0009) and other pain endpoints.

Rescue analgesia (oxycodone 5 mg PO) was available to subjects with inadequate pain control during the treatment phase. The number of rescue doses utilized per subject was significantly lower (p <0.05). The number of subjects utilizing rescue in each assessment test interval (Hours 0-24, Hour 24-48, and Hour 0-48) was numerically lower in the IV meloxicam 30 mg group compared to placebo (Figure 3). . No difference was observed in time to first rescue use.

Data from this study show that meloxicam provided significant pain relief in subjects with moderate to severe pain after abdominoplasty, as evidenced by SPID ₂₄ results and reduced opioid rescue use, was favorable. It has also proven to provide a safety and tolerability profile. This study also demonstrated that once daily dosing with IV meloxicam maintained analgesia over a 24 hour dosing interval.

Claims (14)

A medicament for the treatment of pain comprising meloxicam administered intravenously to a patient once daily, wherein about 1 mL of a 30 mg/mL meloxicam nanocrystalline aqueous dispersion is administered as a first bolus dose and repeated doses Approximately 1 mL of a 30 mg/mL meloxicam nanocrystalline aqueous dispersion was administered 24 hours after the first dose, and patients reported a total pain reduction 48 hours after administration of the first bolus dose compared to placebo. and a statistically significant reduction in rescue analgesic use,
Each bolus dose of approximately 1 mL of 30 mg/mL meloxicam nanocrystal aqueous dispersion is
30 mg meloxicam nanocrystals,
povidone,
sodium deoxycholate (deoxycholic acid),
excipients,
and water
A medicine consisting of The pharmaceutical according to claim 1 , wherein the pain is postoperative pain. A medicament according to claim 1 , wherein the dose of meloxicam is administered after the patient has undergone surgery. The medicament according to claim 3 , wherein the surgical operation is open surgery. The medicine according to claim 3 , wherein the surgical operation is laparoscopic surgery. A medicament according to claim 3 , wherein the surgical operation was performed on hard tissue. 4. A medicament according to claim 3 , wherein the surgical operation is performed on soft tissue. 2. The medicament of claim 1, wherein administration of the first bolus dose results in a statistically significant reduction in change in total pain intensity during the 24 hour period following administration of the first bolus dose. 9. The medicament of claim 8, wherein the change in total pain intensity during 24 hours after administration of the first bolus dose is about -4262.1. Claims that administration of a first bolus dose and repeated bolus doses to an adult human patient results in a statistically significant reduction in change in total pain intensity during 48 hours after administration of the first bolus dose. Item 1. The medicament according to item 1. 11. The medicament of claim 10, wherein the change in total pain intensity during 48 hours after administration of the first bolus dose is -10600.0 (±442.31). Excipients include gum arabic, alginate bentonite, carbomer, carboxymethylcellulose calcium, carboxymethylcellulose sodium, cetostearyl alcohol, methylcellulose, ethylcellulose, gelatin guar gum, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, maltodextrin, polyvinyl alcohol, propylene. 2. The medicament according to claim 1, which is selected from the group consisting of carbonate, propylene glycol alginate, sodium alginate, sodium starch glycolate, tragacanth starch, sucrose and xanthan gum. The pharmaceutical according to claim 1, wherein the excipient is sucrose. 2. The medicament according to claim 1, wherein repeated bolus doses are administered for 2 days.