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(409) An evaluation of the efficacy and safety of N1539, a novel intravenous formulation of NanoCrystal Meloxicam, in subjects with moderate to severe pain following hysterectomy
Abstracts
The Journal of Pain
pain. She started rehabilitation. Further surgical intervention is being planned by neurosurgery. Arnold Chiari malformation 1 has abnormally shaped cerebellar tonsils that are displaced below the level of the foramen magnum. The prevalence is 0.1 to 0.5 percent. It is congenital and occurs due to a defect in closure of the neural tube in fetal development, resulting in leakage of CSF. Syrinx occurs from craniospinal pressure due to the blockage of CSF flow in the subarachnoid space at the foramen magnum, leading to pressure backup, dissipating into the spinal cord and central canal, leading to syrinx formation. Posterior foramen magnum decompression restores the normal flow of CSF at the foramen magnum. Syrinx shunt placement is used for patients with Chiari malformation who fail posterior decompression due to progressive symptoms, as in the case with this patient. In conclusion, the patient presented in an unusual way and required extensive clinical examination, imaging, and appropriate/timely neurosurgical intervention.
F12 Non-Opioids in Acute Pain (409) An evaluation of the efficacy and safety of N1539, a novel intravenous formulation of NanoCrystal Meloxicam, in subjects with moderate to severe pain following hysterectomy R Mack, A Freyer, and W Du; Recro Pharma, Inc., Malvern, PA N1539 is a novel intravenous formulation of NanoCrystal Colloidal Dispersionâ meloxicam, being developed for the management of acute moderate to severe pain. This was a multicenter, randomized, double-blind, placebo- and active-controlled study in female subjects undergoing open abdominal hysterectomy; informed consent was obtained prior to participation. Qualifying subjects with moderate to severe pain were randomized to receive placebo, morphine 10-15 mg, or N1539 5, 7.5, 15, 30, or 60 mg. Efficacy assessments included pain intensity (PI), pain relief (PR), time to PR, rescue analgesia use, and global evaluation score (GES). The primary efficacy endpoints were the summed PI difference and total PR from Hour 0 to 24 (SPID24 and TOTPAR24). This study included 460 evaluable subjects age 25-65 years in efficacy analyses. The greatest SPID24 scores were seen in the N1539 30 and 60 mg groups (P<0.001). Statistically significant differences in SPID24 were seen for each N1539 group compared to placebo (P<0.001), and for N1539 15, 30, and 60 mg doses compared with morphine (P#0.003). Statistically significant differences in TOTPAR24 were seen for all N1539 doses compared to placebo (P<0.001), and for N1539 15, 30, and 60 mg doses compared to morphine (P<0.001). Median time to meaningful PR ranged from 18-27 minutes among N1539 dose groups, compared with 165 minutes for placebo. Rescue medication use was lower in all N1539 groups (38.8-62.5%) compared with morphine (76.7%) and placebo (95.0%). This study demonstrated N1539 as an effective treatment for moderate to severe pain following open abdominal hysterectomy. GES results were significantly greater for all N1539 doses compared to placebo (P<0.001), and for N1539 doses greater than 5 mg compared with morphine (P#0.044). Treatment with N1539 was well-tolerated with no deaths, no treatment related SAEs, one discontinuation due to an AE, and a low incidence of AEs. Supported by Recro Pharma.
S77
change (PGIC). After starting treatment, new incidences of adverse events (AEs) between weeks 1 and 5 were used to assess safety. In FM patients, the likelihood of achieving a $30% pain response incrementally increased from 27.5% (90% CI, 23.8–31.5%) with placebo to 31.5% (27.5–35.8%) at 150mg/day, 33.0% (30.4–35.7%) at 300mg/day, and 33.7% (31.3–36.3%) at 450mg/day. In pDPN patients, a dose-response was also observed; 28.6% (24.3–33.4%) with placebo, 41.9% (36.8–47.2%) at 150mg/day, and 49.0% (44.6– 53.3%) at 300mg/day. Incremental improvements in PGIC occurred for both FM and pDPN patients with increasing doses. Dizziness and somnolence were commonly reported AEs. In FM patients, new incidences of dizziness and somnolence were highest after 1 week of treatment (37.8% and 16.8%, respectively, for 450mg/ day), and were considerably fewer subsequently, decreasing week by week for the same dose (2 weeks: 3.6% and 2.4%; 5 weeks: 0.7% and 1.0%). Similar results were seen for pDPN patients. These data demonstrate the dose-response of pregabalin for pain and PGIC, and highlight the incremental benefit of achieving the maximum recommended dose of 300–450mg/day for FM and 300mg/day for pDPN. Common AEs are generally seen within 1 week of starting treatment, with few subsequent new reports. This study was sponsored by Pfizer.
(412) Patient with altered mental status, an intrathecal pump, and an unknown dose of ziconotide K Noon and T Furnish; University of California, San Diego, La Jolla, CA 72 year old female with past medical history hypertension, CKD, depression, anxiety, remote history of delirium with psychosis during hospitalization, and chronic pain with intrathecal pump presented with altered mental status. Patient underwent CT head which did not show an acute stroke. Patient was treated for UTI early during her hospitalization without improvement in her confusion. An EEG did not show seizure activity or epileptiform discharges and an MRI did not show acute abnormalities. The primary team subsequently obtained a history of cognitive decline over the past 2-3 months that began shortly after the initiation and escalation of intrathecal ziconotide. Primary team consulted the acute pain service to evaluate patient and consider possibility of ziconotide toxicity as well as opioid toxicity. The pump was interrogated and listed drugs/doses were: fentanyl 29 mg/day, bupivacaine 4.1 mg/ day, ziconotide 10.2 mcg/day. The acute pain service obtained outside pain physician’s ‘‘formula sheet’’ which contained information about doses and concentrations of medications placed into the pump. Daily doses calculated based on the formula sheet did not match the daily doses programmed into the pump. Per the formula sheet, the patient received fentanyl 20.34 mg/day, bupivacaine 0.41 mg/day, ziconotide 27.7 mcg/day. The pump was emptied and subsequently refilled with 20 ml: Fentanyl 24.5mg/ml, Bupivacaine 0.5mg/ml, and no ziconotide. Patient’s pump was reprogrammed at a reduced infusion of 18.3 mg/day of fentanyl. Patient improved in terms of alertness after pump change but did not return to baseline with persistent confabulations two weeks after pump medication change. Subsequently, patient was discharged to skilled nursing facility. The patient’s lack of executive cognitive improvement was considered a new baseline, possibly due to pre-existing, low-grade dementia with secondary insult of ziconotide toxicity.
(410) Withdrawn
F13 Non-Opioid Analgesics for Chronic Anticonvulsants, Antidepressants, Others
Pain-
(411) Pregabalin dose-response in fibromyalgia and diabetic peripheral neuropathy A Clair, E Whalen, N Thomas, L Pauer, R Vissing, and P Park; Pfizer, New York, NY
In the US, pregabalin is approved for fibromyalgia (FM: starting dose 150mg/day; recommended dose 300–450mg/day) and painful diabetic peripheral neuropathy (pDPN: starting dose 150mg/day; recommended dose 300mg/day), amongst other indications. In this post-hoc analysis of 3 FM and 3 pDPN placebo-controlled trials, a 3-parameter Emax dose-response model was used to examine the dose-response of pregabalin for pain ($30% pain response – a clinically meaningful improvement) and patient global impression of
(413) Pregabalin and efficacy for pain score reduction in patients with fibromyalgia evaluated with and without potentially confounding effects L Pauer, G Atkinson, and A Clair; Pfizer Inc., New York, NY Pregabalin is an approved treatment for fibromyalgia in many countries with numerous studies supporting its efficacy in reducing fibromyalgia-related pain. To our knowledge, however, no studies have assessed the efficacy of pregabalin, while controlling for potentially confounding effects that might affect response to therapy. In this analysis, we pooled data from three randomized, placebocontrolled, double-blind, 13-14-week clinical trials of pregabalin (ClinicalTrials.gov identifiers NCT00645398, NCT00230776, NCT00333866; dose ranges 300–600 mg/day) for treatment of fibromyalgia and evaluated mean changes in pain scores from baseline. Pain scores were recorded by the subjects using daily pain diaries and an 11-point numeric rating scale. Subjects were classified as 30% and 50% responders (defined by percentage of pain
The Journal of Pain
pain. She started rehabilitation. Further surgical intervention is being planned by neurosurgery. Arnold Chiari malformation 1 has abnormally shaped cerebellar tonsils that are displaced below the level of the foramen magnum. The prevalence is 0.1 to 0.5 percent. It is congenital and occurs due to a defect in closure of the neural tube in fetal development, resulting in leakage of CSF. Syrinx occurs from craniospinal pressure due to the blockage of CSF flow in the subarachnoid space at the foramen magnum, leading to pressure backup, dissipating into the spinal cord and central canal, leading to syrinx formation. Posterior foramen magnum decompression restores the normal flow of CSF at the foramen magnum. Syrinx shunt placement is used for patients with Chiari malformation who fail posterior decompression due to progressive symptoms, as in the case with this patient. In conclusion, the patient presented in an unusual way and required extensive clinical examination, imaging, and appropriate/timely neurosurgical intervention.
F12 Non-Opioids in Acute Pain (409) An evaluation of the efficacy and safety of N1539, a novel intravenous formulation of NanoCrystal Meloxicam, in subjects with moderate to severe pain following hysterectomy R Mack, A Freyer, and W Du; Recro Pharma, Inc., Malvern, PA N1539 is a novel intravenous formulation of NanoCrystal Colloidal Dispersionâ meloxicam, being developed for the management of acute moderate to severe pain. This was a multicenter, randomized, double-blind, placebo- and active-controlled study in female subjects undergoing open abdominal hysterectomy; informed consent was obtained prior to participation. Qualifying subjects with moderate to severe pain were randomized to receive placebo, morphine 10-15 mg, or N1539 5, 7.5, 15, 30, or 60 mg. Efficacy assessments included pain intensity (PI), pain relief (PR), time to PR, rescue analgesia use, and global evaluation score (GES). The primary efficacy endpoints were the summed PI difference and total PR from Hour 0 to 24 (SPID24 and TOTPAR24). This study included 460 evaluable subjects age 25-65 years in efficacy analyses. The greatest SPID24 scores were seen in the N1539 30 and 60 mg groups (P<0.001). Statistically significant differences in SPID24 were seen for each N1539 group compared to placebo (P<0.001), and for N1539 15, 30, and 60 mg doses compared with morphine (P#0.003). Statistically significant differences in TOTPAR24 were seen for all N1539 doses compared to placebo (P<0.001), and for N1539 15, 30, and 60 mg doses compared to morphine (P<0.001). Median time to meaningful PR ranged from 18-27 minutes among N1539 dose groups, compared with 165 minutes for placebo. Rescue medication use was lower in all N1539 groups (38.8-62.5%) compared with morphine (76.7%) and placebo (95.0%). This study demonstrated N1539 as an effective treatment for moderate to severe pain following open abdominal hysterectomy. GES results were significantly greater for all N1539 doses compared to placebo (P<0.001), and for N1539 doses greater than 5 mg compared with morphine (P#0.044). Treatment with N1539 was well-tolerated with no deaths, no treatment related SAEs, one discontinuation due to an AE, and a low incidence of AEs. Supported by Recro Pharma.
S77
change (PGIC). After starting treatment, new incidences of adverse events (AEs) between weeks 1 and 5 were used to assess safety. In FM patients, the likelihood of achieving a $30% pain response incrementally increased from 27.5% (90% CI, 23.8–31.5%) with placebo to 31.5% (27.5–35.8%) at 150mg/day, 33.0% (30.4–35.7%) at 300mg/day, and 33.7% (31.3–36.3%) at 450mg/day. In pDPN patients, a dose-response was also observed; 28.6% (24.3–33.4%) with placebo, 41.9% (36.8–47.2%) at 150mg/day, and 49.0% (44.6– 53.3%) at 300mg/day. Incremental improvements in PGIC occurred for both FM and pDPN patients with increasing doses. Dizziness and somnolence were commonly reported AEs. In FM patients, new incidences of dizziness and somnolence were highest after 1 week of treatment (37.8% and 16.8%, respectively, for 450mg/ day), and were considerably fewer subsequently, decreasing week by week for the same dose (2 weeks: 3.6% and 2.4%; 5 weeks: 0.7% and 1.0%). Similar results were seen for pDPN patients. These data demonstrate the dose-response of pregabalin for pain and PGIC, and highlight the incremental benefit of achieving the maximum recommended dose of 300–450mg/day for FM and 300mg/day for pDPN. Common AEs are generally seen within 1 week of starting treatment, with few subsequent new reports. This study was sponsored by Pfizer.
(412) Patient with altered mental status, an intrathecal pump, and an unknown dose of ziconotide K Noon and T Furnish; University of California, San Diego, La Jolla, CA 72 year old female with past medical history hypertension, CKD, depression, anxiety, remote history of delirium with psychosis during hospitalization, and chronic pain with intrathecal pump presented with altered mental status. Patient underwent CT head which did not show an acute stroke. Patient was treated for UTI early during her hospitalization without improvement in her confusion. An EEG did not show seizure activity or epileptiform discharges and an MRI did not show acute abnormalities. The primary team subsequently obtained a history of cognitive decline over the past 2-3 months that began shortly after the initiation and escalation of intrathecal ziconotide. Primary team consulted the acute pain service to evaluate patient and consider possibility of ziconotide toxicity as well as opioid toxicity. The pump was interrogated and listed drugs/doses were: fentanyl 29 mg/day, bupivacaine 4.1 mg/ day, ziconotide 10.2 mcg/day. The acute pain service obtained outside pain physician’s ‘‘formula sheet’’ which contained information about doses and concentrations of medications placed into the pump. Daily doses calculated based on the formula sheet did not match the daily doses programmed into the pump. Per the formula sheet, the patient received fentanyl 20.34 mg/day, bupivacaine 0.41 mg/day, ziconotide 27.7 mcg/day. The pump was emptied and subsequently refilled with 20 ml: Fentanyl 24.5mg/ml, Bupivacaine 0.5mg/ml, and no ziconotide. Patient’s pump was reprogrammed at a reduced infusion of 18.3 mg/day of fentanyl. Patient improved in terms of alertness after pump change but did not return to baseline with persistent confabulations two weeks after pump medication change. Subsequently, patient was discharged to skilled nursing facility. The patient’s lack of executive cognitive improvement was considered a new baseline, possibly due to pre-existing, low-grade dementia with secondary insult of ziconotide toxicity.
(410) Withdrawn
F13 Non-Opioid Analgesics for Chronic Anticonvulsants, Antidepressants, Others
Pain-
(411) Pregabalin dose-response in fibromyalgia and diabetic peripheral neuropathy A Clair, E Whalen, N Thomas, L Pauer, R Vissing, and P Park; Pfizer, New York, NY
In the US, pregabalin is approved for fibromyalgia (FM: starting dose 150mg/day; recommended dose 300–450mg/day) and painful diabetic peripheral neuropathy (pDPN: starting dose 150mg/day; recommended dose 300mg/day), amongst other indications. In this post-hoc analysis of 3 FM and 3 pDPN placebo-controlled trials, a 3-parameter Emax dose-response model was used to examine the dose-response of pregabalin for pain ($30% pain response – a clinically meaningful improvement) and patient global impression of
(413) Pregabalin and efficacy for pain score reduction in patients with fibromyalgia evaluated with and without potentially confounding effects L Pauer, G Atkinson, and A Clair; Pfizer Inc., New York, NY Pregabalin is an approved treatment for fibromyalgia in many countries with numerous studies supporting its efficacy in reducing fibromyalgia-related pain. To our knowledge, however, no studies have assessed the efficacy of pregabalin, while controlling for potentially confounding effects that might affect response to therapy. In this analysis, we pooled data from three randomized, placebocontrolled, double-blind, 13-14-week clinical trials of pregabalin (ClinicalTrials.gov identifiers NCT00645398, NCT00230776, NCT00333866; dose ranges 300–600 mg/day) for treatment of fibromyalgia and evaluated mean changes in pain scores from baseline. Pain scores were recorded by the subjects using daily pain diaries and an 11-point numeric rating scale. Subjects were classified as 30% and 50% responders (defined by percentage of pain