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(381) Evaluation of headache pain response and nausea relief relative to triptan use and placebo in migraine patients treated with diclofenac potassium for oral solution
S70
Abstracts
The Journal of Pain
F. Treatment Approaches (Medical/ Interventional) F01 Anti-Inflammatory Agents and Acetaminophen (379) Comparative evaluation of prostate tissue distribution profiles of four non-steroidal anti-inflammatory drugs in rats R Radhakrishnan, V Yellepeddi, and J Radhakrishnan; Roseman University of Health Sciences College of Pharmacy, South Jordan, UT
The quality of life of men of all ages is affected considerably by pathologies of prostate often leading to lower urinary tract symptoms (LUTS) and pelvic pain. Chronic prostatitis (CP)/chronic pelvic pain syndrome(CPPS) involving prostate inflammation is one such pathology and the rate of prostatitis-like symptoms ranges from 2.2% to 9.7% with mean prevalence of 8.2%. The current treatment of CP/CPPS mainly involves use of anti-inflammatory drugs, antibiotics, a-adrenergic blockers, hormonal agents etc. However, due to the heterogeneity and elusive pathophysiology of CP/CPPS, no definitive treatment strategy/regimen has been identified. In the current research study, we compared the prostate tissue distribution profile of four non-steroidal anti-inflammatory drugs (NASIDs), diclofenac, ibuprofen, naproxen, and celecoxib after oral administration to male Sprague-Dawley rats. The tissue concentration of all four NSAIDs in prostate was evaluated at various time-points for a period of 24 hours using HPLC technique. Briefly, male SpragueDawley rats (n=5 per group) were fasted overnight and on the day of experiment were administered NSAID’s suspension at a dose of 500 mg/kg by oral gavage. After oral administration, the animals were euthanized at time points 0.5,1,2,3,4,6 and 24 hours and their prostate tissue was harvested. The tissue was homogenized and the NSAID’s were extracted using methanol and injected into HPLC for quantification. The results have shown that celecoxib resided in the prostate tissue (> 24 hours) for longest period of time when compared to other NASIDs. The peak concentration (Cmax) of diclofenac, ibuprofen, naproxen, and celecoxib in prostate was 12.310, 6.877, 17.850, and 7.287 mg/mL respectively. The time to reach peak concentration (Tmax) of diclofenac, ibuprofen, naproxen, and celecoxib in prostate was 0.5, 2, 0.5, and 6 hours respectively. In conclusion, celecoxib due to its long residence time in prostate can be an attractive option for the treatment of CP/CPPS.
(380) A novel application of the Medication Event Monitoring System (MEMS) to track rescue medication use in a phase 3 study of low-dose SoluMatrix meloxicam in patients with osteoarthritis (OA) pain R Altman, A Gibofsky, A Kivitz, D Solorio, C Sheridan, and C Young; Iroko Pharmaceuticals, LLC, Philadelphia, PA
Recording rescue medication use is a common challenge in arthritis studies. FDA guidance regarding OA efficacy studies advises standardization of rescue medication usage and analysis. Pill counts provide data on total rescue medication use; self-reported diary cards provide information on timing of rescue medication events but are limited by issues such as missing data, back-filling, and forward-filling. To achieve a potentially more accurate measure of rescue medication events over time, we used MEMS in a 12week, randomized, double-blind, placebo-controlled study of once-daily low-dose SoluMatrix Meloxicam 5mg and 10mg. Patients (N=403) $40 years with hip or knee OA pain were chronic NSAID and/or acetaminophen users. Rescue medication, acetaminophen 500mg (4-6h as needed), was permitted. Acetaminophen bottles equipped with MEMS recorded bottle opening events. Data were supplemented by clinic-based rescue medication accountability. Patients in the 10mg (LS mean doses6SE; 48.467.13; P=0.0013) and 5mg (52.466.61; P=0.006) groups received less rescue medication over 12-weeks vs placebo (73.267.03). The mean daily rescue medication dosage was lowest in the 10mg group (313.6mg645.50; P=0.0024) followed by 5mg (326.2mg641.36; P=0.0046) and placebo (464.1mg643.73). The mean number of days with a rescue event was lowest in the 10mg group (23.562.34, P<0.0001) followed by 5mg (25.362.16,
P=0.0007) and placebo (33.962.36). A dose-related trend was observed in the average number of rescue events per patient over 12-weeks by time of day. The average number of rescue events per patient over 12-weeks by time of day was as follows (10mg, 5mg, and placebo, respectively): >24:00-6:00: 1.9, 2.1 and 3.9; >6:00-12:00: 7.6, 7.6 and 13.5; >12:00-18:00: 6.5, 7.2 and 12.0; and >18:00-24:00: 8.0, 10.1 and 15.3. The use of MEMS-enabled bottles allowed for real-time capture of rescue events and provided important insight into rescue events relative to time of day over this 12-week study. Supported by funding from Iroko Pharmaceuticals, LLC.
(381) Evaluation of headache pain response and nausea relief relative to triptan use and placebo in migraine patients treated with diclofenac potassium for oral solution P Schmidt; Depomed, Inc, Newark, CA Diclofenac potassium (50 mg) for oral solution (DPOS, Depomed, Newark, CA) is a rapidly absorbed, non-steroidal, anti-inflammatory drug (NSAID) FDA-approved for acute adult migraine. The efficacy of DPOS on headache pain- and nausea relief in patients previously medicated with triptans was studied. Two-hour data were pooled from two Phase-3 studies. Patients with or without prior triptan use, and with or without nausea at dosing were compared for headache pain and nausea relief at 2h post-dose vs. baseline and placebo. P-values were from Cochran-MantelHaenszel test. Of 1272 patients, 644 took placebo and 628 DPOS. At dosing, all patients experienced headache pain; 783 (61.6%) experienced nausea. Significantly more DPOS patients were headache pain-free at 2 h post-dose regardless of whether they had triptan experience (N=56/286; 19.6%,) or not (N=101/342; 29.5%,) compared to placebo patients who had triptan experience (N=20/ 284; 7.0%) or did not (N=50/360; 13.9%) (p-value <0.001). Significantly more patients given DPOS were nausea-free at 2 h postdose regardless of whether they had triptan experience (N= 181/ 286; 63.3%) or not (N=224/342; 65.5%) compared to baseline patients who had triptan experience (N=112/286; 39.2%) or not (N=125/342; 36.5%) (p-value<0.001) and compared to placebo patients who had triptan experience (N=117/284; 41.2%) or not (N=135/360; 37.5%) (p-value<0.001).In conclusion, at 2h postdose, more DPOS patients reported headache pain relief regardless of triptan experience than patients on placebo who were either triptan experienced or triptan na€ıve. Similarly, at 2 h post-dose, more DPOS patients, regardless of triptan experience, were nausea-free compared to both baseline and to placebo-treated patients in both groups. DPOS is an effective analgesic for migraine patients and may be an appropriate choice for patients seeking nausea-free pain relief. Furthermore, the greater relative efficacy shown in the triptan-na€ıve group may support the choice of DPOS prior to triptans for treatment. Disclosure: This study was funded by Depomed, Inc.
F02 Cancer Pain - Palliative Care (382) Efficacy, safety, and tolerability of Fulranumab as adjunctive therapy for cancer-related pain: a randomized, double-blind, placebo-controlled, multicenter study N Slatkin, N Zaki, P Sanga, S Wang, J Louie, K Kelly, and J Thipphawong; Janssen Research & Development, LLC, Titusville, NJ
This phase 2, double-blind (DB), randomized controlled study consisted of a 4-week DB treatment phase and a 48-week open-label extension (OLE) phase. Terminally ill cancer patients were randomized (2:1) to either subcutaneous injection of 9 mg fulranumab or placebo (every 4 weeks) to evaluate the efficacy and safety of fulranumab as an adjunct to opioid therapy in inadequately controlled, moderate to severe, cancer pain. Out of 98 patients (men: 57%, mean age: 58.3 years) who completed DB phase, 81 (83%) were terminally ill and 71 (72%) patients entered the OLE phase. The primary endpoint, mean change(SD) in average cancer pain intensity score from baseline (average of last 3 days prior to randomization) to the end of the DB phase (average of last 7 days), was -0.8 (1.3) for the fulranumab group and -0.7 (1.6) for placebo. Several
Abstracts
The Journal of Pain
F. Treatment Approaches (Medical/ Interventional) F01 Anti-Inflammatory Agents and Acetaminophen (379) Comparative evaluation of prostate tissue distribution profiles of four non-steroidal anti-inflammatory drugs in rats R Radhakrishnan, V Yellepeddi, and J Radhakrishnan; Roseman University of Health Sciences College of Pharmacy, South Jordan, UT
The quality of life of men of all ages is affected considerably by pathologies of prostate often leading to lower urinary tract symptoms (LUTS) and pelvic pain. Chronic prostatitis (CP)/chronic pelvic pain syndrome(CPPS) involving prostate inflammation is one such pathology and the rate of prostatitis-like symptoms ranges from 2.2% to 9.7% with mean prevalence of 8.2%. The current treatment of CP/CPPS mainly involves use of anti-inflammatory drugs, antibiotics, a-adrenergic blockers, hormonal agents etc. However, due to the heterogeneity and elusive pathophysiology of CP/CPPS, no definitive treatment strategy/regimen has been identified. In the current research study, we compared the prostate tissue distribution profile of four non-steroidal anti-inflammatory drugs (NASIDs), diclofenac, ibuprofen, naproxen, and celecoxib after oral administration to male Sprague-Dawley rats. The tissue concentration of all four NSAIDs in prostate was evaluated at various time-points for a period of 24 hours using HPLC technique. Briefly, male SpragueDawley rats (n=5 per group) were fasted overnight and on the day of experiment were administered NSAID’s suspension at a dose of 500 mg/kg by oral gavage. After oral administration, the animals were euthanized at time points 0.5,1,2,3,4,6 and 24 hours and their prostate tissue was harvested. The tissue was homogenized and the NSAID’s were extracted using methanol and injected into HPLC for quantification. The results have shown that celecoxib resided in the prostate tissue (> 24 hours) for longest period of time when compared to other NASIDs. The peak concentration (Cmax) of diclofenac, ibuprofen, naproxen, and celecoxib in prostate was 12.310, 6.877, 17.850, and 7.287 mg/mL respectively. The time to reach peak concentration (Tmax) of diclofenac, ibuprofen, naproxen, and celecoxib in prostate was 0.5, 2, 0.5, and 6 hours respectively. In conclusion, celecoxib due to its long residence time in prostate can be an attractive option for the treatment of CP/CPPS.
(380) A novel application of the Medication Event Monitoring System (MEMS) to track rescue medication use in a phase 3 study of low-dose SoluMatrix meloxicam in patients with osteoarthritis (OA) pain R Altman, A Gibofsky, A Kivitz, D Solorio, C Sheridan, and C Young; Iroko Pharmaceuticals, LLC, Philadelphia, PA
Recording rescue medication use is a common challenge in arthritis studies. FDA guidance regarding OA efficacy studies advises standardization of rescue medication usage and analysis. Pill counts provide data on total rescue medication use; self-reported diary cards provide information on timing of rescue medication events but are limited by issues such as missing data, back-filling, and forward-filling. To achieve a potentially more accurate measure of rescue medication events over time, we used MEMS in a 12week, randomized, double-blind, placebo-controlled study of once-daily low-dose SoluMatrix Meloxicam 5mg and 10mg. Patients (N=403) $40 years with hip or knee OA pain were chronic NSAID and/or acetaminophen users. Rescue medication, acetaminophen 500mg (4-6h as needed), was permitted. Acetaminophen bottles equipped with MEMS recorded bottle opening events. Data were supplemented by clinic-based rescue medication accountability. Patients in the 10mg (LS mean doses6SE; 48.467.13; P=0.0013) and 5mg (52.466.61; P=0.006) groups received less rescue medication over 12-weeks vs placebo (73.267.03). The mean daily rescue medication dosage was lowest in the 10mg group (313.6mg645.50; P=0.0024) followed by 5mg (326.2mg641.36; P=0.0046) and placebo (464.1mg643.73). The mean number of days with a rescue event was lowest in the 10mg group (23.562.34, P<0.0001) followed by 5mg (25.362.16,
P=0.0007) and placebo (33.962.36). A dose-related trend was observed in the average number of rescue events per patient over 12-weeks by time of day. The average number of rescue events per patient over 12-weeks by time of day was as follows (10mg, 5mg, and placebo, respectively): >24:00-6:00: 1.9, 2.1 and 3.9; >6:00-12:00: 7.6, 7.6 and 13.5; >12:00-18:00: 6.5, 7.2 and 12.0; and >18:00-24:00: 8.0, 10.1 and 15.3. The use of MEMS-enabled bottles allowed for real-time capture of rescue events and provided important insight into rescue events relative to time of day over this 12-week study. Supported by funding from Iroko Pharmaceuticals, LLC.
(381) Evaluation of headache pain response and nausea relief relative to triptan use and placebo in migraine patients treated with diclofenac potassium for oral solution P Schmidt; Depomed, Inc, Newark, CA Diclofenac potassium (50 mg) for oral solution (DPOS, Depomed, Newark, CA) is a rapidly absorbed, non-steroidal, anti-inflammatory drug (NSAID) FDA-approved for acute adult migraine. The efficacy of DPOS on headache pain- and nausea relief in patients previously medicated with triptans was studied. Two-hour data were pooled from two Phase-3 studies. Patients with or without prior triptan use, and with or without nausea at dosing were compared for headache pain and nausea relief at 2h post-dose vs. baseline and placebo. P-values were from Cochran-MantelHaenszel test. Of 1272 patients, 644 took placebo and 628 DPOS. At dosing, all patients experienced headache pain; 783 (61.6%) experienced nausea. Significantly more DPOS patients were headache pain-free at 2 h post-dose regardless of whether they had triptan experience (N=56/286; 19.6%,) or not (N=101/342; 29.5%,) compared to placebo patients who had triptan experience (N=20/ 284; 7.0%) or did not (N=50/360; 13.9%) (p-value <0.001). Significantly more patients given DPOS were nausea-free at 2 h postdose regardless of whether they had triptan experience (N= 181/ 286; 63.3%) or not (N=224/342; 65.5%) compared to baseline patients who had triptan experience (N=112/286; 39.2%) or not (N=125/342; 36.5%) (p-value<0.001) and compared to placebo patients who had triptan experience (N=117/284; 41.2%) or not (N=135/360; 37.5%) (p-value<0.001).In conclusion, at 2h postdose, more DPOS patients reported headache pain relief regardless of triptan experience than patients on placebo who were either triptan experienced or triptan na€ıve. Similarly, at 2 h post-dose, more DPOS patients, regardless of triptan experience, were nausea-free compared to both baseline and to placebo-treated patients in both groups. DPOS is an effective analgesic for migraine patients and may be an appropriate choice for patients seeking nausea-free pain relief. Furthermore, the greater relative efficacy shown in the triptan-na€ıve group may support the choice of DPOS prior to triptans for treatment. Disclosure: This study was funded by Depomed, Inc.
F02 Cancer Pain - Palliative Care (382) Efficacy, safety, and tolerability of Fulranumab as adjunctive therapy for cancer-related pain: a randomized, double-blind, placebo-controlled, multicenter study N Slatkin, N Zaki, P Sanga, S Wang, J Louie, K Kelly, and J Thipphawong; Janssen Research & Development, LLC, Titusville, NJ
This phase 2, double-blind (DB), randomized controlled study consisted of a 4-week DB treatment phase and a 48-week open-label extension (OLE) phase. Terminally ill cancer patients were randomized (2:1) to either subcutaneous injection of 9 mg fulranumab or placebo (every 4 weeks) to evaluate the efficacy and safety of fulranumab as an adjunct to opioid therapy in inadequately controlled, moderate to severe, cancer pain. Out of 98 patients (men: 57%, mean age: 58.3 years) who completed DB phase, 81 (83%) were terminally ill and 71 (72%) patients entered the OLE phase. The primary endpoint, mean change(SD) in average cancer pain intensity score from baseline (average of last 3 days prior to randomization) to the end of the DB phase (average of last 7 days), was -0.8 (1.3) for the fulranumab group and -0.7 (1.6) for placebo. Several