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niacin tablets may reduce abuse potential vs dose-equivalent oxycodone HCl in non-dependent recreational opioid users
P68
The Journal of Pain
Abstracts
(368) All-cause and disease-related health care costs in patients with painful diabetic peripheral neuropathy prescribed pregabalin versus duloxetine
(370) Effect of study country on efficacy and adverse event profile of once-daily gabapentin extended-release (G-ER) for the treatment of postherpetic neuralgia (PHN)
R Sanchez, J Burke, A Joshi, J Cappelleri, M Cattaneo, M Kulakodlu, and R Halpren; Pfizer, New York, NY
G Irving, R Sathyanarayana, and M Sweeney; Depomed, Inc., Menlo Park, CA
The study objective was to compare changes in all-cause and painful diabetic peripheral neuropathy (pDPN)-related healthcare costs in patients initiating treatment with pregabalin (PGB) and duloxetine (DLX) in real-world settings. Patients (318 years) initiating PGB or DLX between 6/1/07-12/31/08 were identified from a large US managed care plan database. Those with 3 1 medical claim with: (1) primary or secondary ICD-9-CM code of 357.2; or (2) primary code of 249.xx or 250.xx plus 337.1, 354.4, 354.5, 354.8, 354.9, 355.7x, 355.8, 355.9 or 356.9 on the same claim were considered to have pDPN. The dispense date of the first PGB or DLX prescription was considered the index date. Patients were continuously enrolled for 6 months pre- and post-index date. Outcome variables included pre- and post-index all-cause and pDPN-related total health care costs. The pre-/post-index differences in costs were computed. Student’s t-tests were used to compare descriptive results. Multivariate analyses of allcause and pDPN-related total healthcare costs were conducted using difference-in-differences (DiD) models. A total of 1,785 PGB and 351 DLX patients were identified. Differences (PGB vs. DLX) in the pre-/post-index change in mean (SD) all-cause total health care costs [$1,411 (35,056) vs. $1,560 (26,799); p=0.93] or pDPN-related total health care costs [$704 (5,634) vs. -$240 (14,120); p=0.22] were not significant. DiD models showed significantly higher post-index vs. pre-index all-cause health care costs (cost ratio=1.32, 95% confidence interval [CI]: 1.02-1.72); no significant difference in all-cause costs attributable to PGB vs DLX therapy (0.97, CI: 0.75-1.26); no significant difference in post-index vs. pre-index pDPN-related health care costs (1.08 CI: 0.462.57); and significantly higher pDPN-related costs attributable to PGB vs DLX (2.34, CI: 1.01-5.46). There were no differences in all-cause healthcare costs between the PBG and DLX users but significantly greater pDPN-related health care costs attributable to initiation of PGB vs DLX were noted.
(369) Patterns of therapy switching, augmenting and discontinuation after initiation of treatment with select medications in patients with osteoarthritis: a retrospective claims database analysis A Sadosky, M Gore, D Leslie, K Tai, and M Seleznick; Pfizer Inc., New York, NY The objective of this study was to evaluate the patterns of therapy switching, augmenting and discontinuation after initiation of treatment with select medications in patients with osteoarthritis (OA). Using the LifeLinkÔ Health Plan Claims Database, patients with OA (ICD-9-CM code 715.XX) newly prescribed (index event) non-selective nonsteroidal anti-inflammatory drugs (NSAIDs, N=71,116; average age6SD, 52.969.4 years), Cyclooxygenase-2 inhibitors (COX-2s, N=12,111; 54.469.3 years), acetaminophen (N=1,929; 5169.5 years), tramadol (N=15,678; 53.5610.5 years) weak opioids (N=73,839; 54.3610.4 years) and strong opioids (N=32,337; 52.969.9 years) were identified. Patterns of therapy switching, augmenting, and discontinuation were evaluated during the 12-months post-index period. Substantial proportions of OA patients switched therapy within a year after treatment initiation and rates of therapy switching were significantly different (p<0.0001) across the evaluated drugs groups: NSAIDs, 22.3%; Cox-2s, 27.5%; acetaminophen, 46.0%; tramadol, 44.5%; weak opioids, 27.2%; and strong opioids, 41.1%. Patterns of therapy augmenting at 12-months were also significantly (p<0.0001) different, although rates of therapy augmentation were much lower: NSAIDs 6.7%; Cox2s,10%; acetaminophen, 6.5%; tramadol 8.4%; weak opioids, 4.1 %; and strong opioids, 3.3%. A majority of patients in each group discontinued therapy during the 12-months post-index period (93.2%, 87.4%, 98.7%, 95.6%, 98.3%, and 97% of patients in the NSAIDs, Cox-2s, acetaminophen, tramadol, weak opioids and strong opioids groups, respectively). An evaluation of estimated probabilities suggested that over two thirds of patients who switched, augmented or discontinued therapy did so within the first 2-months, and a majority did so within 6-months of treatment initiation. Results of this study suggest that therapy switching and discontinuation were fairly common among OA patients initiating treatment with the currently recommended medication classes for this painful condition. The observed high rates of therapy switching and discontinuation may be indicative of inadequate pain relief or potentially intolerable side-effects of therapies. This study was funded by Pfizer, Inc
G-ER has been demonstrated to be efficacious and well tolerated for treatment of PHN in a placebo-controlled, Phase 3 study conducted in the USA, Russia and Argentina. We examined the efficacy and tolerability of once-daily G-ER (1800 mg) as a function of study country. Patients with PHN $6 months and average daily pain (ADP) score $4 were randomized to G-ER or placebo for 10 weeks. The primary endpoint was baseline observation carried forward (BOCF) change in ADP, and rates of adverse events were compared. The intent-to-treat population included 450 patients (USA: G-ER, n=126, placebo, n=131; Russia: G-ER, n=81, placebo, n=80; Argentina, G-ER, n=13, placebo, n=19); the safety population included two additional patients from the USA (one each G-ER and placebo). Compared with the USA and Russia, patients from Argentina were older (mean ages [years]: USA, 65; Russia, 65; Argentina, 73), and had higher baseline mean ADP scores (USA, 6.5; Russia, 6.5; Argentina, 7.0). BOCF change in ADP scores were: USA, -0.78; Russia, -0.43; Argentina, 0.64 (p=0.006, 0.109 and 0.455, respectively [not powered for subgroups]). A $50% reduction from baseline ADP score was demonstrated for 35% of G-ER-treated patients in the USA, 24% of those from Russia and 15% of those in Argentina. In G-ERtreated patients from the USA, Russia and Argentina, dizziness was reported in 11.0%, 8.6% and 30.8%, respectively (placebo groups, 0%, 3% and 11%, respectively), and somnolence was reported in 7.1%, 1.2% and 15.4%, respectively (placebo groups, 3%, 3% and 5%, respectively). Gabapentin ER demonstrated greatest efficacy in the USA and less compelling efficacy and tolerability in Argentina. This may be partly attributable to the small numbers of patients in Argentina and may be influenced by differences in baseline characteristics and/or cultural differences in patient/physician interactions. Analysis funded by Depomed, Inc. Medical writing support funded by Abbott.
(371) Oxycodone HCl/niacin tablets may reduce abuse potential vs dose-equivalent oxycodone HCl in non-dependent recreational opioid users L Webster, R Rolleri, G Pixton, and K Sommerville; Lifetree Clinical Researchâ and Pain Clinic, Salt Lake City, UT Increased non-medical use of prescription opioids has created a need for opioid products with reduced abuse potential. Oxycodone HCl/niacin tablets combine oxycodone with niacin and functional inactive excipients to provide limits and impediments to intentional oral overconsumption and intranasal and intravenous abuse. This randomized, double-blind, placebo- and active-controlled, 5way crossover study compared the relative abuse potential of orally-administered immediate-release (IR) oxycodone HCl/niacin tablets to dose-equivalent IR oxycodone HCl tablets in 49 non-dependent recreational opioid users. Dose-response was also assessed. Subjects received: oxycodone/niacin-40/ 240mg, oxycodone/niacin-80/480mg, oxycodone-40mg, oxycodone-80mg, and placebo. Primary endpoint was Drug-Liking (bipolar visual analog scale [VAS]; 0=dislike an awful lot, 50=neither like nor dislike, 100=like an awful lot), assessed by area under effect curve (AUE0-1h, AUE0-2h, AUE0-3h), peak disliking effect (Emin), and effect at 0.5h post-dose (E0.5h). Other assessments included peak-liking effect (Emax), Take Drug Again Assessment (TDAA), and Overall Drug Liking (ODL); bipolar 100-point VAS for TDAA and ODL. There were significant differences between oxycodone/niacin and dose-corresponding IR oxycodone for Drug-Liking AUE0-1h, AUE0-2h, AUE0-3h, Emin, and E0.5h (p<0.0001, all comparisons) and for Emax (oxycodone/niacin-40/240mg, p=0.004; oxycodone/niacin-80/480mg, p<0.0001). Oxycodone/niacin-80/ 480mg was less liked than oxycodone/niacin-40/240mg, suggesting dose-response. Mean (SD) Drug-Liking scores for oxycodone/niacin-40/240mg and oxycodone/niacin-80/480mg were 47.0(20.3) and 40.1(23.4) at 0.5h, while scores for oxycodone-40mg and oxycodone-80mg were 66.0(16.3) and 74.8(16.7) (p<0.0001). TDAA and ODL also showed significant differences with greater liking of oxycodone without niacin compared to equivalent oxycodone with niacin. Adverse events (AEs) were consistent with known effects of oxycodone and niacin; most were mild or moderate in intensity. No serious AEs occurred. Results suggest that abuse potential of oxycodone/niacin tablets may be decreased compared with equivalent doses of IR oxycodone HCl in non-dependent recreational opioid users. Drug-Liking decreased with increased niacin dose. Early effects of overconsumption of oxycodone/niacin tablets may decrease abuse potential. Supported by King Pharmaceuticalsâ, Inc.
The Journal of Pain
Abstracts
(368) All-cause and disease-related health care costs in patients with painful diabetic peripheral neuropathy prescribed pregabalin versus duloxetine
(370) Effect of study country on efficacy and adverse event profile of once-daily gabapentin extended-release (G-ER) for the treatment of postherpetic neuralgia (PHN)
R Sanchez, J Burke, A Joshi, J Cappelleri, M Cattaneo, M Kulakodlu, and R Halpren; Pfizer, New York, NY
G Irving, R Sathyanarayana, and M Sweeney; Depomed, Inc., Menlo Park, CA
The study objective was to compare changes in all-cause and painful diabetic peripheral neuropathy (pDPN)-related healthcare costs in patients initiating treatment with pregabalin (PGB) and duloxetine (DLX) in real-world settings. Patients (318 years) initiating PGB or DLX between 6/1/07-12/31/08 were identified from a large US managed care plan database. Those with 3 1 medical claim with: (1) primary or secondary ICD-9-CM code of 357.2; or (2) primary code of 249.xx or 250.xx plus 337.1, 354.4, 354.5, 354.8, 354.9, 355.7x, 355.8, 355.9 or 356.9 on the same claim were considered to have pDPN. The dispense date of the first PGB or DLX prescription was considered the index date. Patients were continuously enrolled for 6 months pre- and post-index date. Outcome variables included pre- and post-index all-cause and pDPN-related total health care costs. The pre-/post-index differences in costs were computed. Student’s t-tests were used to compare descriptive results. Multivariate analyses of allcause and pDPN-related total healthcare costs were conducted using difference-in-differences (DiD) models. A total of 1,785 PGB and 351 DLX patients were identified. Differences (PGB vs. DLX) in the pre-/post-index change in mean (SD) all-cause total health care costs [$1,411 (35,056) vs. $1,560 (26,799); p=0.93] or pDPN-related total health care costs [$704 (5,634) vs. -$240 (14,120); p=0.22] were not significant. DiD models showed significantly higher post-index vs. pre-index all-cause health care costs (cost ratio=1.32, 95% confidence interval [CI]: 1.02-1.72); no significant difference in all-cause costs attributable to PGB vs DLX therapy (0.97, CI: 0.75-1.26); no significant difference in post-index vs. pre-index pDPN-related health care costs (1.08 CI: 0.462.57); and significantly higher pDPN-related costs attributable to PGB vs DLX (2.34, CI: 1.01-5.46). There were no differences in all-cause healthcare costs between the PBG and DLX users but significantly greater pDPN-related health care costs attributable to initiation of PGB vs DLX were noted.
(369) Patterns of therapy switching, augmenting and discontinuation after initiation of treatment with select medications in patients with osteoarthritis: a retrospective claims database analysis A Sadosky, M Gore, D Leslie, K Tai, and M Seleznick; Pfizer Inc., New York, NY The objective of this study was to evaluate the patterns of therapy switching, augmenting and discontinuation after initiation of treatment with select medications in patients with osteoarthritis (OA). Using the LifeLinkÔ Health Plan Claims Database, patients with OA (ICD-9-CM code 715.XX) newly prescribed (index event) non-selective nonsteroidal anti-inflammatory drugs (NSAIDs, N=71,116; average age6SD, 52.969.4 years), Cyclooxygenase-2 inhibitors (COX-2s, N=12,111; 54.469.3 years), acetaminophen (N=1,929; 5169.5 years), tramadol (N=15,678; 53.5610.5 years) weak opioids (N=73,839; 54.3610.4 years) and strong opioids (N=32,337; 52.969.9 years) were identified. Patterns of therapy switching, augmenting, and discontinuation were evaluated during the 12-months post-index period. Substantial proportions of OA patients switched therapy within a year after treatment initiation and rates of therapy switching were significantly different (p<0.0001) across the evaluated drugs groups: NSAIDs, 22.3%; Cox-2s, 27.5%; acetaminophen, 46.0%; tramadol, 44.5%; weak opioids, 27.2%; and strong opioids, 41.1%. Patterns of therapy augmenting at 12-months were also significantly (p<0.0001) different, although rates of therapy augmentation were much lower: NSAIDs 6.7%; Cox2s,10%; acetaminophen, 6.5%; tramadol 8.4%; weak opioids, 4.1 %; and strong opioids, 3.3%. A majority of patients in each group discontinued therapy during the 12-months post-index period (93.2%, 87.4%, 98.7%, 95.6%, 98.3%, and 97% of patients in the NSAIDs, Cox-2s, acetaminophen, tramadol, weak opioids and strong opioids groups, respectively). An evaluation of estimated probabilities suggested that over two thirds of patients who switched, augmented or discontinued therapy did so within the first 2-months, and a majority did so within 6-months of treatment initiation. Results of this study suggest that therapy switching and discontinuation were fairly common among OA patients initiating treatment with the currently recommended medication classes for this painful condition. The observed high rates of therapy switching and discontinuation may be indicative of inadequate pain relief or potentially intolerable side-effects of therapies. This study was funded by Pfizer, Inc
G-ER has been demonstrated to be efficacious and well tolerated for treatment of PHN in a placebo-controlled, Phase 3 study conducted in the USA, Russia and Argentina. We examined the efficacy and tolerability of once-daily G-ER (1800 mg) as a function of study country. Patients with PHN $6 months and average daily pain (ADP) score $4 were randomized to G-ER or placebo for 10 weeks. The primary endpoint was baseline observation carried forward (BOCF) change in ADP, and rates of adverse events were compared. The intent-to-treat population included 450 patients (USA: G-ER, n=126, placebo, n=131; Russia: G-ER, n=81, placebo, n=80; Argentina, G-ER, n=13, placebo, n=19); the safety population included two additional patients from the USA (one each G-ER and placebo). Compared with the USA and Russia, patients from Argentina were older (mean ages [years]: USA, 65; Russia, 65; Argentina, 73), and had higher baseline mean ADP scores (USA, 6.5; Russia, 6.5; Argentina, 7.0). BOCF change in ADP scores were: USA, -0.78; Russia, -0.43; Argentina, 0.64 (p=0.006, 0.109 and 0.455, respectively [not powered for subgroups]). A $50% reduction from baseline ADP score was demonstrated for 35% of G-ER-treated patients in the USA, 24% of those from Russia and 15% of those in Argentina. In G-ERtreated patients from the USA, Russia and Argentina, dizziness was reported in 11.0%, 8.6% and 30.8%, respectively (placebo groups, 0%, 3% and 11%, respectively), and somnolence was reported in 7.1%, 1.2% and 15.4%, respectively (placebo groups, 3%, 3% and 5%, respectively). Gabapentin ER demonstrated greatest efficacy in the USA and less compelling efficacy and tolerability in Argentina. This may be partly attributable to the small numbers of patients in Argentina and may be influenced by differences in baseline characteristics and/or cultural differences in patient/physician interactions. Analysis funded by Depomed, Inc. Medical writing support funded by Abbott.
(371) Oxycodone HCl/niacin tablets may reduce abuse potential vs dose-equivalent oxycodone HCl in non-dependent recreational opioid users L Webster, R Rolleri, G Pixton, and K Sommerville; Lifetree Clinical Researchâ and Pain Clinic, Salt Lake City, UT Increased non-medical use of prescription opioids has created a need for opioid products with reduced abuse potential. Oxycodone HCl/niacin tablets combine oxycodone with niacin and functional inactive excipients to provide limits and impediments to intentional oral overconsumption and intranasal and intravenous abuse. This randomized, double-blind, placebo- and active-controlled, 5way crossover study compared the relative abuse potential of orally-administered immediate-release (IR) oxycodone HCl/niacin tablets to dose-equivalent IR oxycodone HCl tablets in 49 non-dependent recreational opioid users. Dose-response was also assessed. Subjects received: oxycodone/niacin-40/ 240mg, oxycodone/niacin-80/480mg, oxycodone-40mg, oxycodone-80mg, and placebo. Primary endpoint was Drug-Liking (bipolar visual analog scale [VAS]; 0=dislike an awful lot, 50=neither like nor dislike, 100=like an awful lot), assessed by area under effect curve (AUE0-1h, AUE0-2h, AUE0-3h), peak disliking effect (Emin), and effect at 0.5h post-dose (E0.5h). Other assessments included peak-liking effect (Emax), Take Drug Again Assessment (TDAA), and Overall Drug Liking (ODL); bipolar 100-point VAS for TDAA and ODL. There were significant differences between oxycodone/niacin and dose-corresponding IR oxycodone for Drug-Liking AUE0-1h, AUE0-2h, AUE0-3h, Emin, and E0.5h (p<0.0001, all comparisons) and for Emax (oxycodone/niacin-40/240mg, p=0.004; oxycodone/niacin-80/480mg, p<0.0001). Oxycodone/niacin-80/ 480mg was less liked than oxycodone/niacin-40/240mg, suggesting dose-response. Mean (SD) Drug-Liking scores for oxycodone/niacin-40/240mg and oxycodone/niacin-80/480mg were 47.0(20.3) and 40.1(23.4) at 0.5h, while scores for oxycodone-40mg and oxycodone-80mg were 66.0(16.3) and 74.8(16.7) (p<0.0001). TDAA and ODL also showed significant differences with greater liking of oxycodone without niacin compared to equivalent oxycodone with niacin. Adverse events (AEs) were consistent with known effects of oxycodone and niacin; most were mild or moderate in intensity. No serious AEs occurred. Results suggest that abuse potential of oxycodone/niacin tablets may be decreased compared with equivalent doses of IR oxycodone HCl in non-dependent recreational opioid users. Drug-Liking decreased with increased niacin dose. Early effects of overconsumption of oxycodone/niacin tablets may decrease abuse potential. Supported by King Pharmaceuticalsâ, Inc.