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(225) The effects of nabilone on sleep in fibromyalgia: Results of a randomized controlled trial
P32 (224) Tapentadol immediate release compared with oxycodone immediate release for the relief of moderateto-severe pain in patients with end stage joint disease M Afilalo, C Oh, A Okamoto, I Van Hove, J Stegmann, D Upmalis; SMBD-Jewish General Hospital, Montreal, QC Tapentadol is a novel analgesic in a single molecule with a dual mode of action: mu-opioid receptor agonism and norepinephrine reuptake inhibition. The efficacy of tapentadol immediate release (IR) was studied in a double-blind, randomized, placebo-controlled, multicenter trial of patients with moderate-to-severe pain from end-stage joint disease. A total of 666 patients, randomized 1:1:1:1, received an oral dose of tapentadol IR 50 mg, tapentadol IR 75 mg, oxycodone IR 10 mg, or placebo (every 4-6 hours, maximum 6 doses/day). Statistically significant improvements in pain intensity compared with placebo as measured by the primary endpoint, the sum of pain intensity difference over 5 days, were demonstrated by tapentadol IR and oxycodone IR treatment groups (P ⬍0.001). Prespecified comparisons of efficacy indicated that both tapentadol IR dosing regimens (50 and 75 mg every 4-6 hours) were noninferior to oxycodone IR 10 mg. The most common adverse events were nausea, dizziness, and vomiting. Lower incidences of nausea (tapentadol IR, ⱕ21%; oxycodone IR, 41%), vomiting (tapentadol IR, ⱕ14%; oxycodone IR, 34%), and constipation (tapentadol IR, ⱕ7%; oxycodone IR, 26%) were associated with both doses of tapentadol IR treatment, compared with oxycodone IR 10 mg. Subsequent analyses of the odds ratio and 95% confidence intervals (CI) showed that tapentadol IR 50 and 75 mg have significantly lower odds for the incidence of composite nausea/vomiting and constipation compared with oxycodone IR 10 mg (odds ratios [95% CI]: nausea/vomiting—tapentadol IR 50 mg, 0.21 [0.128, 0.339]; tapentadol IR 75 mg, 0.32 [0.204, 0.501]; constipation— tapentadol IR 50 mg, 0.13 [0.057, 0.302]; tapentadol IR 75 mg, 0.20 [0.098, 0.398]). These findings indicate that tapentadol IR 50 and 75 mg were comparable to oxycodone IR 10 mg but with an improved gastrointestinal tolerability. Johnson & Johnson Pharmaceutical Research and Development and Gru¨nenthal GmbH supported this study.
(225) The effects of nabilone on sleep in fibromyalgia: Results of a randomized controlled trial M Ware, M Fitzcharles, Y Shir; McGill University, Montreal, QC Fibromyalgia (FM) is a chronic pain syndrome with generalized tender points. Insomnia affects over 75% of patients with FM, and tricyclic antidepressants are a mainstay of treatment. Cannabis has been used by patients with FM to help sleep. We evaluated the safety and efficacy of nabilone, a synthetic cannabinoid, for insomnia in FM. We conducted a randomized double-blind active control equivalency crossover trial to compare nabilone (0.5-1.0mg qHS) to amitriptyline (10-20mg qHS) in FM patients with chronic insomnia. Subjects received each drug for two weeks with a two-week washout. The primary outcome was sleep quality using the Insomnia Severity Index (ISI) and the Leeds Sleep Evaluation Questionnaire (LSEQ); secondary outcomes included pain, mood, quality of life and adverse events (AEs).Thirty-one subjects were enrolled and 29 completed the trial (26 female, mean age 49.5y). While sleep was improved by both nabilone and amitriptyline, nabilone was superior to amitriptyline (ISI difference⫽3.2, 95%CI 1.2-5.3). Nabilone was marginally better on the restfulness LSEQ sleep quality scale (difference⫽0.5 (0.0-1.0) but not on wakefulness (difference⫽0.3 (-0.2, 0.8)). Adverse events were all mild-moderate and were more frequent with nabilone (102) than amitriptyline (53). Most common AEs for nabilone were dizziness (10), nausea (9) and dry mouth (7). Nabilone is effective in improving sleep in patients with FM and is well tolerated. Low dose nabilone given once daily at night may be considered as an alternative to amitriptyline. Longer trials are needed to determine the duration of effect and to characterize long-term safety. This investigator-initiated trial was supported by a grant from Valeant Pharmaceuticals (Canada).
Abstracts (226) Tapentadol immediate release is associated with improved gastrointestinal tolerability compared with oxycodone immediate release over 90 days in patients with lower back or osteoarthritis pain C Oh, D Upmalis, A Okamoto, M Buzoianu, J Stegmann, J Gimbel; Johnson & Johnson Pharmaceutical Research and Development, Titusville, NJ Tapentadol is a novel, single-molecule analgesic with a dual mode of action: mu-opioid receptor agonism and norepinephrine reuptake inhibition. A randomized, double-blind, active-control, parallel group, multicenter trial of patients with low back pain or pain from osteoarthritis of the knee or hip studied the tolerability of long-term exposure (90 days) to tapentadol immediate release (IR). Patients (N ⫽ 878) were randomly assigned in a 4:1 ratio to a flexible dose of either tapentadol IR (50 or 100 mg/dose; maximum 600 mg/day) or oxycodone IR (10 or 15 mg/dose; maximum 90 mg/day) every 4 to 6 hours. Study drug was not taken by 29 patients who were excluded from all analyses. The CochranMantel-Haenszel test was used to estimate odds ratios for treatmentemergent nausea, vomiting, constipation, somnolence, and dizziness. Both treatment groups showed similar pain scores throughout the study. Treatment-emergent adverse events (TEAEs) in the tapentadol IR group (76%) were lower than in the oxycodone IR group (83%). The most common TEAEs for both groups were nausea, vomiting, dizziness, constipation, headache, and somnolence. The incidences of nausea, vomiting, constipation, and the composite of nausea/vomiting were significantly lower in the tapentadol IR group than in the oxycodone IR group (P ⬍0.001 for all treatment comparisons). The odds ratios and corresponding confidence intervals for nausea, vomiting, constipation, and composite of nausea/vomiting were 0.542 (0.37, 0.79), 0.476 (0.32, 0.70), 0.396 (0.26, 0.59), and 0.458 (0.33, 0.65), respectively; indicating more favorable incidence rates for the tapentadol IR group compared with the oxycodone IR group. The incidences of somnolence or dizziness were not significantly different between the treatment groups. These findings show tapentadol IR is associated with substantially improved gastrointestinal tolerability compared with oxycodone IR at doses providing similar pain relief. This study was supported by Johnson & Johnson Pharmaceutical Research and Development and Gru¨nenthal GmbH.
(227) Efficacy profile of tapentadol, a novel centrally active analgesic with a combined mode of action, in animal pain models T Tzschentke, T Christoph, M Me´en, B Ko¨gel, K Schiene, J De Vry; Gru¨nenthal GmbH, Aachen, Germany Society for Neuroscience abstract
(225) The effects of nabilone on sleep in fibromyalgia: Results of a randomized controlled trial M Ware, M Fitzcharles, Y Shir; McGill University, Montreal, QC Fibromyalgia (FM) is a chronic pain syndrome with generalized tender points. Insomnia affects over 75% of patients with FM, and tricyclic antidepressants are a mainstay of treatment. Cannabis has been used by patients with FM to help sleep. We evaluated the safety and efficacy of nabilone, a synthetic cannabinoid, for insomnia in FM. We conducted a randomized double-blind active control equivalency crossover trial to compare nabilone (0.5-1.0mg qHS) to amitriptyline (10-20mg qHS) in FM patients with chronic insomnia. Subjects received each drug for two weeks with a two-week washout. The primary outcome was sleep quality using the Insomnia Severity Index (ISI) and the Leeds Sleep Evaluation Questionnaire (LSEQ); secondary outcomes included pain, mood, quality of life and adverse events (AEs).Thirty-one subjects were enrolled and 29 completed the trial (26 female, mean age 49.5y). While sleep was improved by both nabilone and amitriptyline, nabilone was superior to amitriptyline (ISI difference⫽3.2, 95%CI 1.2-5.3). Nabilone was marginally better on the restfulness LSEQ sleep quality scale (difference⫽0.5 (0.0-1.0) but not on wakefulness (difference⫽0.3 (-0.2, 0.8)). Adverse events were all mild-moderate and were more frequent with nabilone (102) than amitriptyline (53). Most common AEs for nabilone were dizziness (10), nausea (9) and dry mouth (7). Nabilone is effective in improving sleep in patients with FM and is well tolerated. Low dose nabilone given once daily at night may be considered as an alternative to amitriptyline. Longer trials are needed to determine the duration of effect and to characterize long-term safety. This investigator-initiated trial was supported by a grant from Valeant Pharmaceuticals (Canada).
Abstracts (226) Tapentadol immediate release is associated with improved gastrointestinal tolerability compared with oxycodone immediate release over 90 days in patients with lower back or osteoarthritis pain C Oh, D Upmalis, A Okamoto, M Buzoianu, J Stegmann, J Gimbel; Johnson & Johnson Pharmaceutical Research and Development, Titusville, NJ Tapentadol is a novel, single-molecule analgesic with a dual mode of action: mu-opioid receptor agonism and norepinephrine reuptake inhibition. A randomized, double-blind, active-control, parallel group, multicenter trial of patients with low back pain or pain from osteoarthritis of the knee or hip studied the tolerability of long-term exposure (90 days) to tapentadol immediate release (IR). Patients (N ⫽ 878) were randomly assigned in a 4:1 ratio to a flexible dose of either tapentadol IR (50 or 100 mg/dose; maximum 600 mg/day) or oxycodone IR (10 or 15 mg/dose; maximum 90 mg/day) every 4 to 6 hours. Study drug was not taken by 29 patients who were excluded from all analyses. The CochranMantel-Haenszel test was used to estimate odds ratios for treatmentemergent nausea, vomiting, constipation, somnolence, and dizziness. Both treatment groups showed similar pain scores throughout the study. Treatment-emergent adverse events (TEAEs) in the tapentadol IR group (76%) were lower than in the oxycodone IR group (83%). The most common TEAEs for both groups were nausea, vomiting, dizziness, constipation, headache, and somnolence. The incidences of nausea, vomiting, constipation, and the composite of nausea/vomiting were significantly lower in the tapentadol IR group than in the oxycodone IR group (P ⬍0.001 for all treatment comparisons). The odds ratios and corresponding confidence intervals for nausea, vomiting, constipation, and composite of nausea/vomiting were 0.542 (0.37, 0.79), 0.476 (0.32, 0.70), 0.396 (0.26, 0.59), and 0.458 (0.33, 0.65), respectively; indicating more favorable incidence rates for the tapentadol IR group compared with the oxycodone IR group. The incidences of somnolence or dizziness were not significantly different between the treatment groups. These findings show tapentadol IR is associated with substantially improved gastrointestinal tolerability compared with oxycodone IR at doses providing similar pain relief. This study was supported by Johnson & Johnson Pharmaceutical Research and Development and Gru¨nenthal GmbH.
(227) Efficacy profile of tapentadol, a novel centrally active analgesic with a combined mode of action, in animal pain models T Tzschentke, T Christoph, M Me´en, B Ko¨gel, K Schiene, J De Vry; Gru¨nenthal GmbH, Aachen, Germany Society for Neuroscience abstract