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Fentanyl Sublingual (SL) Spray: reduction of breakthrough cancer pain 5-minutes post dose
P50
The Journal of Pain
F05 Cancer Pain - Opioids (296) Fentanyl Sublingual (SL) Spray: reduction of breakthrough cancer pain 5-minutes post dose R Rauck, L Stearns, M Scherlis, N Parikh, and L Dillaha; Carolinas Pain Institute Center for Clinical Research, Winston-Salem, NC This randomized, double-blind, placebo-controlled, multicenter phase 3 study assessed Fentanyl SL Spray for the treatment of breakthrough cancer pain. The primary endpoint was assessment of summed pain intensity differences (SPID) at 30 minutes post treatment. We present pain assessment data for Fentanyl SL Spray versus placebo at the 5-minute postdose time point. Fentanyl SL Spray doses of 100, 200, 400, 600, 800, 1200 (2x600), or 1600 (2x800)mg were available during titration and double-blind study periods. Of 130 opioid-tolerant patients enrolled in the 21(+5)-day open-label titration period, 98 (75%) were randomized to the 21(+5)-day double-blind period. Mean (standard deviation [SD]) age of the double-blind population was 54.1 (11.7) years. Median (range) dose of Fentanyl SL Spray during the double-blind period was 800 (100, 1600) mg. At 5-minutes post dose, mean (SD) SPID scores were 40.3 (57.7) and 32.0 (52.1) for Fentanyl SL Spray and placebo treatments, respectively; a significant difference of 8.3 (34.1; P=.0219) was reported. Total pain relief (TOTPAR) scores 5-minutes post dose were significantly improved with Fentanyl SL Spray (8.6 [3.5]) versus placebo (7.6 [3.3]); (difference, 1.0 [2.2]; P<.0001). Adverse events (AEs) reported most frequently ($5% of patients) in the titration period included nausea (13.1%), somnolence (8.5%), dizziness (7.7%), vomiting (7.7%), pyrexia (6.2%), diarrhea (5.4%), and peripheral edema (5.4%). Most frequently reported AEs in the double-blind period were nausea (7.1%), hyperhidrosis (5.1%), and peripheral edema (5.1%). Three deaths were reported (titration period, n=2; double-blind period, n=1), all of which were due to underlying disease progression and considered unrelated to study drug. Fentanyl SL Spray demonstrated statistically significant improvements in breakthrough cancer pain relief compared with placebo at 5-minutes post dose. No unexpected safety issues were reported. Financial support for this study was provided by INSYS Therapeutics.
Abstracts (298) Safety and efficacy of Fentanyl Sublingual (SL) Spray in the treatment of breakthrough cancer pain L Reynolds, J Geach, N Parikh, L Dillaha, and J Bull; Loma Linda University, Loma Linda, CA This randomized, double-blind, placebo-controlled, phase 3 study evaluated the safety and efficacy of Fentanyl SL Spray for the treatment of breakthrough cancer pain. Fentanyl SL Spray at doses of 100, 200, 400, 600, 800, 1200 (2x600), or 1600 (2x800) mg were available for the titration and double-blind study periods. The primary endpoint was evaluation of summed pain intensity differences at 30 minutes post treatment (SPID30). Safety was assessed throughout the study. A total of 98/130 (75%) opioid-tolerant patients that enrolled in the 21(+5)-day open-label titration study period were randomized to the 21 (+5)-day double-blind period. Mean (standard deviation [SD]) age for the double-blind population was 54.1 (11.7) years. Median (range) dose of Fentanyl SL Spray in the double-blind period was 800 (100, 1600) mg. Mean (SD) SPID30 scores were 640.3 (458.8) and 399.6 (391.2) for the Fentanyl SL Spray and placebo treatments, respectively; a significant difference of 240.7 (362.9; P<.0001) was reported between treatments. Mean (SD) total pain relief at 30 minutes was significantly improved (P<.0001) in patients treated with Fentanyl SL Spray (78.3 [20.4]) versus placebo (61.0 [20.8]). Most frequently reported ($5% of patients) adverse events (AEs) during the titration period included nausea (13.1%), somnolence (8.5%), dizziness (7.7%), vomiting (7.7%), pyrexia (6.2%), diarrhea (5.4%), and peripheral edema (5.4%). In the double-blind period, most frequently reported AEs were nausea (7.1%), hyperhidrosis (5.1%), and peripheral edema (5.1%). Three deaths were reported; 2 in the titration period and one in the double-blind period. All deaths were due to the underlying disease progression and were considered unrelated to study drug. Fentanyl SL Spray was significantly more effective at relieving breakthrough cancer pain compared with placebo. No new safety concerns were identified. Financial support for this study was provided by INSYS Therapeutics.
(297) Evaluation of fentanyl buccal soluble film (FBSF) in opioid tolerant cancer patients with neuropathic breakthrough cancer pain (BTP)
(299) Impact of pain variability on response to sublingual fentanyl tablets and placebo in opioid-tolerant patients with breakthrough cancer pain
K Stanley, L Gever, and W Wheeler; Copernicus Group IRB, Cary, NC
J Howell, A Yellowlees, and G Guillory; ProStrakan Group, Galashiels, UK
Neuropathic pain, in particular neuropathic breakthrough cancer pain (BTP), is poorly understood and difficult to effectively control. Pain clinicians generally use agents that are not ordinarily used as analgesics, such as anticonvulsants and antidepressants, alpha-2 adrenergic agonists and NMDA receptor antagonists in combination with opioids as treatments. In 2009, a fentanyl buccal soluble film (FBSF) was approved for the management of BTP in opioid-tolerant cancer patients $18 years of age. The safety and efficacy of FBSF was studied in a multicenter, randomized, double-blind, placebo-controlled, multiplecrossover study in adult cancer patients on stable opioid therapy who reported #4 BTP episodes per day. A subgroup of patients from that trial was analyzed to evaluate the efficacy and safety of FBSF in patients with neuropathic BTP pain. The primary variable evaluated was the sum of pain intensity differences (SPID) at 30 minutes with higher scores correlating with greater pain relief. Adverse events were recorded and summarized. Fourteen females and nine males (mean age 51 years) were included in the subgroup analysis and breast cancer (n=6) was the most prevalent type of cancer among these patients. Pain reduction after treatment with FBSF was greater than after treatment with placebo. SPID values in patients with neuropathic BTP were significantly higher for FBSFtreated episodes than for those episodes treated with placebo beginning 15 minutes after dosing. FBSF was as effective in this subgroup as in the entire population. The most commonly reported adverse events included somnolence, nausea, and dizziness. The results of this subgroup analysis indicate that FBSF may aid in the management of breakthrough cancer pain in patients experiencing neuropathic pain. This subgroup analysis was supported by a grant from Meda Pharmaceuticals, Inc.
Recent research suggests that pain variability at baseline impacts response to active and placebo treatments in painful conditions, including fibromyalgia. This relationship has not been previously explored for breakthrough pain (BTP) and could have implications for treatment choice and trial design. This analysis was conducted to assess whether a relationship exists between baseline pain intensity variability and treatment response in opioid-tolerant patients receiving sublingual fentanyl tablets (Abstralâ) for cancer-associated BTP. Analyses are based on data from a randomized, placebo-controlled, multicenter, phase 3 trial of sublingual fentanyl for BTP in patients with cancer. A total of 64 patients (intent-to-treat population) received 10 doses of study medication (7 doses of sublingual fentanyl and 3 doses of placebo, in random order), administered by placing tablets on the floor of the mouth directly beneath the tongue, until completely dissolved. Pain variability was measured by variance of pain intensity at baseline over all BTP episodes. Efficacy measures included mean sum of pain intensity difference (SPID) at 30 minutes and mean pain intensity difference at 10 and 15 minutes. Baseline pain intensity variability was evaluated in relationship to response to placebo, response to sublingual fentanyl, and difference in response between treatments. Linear regression was used to test whether baseline BTP variability affected response. There was no evidence of a relationship between BTP variability at baseline and response to placebo, response to active treatment, or difference in response for any measures of pain evaluated. For SPID30, the P value for response to sublingual fentanyl was P=.978 and for response to placebo was P=.702. The results of this exploratory analysis suggest that BTP variability at baseline has no impact on response to sublingual fentanyl or placebo. Editorial and writing support was provided by Synchrony Medical LLC, funded by ProStrakan Group plc.
The Journal of Pain
F05 Cancer Pain - Opioids (296) Fentanyl Sublingual (SL) Spray: reduction of breakthrough cancer pain 5-minutes post dose R Rauck, L Stearns, M Scherlis, N Parikh, and L Dillaha; Carolinas Pain Institute Center for Clinical Research, Winston-Salem, NC This randomized, double-blind, placebo-controlled, multicenter phase 3 study assessed Fentanyl SL Spray for the treatment of breakthrough cancer pain. The primary endpoint was assessment of summed pain intensity differences (SPID) at 30 minutes post treatment. We present pain assessment data for Fentanyl SL Spray versus placebo at the 5-minute postdose time point. Fentanyl SL Spray doses of 100, 200, 400, 600, 800, 1200 (2x600), or 1600 (2x800)mg were available during titration and double-blind study periods. Of 130 opioid-tolerant patients enrolled in the 21(+5)-day open-label titration period, 98 (75%) were randomized to the 21(+5)-day double-blind period. Mean (standard deviation [SD]) age of the double-blind population was 54.1 (11.7) years. Median (range) dose of Fentanyl SL Spray during the double-blind period was 800 (100, 1600) mg. At 5-minutes post dose, mean (SD) SPID scores were 40.3 (57.7) and 32.0 (52.1) for Fentanyl SL Spray and placebo treatments, respectively; a significant difference of 8.3 (34.1; P=.0219) was reported. Total pain relief (TOTPAR) scores 5-minutes post dose were significantly improved with Fentanyl SL Spray (8.6 [3.5]) versus placebo (7.6 [3.3]); (difference, 1.0 [2.2]; P<.0001). Adverse events (AEs) reported most frequently ($5% of patients) in the titration period included nausea (13.1%), somnolence (8.5%), dizziness (7.7%), vomiting (7.7%), pyrexia (6.2%), diarrhea (5.4%), and peripheral edema (5.4%). Most frequently reported AEs in the double-blind period were nausea (7.1%), hyperhidrosis (5.1%), and peripheral edema (5.1%). Three deaths were reported (titration period, n=2; double-blind period, n=1), all of which were due to underlying disease progression and considered unrelated to study drug. Fentanyl SL Spray demonstrated statistically significant improvements in breakthrough cancer pain relief compared with placebo at 5-minutes post dose. No unexpected safety issues were reported. Financial support for this study was provided by INSYS Therapeutics.
Abstracts (298) Safety and efficacy of Fentanyl Sublingual (SL) Spray in the treatment of breakthrough cancer pain L Reynolds, J Geach, N Parikh, L Dillaha, and J Bull; Loma Linda University, Loma Linda, CA This randomized, double-blind, placebo-controlled, phase 3 study evaluated the safety and efficacy of Fentanyl SL Spray for the treatment of breakthrough cancer pain. Fentanyl SL Spray at doses of 100, 200, 400, 600, 800, 1200 (2x600), or 1600 (2x800) mg were available for the titration and double-blind study periods. The primary endpoint was evaluation of summed pain intensity differences at 30 minutes post treatment (SPID30). Safety was assessed throughout the study. A total of 98/130 (75%) opioid-tolerant patients that enrolled in the 21(+5)-day open-label titration study period were randomized to the 21 (+5)-day double-blind period. Mean (standard deviation [SD]) age for the double-blind population was 54.1 (11.7) years. Median (range) dose of Fentanyl SL Spray in the double-blind period was 800 (100, 1600) mg. Mean (SD) SPID30 scores were 640.3 (458.8) and 399.6 (391.2) for the Fentanyl SL Spray and placebo treatments, respectively; a significant difference of 240.7 (362.9; P<.0001) was reported between treatments. Mean (SD) total pain relief at 30 minutes was significantly improved (P<.0001) in patients treated with Fentanyl SL Spray (78.3 [20.4]) versus placebo (61.0 [20.8]). Most frequently reported ($5% of patients) adverse events (AEs) during the titration period included nausea (13.1%), somnolence (8.5%), dizziness (7.7%), vomiting (7.7%), pyrexia (6.2%), diarrhea (5.4%), and peripheral edema (5.4%). In the double-blind period, most frequently reported AEs were nausea (7.1%), hyperhidrosis (5.1%), and peripheral edema (5.1%). Three deaths were reported; 2 in the titration period and one in the double-blind period. All deaths were due to the underlying disease progression and were considered unrelated to study drug. Fentanyl SL Spray was significantly more effective at relieving breakthrough cancer pain compared with placebo. No new safety concerns were identified. Financial support for this study was provided by INSYS Therapeutics.
(297) Evaluation of fentanyl buccal soluble film (FBSF) in opioid tolerant cancer patients with neuropathic breakthrough cancer pain (BTP)
(299) Impact of pain variability on response to sublingual fentanyl tablets and placebo in opioid-tolerant patients with breakthrough cancer pain
K Stanley, L Gever, and W Wheeler; Copernicus Group IRB, Cary, NC
J Howell, A Yellowlees, and G Guillory; ProStrakan Group, Galashiels, UK
Neuropathic pain, in particular neuropathic breakthrough cancer pain (BTP), is poorly understood and difficult to effectively control. Pain clinicians generally use agents that are not ordinarily used as analgesics, such as anticonvulsants and antidepressants, alpha-2 adrenergic agonists and NMDA receptor antagonists in combination with opioids as treatments. In 2009, a fentanyl buccal soluble film (FBSF) was approved for the management of BTP in opioid-tolerant cancer patients $18 years of age. The safety and efficacy of FBSF was studied in a multicenter, randomized, double-blind, placebo-controlled, multiplecrossover study in adult cancer patients on stable opioid therapy who reported #4 BTP episodes per day. A subgroup of patients from that trial was analyzed to evaluate the efficacy and safety of FBSF in patients with neuropathic BTP pain. The primary variable evaluated was the sum of pain intensity differences (SPID) at 30 minutes with higher scores correlating with greater pain relief. Adverse events were recorded and summarized. Fourteen females and nine males (mean age 51 years) were included in the subgroup analysis and breast cancer (n=6) was the most prevalent type of cancer among these patients. Pain reduction after treatment with FBSF was greater than after treatment with placebo. SPID values in patients with neuropathic BTP were significantly higher for FBSFtreated episodes than for those episodes treated with placebo beginning 15 minutes after dosing. FBSF was as effective in this subgroup as in the entire population. The most commonly reported adverse events included somnolence, nausea, and dizziness. The results of this subgroup analysis indicate that FBSF may aid in the management of breakthrough cancer pain in patients experiencing neuropathic pain. This subgroup analysis was supported by a grant from Meda Pharmaceuticals, Inc.
Recent research suggests that pain variability at baseline impacts response to active and placebo treatments in painful conditions, including fibromyalgia. This relationship has not been previously explored for breakthrough pain (BTP) and could have implications for treatment choice and trial design. This analysis was conducted to assess whether a relationship exists between baseline pain intensity variability and treatment response in opioid-tolerant patients receiving sublingual fentanyl tablets (Abstralâ) for cancer-associated BTP. Analyses are based on data from a randomized, placebo-controlled, multicenter, phase 3 trial of sublingual fentanyl for BTP in patients with cancer. A total of 64 patients (intent-to-treat population) received 10 doses of study medication (7 doses of sublingual fentanyl and 3 doses of placebo, in random order), administered by placing tablets on the floor of the mouth directly beneath the tongue, until completely dissolved. Pain variability was measured by variance of pain intensity at baseline over all BTP episodes. Efficacy measures included mean sum of pain intensity difference (SPID) at 30 minutes and mean pain intensity difference at 10 and 15 minutes. Baseline pain intensity variability was evaluated in relationship to response to placebo, response to sublingual fentanyl, and difference in response between treatments. Linear regression was used to test whether baseline BTP variability affected response. There was no evidence of a relationship between BTP variability at baseline and response to placebo, response to active treatment, or difference in response for any measures of pain evaluated. For SPID30, the P value for response to sublingual fentanyl was P=.978 and for response to placebo was P=.702. The results of this exploratory analysis suggest that BTP variability at baseline has no impact on response to sublingual fentanyl or placebo. Editorial and writing support was provided by Synchrony Medical LLC, funded by ProStrakan Group plc.