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Effective dose titration of fentanyl sublingual spray in patients with breakthrough cancer pain: results from the open-label phase of a double-blind, placebo-controlled study
S64
The Journal of Pain
Abstracts
(352) Intrathecal morphine in cancer pain management: common findings in clinical status and basic science
(354) Long-term safety of fentanyl sublingual spray in opioidtolerant patients with breakthrough cancer pain
S Hattori, H Sano, J Takarada, and M Yokota; The Cancer Institute Hospital of JFCR, Tokyo, Japan
L Stearns, R Brownlow, N Parikh, L Dillaha, and S Atkinson; The Center for Pain and Supportive Care, Scottsdale, AZ
In a case of intractable cancer pain in spite of high dose of opioids, intrathecal administration of morphine is often selected. We implant intrathecal(IT) catheter insertion with subcutaneous port for the route of morphine and local anesthetic infusion (no implantable pumps are available in Japan). In 49 patients, average pain score decreased from 7.09 to 2.31, given opioid decreased from 705mg/day(oral) to 10.0mg/day(IT). Additionally, median adjuvant drug numbers had decreased from 3drugs to none. From the basic study data from Hoshi Univ.Sch.Pharm, antinociceptive action induced by s.c. injection of morphine was suppressed in mice with severe pain. However, there were no significant differences between normal and severe pain groups in antinociception induced by i.t. administration of morphine. It is also noteworthy that either s.c. or i.t. administered morphine-6-glucuronide (M6G)-induced antinociception was significantly suppressed under the long-lasting pain. These animal data supports the fact of adjuvant drugs reduction in cases of IT morphine of our clinical data.
A sublingual formulation of fentanyl, fentanyl sublingual spray, has been developed to treat breakthrough cancer pain (BTCP) in opioid-tolerant patients. Efficacy and safety of this formulation were assessed in a phase 3, double-blind, placebo-controlled trial. The study objective was to examine the longer-term safety of fentanyl sublingual spray in a 90-day open-label, maintenance period. Patients completing the double-blind trial were offered enrollment into the open-label maintenance period at their optimal dose achieved in the doubleblind trial. De novo patients were also enrolled and titrated to an optimal dose (100-1600 mcg) that provided effective analgesia for 2 consecutive BTCP episodes. Adverse events (AEs) were recorded at all visits. Of the 229 de novo patients, 184 (80%) completed titration. One hundred seventy-nine (78%) de novo patients and 90 rollover patients entered the maintenance period (n=269), and 163 (61%) completed the period. Median dose was 600 mcg. During titration, 59.0% of de novo patients reported $1 AE, the most common being nausea (13.1%), vomiting (11.8%), and somnolence (10.0%). Thirty-two percent of patients reported AEs considered at least possibly related to study treatment. During maintenance, 80.7% of patients reported $1 AE, most commonly malignant disease progression (24.2%), vomiting (16.0%), and peripheral edema (11.5%). AEs considered at least possibly related to study treatment were reported in 24.5% of patients. Eighty-nine deaths occurred, with 88 unrelated to treatment, and 1 (cardiac arrhythmia) considered possibly related. Serious AEs other than death were reported in 6.1% and 11.9% of patients in each period and were most commonly related to underlying cancer. This analysis indicates that fentanyl sublingual spray is generally safe and well tolerated. Technical editorial and medical writing assistance provided by Synchrony Medical, LLC, West Chester, PA, funded by INSYS Therapeutics, Phoenix, AZ.
(353) Effective dose titration of fentanyl sublingual spray in patients with breakthrough cancer pain: results from the open-label phase of a double-blind, placebo-controlled study
(355) Patient satisfaction with fentanyl sublingual spray in opioid-tolerant patients with breakthrough cancer pain
R Rauck, J Bull, N Parikh, L Dillaha, and L Stearns; Center for Clinical Research, Winston-Salem, NC
Breakthrough cancer pain (BTCP) is associated with decreased satisfaction with around-the-clock opioid therapy. The objective of this analysis was to examine patient satisfaction with a sublingual formulation of fentanyl, fentanyl sublingual spray, during open-label titration (n=130) and double-blind treatment (n=96) in a randomized, placebo-controlled study. Opioid-tolerant patients with 1-4 episodes of BTCP/day were included. During a 26-day, open-label titration phase, a successful dose (100-1600 mcg) was established that provided effective analgesia for 2 consecutive BTCP episodes. During a 26-day doubleblind phase, patients received 7 units of study medication and 3 units of placebo. The Treatment Satisfaction Questionnaire for Medication (TSQM) was administered at baseline to assess satisfaction with previous BTCP medication and end of titration to assess satisfaction with fentanyl sublingual spray. Global evaluation (GE) of study medication was performed 30 and 60 minutes post-dose during double-blind treatment. All TSQM domains increased from baseline to end of titration, with effectiveness (mean [SE]: 48.8 [1.6] to 75.2 [1.2]) and global satisfaction (55.1 [1.8] to 75.4 [1.4]) showing greatest improvement. Satisfaction with symptom relief improved to 88%, from 27% with previous BTCP medication. Mean GE scores were significantly improved at 30 and 60 minutes with fentanyl sublingual spray versus placebo (P<0.0001). Seventyeight patients (60%) during titration and 47 (48%) during double-blind treatment reported $1 adverse event (AE). Common AEs were nausea (13.1%) and somnolence (8.5%) during titration, and nausea (7.1%), peripheral edema (5.1%), and hyperhidrosis (5.1%) during double-blind treatment. Most (88%) AEs were mild or moderate in severity. These data indicate markedly improved satisfaction among patients receiving fentanyl sublingual spray relative to previous BTCP medications. Technical editorial and medical writing assistance provided by Synchrony Medical, LLC, West Chester, PA, funded by INSYS Therapeutics, Phoenix, AZ.
Breakthrough cancer pain (BTCP) is commonly managed with formulations of transmucosal fentanyl. A novel sublingual formulation of fentanyl, fentanyl sublingual spray, has been developed to enhance the rate and extent of fentanyl absorption and potentially the onset of analgesia. This analysis presents results from the 26-day open-label titration phase of a phase 3, randomized, double-blind, placebo-controlled study. Opioid-tolerant patients with 1-4 episodes of BTCP/d were enrolled. For randomization into double-blind treatment, patients must have successfully titrated to a dose (100-1600 mcg) that provided effective analgesia for 2 consecutive BTCP episodes. The Treatment Satisfaction Questionnaire for Medication was assessed at screening to determine satisfaction with previous BTCP medication and at the end of titration to determine satisfaction with fentanyl sublingual spray. Of 130 patients undergoing titration, 98 (75%) achieved a successful dose; the median dose was 800 mcg, and the most common doses were 800 mcg (22.4%) and 1200 mcg (20.4%). Of 32 (25%) patients that withdrew from titration, only 3 (2.3%) were unable to establish an effective dose. At the end of titration, 89% were satisfied, very satisfied, or extremely satisfied with fentanyl sublingual spray, compared with 41% with their previous BTCP medication. Notably, 90% were at least satisfied with the onset of effect of fentanyl sublingual spray versus 21% in relation to previous BTCP treatment. Seventy-eight patients (60%) reported $1 adverse event (AE). Thirty-three AEs (25.4%) were considered probably related to treatment, the most common being nausea (6.2%) and somnolence (4.6%). These data demonstrate that in patients with BTCP, fentanyl sublingual spray can be safely titrated to an effective dose, and many prefer this treatment over previous BTCP medications. Technical editorial and medical writing assistance provided by Synchrony Medical, LLC, West Chester, PA, funded by INSYS Therapeutics, Phoenix, AZ.
L Reynolds, J Barker, N Parikh, L Dillaha, and R Rauck; Loma Linda University, Loma Linda, CA
The Journal of Pain
Abstracts
(352) Intrathecal morphine in cancer pain management: common findings in clinical status and basic science
(354) Long-term safety of fentanyl sublingual spray in opioidtolerant patients with breakthrough cancer pain
S Hattori, H Sano, J Takarada, and M Yokota; The Cancer Institute Hospital of JFCR, Tokyo, Japan
L Stearns, R Brownlow, N Parikh, L Dillaha, and S Atkinson; The Center for Pain and Supportive Care, Scottsdale, AZ
In a case of intractable cancer pain in spite of high dose of opioids, intrathecal administration of morphine is often selected. We implant intrathecal(IT) catheter insertion with subcutaneous port for the route of morphine and local anesthetic infusion (no implantable pumps are available in Japan). In 49 patients, average pain score decreased from 7.09 to 2.31, given opioid decreased from 705mg/day(oral) to 10.0mg/day(IT). Additionally, median adjuvant drug numbers had decreased from 3drugs to none. From the basic study data from Hoshi Univ.Sch.Pharm, antinociceptive action induced by s.c. injection of morphine was suppressed in mice with severe pain. However, there were no significant differences between normal and severe pain groups in antinociception induced by i.t. administration of morphine. It is also noteworthy that either s.c. or i.t. administered morphine-6-glucuronide (M6G)-induced antinociception was significantly suppressed under the long-lasting pain. These animal data supports the fact of adjuvant drugs reduction in cases of IT morphine of our clinical data.
A sublingual formulation of fentanyl, fentanyl sublingual spray, has been developed to treat breakthrough cancer pain (BTCP) in opioid-tolerant patients. Efficacy and safety of this formulation were assessed in a phase 3, double-blind, placebo-controlled trial. The study objective was to examine the longer-term safety of fentanyl sublingual spray in a 90-day open-label, maintenance period. Patients completing the double-blind trial were offered enrollment into the open-label maintenance period at their optimal dose achieved in the doubleblind trial. De novo patients were also enrolled and titrated to an optimal dose (100-1600 mcg) that provided effective analgesia for 2 consecutive BTCP episodes. Adverse events (AEs) were recorded at all visits. Of the 229 de novo patients, 184 (80%) completed titration. One hundred seventy-nine (78%) de novo patients and 90 rollover patients entered the maintenance period (n=269), and 163 (61%) completed the period. Median dose was 600 mcg. During titration, 59.0% of de novo patients reported $1 AE, the most common being nausea (13.1%), vomiting (11.8%), and somnolence (10.0%). Thirty-two percent of patients reported AEs considered at least possibly related to study treatment. During maintenance, 80.7% of patients reported $1 AE, most commonly malignant disease progression (24.2%), vomiting (16.0%), and peripheral edema (11.5%). AEs considered at least possibly related to study treatment were reported in 24.5% of patients. Eighty-nine deaths occurred, with 88 unrelated to treatment, and 1 (cardiac arrhythmia) considered possibly related. Serious AEs other than death were reported in 6.1% and 11.9% of patients in each period and were most commonly related to underlying cancer. This analysis indicates that fentanyl sublingual spray is generally safe and well tolerated. Technical editorial and medical writing assistance provided by Synchrony Medical, LLC, West Chester, PA, funded by INSYS Therapeutics, Phoenix, AZ.
(353) Effective dose titration of fentanyl sublingual spray in patients with breakthrough cancer pain: results from the open-label phase of a double-blind, placebo-controlled study
(355) Patient satisfaction with fentanyl sublingual spray in opioid-tolerant patients with breakthrough cancer pain
R Rauck, J Bull, N Parikh, L Dillaha, and L Stearns; Center for Clinical Research, Winston-Salem, NC
Breakthrough cancer pain (BTCP) is associated with decreased satisfaction with around-the-clock opioid therapy. The objective of this analysis was to examine patient satisfaction with a sublingual formulation of fentanyl, fentanyl sublingual spray, during open-label titration (n=130) and double-blind treatment (n=96) in a randomized, placebo-controlled study. Opioid-tolerant patients with 1-4 episodes of BTCP/day were included. During a 26-day, open-label titration phase, a successful dose (100-1600 mcg) was established that provided effective analgesia for 2 consecutive BTCP episodes. During a 26-day doubleblind phase, patients received 7 units of study medication and 3 units of placebo. The Treatment Satisfaction Questionnaire for Medication (TSQM) was administered at baseline to assess satisfaction with previous BTCP medication and end of titration to assess satisfaction with fentanyl sublingual spray. Global evaluation (GE) of study medication was performed 30 and 60 minutes post-dose during double-blind treatment. All TSQM domains increased from baseline to end of titration, with effectiveness (mean [SE]: 48.8 [1.6] to 75.2 [1.2]) and global satisfaction (55.1 [1.8] to 75.4 [1.4]) showing greatest improvement. Satisfaction with symptom relief improved to 88%, from 27% with previous BTCP medication. Mean GE scores were significantly improved at 30 and 60 minutes with fentanyl sublingual spray versus placebo (P<0.0001). Seventyeight patients (60%) during titration and 47 (48%) during double-blind treatment reported $1 adverse event (AE). Common AEs were nausea (13.1%) and somnolence (8.5%) during titration, and nausea (7.1%), peripheral edema (5.1%), and hyperhidrosis (5.1%) during double-blind treatment. Most (88%) AEs were mild or moderate in severity. These data indicate markedly improved satisfaction among patients receiving fentanyl sublingual spray relative to previous BTCP medications. Technical editorial and medical writing assistance provided by Synchrony Medical, LLC, West Chester, PA, funded by INSYS Therapeutics, Phoenix, AZ.
Breakthrough cancer pain (BTCP) is commonly managed with formulations of transmucosal fentanyl. A novel sublingual formulation of fentanyl, fentanyl sublingual spray, has been developed to enhance the rate and extent of fentanyl absorption and potentially the onset of analgesia. This analysis presents results from the 26-day open-label titration phase of a phase 3, randomized, double-blind, placebo-controlled study. Opioid-tolerant patients with 1-4 episodes of BTCP/d were enrolled. For randomization into double-blind treatment, patients must have successfully titrated to a dose (100-1600 mcg) that provided effective analgesia for 2 consecutive BTCP episodes. The Treatment Satisfaction Questionnaire for Medication was assessed at screening to determine satisfaction with previous BTCP medication and at the end of titration to determine satisfaction with fentanyl sublingual spray. Of 130 patients undergoing titration, 98 (75%) achieved a successful dose; the median dose was 800 mcg, and the most common doses were 800 mcg (22.4%) and 1200 mcg (20.4%). Of 32 (25%) patients that withdrew from titration, only 3 (2.3%) were unable to establish an effective dose. At the end of titration, 89% were satisfied, very satisfied, or extremely satisfied with fentanyl sublingual spray, compared with 41% with their previous BTCP medication. Notably, 90% were at least satisfied with the onset of effect of fentanyl sublingual spray versus 21% in relation to previous BTCP treatment. Seventy-eight patients (60%) reported $1 adverse event (AE). Thirty-three AEs (25.4%) were considered probably related to treatment, the most common being nausea (6.2%) and somnolence (4.6%). These data demonstrate that in patients with BTCP, fentanyl sublingual spray can be safely titrated to an effective dose, and many prefer this treatment over previous BTCP medications. Technical editorial and medical writing assistance provided by Synchrony Medical, LLC, West Chester, PA, funded by INSYS Therapeutics, Phoenix, AZ.
L Reynolds, J Barker, N Parikh, L Dillaha, and R Rauck; Loma Linda University, Loma Linda, CA