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The adverse event profile of Butrans™ (buprenorphine) transdermal system in patients ≥ 65 and < 65 years of age
Abstracts (348) The adverse event profile of ButransÔ (buprenorphine) transdermal system in patients $ 65 and < 65 years of age W Wen, S Lynch, C Munera, S Ripa, and R Swanton; Purdue Pharma LP, Stamford, CT Elderly patients may have an adverse event profile to drug treatments that differs from younger patients. Butrans is an approved 7-day buprenorphine transdermal system with 3 dose strengths (5, 10, and 20 mcg/hour). The objective of the analyses is to evaluate the incidence of AEs during Butrans treatment in patients <65 and $65 years of age. The incidences of AEs and AEs that led to treatment discontinuation were analyzed by age (<65 and $65 years) in 5415 Butrans-treated patients from 15 controlled and uncontrolled chronic pain studies, and in 1345 patients (receiving Butrans, placebo, Oxy/APAP, and HCD/APAP treatments) from 6 controlled chronic pain studies (a subset of the 15 studies); the odds ratios (95% CIs) of selected AEs were examined across treatments in the latter group. Of the 5415 Butrans-treated patients in chronic pain studies, 74.4% were <65 years old and 25.4% were $65 years old; 8.4% were $75 years old. Compared to patients <65 years of age, patients $65 years reported a higher incidence of AEs, including constipation, dry mouth, diarrhea, dizziness, fatigue, and somnolence. In contrast, patients <65 years reported higher incidence of headaches and application site-related AEs (such as pruritus, erythema, and rash). Among the patients in controlled chronic studies, a Butrans treatment-by-age interaction was suggested for dry mouth and fatigue. No such interaction was observed for other AEs. Of the AEs that led to treatment discontinuation, only constipation emerged with a notable difference in patients $65 years in both Butrans and placebo treatment groups. In conclusion, patients $65 years of age reported higher incidence of commonly occurring AEs due to age alone (eg, constipation, diarrhea, dizziness, and somnolence) or due to both age and treatment (eg, dry mouth and fatigue), compared to those <65 years of age.
The Journal of Pain
P63
F17 Patient Controlled Analgesia (350) Combined Analyses of Phase 2 studies for ARX-01 Sufentanil NanoTab PCA System for the management of moderate to severe post-operative pain H Minkowitz, N Singla, and P Palmer; Memorial Hermann Memorial City Medical Center, Houston, TX The ARX-01 Sufentanil NanoTab PCA System is a non-invasive, preprogrammed approach to patient-controlled analgesia (PCA) that avoids the issues of medication and programming errors which occur frequently with intravenous PCA (IV PCA). Patients utilize ARX-01 to sublingually deliver NanoTabs, a novel small dosage form of sufentanil, with a 20-minute lockout between dosing. ARX-01 uses radiofrequency identification to uniquely match each patient to the System dispensing device. Completion of two randomized, placebo-controlled Phase 2 studies and an open-label device functionality Phase 2 study have demonstrated that sufentanil NanoTabs are effective in treating both major orthopedic and abdominal post-operative pain with minimal adverse events. A total of 212 patients received study drug and were included in the overall safety analysis. ARX-01 (15 mcg) was the most efficacious dose of the three dosage strengths studied (5, 10 and 15 mcg), however, ARX-01 (10 mcg) also showed efficacy compared to placebo in a subgroup analysis of women in the orthopedic surgery placebo-controlled study (p<0.05), as well as in the overall population in the abdominal surgery study (p<0.001). Drop-out due to inadequate analgesia for ARX-01 (15 mcg) averaged 16% in the placebo-controlled studies and 7% in the open-label knee replacement study without any rescue or adjuvant analgesic agents being allowed after the initial 30 minutes of the study. The adverse event profile of ARX-01 (15 mcg; n=79) demonstrated a low incidence of somnolence (3%), oxygen desaturation (1%) and respiratory depression (0%) compared to published rates for IV PCA. The average redosing time was approximately 80 minutes for ARX-01 (15 mcg), whereas published IV PCA data indicates an average redosing time of 20 – 40 minutes. These Phase 2 data demonstrate ARX-01 is efficacious and well-tolerated and may be an optimal non-invasive PCA system. Supported by a grant from AcelRx Pharmaceuticals, Inc.
(349) Safety and efficacy of once-daily hydromorphone ER (OROS hydromorphone) compared with twice-daily oxycodone CR over 52 weeks in patients with moderate to severe chronic noncancer pain
(351) A pilot study comparing pain intensity before and after conversion from patient controlled analgesia (PCA) to oral or transdermal extended-release opioids
U Richarz, S Waechter, R Sabatowski, L Szczepanski, and H Binsfeld; Janssen-Cilag EMEA, Beerse, Belgium
The primary objective of this study was to compare patients’ self-reported pain intensity, level of satisfaction with their pain control, and side effects (drowsiness, pruritis, urinary retention, nausea and vomiting) before and after conversion from IV PCA to oral or transdermal extended-release opioids using a novel approach of initiating the oral or transdermal opioid prior to discontinuation of the PCA. Additionally, we collected the number of supplemental analgesic rescue doses required and opioid dose before and after conversion, as secondary endpoints. This prospective non-randomized, non-controlled, single-center, pilot study, collected patients’ self-reported variables by using a survey tool completed by patients, patient surrogate, or study investigator, at 2 pre-determined time intervals; within 4 hours before conversion to oral/transdermal extended-release opioids and then again within 4 hours after the discontinuation of the IV PCA. Pain intensity, level of patient satisfaction with their pain control, and side effects, were collected using an 11-point scale (0=none to 10=worst) prior to and after conversion. Analysis of the data will be conducted using appropriate statistical tests to determine if there were any measurable differences in patients’ pain intensity, satisfaction with their pain control and side effects when converted from IV PCA to oral or transdermal extended-release opioids.
Once-daily hydromorphone ER (OROSâ hydromorphone) and oxycodone CR are semisynthetic, extended-release opioid analgesics with established efficacy. An open-label, randomized, 24-week, flexible-dose study demonstrated noninferiority of once-daily hydromorphone ER versus oxycodone CR twice-daily for treatment of chronic noncancer pain. A total of 112 patients (60 once-daily hydromorphone ER, 52 oxycodone CR; mean age, 58.1 y; 54% female; 100% Caucasian) who completed the previously published core-phase study were enrolled in a 28-week, open-label extension study. The primary efficacy measure in the extension phase was change in Brief Pain Inventory (BPI) item ‘‘pain right now,’’ assessed at Weeks 38 and 52. Global assessments of efficacy, dosing convenience, and tolerability were secondary endpoints. Mean change in pain assessment from baseline to Week 38 was -3.0 (once-daily hydromorphone ER) vs 2.8 (oxycodone CR), and from baseline to the end of the extension phase was 2.9 vs. 2.8; these changes were similar to those observed in the core phase ( 3.0 vs 3.3). After 52 weeks, global assessment of efficacy was rated as ‘‘very good’’ or ‘‘good’’ in the majority of patients who entered the extension phase (once-daily hydromorphone ER, n=55 [91.7%]; oxycodone CR, n=45 [86.5%]). More patients in the once-daily hydromorphone ER group (n=21 [35.0%]) vs the oxycodone CR group (n=11 [21.2%]) assessed mode of drug intake as ‘‘very convenient.’’ The majority of patients receiving once-daily hydromorphone ER (88.3%) and oxycodone CR (88.5%) rated tolerability as ‘‘good’’ or ‘‘very good’’ at 52 weeks, with few patients discontinuing due to an adverse event (1.6% vs 0.4%). This extension study demonstrated that the effectiveness of once-daily hydromorphone ER and oxycodone CR was maintained through 1 year. Editorial and writing support was provided by Synchrony Medical LLC, funded by Covidien.
S Ustic, D Craig, S Kareem, and L Lau; H. Lee Moffitt Cancer Center, Tampa, FL
The Journal of Pain
P63
F17 Patient Controlled Analgesia (350) Combined Analyses of Phase 2 studies for ARX-01 Sufentanil NanoTab PCA System for the management of moderate to severe post-operative pain H Minkowitz, N Singla, and P Palmer; Memorial Hermann Memorial City Medical Center, Houston, TX The ARX-01 Sufentanil NanoTab PCA System is a non-invasive, preprogrammed approach to patient-controlled analgesia (PCA) that avoids the issues of medication and programming errors which occur frequently with intravenous PCA (IV PCA). Patients utilize ARX-01 to sublingually deliver NanoTabs, a novel small dosage form of sufentanil, with a 20-minute lockout between dosing. ARX-01 uses radiofrequency identification to uniquely match each patient to the System dispensing device. Completion of two randomized, placebo-controlled Phase 2 studies and an open-label device functionality Phase 2 study have demonstrated that sufentanil NanoTabs are effective in treating both major orthopedic and abdominal post-operative pain with minimal adverse events. A total of 212 patients received study drug and were included in the overall safety analysis. ARX-01 (15 mcg) was the most efficacious dose of the three dosage strengths studied (5, 10 and 15 mcg), however, ARX-01 (10 mcg) also showed efficacy compared to placebo in a subgroup analysis of women in the orthopedic surgery placebo-controlled study (p<0.05), as well as in the overall population in the abdominal surgery study (p<0.001). Drop-out due to inadequate analgesia for ARX-01 (15 mcg) averaged 16% in the placebo-controlled studies and 7% in the open-label knee replacement study without any rescue or adjuvant analgesic agents being allowed after the initial 30 minutes of the study. The adverse event profile of ARX-01 (15 mcg; n=79) demonstrated a low incidence of somnolence (3%), oxygen desaturation (1%) and respiratory depression (0%) compared to published rates for IV PCA. The average redosing time was approximately 80 minutes for ARX-01 (15 mcg), whereas published IV PCA data indicates an average redosing time of 20 – 40 minutes. These Phase 2 data demonstrate ARX-01 is efficacious and well-tolerated and may be an optimal non-invasive PCA system. Supported by a grant from AcelRx Pharmaceuticals, Inc.
(349) Safety and efficacy of once-daily hydromorphone ER (OROS hydromorphone) compared with twice-daily oxycodone CR over 52 weeks in patients with moderate to severe chronic noncancer pain
(351) A pilot study comparing pain intensity before and after conversion from patient controlled analgesia (PCA) to oral or transdermal extended-release opioids
U Richarz, S Waechter, R Sabatowski, L Szczepanski, and H Binsfeld; Janssen-Cilag EMEA, Beerse, Belgium
The primary objective of this study was to compare patients’ self-reported pain intensity, level of satisfaction with their pain control, and side effects (drowsiness, pruritis, urinary retention, nausea and vomiting) before and after conversion from IV PCA to oral or transdermal extended-release opioids using a novel approach of initiating the oral or transdermal opioid prior to discontinuation of the PCA. Additionally, we collected the number of supplemental analgesic rescue doses required and opioid dose before and after conversion, as secondary endpoints. This prospective non-randomized, non-controlled, single-center, pilot study, collected patients’ self-reported variables by using a survey tool completed by patients, patient surrogate, or study investigator, at 2 pre-determined time intervals; within 4 hours before conversion to oral/transdermal extended-release opioids and then again within 4 hours after the discontinuation of the IV PCA. Pain intensity, level of patient satisfaction with their pain control, and side effects, were collected using an 11-point scale (0=none to 10=worst) prior to and after conversion. Analysis of the data will be conducted using appropriate statistical tests to determine if there were any measurable differences in patients’ pain intensity, satisfaction with their pain control and side effects when converted from IV PCA to oral or transdermal extended-release opioids.
Once-daily hydromorphone ER (OROSâ hydromorphone) and oxycodone CR are semisynthetic, extended-release opioid analgesics with established efficacy. An open-label, randomized, 24-week, flexible-dose study demonstrated noninferiority of once-daily hydromorphone ER versus oxycodone CR twice-daily for treatment of chronic noncancer pain. A total of 112 patients (60 once-daily hydromorphone ER, 52 oxycodone CR; mean age, 58.1 y; 54% female; 100% Caucasian) who completed the previously published core-phase study were enrolled in a 28-week, open-label extension study. The primary efficacy measure in the extension phase was change in Brief Pain Inventory (BPI) item ‘‘pain right now,’’ assessed at Weeks 38 and 52. Global assessments of efficacy, dosing convenience, and tolerability were secondary endpoints. Mean change in pain assessment from baseline to Week 38 was -3.0 (once-daily hydromorphone ER) vs 2.8 (oxycodone CR), and from baseline to the end of the extension phase was 2.9 vs. 2.8; these changes were similar to those observed in the core phase ( 3.0 vs 3.3). After 52 weeks, global assessment of efficacy was rated as ‘‘very good’’ or ‘‘good’’ in the majority of patients who entered the extension phase (once-daily hydromorphone ER, n=55 [91.7%]; oxycodone CR, n=45 [86.5%]). More patients in the once-daily hydromorphone ER group (n=21 [35.0%]) vs the oxycodone CR group (n=11 [21.2%]) assessed mode of drug intake as ‘‘very convenient.’’ The majority of patients receiving once-daily hydromorphone ER (88.3%) and oxycodone CR (88.5%) rated tolerability as ‘‘good’’ or ‘‘very good’’ at 52 weeks, with few patients discontinuing due to an adverse event (1.6% vs 0.4%). This extension study demonstrated that the effectiveness of once-daily hydromorphone ER and oxycodone CR was maintained through 1 year. Editorial and writing support was provided by Synchrony Medical LLC, funded by Covidien.
S Ustic, D Craig, S Kareem, and L Lau; H. Lee Moffitt Cancer Center, Tampa, FL