Martin Hale | SUNY: University at Buffalo (original) (raw)
Papers by Martin Hale
The Journal of Pain, 2014
The Journal of Pain, 2014
The Journal of Pain, 2017
We evaluated the long-term efficacy of oral once-daily AVINZA® vs. twice-daily OxyContin® in pati... more We evaluated the long-term efficacy of oral once-daily AVINZA® vs. twice-daily OxyContin® in patients 30-70 years old requiring opioid therapy for chronic moderate-to-severe low back pain. This was a randomized, open-label, parallel-group multi-center extension study. Following Part I of the ACTION Trial (AVINZA vs. OxyContin Comparator Trial In Opioid Naïve low back pain patients), patients were eligible to enroll in a four-month open-label extension study continuing on the same medication prescribed during the acute phase (Part I). Subjects were evaluated monthly for pain, sleep, and rescue medication usage for the next four months. The Investigator was allowed to adjust the subject's dose as needed to maintain an optimal risk/benefit balance. From the initial 8-week ITT study population of 132 and 134 subjects (AVINZA and OxyContin, respectively), 95 and 79 patients entered and 77 and 55 completed the extension study. The improvements in aroundthe-clock pain control and quality of sleep observed for AVINZA in Part I of the ACTION Study were maintained or further improved during the four-month extension phase. Mean NRS pain scores decreased to 3.1 for AVINZA and 3.5 for OxyContin (P ϭ 0.01 favoring AVINZA) compared to final week-8 scores of 3.5 for AVINZA and 3.8 for OxyContin. The improvement shown in the quality of sleep was also maintained. These results were achieved with a significantly lower daily morphine-equivalent requirement in the AVINZA group (86 mg) compared to patients using OxyContin (119 mg, P ϭ 0.0029). The incidence of elicited opioid side effects remained similar in the two groups. This open-label, 4-month extension study showed that improvements in around-theclock pain control and quality of sleep with once-a-day AVINZA observed in Part I of the ACTION Study were maintained for an extended period. Complete final data will be presented. Supported by Ligand Pharmaceuticals Inc. and Organon Pharmaceuticals USA Inc.
Pain Management, 2020
Buprenorphine is a Schedule III opioid with unique pharmacodynamic and pharmacokinetic properties... more Buprenorphine is a Schedule III opioid with unique pharmacodynamic and pharmacokinetic properties that contribute to effective analgesia and fewer safety risks than other opioids. This review article focuses on the buccal film formulation, which is preferable to other buprenorphine formulations on the basis of bioavailability, safety and efficacy. The clinical studies reviewed here confirm that buprenorphine buccal film offers effective and continuous pain relief that is generally well tolerated, with no cases of respiratory depression reported in any of the studies. On the basis of these clinical data and individual patient risk/benefit assessments, clinicians should consider utilizing buprenorphine buccal film as a first-line opioid treatment for chronic pain over other buprenorphine formulations or other opioids.
Journal of Pain Research
Objective: Opioid-induced constipation is among the most common side effects associated with opio... more Objective: Opioid-induced constipation is among the most common side effects associated with opioid use in patients with chronic non-cancer pain, and it can have a significant negative impact on health-related quality of life (QOL). This analysis evaluated the effect of naldemedine 0.2 mg on patient-reported outcomes in three phase 3 clinical studies. Methods: COMPOSE-1 and COMPOSE-2 were identical randomized, double-blind, placebocontrolled, parallel-group studies of 12 weeks' duration, allowing data to be integrated (n=1095). COMPOSE-3 was similar in design, but of 52 weeks' duration (n=1241). Patients were adults with chronic non-cancer pain who had been treated with opioid analgesics for ≥3 months and experiencing opioid-induced constipation. Patient-reported outcomes included Patient Assessment of Constipation Symptoms (PAC-SYM; 12 questions assessed on a 5-point Likert scale), PAC-QOL (28 questions assessed on a 5-point Likert scale), and Subject Global Satisfaction (measured on a 7-point Likert scale). The proportion of patients achieving a ≥1.5 improvement in PAC-SYM and PAC-QOL was calculated. The correlation between change in PAC-SYM and PAC-QOL scores and frequency of bowel movements was also explored. Results: The proportion of PAC-SYM and PAC-QOL responders was significantly higher for naldemedine than for placebo at all assessed time points in COMPOSE-1/COMPOSE-2 (p<0.005 for both) and COMPOSE-3 (p<0.005 and p<0.0001, respectively). There was a statistically significant correlation between improvement in PAC-SYM/PAC-QOL and frequency of bowel movements at all time points (p≤0.0002). The majority of patients treated with naldemedine reported markedly or moderately improved satisfaction with constipation and abdominal symptoms on the Subject Global Satisfaction questionnaire. Discussion: Naldemedine treatment was associated with a rapid and sustained clinically relevant improvement in patient-reported outcomes, indicating improvement in opioidinduced constipation-related symptoms and QOL. ClinicalTrials.gov Registration:
Supplemental material, sj-docx-1-tag-10.1177_17562848211032320 for Naldemedine is effective in th... more Supplemental material, sj-docx-1-tag-10.1177_17562848211032320 for Naldemedine is effective in the treatment of opioid-induced constipation in patients with chronic non-cancer pain who had a poor response to laxatives by Martin E. Hale, James E. Wild, Tadaaki Yamada, Takaaki Yokota, Jan Tack, Viola Andresen and Asbjørn Mohr Drewes in Therapeutic Advances in Gastroenterology
Effectiveness and gastrointestinal tolerability during conversion and titration with once-daily O... more Effectiveness and gastrointestinal tolerability during conversion and titration with once-daily OROS ® hydromorphone extended release in opioid-tolerant patients with chronic low back pain
Journal of Pain Research, 2021
Health care providers in the United States are facing challenges in selecting appropriate medicat... more Health care providers in the United States are facing challenges in selecting appropriate medication for patients with acute and chronic pain in the midst of the current opioid crisis and COVID-19 pandemic. When compared with conventional opioids, the partial µ-opioid receptor agonist buprenorphine has unique pharmacologic properties that may be more desirable for pain management. The formulations of buprenorphine approved by the US Food and Drug Administration for pain management include intravenous injection, transdermal patch, and buccal film. A comparison of efficacy and safety data from studies of buprenorphine and conventional opioids suggests that buprenorphine may be a better-tolerated treatment option for many patients that provides similar or superior analgesia. Our benefit-risk assessment in this narrative review suggests that health care providers should consider that buprenorphine may be an appropriate alternative for pain management over other opioids.
Drugs & Aging, 2020
Background Opioid-induced constipation (OIC), the most common side effect of opioid treatment, is... more Background Opioid-induced constipation (OIC), the most common side effect of opioid treatment, is under-recognized and undertreated in older patients. Naldemedine, an oral, peripherally acting μ-opioid receptor antagonist (PAMORA), is approved in Japan, the United States, and the European Union for treatment of OIC in adult patients. Objective This integrated analysis of three phase 3 trials (COMPOSE-1, COMPOSE-2, and COMPOSE-3) evaluated the safety and efficacy of naldemedine for up to 12 weeks in a subgroup of patients aged ≥ 65 years. Methods Patients aged 18-80 years with chronic non-cancer pain for ≥ 3 months (treated with opioids for ≥ 3 months in COMPOSE-1 and COMPOSE-2) and OIC received oral naldemedine 0.2 mg or placebo once daily. Safety assessments included overall incidence of treatment-emergent adverse events (TEAEs), TEAEs in the gastrointestinal disorders System Organ Class, and TEAEs of opioid withdrawal or possible opioid withdrawal. Efficacy was based on the proportion of responders in COMPOSE-1 and COMPOSE-2, defined as having ≥ 3 spontaneous bowel movements/week and a ≥ 1-spontaneous bowel movement/week increase from baseline for ≥ 9 of 12 weeks and ≥ 3 of the last 4 weeks. Results A total of 14.8% (344/2328) of patients were aged ≥ 65 years in all studies. The incidence of TEAEs in naldemedinetreated patients aged ≥ 65 years (45.9%) was comparable to that in patients aged ≥ 65 years receiving placebo (51.6%) and in the overall naldemedine group (47.1%). The incidence of gastrointestinal disorders System Organ Class TEAEs in naldemedine-treated patients aged ≥ 65 years (20.2%) was also comparable to that in patients aged ≥ 65 years receiving placebo (16.1%) and in the overall naldemedine group (21.8%). The incidence of TEAEs of opioid withdrawal with naldemedine was 1.1% in patients aged ≥ 65 years and 1.0% overall, and the incidence of TEAEs of possible opioid withdrawal was 1.1% in patients aged ≥ 65 years and 1.7% overall. The proportion of responders was higher in naldemedine-treated patients versus placebo, both overall (50.1% vs 34.1%; p < 0.0001) and in those aged ≥ 65 years (51.8% vs 37.6%). Conclusions This integrated analysis confirmed that OIC treatment with naldemedine 0.2 mg was generally well tolerated and effective in patients aged ≥ 65 years with chronic non-cancer pain. Safety and efficacy results were consistent with the overall patient population. ClinicalTrials.gov registration NCT01965158, NCT01993940, NCT01965652.
The Journal of Pain, 2014
The Journal of Pain, 2014
An extended-release (ER) hydrocodone tablet formulated using OraGuard Ô technology was developed ... more An extended-release (ER) hydrocodone tablet formulated using OraGuard Ô technology was developed to provide sustained pain relief while protecting against rapid release of hydrocodone when tablets are comminuted or taken with alcohol. Aberrant drug-related behaviors and addiction were evaluated in a 12-month, phase 3, open-label study. Eligible patients had either previously completed a 12-week, randomized, placebo-controlled study of ER hydrocodone or were newly enrolled with chronic ($3 months) noncancer pain; excluded were those taking oxycodone 135 mg/day (or equivalent) for 14 days or with recent history/current substance/alcohol abuse. After titrating ER hydrocodone (15-90 mg every 12 hours) to a successful dose, patients received up to 52 weeks of open-label treatment. Aberrant drug-related behaviors or addiction were assessed using Screener and Opioid Assessment for Patients with Pain-Revised (SOAPP-R), Addiction Behavior Checklist (ABC), and Current Opioid Misuse Measure (COMM) questionnaires. Study drug diversion and loss were monitored throughout the study. In total, 329 patients received 1ERhydrocodonedose.Atweek4,mean(SD)SOAPP−Rtotalscorewas6.7(6.7)and751 ER hydrocodone dose. At week 4, mean (SD) SOAPP-R total score was 6.7 (6.7) and 75% of patients had SOAPP-R scores <18 (indicative of patients with lower occurrence of aberrant drug use behavior). The majority of patients had ABC scores <3 at baseline (97%) and endpoint (99%) and COMM scores <9 at baseline (86%) and endpoint (91%); ABC scores 1ERhydrocodonedose.Atweek4,mean(SD)SOAPP−Rtotalscorewas6.7(6.7)and753 and COMM scores $9 are considered predictive of aberrant drug-related behavior. Eight (2.4%) patients reported study drug diversion, and 36 (10.9%) reported loss of study drug. No patients were withdrawn from the study owing to diversion or loss of study drug. The low occurrences of inappropriate opioid use, aberrant drug use behavior, and study drug diversion during this long-term safety study may support the potential abuse-deterrent properties of the new ER hydrocodone tablet formulated with OraGuard Ô technology. Sponsored by Cephalon, now a subsidiary of Teva Pharmaceuticals.
The Journal of Pain, 2011
In this enriched design study, 1,160 opioid-experienced patients with chronic, moderate to severe... more In this enriched design study, 1,160 opioid-experienced patients with chronic, moderate to severe low back pain entered an open-label run-in period; 660 demonstrated analgesic benefit from and tolerability to buprenorphine transdermal system 20 mcg/hour (BTDS 20) treatment and were randomized to receive either BTDS 20, BTDS 5 mcg/hour (BTDS 5), or the active control (immediate release oxycodone 40-mg/day) during an 84-day double-blind phase. The primary endpoint, ''average pain in the last 24 hours'' during double-blind weeks 4, 8, and 12, was significantly lower for patients receiving BTDS 20 compared with patients receiving BTDS 5 (P < .001, treatment difference of À.67). A treatment difference of À.75 in favor of oxycodone 40 mg/day versus BTDS 5 (P < .001) indicated the assay sensitivity of the study. Four sensitivity analyses, secondary, and exploratory analyses supported the results of the primary analysis. Incidences of treatment-emergent adverse events were 56% during the open-label period, and 59, 77, and 73% for the BTDS 5, BTDS 20, and oxycodone 40 mg/day treatment groups, respectively, during the double-blind phase. One death considered unrelated to study treatment occurred in a patient receiving BTDS 10 during the run-in period. BTDS 20 treatment was demonstrated to be efficacious and generally well tolerated. Perspective: This article presents results of a pivotal Phase 3 study that assesses a new treatment for the management of chronic low back pain: a transdermal patch containing the opioid buprenorphine (BTDS). In this active controlled, superiority study with an enriched design, BTDS 20 was found to be efficacious and generally well tolerated.
American Journal of Gastroenterology
American Journal of Gastroenterology
Background: Two studies demonstrated the efficacy and safety of naldemedine in adult patients wit... more Background: Two studies demonstrated the efficacy and safety of naldemedine in adult patients with chronic non-cancer pain and opioid-induced constipation (OIC). However, no studies have compared the efficacy of peripherally acting µ-opioid receptor antagonists in patients with adequate and inadequate responses to prior OIC therapy with laxatives. This post hoc analysis of integrated data from the two previous studies compared the efficacy of naldemedine in patients who were unsuccessfully treated with laxatives [poor laxative responders (PLRs)] with those who either did not receive laxatives >30 days prior to screening or those who only received rescue laxative at or after screening (non-PLRs). Methods: Patients with OIC were randomized to once-daily treatment with naldemedine 0.2 mg or placebo. The primary efficacy endpoint was the proportion of responders [⩾3 spontaneous bowel movements (SBMs)/week and an increase from baseline of ⩾1 SBM/week for ⩾9 weeks of the 12-week treatm...
Journal of Pain Research
Purpose: Naldemedine, an oral, peripherally acting μ-opioid receptor antagonist approved for the ... more Purpose: Naldemedine, an oral, peripherally acting μ-opioid receptor antagonist approved for the treatment of opioid-induced constipation (OIC), is renally excreted. This subgroup analysis integrated data from 3 Phase 3 trials (COMPOSE-1, COMPOSE-2, COMPOSE-3) to evaluate the safety and efficacy of naldemedine in patients with renal impairment (RI). Patients and Methods: Patients age 18-80 years with chronic non-cancer pain (CNCP) and OIC received oral naldemedine 0.2 mg or placebo once daily. RI subgroups consisted of patients with normal function (baseline glomerular filtration rate ≥90 mL/min/1.73 m 2), mild (≥60 to <90 mL/min/1.73 m 2), and moderate (≥30 to <60 mL/min/1.73 m 2) RI. Safety assessments based on ≤12 weeks of treatment from all 3 studies included incidence of treatment-emergent adverse events (TEAEs). Efficacy was based on the proportion of responders in COMPOSE-1 and COMPOSE-2 only, defined as ≥3 spontaneous bowel movements (SBMs)/week and a ≥1-SBM/week increase from baseline for ≥9 of 12 weeks and ≥3 of the last 4 weeks. Results: In total, 2328 patients were included in this analysis. The incidence of TEAEs was similar in the naldemedine and placebo groups (overall, 47.1% vs 45.6%; normal, 44.6% vs 43.6%; mild RI, 49.0% vs 44.7%; moderate RI, 46.6% vs 55.9%). GI-related TEAEs occurred more frequently in the naldemedine group versus placebo (overall, 21.8% vs 13.8%; normal, 21.6% vs 12.5%; mild RI, 22.6% vs 14.7%; moderate RI, 18.0% vs 14.2%). A significantly greater proportion of patients in the naldemedine 0.2 mg group were responders versus the placebo group (overall, 50.1% vs 34.1%, P<0.0001; normal, 52.0% vs 39.3%; mild RI, 48.3% vs 30.3%; moderate RI, 52.5% vs 31.7%). Conclusion: This integrated analysis confirmed that OIC treatment with naldemedine 0.2 mg was generally well tolerated and effective in patients with CNCP and mild or moderate RI. Safety and efficacy results were consistent with the overall population.
American Journal of Gastroenterology
The Journal of Pain, 2014
The Journal of Pain, 2014
The Journal of Pain, 2017
We evaluated the long-term efficacy of oral once-daily AVINZA® vs. twice-daily OxyContin® in pati... more We evaluated the long-term efficacy of oral once-daily AVINZA® vs. twice-daily OxyContin® in patients 30-70 years old requiring opioid therapy for chronic moderate-to-severe low back pain. This was a randomized, open-label, parallel-group multi-center extension study. Following Part I of the ACTION Trial (AVINZA vs. OxyContin Comparator Trial In Opioid Naïve low back pain patients), patients were eligible to enroll in a four-month open-label extension study continuing on the same medication prescribed during the acute phase (Part I). Subjects were evaluated monthly for pain, sleep, and rescue medication usage for the next four months. The Investigator was allowed to adjust the subject's dose as needed to maintain an optimal risk/benefit balance. From the initial 8-week ITT study population of 132 and 134 subjects (AVINZA and OxyContin, respectively), 95 and 79 patients entered and 77 and 55 completed the extension study. The improvements in aroundthe-clock pain control and quality of sleep observed for AVINZA in Part I of the ACTION Study were maintained or further improved during the four-month extension phase. Mean NRS pain scores decreased to 3.1 for AVINZA and 3.5 for OxyContin (P ϭ 0.01 favoring AVINZA) compared to final week-8 scores of 3.5 for AVINZA and 3.8 for OxyContin. The improvement shown in the quality of sleep was also maintained. These results were achieved with a significantly lower daily morphine-equivalent requirement in the AVINZA group (86 mg) compared to patients using OxyContin (119 mg, P ϭ 0.0029). The incidence of elicited opioid side effects remained similar in the two groups. This open-label, 4-month extension study showed that improvements in around-theclock pain control and quality of sleep with once-a-day AVINZA observed in Part I of the ACTION Study were maintained for an extended period. Complete final data will be presented. Supported by Ligand Pharmaceuticals Inc. and Organon Pharmaceuticals USA Inc.
Pain Management, 2020
Buprenorphine is a Schedule III opioid with unique pharmacodynamic and pharmacokinetic properties... more Buprenorphine is a Schedule III opioid with unique pharmacodynamic and pharmacokinetic properties that contribute to effective analgesia and fewer safety risks than other opioids. This review article focuses on the buccal film formulation, which is preferable to other buprenorphine formulations on the basis of bioavailability, safety and efficacy. The clinical studies reviewed here confirm that buprenorphine buccal film offers effective and continuous pain relief that is generally well tolerated, with no cases of respiratory depression reported in any of the studies. On the basis of these clinical data and individual patient risk/benefit assessments, clinicians should consider utilizing buprenorphine buccal film as a first-line opioid treatment for chronic pain over other buprenorphine formulations or other opioids.
Journal of Pain Research
Objective: Opioid-induced constipation is among the most common side effects associated with opio... more Objective: Opioid-induced constipation is among the most common side effects associated with opioid use in patients with chronic non-cancer pain, and it can have a significant negative impact on health-related quality of life (QOL). This analysis evaluated the effect of naldemedine 0.2 mg on patient-reported outcomes in three phase 3 clinical studies. Methods: COMPOSE-1 and COMPOSE-2 were identical randomized, double-blind, placebocontrolled, parallel-group studies of 12 weeks' duration, allowing data to be integrated (n=1095). COMPOSE-3 was similar in design, but of 52 weeks' duration (n=1241). Patients were adults with chronic non-cancer pain who had been treated with opioid analgesics for ≥3 months and experiencing opioid-induced constipation. Patient-reported outcomes included Patient Assessment of Constipation Symptoms (PAC-SYM; 12 questions assessed on a 5-point Likert scale), PAC-QOL (28 questions assessed on a 5-point Likert scale), and Subject Global Satisfaction (measured on a 7-point Likert scale). The proportion of patients achieving a ≥1.5 improvement in PAC-SYM and PAC-QOL was calculated. The correlation between change in PAC-SYM and PAC-QOL scores and frequency of bowel movements was also explored. Results: The proportion of PAC-SYM and PAC-QOL responders was significantly higher for naldemedine than for placebo at all assessed time points in COMPOSE-1/COMPOSE-2 (p<0.005 for both) and COMPOSE-3 (p<0.005 and p<0.0001, respectively). There was a statistically significant correlation between improvement in PAC-SYM/PAC-QOL and frequency of bowel movements at all time points (p≤0.0002). The majority of patients treated with naldemedine reported markedly or moderately improved satisfaction with constipation and abdominal symptoms on the Subject Global Satisfaction questionnaire. Discussion: Naldemedine treatment was associated with a rapid and sustained clinically relevant improvement in patient-reported outcomes, indicating improvement in opioidinduced constipation-related symptoms and QOL. ClinicalTrials.gov Registration:
Supplemental material, sj-docx-1-tag-10.1177_17562848211032320 for Naldemedine is effective in th... more Supplemental material, sj-docx-1-tag-10.1177_17562848211032320 for Naldemedine is effective in the treatment of opioid-induced constipation in patients with chronic non-cancer pain who had a poor response to laxatives by Martin E. Hale, James E. Wild, Tadaaki Yamada, Takaaki Yokota, Jan Tack, Viola Andresen and Asbjørn Mohr Drewes in Therapeutic Advances in Gastroenterology
Effectiveness and gastrointestinal tolerability during conversion and titration with once-daily O... more Effectiveness and gastrointestinal tolerability during conversion and titration with once-daily OROS ® hydromorphone extended release in opioid-tolerant patients with chronic low back pain
Journal of Pain Research, 2021
Health care providers in the United States are facing challenges in selecting appropriate medicat... more Health care providers in the United States are facing challenges in selecting appropriate medication for patients with acute and chronic pain in the midst of the current opioid crisis and COVID-19 pandemic. When compared with conventional opioids, the partial µ-opioid receptor agonist buprenorphine has unique pharmacologic properties that may be more desirable for pain management. The formulations of buprenorphine approved by the US Food and Drug Administration for pain management include intravenous injection, transdermal patch, and buccal film. A comparison of efficacy and safety data from studies of buprenorphine and conventional opioids suggests that buprenorphine may be a better-tolerated treatment option for many patients that provides similar or superior analgesia. Our benefit-risk assessment in this narrative review suggests that health care providers should consider that buprenorphine may be an appropriate alternative for pain management over other opioids.
Drugs & Aging, 2020
Background Opioid-induced constipation (OIC), the most common side effect of opioid treatment, is... more Background Opioid-induced constipation (OIC), the most common side effect of opioid treatment, is under-recognized and undertreated in older patients. Naldemedine, an oral, peripherally acting μ-opioid receptor antagonist (PAMORA), is approved in Japan, the United States, and the European Union for treatment of OIC in adult patients. Objective This integrated analysis of three phase 3 trials (COMPOSE-1, COMPOSE-2, and COMPOSE-3) evaluated the safety and efficacy of naldemedine for up to 12 weeks in a subgroup of patients aged ≥ 65 years. Methods Patients aged 18-80 years with chronic non-cancer pain for ≥ 3 months (treated with opioids for ≥ 3 months in COMPOSE-1 and COMPOSE-2) and OIC received oral naldemedine 0.2 mg or placebo once daily. Safety assessments included overall incidence of treatment-emergent adverse events (TEAEs), TEAEs in the gastrointestinal disorders System Organ Class, and TEAEs of opioid withdrawal or possible opioid withdrawal. Efficacy was based on the proportion of responders in COMPOSE-1 and COMPOSE-2, defined as having ≥ 3 spontaneous bowel movements/week and a ≥ 1-spontaneous bowel movement/week increase from baseline for ≥ 9 of 12 weeks and ≥ 3 of the last 4 weeks. Results A total of 14.8% (344/2328) of patients were aged ≥ 65 years in all studies. The incidence of TEAEs in naldemedinetreated patients aged ≥ 65 years (45.9%) was comparable to that in patients aged ≥ 65 years receiving placebo (51.6%) and in the overall naldemedine group (47.1%). The incidence of gastrointestinal disorders System Organ Class TEAEs in naldemedine-treated patients aged ≥ 65 years (20.2%) was also comparable to that in patients aged ≥ 65 years receiving placebo (16.1%) and in the overall naldemedine group (21.8%). The incidence of TEAEs of opioid withdrawal with naldemedine was 1.1% in patients aged ≥ 65 years and 1.0% overall, and the incidence of TEAEs of possible opioid withdrawal was 1.1% in patients aged ≥ 65 years and 1.7% overall. The proportion of responders was higher in naldemedine-treated patients versus placebo, both overall (50.1% vs 34.1%; p < 0.0001) and in those aged ≥ 65 years (51.8% vs 37.6%). Conclusions This integrated analysis confirmed that OIC treatment with naldemedine 0.2 mg was generally well tolerated and effective in patients aged ≥ 65 years with chronic non-cancer pain. Safety and efficacy results were consistent with the overall patient population. ClinicalTrials.gov registration NCT01965158, NCT01993940, NCT01965652.
The Journal of Pain, 2014
The Journal of Pain, 2014
An extended-release (ER) hydrocodone tablet formulated using OraGuard Ô technology was developed ... more An extended-release (ER) hydrocodone tablet formulated using OraGuard Ô technology was developed to provide sustained pain relief while protecting against rapid release of hydrocodone when tablets are comminuted or taken with alcohol. Aberrant drug-related behaviors and addiction were evaluated in a 12-month, phase 3, open-label study. Eligible patients had either previously completed a 12-week, randomized, placebo-controlled study of ER hydrocodone or were newly enrolled with chronic ($3 months) noncancer pain; excluded were those taking oxycodone 135 mg/day (or equivalent) for 14 days or with recent history/current substance/alcohol abuse. After titrating ER hydrocodone (15-90 mg every 12 hours) to a successful dose, patients received up to 52 weeks of open-label treatment. Aberrant drug-related behaviors or addiction were assessed using Screener and Opioid Assessment for Patients with Pain-Revised (SOAPP-R), Addiction Behavior Checklist (ABC), and Current Opioid Misuse Measure (COMM) questionnaires. Study drug diversion and loss were monitored throughout the study. In total, 329 patients received 1ERhydrocodonedose.Atweek4,mean(SD)SOAPP−Rtotalscorewas6.7(6.7)and751 ER hydrocodone dose. At week 4, mean (SD) SOAPP-R total score was 6.7 (6.7) and 75% of patients had SOAPP-R scores <18 (indicative of patients with lower occurrence of aberrant drug use behavior). The majority of patients had ABC scores <3 at baseline (97%) and endpoint (99%) and COMM scores <9 at baseline (86%) and endpoint (91%); ABC scores 1ERhydrocodonedose.Atweek4,mean(SD)SOAPP−Rtotalscorewas6.7(6.7)and753 and COMM scores $9 are considered predictive of aberrant drug-related behavior. Eight (2.4%) patients reported study drug diversion, and 36 (10.9%) reported loss of study drug. No patients were withdrawn from the study owing to diversion or loss of study drug. The low occurrences of inappropriate opioid use, aberrant drug use behavior, and study drug diversion during this long-term safety study may support the potential abuse-deterrent properties of the new ER hydrocodone tablet formulated with OraGuard Ô technology. Sponsored by Cephalon, now a subsidiary of Teva Pharmaceuticals.
The Journal of Pain, 2011
In this enriched design study, 1,160 opioid-experienced patients with chronic, moderate to severe... more In this enriched design study, 1,160 opioid-experienced patients with chronic, moderate to severe low back pain entered an open-label run-in period; 660 demonstrated analgesic benefit from and tolerability to buprenorphine transdermal system 20 mcg/hour (BTDS 20) treatment and were randomized to receive either BTDS 20, BTDS 5 mcg/hour (BTDS 5), or the active control (immediate release oxycodone 40-mg/day) during an 84-day double-blind phase. The primary endpoint, ''average pain in the last 24 hours'' during double-blind weeks 4, 8, and 12, was significantly lower for patients receiving BTDS 20 compared with patients receiving BTDS 5 (P < .001, treatment difference of À.67). A treatment difference of À.75 in favor of oxycodone 40 mg/day versus BTDS 5 (P < .001) indicated the assay sensitivity of the study. Four sensitivity analyses, secondary, and exploratory analyses supported the results of the primary analysis. Incidences of treatment-emergent adverse events were 56% during the open-label period, and 59, 77, and 73% for the BTDS 5, BTDS 20, and oxycodone 40 mg/day treatment groups, respectively, during the double-blind phase. One death considered unrelated to study treatment occurred in a patient receiving BTDS 10 during the run-in period. BTDS 20 treatment was demonstrated to be efficacious and generally well tolerated. Perspective: This article presents results of a pivotal Phase 3 study that assesses a new treatment for the management of chronic low back pain: a transdermal patch containing the opioid buprenorphine (BTDS). In this active controlled, superiority study with an enriched design, BTDS 20 was found to be efficacious and generally well tolerated.
American Journal of Gastroenterology
American Journal of Gastroenterology
Background: Two studies demonstrated the efficacy and safety of naldemedine in adult patients wit... more Background: Two studies demonstrated the efficacy and safety of naldemedine in adult patients with chronic non-cancer pain and opioid-induced constipation (OIC). However, no studies have compared the efficacy of peripherally acting µ-opioid receptor antagonists in patients with adequate and inadequate responses to prior OIC therapy with laxatives. This post hoc analysis of integrated data from the two previous studies compared the efficacy of naldemedine in patients who were unsuccessfully treated with laxatives [poor laxative responders (PLRs)] with those who either did not receive laxatives >30 days prior to screening or those who only received rescue laxative at or after screening (non-PLRs). Methods: Patients with OIC were randomized to once-daily treatment with naldemedine 0.2 mg or placebo. The primary efficacy endpoint was the proportion of responders [⩾3 spontaneous bowel movements (SBMs)/week and an increase from baseline of ⩾1 SBM/week for ⩾9 weeks of the 12-week treatm...
Journal of Pain Research
Purpose: Naldemedine, an oral, peripherally acting μ-opioid receptor antagonist approved for the ... more Purpose: Naldemedine, an oral, peripherally acting μ-opioid receptor antagonist approved for the treatment of opioid-induced constipation (OIC), is renally excreted. This subgroup analysis integrated data from 3 Phase 3 trials (COMPOSE-1, COMPOSE-2, COMPOSE-3) to evaluate the safety and efficacy of naldemedine in patients with renal impairment (RI). Patients and Methods: Patients age 18-80 years with chronic non-cancer pain (CNCP) and OIC received oral naldemedine 0.2 mg or placebo once daily. RI subgroups consisted of patients with normal function (baseline glomerular filtration rate ≥90 mL/min/1.73 m 2), mild (≥60 to <90 mL/min/1.73 m 2), and moderate (≥30 to <60 mL/min/1.73 m 2) RI. Safety assessments based on ≤12 weeks of treatment from all 3 studies included incidence of treatment-emergent adverse events (TEAEs). Efficacy was based on the proportion of responders in COMPOSE-1 and COMPOSE-2 only, defined as ≥3 spontaneous bowel movements (SBMs)/week and a ≥1-SBM/week increase from baseline for ≥9 of 12 weeks and ≥3 of the last 4 weeks. Results: In total, 2328 patients were included in this analysis. The incidence of TEAEs was similar in the naldemedine and placebo groups (overall, 47.1% vs 45.6%; normal, 44.6% vs 43.6%; mild RI, 49.0% vs 44.7%; moderate RI, 46.6% vs 55.9%). GI-related TEAEs occurred more frequently in the naldemedine group versus placebo (overall, 21.8% vs 13.8%; normal, 21.6% vs 12.5%; mild RI, 22.6% vs 14.7%; moderate RI, 18.0% vs 14.2%). A significantly greater proportion of patients in the naldemedine 0.2 mg group were responders versus the placebo group (overall, 50.1% vs 34.1%, P<0.0001; normal, 52.0% vs 39.3%; mild RI, 48.3% vs 30.3%; moderate RI, 52.5% vs 31.7%). Conclusion: This integrated analysis confirmed that OIC treatment with naldemedine 0.2 mg was generally well tolerated and effective in patients with CNCP and mild or moderate RI. Safety and efficacy results were consistent with the overall population.
American Journal of Gastroenterology