{"title":"Corrigendum to: A Multicenter, Prospective, Randomized, Placebo-Controlled, Double-Blind Study of a Novel Pain Management Device, AT-02, in Patients with Fibromyalgia","authors":"","doi":"10.1093/pm/pnz308","DOIUrl":"https://doi.org/10.1093/pm/pnz308","url":null,"abstract":"","PeriodicalId":19909,"journal":{"name":"Pain Medicine: The Official Journal of the American Academy of Pain Medicine","volume":"76 1","pages":"654 - 654"},"PeriodicalIF":0.0,"publicationDate":"2019-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88376356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S. Vosburg, Jared Beaumont, S. T. Dailey-Govoni, S. Butler, Jody L. Green
Abstract Background Tapentadol is a molecule incorporating mu opioid receptor agonism and norepinephrine reuptake inhibition to provide analgesia, with the potential for a lower incidence of gastrointestinal side effects than full mu opioid agonists. Postmarketing surveillance of tapentadol as an active pharmaceutical ingredient has consistently revealed low levels of abuse and diversion. Objective The purpose of the present study was to further characterize the abuse liability of tapentadol extended-release (ER) by evaluating the prevalence of past 30-day tapentadol ER abuse and reported routes of administration as compared with ER opioids with Food and Drug Administration (FDA) abuse-deterrent labeling (“ADF opioids”) and ER opioids without FDA abuse-deterrent labeling (“non-ADF opioids”). Methods Data were collected from January 2014 through December 2017 from 776 centers located in 43 states throughout the United States using the Addiction Severity Index–Multimedia Version (ASI-MV), an instrument that is integral to the National Addictions Vigilance Intervention and Prevention Program (NAVIPPRO, Inflexxion, an IBH Company, Costa Mesa, CA, USA). Results Tapentadol ER had lower rates of past 30-day abuse than ADF ER and non-ADF ER opioid comparators, both at a population level and when adjusted for drug utilization. Tapentadol ER was primarily abused orally, although it was also abused through alternate routes of administration. Cumulative rates of tapentadol ER abuse by alternative routes of administration were lower than both ADF and non-ADF ER opioid comparators, although large confidence intervals resulting from the small sample size of reported tapentadol ER use limit firm conclusions. Conclusions In summary, tapentadol ER was found to have lower rates of both past 30-day abuse and use via alternate routes of administration, specifically snorting and smoking, than ADF and non-ADF ER comparators.
{"title":"Evaluation of Abuse and Route of Administration of Extended-Release Tapentadol Among Treatment-Seeking Individuals, as Captured by the Addiction Severity Index–Multimedia Version (ASI-MV)","authors":"S. Vosburg, Jared Beaumont, S. T. Dailey-Govoni, S. Butler, Jody L. Green","doi":"10.1093/pm/pnz250","DOIUrl":"https://doi.org/10.1093/pm/pnz250","url":null,"abstract":"Abstract Background Tapentadol is a molecule incorporating mu opioid receptor agonism and norepinephrine reuptake inhibition to provide analgesia, with the potential for a lower incidence of gastrointestinal side effects than full mu opioid agonists. Postmarketing surveillance of tapentadol as an active pharmaceutical ingredient has consistently revealed low levels of abuse and diversion. Objective The purpose of the present study was to further characterize the abuse liability of tapentadol extended-release (ER) by evaluating the prevalence of past 30-day tapentadol ER abuse and reported routes of administration as compared with ER opioids with Food and Drug Administration (FDA) abuse-deterrent labeling (“ADF opioids”) and ER opioids without FDA abuse-deterrent labeling (“non-ADF opioids”). Methods Data were collected from January 2014 through December 2017 from 776 centers located in 43 states throughout the United States using the Addiction Severity Index–Multimedia Version (ASI-MV), an instrument that is integral to the National Addictions Vigilance Intervention and Prevention Program (NAVIPPRO, Inflexxion, an IBH Company, Costa Mesa, CA, USA). Results Tapentadol ER had lower rates of past 30-day abuse than ADF ER and non-ADF ER opioid comparators, both at a population level and when adjusted for drug utilization. Tapentadol ER was primarily abused orally, although it was also abused through alternate routes of administration. Cumulative rates of tapentadol ER abuse by alternative routes of administration were lower than both ADF and non-ADF ER opioid comparators, although large confidence intervals resulting from the small sample size of reported tapentadol ER use limit firm conclusions. Conclusions In summary, tapentadol ER was found to have lower rates of both past 30-day abuse and use via alternate routes of administration, specifically snorting and smoking, than ADF and non-ADF ER comparators.","PeriodicalId":19909,"journal":{"name":"Pain Medicine: The Official Journal of the American Academy of Pain Medicine","volume":"62 1","pages":"1891 - 1901"},"PeriodicalIF":0.0,"publicationDate":"2019-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85482927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
1. Burch R, Rizzoli P, Loder E. The prevalence and impact of migraine and severe headache in the United States: Figures and trends from government health studies. Headache 2018;58(4):496–505. 2. Smitherman TA, Burch R, Sheikh H, Loder E. The prevalence, impact, and treatment of migraine and severe headaches in the United States: A review of statistics from national surveillance studies. Headache 2013;53(3):427–36. 3. Lisa M. Sullivan. Essentials of Biostatistics in Public Health. 2nd ed. Sudbury, MA: Jones & Bartlett Learning; 2012. 4. McHugh ML. Multiple comparison analysis testing in ANOVA. Biochem Med (Zagreb) 2011;21(3): 203–9.
{"title":"Epicrania Fugax with a Novel Sign: Pain Paroxysms with Parallel Forward or Backward Trajectories","authors":"Yu-hong Man, Jing-jing Qi, Tingmin Yu, Gang Yao","doi":"10.1093/pm/pnz239","DOIUrl":"https://doi.org/10.1093/pm/pnz239","url":null,"abstract":"1. Burch R, Rizzoli P, Loder E. The prevalence and impact of migraine and severe headache in the United States: Figures and trends from government health studies. Headache 2018;58(4):496–505. 2. Smitherman TA, Burch R, Sheikh H, Loder E. The prevalence, impact, and treatment of migraine and severe headaches in the United States: A review of statistics from national surveillance studies. Headache 2013;53(3):427–36. 3. Lisa M. Sullivan. Essentials of Biostatistics in Public Health. 2nd ed. Sudbury, MA: Jones & Bartlett Learning; 2012. 4. McHugh ML. Multiple comparison analysis testing in ANOVA. Biochem Med (Zagreb) 2011;21(3): 203–9.","PeriodicalId":19909,"journal":{"name":"Pain Medicine: The Official Journal of the American Academy of Pain Medicine","volume":"24 1","pages":"873 - 875"},"PeriodicalIF":0.0,"publicationDate":"2019-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85134894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abstract Objective To evaluate the short-term safety and effectiveness of amniotic membrane/umbilical cord particulate (AMUC) in managing pain in patients with various severities of knee osteoarthritis (OA). Design Single-center, prospective, investigator-initiated pilot study. Setting Private practice. Subjects A total of 20 knee OA patients aged ≥18 years were enrolled with pain >40 mm, as determined by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)–A. Methods Patients received an ultrasound-guided, intra-articular injection of 50 mg of AMUC particulate reconstituted in 2 mL of preservative-free saline. All patients were then monitored at six weeks, 12 weeks, and 24 weeks postinjection. Patients who did not show >30% reduction in pain received a second injection of AMUC at six weeks. WOMAC, Patient Global Assessment, medication usage, and magnetic resonance imaging (MRI) were assessed. Results Knee OA pain significantly decreased from 74.3 ± 17.2 at baseline to 45.0 ± 25.4 at six weeks (P < 0.01), 35.4 ± 26.6 at 12 weeks (P < 0.001), and 37.4 ± 26.7 at 24 weeks (P < 0.001). This pain reduction was associated with a significant improvement in physical function (WOMAC-C) at all time points (P < 0.05) and stiffness (WOMAC-B) at 12 weeks (P = 0.01). Eleven patients received a second injection, which was significantly correlated with body mass index >30 kg/m2 (P = 0.025). MRI evaluation of the overall population revealed an improvement in the severity of bone marrow lesions in seven patients. No adverse events were observed. Conclusions AMUC particulate injection relieved pain and improved physical function in patients with symptomatic knee OA.
{"title":"Injectable Amniotic Membrane/Umbilical Cord Particulate for Knee Osteoarthritis: A Prospective, Single-Center Pilot Study","authors":"Ramon Castellanos, Sean Tighe","doi":"10.1093/pm/pnz143","DOIUrl":"https://doi.org/10.1093/pm/pnz143","url":null,"abstract":"Abstract Objective To evaluate the short-term safety and effectiveness of amniotic membrane/umbilical cord particulate (AMUC) in managing pain in patients with various severities of knee osteoarthritis (OA). Design Single-center, prospective, investigator-initiated pilot study. Setting Private practice. Subjects A total of 20 knee OA patients aged ≥18 years were enrolled with pain >40 mm, as determined by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)–A. Methods Patients received an ultrasound-guided, intra-articular injection of 50 mg of AMUC particulate reconstituted in 2 mL of preservative-free saline. All patients were then monitored at six weeks, 12 weeks, and 24 weeks postinjection. Patients who did not show >30% reduction in pain received a second injection of AMUC at six weeks. WOMAC, Patient Global Assessment, medication usage, and magnetic resonance imaging (MRI) were assessed. Results Knee OA pain significantly decreased from 74.3 ± 17.2 at baseline to 45.0 ± 25.4 at six weeks (P < 0.01), 35.4 ± 26.6 at 12 weeks (P < 0.001), and 37.4 ± 26.7 at 24 weeks (P < 0.001). This pain reduction was associated with a significant improvement in physical function (WOMAC-C) at all time points (P < 0.05) and stiffness (WOMAC-B) at 12 weeks (P = 0.01). Eleven patients received a second injection, which was significantly correlated with body mass index >30 kg/m2 (P = 0.025). MRI evaluation of the overall population revealed an improvement in the severity of bone marrow lesions in seven patients. No adverse events were observed. Conclusions AMUC particulate injection relieved pain and improved physical function in patients with symptomatic knee OA.","PeriodicalId":19909,"journal":{"name":"Pain Medicine: The Official Journal of the American Academy of Pain Medicine","volume":"82 1","pages":"2283 - 2291"},"PeriodicalIF":0.0,"publicationDate":"2019-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84220149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
J. Gudin, R. Rauck, C. Argoff, Eva Agaiby, J. Gimbel, Nathaniel Katz, S. Doberstein, M. Tagliaferri, M. Tagliaferri, J. Potts, James E Wild, Lin Lu, S. Siddhanti, M. Hale, J. Markman
Abstract Objective To evaluate the long-term safety of NKTR-181, a novel mu-opioid receptor agonist that may have reduced human abuse potential, in patients with moderate to severe chronic low back pain (CLBP) or other chronic noncancer pain (CNP). Design Uncontrolled, multicenter, open-label, long-term study of NKTR-181 comprised of three periods: screening (≤21 days), treatment (52 weeks), and safety follow-up (∼14 days after the last dose of NKTR-181). Setting Multicenter, long-term clinical research study. Methods NKTR-181 administered at doses of 100–600 mg twice daily (BID) was evaluated in opioid-naïve and opioid-experienced patients. Patients were enrolled de novo or following completion of the randomized, placebo-controlled phase 3 efficacy study (SUMMIT-07). Safety assessments included adverse event documentation, measurements of opioid withdrawal, and clinical laboratory tests. Effectiveness was assessed using the modified Brief Pain Inventory Short Form (mBPI-SF). Results The study enrolled 638 patients. The most frequently reported treatment-emergent adverse events (TEAEs) were constipation (26%) and nausea (12%). Serious TEAEs, reported in 5% of patients, were deemed by investigators to be unrelated to NKTR-181. There were no deaths or reported cases of respiratory depression. A sustained reduction in mBPI-SF pain intensity and pain interference from baseline to study termination was observed throughout treatment. Only 2% of patients discontinued NKTR-181 due to lack of efficacy, and 11% discontinued due to treatment-related AEs. NKTR-181 doses of up to 600 mg BID were generally well tolerated, and patients experienced low rates of opioid-related adverse events. Conclusions The study results support the premise that NKTR-181 is a safe and effective option for patients with moderate to severe CLBP or CNP.
{"title":"Long-term Safety and Tolerability of NKTR-181 in Patients with Moderate to Severe Chronic Low Back Pain or Chronic Noncancer Pain: A Phase 3 Multicenter, Open-Label, 52-Week Study (SUMMIT-08 LTS)","authors":"J. Gudin, R. Rauck, C. Argoff, Eva Agaiby, J. Gimbel, Nathaniel Katz, S. Doberstein, M. Tagliaferri, M. Tagliaferri, J. Potts, James E Wild, Lin Lu, S. Siddhanti, M. Hale, J. Markman","doi":"10.1093/pm/pnz169","DOIUrl":"https://doi.org/10.1093/pm/pnz169","url":null,"abstract":"Abstract Objective To evaluate the long-term safety of NKTR-181, a novel mu-opioid receptor agonist that may have reduced human abuse potential, in patients with moderate to severe chronic low back pain (CLBP) or other chronic noncancer pain (CNP). Design Uncontrolled, multicenter, open-label, long-term study of NKTR-181 comprised of three periods: screening (≤21 days), treatment (52 weeks), and safety follow-up (∼14 days after the last dose of NKTR-181). Setting Multicenter, long-term clinical research study. Methods NKTR-181 administered at doses of 100–600 mg twice daily (BID) was evaluated in opioid-naïve and opioid-experienced patients. Patients were enrolled de novo or following completion of the randomized, placebo-controlled phase 3 efficacy study (SUMMIT-07). Safety assessments included adverse event documentation, measurements of opioid withdrawal, and clinical laboratory tests. Effectiveness was assessed using the modified Brief Pain Inventory Short Form (mBPI-SF). Results The study enrolled 638 patients. The most frequently reported treatment-emergent adverse events (TEAEs) were constipation (26%) and nausea (12%). Serious TEAEs, reported in 5% of patients, were deemed by investigators to be unrelated to NKTR-181. There were no deaths or reported cases of respiratory depression. A sustained reduction in mBPI-SF pain intensity and pain interference from baseline to study termination was observed throughout treatment. Only 2% of patients discontinued NKTR-181 due to lack of efficacy, and 11% discontinued due to treatment-related AEs. NKTR-181 doses of up to 600 mg BID were generally well tolerated, and patients experienced low rates of opioid-related adverse events. Conclusions The study results support the premise that NKTR-181 is a safe and effective option for patients with moderate to severe CLBP or CNP.","PeriodicalId":19909,"journal":{"name":"Pain Medicine: The Official Journal of the American Academy of Pain Medicine","volume":"49 1","pages":"1347 - 1356"},"PeriodicalIF":0.0,"publicationDate":"2019-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73840006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dear Editor, We appreciate Crudele and colleagues taking the time to read our publication “Comparing the Effect of Tampering on the Oral Pharmacokinetic Profiles of Two Extended-Release Oxycodone Formulations with Abuse-Deterrent Properties” [1], in which the pharmacokinetic (PK) profiles of manipulated Xtampza extended release (ER) were compared with manipulated reformulated OxyContin. We are grateful to the editors for a chance to respond to their comments. Crudele states that the paper “implies that these PK results are supported by comparative pharmacodynamic (drug liking effects) or human abuse potential study data, when such is not the case.” The study in reference (Gudin et al. 2015) [1] did not collect comparative pharmacodynamic data as the differences of the PK results of the manipulated treatment groups were quite compelling and stand on their own: Crushed Xtampza ER (oxycodone) had a PK profile that was bioequivalent to Xtampza ER taken intact (Figure 1A) [1]. This was in contrast to the crushed OxyContin (oxycodone HCl) profile, which was significantly different than OxyContin taken intact and bioequivalent to crushed immediate-release oxycodone tablets (Figure 1B) [1]. The data presented in the referenced study have been recently duplicated in a second study [2] and are …
尊敬的编辑，我们感谢Crudele和同事花时间阅读我们的出版物“比较篡改对两种具有抗滥用特性的羟考酮缓释制剂的口服药代动力学特征的影响”[1]，其中比较了操纵Xtampza缓释(ER)和操纵重新配制的奥施康定的药代动力学(PK)特征。我们非常感谢编辑们给我们一个回复他们评论的机会。Crudele指出，这篇论文“暗示这些PK结果得到了比较药效学(药物喜欢效应)或人类滥用潜力研究数据的支持，而事实并非如此。”参考文献中的研究(Gudin et al. 2015)[1]没有收集比较药效学数据，因为操纵处理组的PK结果差异非常明显，并且是独立的:粉碎的Xtampza ER(羟考酮)的PK谱与完整的Xtampza ER具有生物等效性(图1A)[1]。这与压碎后的奥施康定(盐酸羟考酮)的情况形成对比，后者与压碎后的奥施康定完全不同，与压碎后的羟考酮片具有生物等效性(图1B)[1]。参考研究中提供的数据最近在第二项研究中得到了重复[2]，并且是…
{"title":"Response to Crudele et al. Commentary on Gudin et al. “Comparing the Effect of Tampering on the Oral Pharmacokinetic Profiles of Two Extended-Release Oxycodone Formulations with Abuse-Deterrent Properties”","authors":"J. Gudin, E. Kopecky, A. Fleming","doi":"10.1093/pm/pnw279","DOIUrl":"https://doi.org/10.1093/pm/pnw279","url":null,"abstract":"Dear Editor,\u0000\u0000We appreciate Crudele and colleagues taking the time to read our publication “Comparing the Effect of Tampering on the Oral Pharmacokinetic Profiles of Two Extended-Release Oxycodone Formulations with Abuse-Deterrent Properties” [1], in which the pharmacokinetic (PK) profiles of manipulated Xtampza extended release (ER) were compared with manipulated reformulated OxyContin. We are grateful to the editors for a chance to respond to their comments.\u0000\u0000Crudele states that the paper “implies that these PK results are supported by comparative pharmacodynamic (drug liking effects) or human abuse potential study data, when such is not the case.” The study in reference (Gudin et al. 2015) [1] did not collect comparative pharmacodynamic data as the differences of the PK results of the manipulated treatment groups were quite compelling and stand on their own: Crushed Xtampza ER (oxycodone) had a PK profile that was bioequivalent to Xtampza ER taken intact (Figure 1A) [1]. This was in contrast to the crushed OxyContin (oxycodone HCl) profile, which was significantly different than OxyContin taken intact and bioequivalent to crushed immediate-release oxycodone tablets (Figure 1B) [1]. The data presented in the referenced study have been recently duplicated in a second study [2] and are …","PeriodicalId":19909,"journal":{"name":"Pain Medicine: The Official Journal of the American Academy of Pain Medicine","volume":"6 1","pages":"992 - 994"},"PeriodicalIF":0.0,"publicationDate":"2017-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84806544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
It was with great interest that we reviewed the article by Rho et al. “Deconstructing Chronic Low Back pain in the Older Adult-Step by Step Evidence and Expert-Based Recommendations for Evaluation and Treatment. Part VIII: Lateral Hip and Thigh Pain” [1]. We applaud the authors for addressing this common issue of lateral hip pain, and their thoughtfulness and evidence supported discussion regarding the diagnosis of greater trochanteric pain syndrome (GTPS) rather than the commonly used and inaccurate term “greater trochanteric bursitis.” The authors nicely review the literature summarizing that there is a lack of findings on MRI and ultrasound, as well as in histological evidence to support the diagnosis of “bursitis” and/or “tendinitis” in the vast majority of these patients. Additionally, we fully agree with the authors’ noting that there is a lack of inflammatory findings in patients suffering from GTPS and that effective treatment consists of strengthening the weak hip abductors that are often noted in these patients. We have found this to be true in the patients we have treated with GTPS. The authors also note the deficiency of evidence for the use of corticosteroid injections and both the potential systemic side effects and the now well-known toxic effects of corticosteroids to tenocytes, which they note “can potentially contribute to progressive tendinopathy and partial tears.”
{"title":"Response to: Rho et al. “Deconstructing Chronic Low Back Pain in the Older Adult-Step by Step Evidence and Expert- Based Recommendations for Evaluation and Treatment. Part VIII: Lateral Hip and Thigh Pain”","authors":"G. Malanga","doi":"10.1093/pm/pnw296","DOIUrl":"https://doi.org/10.1093/pm/pnw296","url":null,"abstract":"It was with great interest that we reviewed the article by Rho et al. “Deconstructing Chronic Low Back pain in the Older Adult-Step by Step Evidence and Expert-Based Recommendations for Evaluation and Treatment. Part VIII: Lateral Hip and Thigh Pain” [1]. We applaud the authors for addressing this common issue of lateral hip pain, and their thoughtfulness and evidence supported discussion regarding the diagnosis of greater trochanteric pain syndrome (GTPS) rather than the commonly used and inaccurate term “greater trochanteric bursitis.” The authors nicely review the literature summarizing that there is a lack of findings on MRI and ultrasound, as well as in histological evidence to support the diagnosis of “bursitis” and/or “tendinitis” in the vast majority of these patients. Additionally, we fully agree with the authors’ noting that there is a lack of inflammatory findings in patients suffering from GTPS and that effective treatment consists of strengthening the weak hip abductors that are often noted in these patients. We have found this to be true in the patients we have treated with GTPS. The authors also note the deficiency of evidence for the use of corticosteroid injections and both the potential systemic side effects and the now well-known toxic effects of corticosteroids to tenocytes, which they note “can potentially contribute to progressive tendinopathy and partial tears.”","PeriodicalId":19909,"journal":{"name":"Pain Medicine: The Official Journal of the American Academy of Pain Medicine","volume":"75 1","pages":"1195 - 1195"},"PeriodicalIF":0.0,"publicationDate":"2017-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86291091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
N. Crudele, J. Giordano, R. Kapil, Amarita S. Randhawa
• "“It is likely that the ability to retain ER features following manipulation will make it less attractive to abusers compared to existing ADFs. . ."” This statement implies that these PK results are supported by comparative pharmacodynamic (drug liking effects) or human abuse potential study data, when such is not the case. • PK profiles of Xtampza ER and OxyContin were examined when ingested with food, "“as this is a common form of administration in the intended patient population.”" This statement is misleading as it suggests Xtampza can be dosed with or without regard to food, when such is not the case. Xtampza ER can only be taken with carefully modulated complete food intake. Failure to follow this stringent procedure, either by physician or patient, will result in variability in the extent of oxycodone absorption and ultimately impact the safety and efficacy of Xtampza ER. • "“Although results of this study showed some minor differences in the PK profile between intact Oxycodone DETERx and intact OxyContin, the two products were bioequivalent on Cmax, AUClast, and AUCinf.”" Authors fail to clarify that Xtampza ER is not bioequivalent to OxyContin in fasting condition. Stated as such, this statement invites the potential for serious dosing errors with OxyContin.
{"title":"In response to Gudin et al. — Comparing the Effect of Tampering on the Oral Pharmacokinetic Profiles of Two Extended-Release Oxycodone Formulations with Abuse-Deterrent Properties","authors":"N. Crudele, J. Giordano, R. Kapil, Amarita S. Randhawa","doi":"10.1093/pm/pnw278","DOIUrl":"https://doi.org/10.1093/pm/pnw278","url":null,"abstract":"• \"“It is likely that the ability to retain ER features following manipulation will make it less attractive to abusers compared to existing ADFs. . .\"” This statement implies that these PK results are supported by comparative pharmacodynamic (drug liking effects) or human abuse potential study data, when such is not the case. • PK profiles of Xtampza ER and OxyContin were examined when ingested with food, \"“as this is a common form of administration in the intended patient population.”\" This statement is misleading as it suggests Xtampza can be dosed with or without regard to food, when such is not the case. Xtampza ER can only be taken with carefully modulated complete food intake. Failure to follow this stringent procedure, either by physician or patient, will result in variability in the extent of oxycodone absorption and ultimately impact the safety and efficacy of Xtampza ER. • \"“Although results of this study showed some minor differences in the PK profile between intact Oxycodone DETERx and intact OxyContin, the two products were bioequivalent on Cmax, AUClast, and AUCinf.”\" Authors fail to clarify that Xtampza ER is not bioequivalent to OxyContin in fasting condition. Stated as such, this statement invites the potential for serious dosing errors with OxyContin.","PeriodicalId":19909,"journal":{"name":"Pain Medicine: The Official Journal of the American Academy of Pain Medicine","volume":"243 1","pages":"990 - 991"},"PeriodicalIF":0.0,"publicationDate":"2016-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74728493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S. Harris, A. Cipriano, S. Colucci, R. Kapil, P. Geoffroy, T. Hopyan, N. Levy‐Cooperman
Abstract Objectives. A once-daily, extended-release hydrocodone bitartrate tablet with abuse-deterrent properties (Hysingla ER [HYD]) is available for the treatment of chronic pain in appropriate patients. This study evaluated the oral abuse potential and pharmacokinetics (PK) of HYD intact, chewed, or milled to fine particles in comparison with hydrocodone solution or placebo. Design. Single-center, double-blind, randomized, five-period, five-treatment crossover study. Subjects. Healthy adult, nondependent, recreational opioid users. Methods. Forty subjects received orally administered treatments of hydrocodone 60 mg solution, HYD 60 mg intact, HYD 60 mg chewed, HYD 60 mg milled to fine particles, or placebo, separated by a five- to seven-day washout. Assessments over 36 hours postdose included subjective measures of drug liking and willingness to take drug again (assessed using visual analog scales [VAS]), pupillometry, PK, and safety measures. Results. Following oral administration, HYD intact, HYD chewed, and HYD fine particles led to significantly lower “at this moment” drug liking compared with hydrocodone solution. HYD intact and chewed were significantly different from hydrocodone solution on overall drug liking, take drug again, and good effects. Pupil constriction, as measured by pupillometry, occurred later with HYD intact and HYD chewed than with hydrocodone solution. Across treatments (hydrocodone solution, HYD fine particles, HYD chewed, and HYD intact, respectively), mean Cmax and rate of absorption (Cmax/Tmax) values decreased, respectively, and median Tmax values increased, respectively. Safety was consistent with the known effects of opioid agonists. Conclusion. HYD demonstrated reduced oral abuse potential compared with hydrocodone solution in healthy adult, nondependent, recreational opioid users.*
抽象的目标。每日一次，缓释双酒石酸氢可酮片具有滥用威慑性能(Hysingla ER [HYD])可用于治疗慢性疼痛的适当患者。本研究评估了HYD的口服滥用潜力和药代动力学(PK)，与氢可酮溶液或安慰剂相比，完整的、咀嚼的或磨成细颗粒的HYD。设计。单中心、双盲、随机、五期、五治疗交叉研究。科目。健康成人，非依赖性，娱乐性阿片类药物使用者。方法。40名受试者接受口服治疗:氢可酮60毫克溶液、HYD 60毫克完整、HYD 60毫克咀嚼、HYD 60毫克磨成细颗粒或安慰剂，通过5至7天的洗脱期分开。服药后36小时的评估包括药物喜好和再次服药意愿的主观测量(使用视觉模拟量表[VAS]评估)、瞳孔测量、PK和安全性措施。结果。与氢可酮溶液相比，口服给药后，HYD完整、HYD咀嚼、HYD细颗粒导致“此时”药物喜爱度明显降低。与氢可酮溶液相比，HYD完整组和咀嚼组在整体药物喜好、再服药、效果均有显著性差异。用瞳孔测量法测得，嚼食HYD组瞳孔收缩时间晚于氢可酮组。不同处理(氢可酮溶液处理、HYD细颗粒处理、HYD咀嚼处理和HYD完整处理)，平均Cmax和吸收率(Cmax/Tmax)值分别降低，中位数Tmax值分别升高。安全性与阿片类激动剂的已知作用一致。结论。在健康成人、非依赖性、娱乐性阿片类药物使用者中，与氢可酮溶液相比，HYD的口服滥用可能性降低*
{"title":"Oral Abuse Potential, Pharmacokinetics, and Safety of Once-Daily, Single-Entity, Extended-Release Hydrocodone (HYD) in Recreational Opioid Users","authors":"S. Harris, A. Cipriano, S. Colucci, R. Kapil, P. Geoffroy, T. Hopyan, N. Levy‐Cooperman","doi":"10.1093/pm/pnw208","DOIUrl":"https://doi.org/10.1093/pm/pnw208","url":null,"abstract":"Abstract Objectives. A once-daily, extended-release hydrocodone bitartrate tablet with abuse-deterrent properties (Hysingla ER [HYD]) is available for the treatment of chronic pain in appropriate patients. This study evaluated the oral abuse potential and pharmacokinetics (PK) of HYD intact, chewed, or milled to fine particles in comparison with hydrocodone solution or placebo. Design. Single-center, double-blind, randomized, five-period, five-treatment crossover study. Subjects. Healthy adult, nondependent, recreational opioid users. Methods. Forty subjects received orally administered treatments of hydrocodone 60 mg solution, HYD 60 mg intact, HYD 60 mg chewed, HYD 60 mg milled to fine particles, or placebo, separated by a five- to seven-day washout. Assessments over 36 hours postdose included subjective measures of drug liking and willingness to take drug again (assessed using visual analog scales [VAS]), pupillometry, PK, and safety measures. Results. Following oral administration, HYD intact, HYD chewed, and HYD fine particles led to significantly lower “at this moment” drug liking compared with hydrocodone solution. HYD intact and chewed were significantly different from hydrocodone solution on overall drug liking, take drug again, and good effects. Pupil constriction, as measured by pupillometry, occurred later with HYD intact and HYD chewed than with hydrocodone solution. Across treatments (hydrocodone solution, HYD fine particles, HYD chewed, and HYD intact, respectively), mean Cmax and rate of absorption (Cmax/Tmax) values decreased, respectively, and median Tmax values increased, respectively. Safety was consistent with the known effects of opioid agonists. Conclusion. HYD demonstrated reduced oral abuse potential compared with hydrocodone solution in healthy adult, nondependent, recreational opioid users.*","PeriodicalId":19909,"journal":{"name":"Pain Medicine: The Official Journal of the American Academy of Pain Medicine","volume":"88 1","pages":"1278 - 1291"},"PeriodicalIF":0.0,"publicationDate":"2016-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88297222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Michael D. Smith, L. Webster, J. Lawler, K. Lindhardt, J. Dayno
Objective. To compare the relative human abuse potential of intact and manipulated morphine abuse-deterrent, extended-release injection-molded tablets (morphine-ADER-IMT) with that of marketed morphine sulfate ER tablets Methods. This randomized, double-blind, triple-dummy, active- and placebo-controlled, 4-way crossover, single-center study included adult volunteers who were experienced, nondependent, recreational opioid users. Participants were randomized 1:1:1:1 to placebo, morphine-ADER-IMT (60 mg, intact), morphine-ADER-IMT (60 mg, manipulated), and morphine ER (60 mg, manipulated) and received 1 dose of each oral agent in crossover fashion, separated by ≥5 days. Pharmacodynamic and pharmacokinetic endpoints were assessed, including the primary endpoint of peak effect of Drug Liking (Emax) via Drug Liking Visual Analog Scale (VAS) score and the secondary endpoints of time to Emax (TEmax) and mean abuse quotient (AQ; a pharmacokinetic parameter associated with drug liking). Results. Thirty-eight participants completed the study. Median Drug Liking VAS Emax was significantly lower after treatment with manipulated morphine-ADER-IMT (67) compared with manipulated morphine ER (74; P = 0.007). TEmax was significantly shorter after treatment with manipulated morphine ER compared with intact (P < 0.0001) or manipulated (P = 0.004) morphine-ADER-IMT. Mean AQ was lower after treatment with intact (5.7) or manipulated (16.4) morphine-ADER-IMT compared with manipulated morphine ER (45.9). Conclusions. Manipulated morphine-ADER-IMT demonstrated significantly lower Drug Liking Emax compared with manipulated morphine ER when administered orally. Morphine-ADER-IMT would be an important new AD, ER morphine product with lower potential for unintentional misuse by chewing or intentional manipulation for oral abuse than currently available non-AD morphine ER products.
{"title":"Human Abuse Potential of an Abuse-Deterrent (AD), Extended-Release (ER) Morphine Product Candidate (Morphine-ADER Injection-Molded Tablets) versus Extended-Release Morphine Administered Orally in Nondependent Recreational Opioid Users","authors":"Michael D. Smith, L. Webster, J. Lawler, K. Lindhardt, J. Dayno","doi":"10.1093/pm/pnw174","DOIUrl":"https://doi.org/10.1093/pm/pnw174","url":null,"abstract":"Objective. To compare the relative human abuse potential of intact and manipulated morphine abuse-deterrent, extended-release injection-molded tablets (morphine-ADER-IMT) with that of marketed morphine sulfate ER tablets Methods. This randomized, double-blind, triple-dummy, active- and placebo-controlled, 4-way crossover, single-center study included adult volunteers who were experienced, nondependent, recreational opioid users. Participants were randomized 1:1:1:1 to placebo, morphine-ADER-IMT (60 mg, intact), morphine-ADER-IMT (60 mg, manipulated), and morphine ER (60 mg, manipulated) and received 1 dose of each oral agent in crossover fashion, separated by ≥5 days. Pharmacodynamic and pharmacokinetic endpoints were assessed, including the primary endpoint of peak effect of Drug Liking (Emax) via Drug Liking Visual Analog Scale (VAS) score and the secondary endpoints of time to Emax (TEmax) and mean abuse quotient (AQ; a pharmacokinetic parameter associated with drug liking). Results. Thirty-eight participants completed the study. Median Drug Liking VAS Emax was significantly lower after treatment with manipulated morphine-ADER-IMT (67) compared with manipulated morphine ER (74; P = 0.007). TEmax was significantly shorter after treatment with manipulated morphine ER compared with intact (P < 0.0001) or manipulated (P = 0.004) morphine-ADER-IMT. Mean AQ was lower after treatment with intact (5.7) or manipulated (16.4) morphine-ADER-IMT compared with manipulated morphine ER (45.9). Conclusions. Manipulated morphine-ADER-IMT demonstrated significantly lower Drug Liking Emax compared with manipulated morphine ER when administered orally. Morphine-ADER-IMT would be an important new AD, ER morphine product with lower potential for unintentional misuse by chewing or intentional manipulation for oral abuse than currently available non-AD morphine ER products.","PeriodicalId":19909,"journal":{"name":"Pain Medicine: The Official Journal of the American Academy of Pain Medicine","volume":"22 1","pages":"898 - 907"},"PeriodicalIF":0.0,"publicationDate":"2016-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86051712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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