The Experts below are selected from a list of 567 Experts worldwide ranked by ideXlab platform
Stefan Aigner - One of the best experts on this subject based on the ideXlab platform.
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A Randomized, Crossover Study on the Effect of Food on the Pharmacokinetic Characteristics of Morphine ARER (MorphaBond™ ER), an Abuse-Deterrent Formulation of Extended-Release Morphine.
Advances in Therapy, 2019Co-Authors: Eric R. Kinzler, Carmela Pantaleon, Matthew Iverson, Stefan AignerAbstract:Introduction Food can alter the pharmacokinetics of certain Abuse-Deterrent Formulations. Morphine ARER is an oral Abuse-Deterrent Formulation of ER morphine sulfate tablets formulated with physical and chemical properties that contribute to the Abuse-Deterrent aspects of the drug. This study compared the relative bioavailability of Morphine ARER in the presence and absence of food.
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Syringeability of morphine ARER, a novel, Abuse-Deterrent, extended-release morphine Formulation
The American Journal of Drug and Alcohol Abuse, 2019Co-Authors: Eric R. Kinzler, Carmela Pantaleon, Matthew Iverson, Stefan AignerAbstract:Background: Extended-release (ER) morphine Formulations are commonly manipulated for non-oral routes of administration, particularly via injection. Morphine ARER, an Abuse-Deterrent Formulation of ...
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a randomized double blind double dummy placebo controlled intranasal human Abuse potential study of oxycodone arir a novel immediate release Abuse Deterrent Formulation
Pain Medicine, 2019Co-Authors: Lynn R. Webster, Eric R. Kinzler, Carmela Pantaleon, Matthew Iverson, Michael D. Smith, Stefan AignerAbstract:OBJECTIVE Prescription opioid Abuse continues to be a public health concern. Oxycodone ARIR is an immediate-release (IR) oxycodone tablet composed of multiple overlapping barriers that deter manipulation of the tablet for non-oral Abuse. DESIGN This randomized, double-blind, double-dummy, active- and placebo-controlled, four-way crossover, intranasal human Abuse potential study assessed the pharmacodynamics and pharmacokinetics of crushed intranasal oxycodone ARIR compared with crushed intranasal IR oxycodone and intact oral oxycodone ARIR. OUTCOME MEASURES Pharmacodynamic end points included mean maximum drug liking (Emax), as measured by subjects on a bipolar 100-mm visual analog scale (primary), and desire to take the drug again, overall drug liking, drug high, and good effects (secondary). Pharmacokinetic assessments included peak concentration and time to peak concentration. RESULTS Twenty-nine subjects completed the treatment phase. Crushed intranasal oxycodone ARIR demonstrated a significant reduction of 46.9% and 23.4% in drug liking Emax compared with crushed intranasal IR oxycodone and intact oral oxycodone ARIR, respectively (P < 0.0001 for both). Significant reductions also were observed in desire to take the drug again, drug high, overall drug liking, and good effects when comparing crushed intranasal oxycodone ARIR with crushed intranasal IR oxycodone and intact oral oxycodone ARIR (P < 0.001 for all). Crushed intranasal oxycodone ARIR exhibited lower peak oxycodone plasma concentrations and slower time to peak concentration compared with crushed intranasal IR oxycodone and intact oral oxycodone ARIR. All treatments were well tolerated; adverse effects were typical of opioids or intranasal administration. CONCLUSIONS These data indicate that oxycodone ARIR has the potential to reduce Abuse via the intranasal route.
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Intranasal Pharmacokinetics of Morphine ARER, a Novel Abuse-Deterrent Formulation: Results from a Randomized, Double-Blind, Four-Way Crossover Study in Nondependent, Opioid-Experienced Subjects.
Pain Research and Management, 2018Co-Authors: Lynn R. Webster, Eric R. Kinzler, Carmela Pantaleon, Matthew Iverson, Michael D. Smith, Stefan AignerAbstract:Objective. To investigate the pharmacokinetics (PK) of Morphine ARER, an extended-release (ER), Abuse-Deterrent Formulation of morphine sulfate after oral and intranasal administration. Methods. This randomized, double-blind, double-dummy, placebo-controlled, four-way crossover study assessed the PK of morphine and its active metabolite, M6G, from crushed intranasal Morphine ARER and intact oral Morphine ARER compared with crushed intranasal ER morphine following administration to nondependent, recreational opioid users. The correlation between morphine PK and the pharmacodynamic parameter of drug liking, a measure of Abuse potential, was also evaluated. Results. Mean maximum observed plasma concentration (Cmax) for morphine was lower with crushed intranasal Morphine ARER (26.2 ng/mL) and intact oral Morphine ARER (18.6 ng/mL), compared with crushed intranasal ER morphine (49.5 ng/mL). The time to Cmax (Tmax) was the same for intact oral and crushed intranasal Morphine ARER (1.6 hours) and longer for crushed intranasal morphine ER (1.1 hours). Higher mean maximum morphine Cmax, Tmax, and Abuse quotient (Cmax/Tmax) were positively correlated with maximum effect for drug liking (R2 ≥ 0.9795). Conclusion. These data suggest that Morphine ARER maintains its ER profile despite physical manipulation and intranasal administration, which may be predictive of a lower intranasal Abuse potential compared with ER morphine.
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A Randomized, Double-Blind, Double-Dummy, Placebo-Controlled, Intranasal Drug Liking Study on a Novel Abuse-Deterrent Formulation of Morphine—Morphine ARER
Pain Medicine, 2016Co-Authors: Lynn R. Webster, Eric R. Kinzler, Carmela Pantaleon, Matthew Iverson, Michael D. Smith, Manish S. Shah, Ray J. Difalco, Stefan AignerAbstract:Objective. Misuse and Abuse of prescription opioids remains a major healthcare concern despite considerable efforts to increase public awareness. Abuse-Deterrent Formulations of prescription opioids are designed to reduce intentional misuse, Abuse, and prescription opioid–related death. A novel extended-release (ER) Formulation of morphine (Morphine ARER; MorphaBond™) resists physical manipulation and retains the drug’s ER characteristics, even if attempts are made to manipulate the Formulation. Design. This randomized, double-blind, double-dummy, placebo-controlled, four-way crossover study investigated the Abuse potential and safety of crushed intranasal and intact oral Morphine ARER compared with commercially available crushed intranasal ER morphine sulfate (ER morphine). Outcome Measures. Endpoints included maximum mean drug liking (Emax) as measured by subjects on a bipolar 100 mm visual analog scale (primary), a subject’s desire to take the drug again, good effects of the drug, and drug high. Results. Twenty-five subjects completed the treatment phase. There was a 40% reduction in Emax for crushed intranasal Morphine ARER compared with crushed intranasal ER morphine ( P
Lynn R. Webster - One of the best experts on this subject based on the ideXlab platform.
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a randomized double blind double dummy placebo controlled intranasal human Abuse potential study of oxycodone arir a novel immediate release Abuse Deterrent Formulation
Pain Medicine, 2019Co-Authors: Lynn R. Webster, Eric R. Kinzler, Carmela Pantaleon, Matthew Iverson, Michael D. Smith, Stefan AignerAbstract:OBJECTIVE Prescription opioid Abuse continues to be a public health concern. Oxycodone ARIR is an immediate-release (IR) oxycodone tablet composed of multiple overlapping barriers that deter manipulation of the tablet for non-oral Abuse. DESIGN This randomized, double-blind, double-dummy, active- and placebo-controlled, four-way crossover, intranasal human Abuse potential study assessed the pharmacodynamics and pharmacokinetics of crushed intranasal oxycodone ARIR compared with crushed intranasal IR oxycodone and intact oral oxycodone ARIR. OUTCOME MEASURES Pharmacodynamic end points included mean maximum drug liking (Emax), as measured by subjects on a bipolar 100-mm visual analog scale (primary), and desire to take the drug again, overall drug liking, drug high, and good effects (secondary). Pharmacokinetic assessments included peak concentration and time to peak concentration. RESULTS Twenty-nine subjects completed the treatment phase. Crushed intranasal oxycodone ARIR demonstrated a significant reduction of 46.9% and 23.4% in drug liking Emax compared with crushed intranasal IR oxycodone and intact oral oxycodone ARIR, respectively (P < 0.0001 for both). Significant reductions also were observed in desire to take the drug again, drug high, overall drug liking, and good effects when comparing crushed intranasal oxycodone ARIR with crushed intranasal IR oxycodone and intact oral oxycodone ARIR (P < 0.001 for all). Crushed intranasal oxycodone ARIR exhibited lower peak oxycodone plasma concentrations and slower time to peak concentration compared with crushed intranasal IR oxycodone and intact oral oxycodone ARIR. All treatments were well tolerated; adverse effects were typical of opioids or intranasal administration. CONCLUSIONS These data indicate that oxycodone ARIR has the potential to reduce Abuse via the intranasal route.
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Intranasal Pharmacokinetics of Morphine ARER, a Novel Abuse-Deterrent Formulation: Results from a Randomized, Double-Blind, Four-Way Crossover Study in Nondependent, Opioid-Experienced Subjects.
Pain Research and Management, 2018Co-Authors: Lynn R. Webster, Eric R. Kinzler, Carmela Pantaleon, Matthew Iverson, Michael D. Smith, Stefan AignerAbstract:Objective. To investigate the pharmacokinetics (PK) of Morphine ARER, an extended-release (ER), Abuse-Deterrent Formulation of morphine sulfate after oral and intranasal administration. Methods. This randomized, double-blind, double-dummy, placebo-controlled, four-way crossover study assessed the PK of morphine and its active metabolite, M6G, from crushed intranasal Morphine ARER and intact oral Morphine ARER compared with crushed intranasal ER morphine following administration to nondependent, recreational opioid users. The correlation between morphine PK and the pharmacodynamic parameter of drug liking, a measure of Abuse potential, was also evaluated. Results. Mean maximum observed plasma concentration (Cmax) for morphine was lower with crushed intranasal Morphine ARER (26.2 ng/mL) and intact oral Morphine ARER (18.6 ng/mL), compared with crushed intranasal ER morphine (49.5 ng/mL). The time to Cmax (Tmax) was the same for intact oral and crushed intranasal Morphine ARER (1.6 hours) and longer for crushed intranasal morphine ER (1.1 hours). Higher mean maximum morphine Cmax, Tmax, and Abuse quotient (Cmax/Tmax) were positively correlated with maximum effect for drug liking (R2 ≥ 0.9795). Conclusion. These data suggest that Morphine ARER maintains its ER profile despite physical manipulation and intranasal administration, which may be predictive of a lower intranasal Abuse potential compared with ER morphine.
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A Randomized, Double-Blind, Double-Dummy, Placebo-Controlled, Intranasal Drug Liking Study on a Novel Abuse-Deterrent Formulation of Morphine—Morphine ARER
Pain Medicine, 2016Co-Authors: Lynn R. Webster, Eric R. Kinzler, Carmela Pantaleon, Matthew Iverson, Michael D. Smith, Manish S. Shah, Ray J. Difalco, Stefan AignerAbstract:Objective. Misuse and Abuse of prescription opioids remains a major healthcare concern despite considerable efforts to increase public awareness. Abuse-Deterrent Formulations of prescription opioids are designed to reduce intentional misuse, Abuse, and prescription opioid–related death. A novel extended-release (ER) Formulation of morphine (Morphine ARER; MorphaBond™) resists physical manipulation and retains the drug’s ER characteristics, even if attempts are made to manipulate the Formulation. Design. This randomized, double-blind, double-dummy, placebo-controlled, four-way crossover study investigated the Abuse potential and safety of crushed intranasal and intact oral Morphine ARER compared with commercially available crushed intranasal ER morphine sulfate (ER morphine). Outcome Measures. Endpoints included maximum mean drug liking (Emax) as measured by subjects on a bipolar 100 mm visual analog scale (primary), a subject’s desire to take the drug again, good effects of the drug, and drug high. Results. Twenty-five subjects completed the treatment phase. There was a 40% reduction in Emax for crushed intranasal Morphine ARER compared with crushed intranasal ER morphine ( P
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a randomized double blind double dummy placebo controlled intranasal drug liking study on a novel Abuse Deterrent Formulation of morphine morphine arer
Pain Medicine, 2016Co-Authors: Lynn R. Webster, Eric R. Kinzler, Carmela Pantaleon, Matthew Iverson, Michael D. Smith, Manish S. Shah, Ray J. Difalco, Stefan AignerAbstract:Objective. Misuse and Abuse of prescription opioids remains a major healthcare concern despite considerable efforts to increase public awareness. Abuse-Deterrent Formulations of prescription opioids are designed to reduce intentional misuse, Abuse, and prescription opioid–related death. A novel extended-release (ER) Formulation of morphine (Morphine ARER; MorphaBond™) resists physical manipulation and retains the drug’s ER characteristics, even if attempts are made to manipulate the Formulation. Design. This randomized, double-blind, double-dummy, placebo-controlled, four-way crossover study investigated the Abuse potential and safety of crushed intranasal and intact oral Morphine ARER compared with commercially available crushed intranasal ER morphine sulfate (ER morphine). Outcome Measures. Endpoints included maximum mean drug liking (Emax) as measured by subjects on a bipolar 100 mm visual analog scale (primary), a subject’s desire to take the drug again, good effects of the drug, and drug high. Results. Twenty-five subjects completed the treatment phase. There was a 40% reduction in Emax for crushed intranasal Morphine ARER compared with crushed intranasal ER morphine ( P < .0001). There was no significant difference when comparing the Emax for crushed intranasal vs intact Morphine ARER. When comparing crushed intranasal Morphine ARER with ER morphine, subjects reported lower mean scores for good effects of the drug, drug high, and overall drug liking, as well as a lower desire to use Morphine ARER again. Other than adverse events associated with intranasal administration of a drug, all adverse events were typical of those reported for opioid-containing drugs. Conclusions. Overall, these data suggest that Morphine ARER has a lower Abuse potential via the intranasal route of administration when compared with ER morphine.
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Call For Papers - Special Abuse Deterrent Formulation Issue
Journal of opioid management, 2016Co-Authors: Lynn R. WebsterAbstract:Journal of Opioid Management (JOM) is pleased to present a special issue, Abuse Deterrent Formulations: Clinical and Public Policy Implications focused on Abuse Deterrent Formulations (ADF) of opioids. This issue will provide a comprehensive roadmap for healthcare professionals prescribing opioids in the treatment of pain and the proper utilization of AD Formulations in clinical practice. Journal of Opioid Management invites the submission of original papers, research articles, case studies, literature reviews and expert analysis on the topics of this special issue. Click to read more!
Michael D. Smith - One of the best experts on this subject based on the ideXlab platform.
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a randomized double blind double dummy placebo controlled intranasal human Abuse potential study of oxycodone arir a novel immediate release Abuse Deterrent Formulation
Pain Medicine, 2019Co-Authors: Lynn R. Webster, Eric R. Kinzler, Carmela Pantaleon, Matthew Iverson, Michael D. Smith, Stefan AignerAbstract:OBJECTIVE Prescription opioid Abuse continues to be a public health concern. Oxycodone ARIR is an immediate-release (IR) oxycodone tablet composed of multiple overlapping barriers that deter manipulation of the tablet for non-oral Abuse. DESIGN This randomized, double-blind, double-dummy, active- and placebo-controlled, four-way crossover, intranasal human Abuse potential study assessed the pharmacodynamics and pharmacokinetics of crushed intranasal oxycodone ARIR compared with crushed intranasal IR oxycodone and intact oral oxycodone ARIR. OUTCOME MEASURES Pharmacodynamic end points included mean maximum drug liking (Emax), as measured by subjects on a bipolar 100-mm visual analog scale (primary), and desire to take the drug again, overall drug liking, drug high, and good effects (secondary). Pharmacokinetic assessments included peak concentration and time to peak concentration. RESULTS Twenty-nine subjects completed the treatment phase. Crushed intranasal oxycodone ARIR demonstrated a significant reduction of 46.9% and 23.4% in drug liking Emax compared with crushed intranasal IR oxycodone and intact oral oxycodone ARIR, respectively (P < 0.0001 for both). Significant reductions also were observed in desire to take the drug again, drug high, overall drug liking, and good effects when comparing crushed intranasal oxycodone ARIR with crushed intranasal IR oxycodone and intact oral oxycodone ARIR (P < 0.001 for all). Crushed intranasal oxycodone ARIR exhibited lower peak oxycodone plasma concentrations and slower time to peak concentration compared with crushed intranasal IR oxycodone and intact oral oxycodone ARIR. All treatments were well tolerated; adverse effects were typical of opioids or intranasal administration. CONCLUSIONS These data indicate that oxycodone ARIR has the potential to reduce Abuse via the intranasal route.
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Intranasal Pharmacokinetics of Morphine ARER, a Novel Abuse-Deterrent Formulation: Results from a Randomized, Double-Blind, Four-Way Crossover Study in Nondependent, Opioid-Experienced Subjects.
Pain Research and Management, 2018Co-Authors: Lynn R. Webster, Eric R. Kinzler, Carmela Pantaleon, Matthew Iverson, Michael D. Smith, Stefan AignerAbstract:Objective. To investigate the pharmacokinetics (PK) of Morphine ARER, an extended-release (ER), Abuse-Deterrent Formulation of morphine sulfate after oral and intranasal administration. Methods. This randomized, double-blind, double-dummy, placebo-controlled, four-way crossover study assessed the PK of morphine and its active metabolite, M6G, from crushed intranasal Morphine ARER and intact oral Morphine ARER compared with crushed intranasal ER morphine following administration to nondependent, recreational opioid users. The correlation between morphine PK and the pharmacodynamic parameter of drug liking, a measure of Abuse potential, was also evaluated. Results. Mean maximum observed plasma concentration (Cmax) for morphine was lower with crushed intranasal Morphine ARER (26.2 ng/mL) and intact oral Morphine ARER (18.6 ng/mL), compared with crushed intranasal ER morphine (49.5 ng/mL). The time to Cmax (Tmax) was the same for intact oral and crushed intranasal Morphine ARER (1.6 hours) and longer for crushed intranasal morphine ER (1.1 hours). Higher mean maximum morphine Cmax, Tmax, and Abuse quotient (Cmax/Tmax) were positively correlated with maximum effect for drug liking (R2 ≥ 0.9795). Conclusion. These data suggest that Morphine ARER maintains its ER profile despite physical manipulation and intranasal administration, which may be predictive of a lower intranasal Abuse potential compared with ER morphine.
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A Randomized, Double-Blind, Double-Dummy, Placebo-Controlled, Intranasal Drug Liking Study on a Novel Abuse-Deterrent Formulation of Morphine—Morphine ARER
Pain Medicine, 2016Co-Authors: Lynn R. Webster, Eric R. Kinzler, Carmela Pantaleon, Matthew Iverson, Michael D. Smith, Manish S. Shah, Ray J. Difalco, Stefan AignerAbstract:Objective. Misuse and Abuse of prescription opioids remains a major healthcare concern despite considerable efforts to increase public awareness. Abuse-Deterrent Formulations of prescription opioids are designed to reduce intentional misuse, Abuse, and prescription opioid–related death. A novel extended-release (ER) Formulation of morphine (Morphine ARER; MorphaBond™) resists physical manipulation and retains the drug’s ER characteristics, even if attempts are made to manipulate the Formulation. Design. This randomized, double-blind, double-dummy, placebo-controlled, four-way crossover study investigated the Abuse potential and safety of crushed intranasal and intact oral Morphine ARER compared with commercially available crushed intranasal ER morphine sulfate (ER morphine). Outcome Measures. Endpoints included maximum mean drug liking (Emax) as measured by subjects on a bipolar 100 mm visual analog scale (primary), a subject’s desire to take the drug again, good effects of the drug, and drug high. Results. Twenty-five subjects completed the treatment phase. There was a 40% reduction in Emax for crushed intranasal Morphine ARER compared with crushed intranasal ER morphine ( P
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a randomized double blind double dummy placebo controlled intranasal drug liking study on a novel Abuse Deterrent Formulation of morphine morphine arer
Pain Medicine, 2016Co-Authors: Lynn R. Webster, Eric R. Kinzler, Carmela Pantaleon, Matthew Iverson, Michael D. Smith, Manish S. Shah, Ray J. Difalco, Stefan AignerAbstract:Objective. Misuse and Abuse of prescription opioids remains a major healthcare concern despite considerable efforts to increase public awareness. Abuse-Deterrent Formulations of prescription opioids are designed to reduce intentional misuse, Abuse, and prescription opioid–related death. A novel extended-release (ER) Formulation of morphine (Morphine ARER; MorphaBond™) resists physical manipulation and retains the drug’s ER characteristics, even if attempts are made to manipulate the Formulation. Design. This randomized, double-blind, double-dummy, placebo-controlled, four-way crossover study investigated the Abuse potential and safety of crushed intranasal and intact oral Morphine ARER compared with commercially available crushed intranasal ER morphine sulfate (ER morphine). Outcome Measures. Endpoints included maximum mean drug liking (Emax) as measured by subjects on a bipolar 100 mm visual analog scale (primary), a subject’s desire to take the drug again, good effects of the drug, and drug high. Results. Twenty-five subjects completed the treatment phase. There was a 40% reduction in Emax for crushed intranasal Morphine ARER compared with crushed intranasal ER morphine ( P < .0001). There was no significant difference when comparing the Emax for crushed intranasal vs intact Morphine ARER. When comparing crushed intranasal Morphine ARER with ER morphine, subjects reported lower mean scores for good effects of the drug, drug high, and overall drug liking, as well as a lower desire to use Morphine ARER again. Other than adverse events associated with intranasal administration of a drug, all adverse events were typical of those reported for opioid-containing drugs. Conclusions. Overall, these data suggest that Morphine ARER has a lower Abuse potential via the intranasal route of administration when compared with ER morphine.
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A randomized, double-blind, double-dummy study to evaluate the intranasal human Abuse potential and pharmacokinetics of a novel extended-release Abuse-Deterrent Formulation of oxycodone
Pain Medicine, 2015Co-Authors: Lynn R. Webster, Michael D. Smith, Ernest A. Kopecky, Alison B. FlemingAbstract:Objective . Evaluate the human Abuse potential (HAP) of an experimental, microsphere-in-capsule Formulation of extended-release oxycodone (oxycodone DETERx®) (herein “DETERx”). Design . Randomized, double-blind, double-dummy, positive- and placebo-controlled, single-dose, four-phase, four-treatment, crossover study. Setting . Clinical research site. Subjects . There were 39 qualifying subjects (72% male, 85% white, mean age of 27 years) with 36 completing all four Double-blind Treatment Periods. Methods . The four phases encompassed: 1) Screening; 2) Drug Discrimination; 3) Double-blind Treatment; and 4) Follow-up. Drug Discrimination tests ensured that subjects could distinguish placebo from opioid. The four Double-blind Treatments compared DETERx—administered as either a crushed intranasal (IN) or an intact oral (PO) preparation—with immediate-release oxycodone IN (OXY-IR IN) and with an intact IN and PO placebo DETERx control. Results . For primary pharmacokinetic (PK) assessments, Abuse quotient (Cmax/Tmax) was lower with DETERx IN than DETERx PO; both treatments were substantially lower than OXY-IR IN (6.24, 8.60, and 69.6 ng/mL/h, respectively). For drug liking, the primary subjective pharmacodynamic (PD) endpoint, both DETERx IN and DETERx PO produced significantly lower scores than OXY-IR IN ( P ≤ 0.0001 for each); DETERx IN was less liked than DETERx PO ( P ≤ 0.05), mirroring the PK relationships. Objectively assessed pupillometry corroborated the more rapid and significantly greater effect of OXY-IR IN than either DETERx IN or DETERx PO ( P ≤ 0.007 for each). Overall safety profiles of DETERx and OXY-IR were comparable and both were well tolerated. Conclusions . Pharmacokinetic and pharmacodynamic outcomes suggest that DETERx IN has relatively low HAP; continued research in larger populations is suggested.
Eric R. Kinzler - One of the best experts on this subject based on the ideXlab platform.
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A Randomized, Crossover Study on the Effect of Food on the Pharmacokinetic Characteristics of Morphine ARER (MorphaBond™ ER), an Abuse-Deterrent Formulation of Extended-Release Morphine.
Advances in Therapy, 2019Co-Authors: Eric R. Kinzler, Carmela Pantaleon, Matthew Iverson, Stefan AignerAbstract:Introduction Food can alter the pharmacokinetics of certain Abuse-Deterrent Formulations. Morphine ARER is an oral Abuse-Deterrent Formulation of ER morphine sulfate tablets formulated with physical and chemical properties that contribute to the Abuse-Deterrent aspects of the drug. This study compared the relative bioavailability of Morphine ARER in the presence and absence of food.
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Syringeability of morphine ARER, a novel, Abuse-Deterrent, extended-release morphine Formulation
The American Journal of Drug and Alcohol Abuse, 2019Co-Authors: Eric R. Kinzler, Carmela Pantaleon, Matthew Iverson, Stefan AignerAbstract:Background: Extended-release (ER) morphine Formulations are commonly manipulated for non-oral routes of administration, particularly via injection. Morphine ARER, an Abuse-Deterrent Formulation of ...
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a randomized double blind double dummy placebo controlled intranasal human Abuse potential study of oxycodone arir a novel immediate release Abuse Deterrent Formulation
Pain Medicine, 2019Co-Authors: Lynn R. Webster, Eric R. Kinzler, Carmela Pantaleon, Matthew Iverson, Michael D. Smith, Stefan AignerAbstract:OBJECTIVE Prescription opioid Abuse continues to be a public health concern. Oxycodone ARIR is an immediate-release (IR) oxycodone tablet composed of multiple overlapping barriers that deter manipulation of the tablet for non-oral Abuse. DESIGN This randomized, double-blind, double-dummy, active- and placebo-controlled, four-way crossover, intranasal human Abuse potential study assessed the pharmacodynamics and pharmacokinetics of crushed intranasal oxycodone ARIR compared with crushed intranasal IR oxycodone and intact oral oxycodone ARIR. OUTCOME MEASURES Pharmacodynamic end points included mean maximum drug liking (Emax), as measured by subjects on a bipolar 100-mm visual analog scale (primary), and desire to take the drug again, overall drug liking, drug high, and good effects (secondary). Pharmacokinetic assessments included peak concentration and time to peak concentration. RESULTS Twenty-nine subjects completed the treatment phase. Crushed intranasal oxycodone ARIR demonstrated a significant reduction of 46.9% and 23.4% in drug liking Emax compared with crushed intranasal IR oxycodone and intact oral oxycodone ARIR, respectively (P < 0.0001 for both). Significant reductions also were observed in desire to take the drug again, drug high, overall drug liking, and good effects when comparing crushed intranasal oxycodone ARIR with crushed intranasal IR oxycodone and intact oral oxycodone ARIR (P < 0.001 for all). Crushed intranasal oxycodone ARIR exhibited lower peak oxycodone plasma concentrations and slower time to peak concentration compared with crushed intranasal IR oxycodone and intact oral oxycodone ARIR. All treatments were well tolerated; adverse effects were typical of opioids or intranasal administration. CONCLUSIONS These data indicate that oxycodone ARIR has the potential to reduce Abuse via the intranasal route.
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Intranasal Pharmacokinetics of Morphine ARER, a Novel Abuse-Deterrent Formulation: Results from a Randomized, Double-Blind, Four-Way Crossover Study in Nondependent, Opioid-Experienced Subjects.
Pain Research and Management, 2018Co-Authors: Lynn R. Webster, Eric R. Kinzler, Carmela Pantaleon, Matthew Iverson, Michael D. Smith, Stefan AignerAbstract:Objective. To investigate the pharmacokinetics (PK) of Morphine ARER, an extended-release (ER), Abuse-Deterrent Formulation of morphine sulfate after oral and intranasal administration. Methods. This randomized, double-blind, double-dummy, placebo-controlled, four-way crossover study assessed the PK of morphine and its active metabolite, M6G, from crushed intranasal Morphine ARER and intact oral Morphine ARER compared with crushed intranasal ER morphine following administration to nondependent, recreational opioid users. The correlation between morphine PK and the pharmacodynamic parameter of drug liking, a measure of Abuse potential, was also evaluated. Results. Mean maximum observed plasma concentration (Cmax) for morphine was lower with crushed intranasal Morphine ARER (26.2 ng/mL) and intact oral Morphine ARER (18.6 ng/mL), compared with crushed intranasal ER morphine (49.5 ng/mL). The time to Cmax (Tmax) was the same for intact oral and crushed intranasal Morphine ARER (1.6 hours) and longer for crushed intranasal morphine ER (1.1 hours). Higher mean maximum morphine Cmax, Tmax, and Abuse quotient (Cmax/Tmax) were positively correlated with maximum effect for drug liking (R2 ≥ 0.9795). Conclusion. These data suggest that Morphine ARER maintains its ER profile despite physical manipulation and intranasal administration, which may be predictive of a lower intranasal Abuse potential compared with ER morphine.
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A Randomized, Double-Blind, Double-Dummy, Placebo-Controlled, Intranasal Drug Liking Study on a Novel Abuse-Deterrent Formulation of Morphine—Morphine ARER
Pain Medicine, 2016Co-Authors: Lynn R. Webster, Eric R. Kinzler, Carmela Pantaleon, Matthew Iverson, Michael D. Smith, Manish S. Shah, Ray J. Difalco, Stefan AignerAbstract:Objective. Misuse and Abuse of prescription opioids remains a major healthcare concern despite considerable efforts to increase public awareness. Abuse-Deterrent Formulations of prescription opioids are designed to reduce intentional misuse, Abuse, and prescription opioid–related death. A novel extended-release (ER) Formulation of morphine (Morphine ARER; MorphaBond™) resists physical manipulation and retains the drug’s ER characteristics, even if attempts are made to manipulate the Formulation. Design. This randomized, double-blind, double-dummy, placebo-controlled, four-way crossover study investigated the Abuse potential and safety of crushed intranasal and intact oral Morphine ARER compared with commercially available crushed intranasal ER morphine sulfate (ER morphine). Outcome Measures. Endpoints included maximum mean drug liking (Emax) as measured by subjects on a bipolar 100 mm visual analog scale (primary), a subject’s desire to take the drug again, good effects of the drug, and drug high. Results. Twenty-five subjects completed the treatment phase. There was a 40% reduction in Emax for crushed intranasal Morphine ARER compared with crushed intranasal ER morphine ( P
Carmela Pantaleon - One of the best experts on this subject based on the ideXlab platform.
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A Randomized, Crossover Study on the Effect of Food on the Pharmacokinetic Characteristics of Morphine ARER (MorphaBond™ ER), an Abuse-Deterrent Formulation of Extended-Release Morphine.
Advances in Therapy, 2019Co-Authors: Eric R. Kinzler, Carmela Pantaleon, Matthew Iverson, Stefan AignerAbstract:Introduction Food can alter the pharmacokinetics of certain Abuse-Deterrent Formulations. Morphine ARER is an oral Abuse-Deterrent Formulation of ER morphine sulfate tablets formulated with physical and chemical properties that contribute to the Abuse-Deterrent aspects of the drug. This study compared the relative bioavailability of Morphine ARER in the presence and absence of food.
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Syringeability of morphine ARER, a novel, Abuse-Deterrent, extended-release morphine Formulation
The American Journal of Drug and Alcohol Abuse, 2019Co-Authors: Eric R. Kinzler, Carmela Pantaleon, Matthew Iverson, Stefan AignerAbstract:Background: Extended-release (ER) morphine Formulations are commonly manipulated for non-oral routes of administration, particularly via injection. Morphine ARER, an Abuse-Deterrent Formulation of ...
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a randomized double blind double dummy placebo controlled intranasal human Abuse potential study of oxycodone arir a novel immediate release Abuse Deterrent Formulation
Pain Medicine, 2019Co-Authors: Lynn R. Webster, Eric R. Kinzler, Carmela Pantaleon, Matthew Iverson, Michael D. Smith, Stefan AignerAbstract:OBJECTIVE Prescription opioid Abuse continues to be a public health concern. Oxycodone ARIR is an immediate-release (IR) oxycodone tablet composed of multiple overlapping barriers that deter manipulation of the tablet for non-oral Abuse. DESIGN This randomized, double-blind, double-dummy, active- and placebo-controlled, four-way crossover, intranasal human Abuse potential study assessed the pharmacodynamics and pharmacokinetics of crushed intranasal oxycodone ARIR compared with crushed intranasal IR oxycodone and intact oral oxycodone ARIR. OUTCOME MEASURES Pharmacodynamic end points included mean maximum drug liking (Emax), as measured by subjects on a bipolar 100-mm visual analog scale (primary), and desire to take the drug again, overall drug liking, drug high, and good effects (secondary). Pharmacokinetic assessments included peak concentration and time to peak concentration. RESULTS Twenty-nine subjects completed the treatment phase. Crushed intranasal oxycodone ARIR demonstrated a significant reduction of 46.9% and 23.4% in drug liking Emax compared with crushed intranasal IR oxycodone and intact oral oxycodone ARIR, respectively (P < 0.0001 for both). Significant reductions also were observed in desire to take the drug again, drug high, overall drug liking, and good effects when comparing crushed intranasal oxycodone ARIR with crushed intranasal IR oxycodone and intact oral oxycodone ARIR (P < 0.001 for all). Crushed intranasal oxycodone ARIR exhibited lower peak oxycodone plasma concentrations and slower time to peak concentration compared with crushed intranasal IR oxycodone and intact oral oxycodone ARIR. All treatments were well tolerated; adverse effects were typical of opioids or intranasal administration. CONCLUSIONS These data indicate that oxycodone ARIR has the potential to reduce Abuse via the intranasal route.
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Intranasal Pharmacokinetics of Morphine ARER, a Novel Abuse-Deterrent Formulation: Results from a Randomized, Double-Blind, Four-Way Crossover Study in Nondependent, Opioid-Experienced Subjects.
Pain Research and Management, 2018Co-Authors: Lynn R. Webster, Eric R. Kinzler, Carmela Pantaleon, Matthew Iverson, Michael D. Smith, Stefan AignerAbstract:Objective. To investigate the pharmacokinetics (PK) of Morphine ARER, an extended-release (ER), Abuse-Deterrent Formulation of morphine sulfate after oral and intranasal administration. Methods. This randomized, double-blind, double-dummy, placebo-controlled, four-way crossover study assessed the PK of morphine and its active metabolite, M6G, from crushed intranasal Morphine ARER and intact oral Morphine ARER compared with crushed intranasal ER morphine following administration to nondependent, recreational opioid users. The correlation between morphine PK and the pharmacodynamic parameter of drug liking, a measure of Abuse potential, was also evaluated. Results. Mean maximum observed plasma concentration (Cmax) for morphine was lower with crushed intranasal Morphine ARER (26.2 ng/mL) and intact oral Morphine ARER (18.6 ng/mL), compared with crushed intranasal ER morphine (49.5 ng/mL). The time to Cmax (Tmax) was the same for intact oral and crushed intranasal Morphine ARER (1.6 hours) and longer for crushed intranasal morphine ER (1.1 hours). Higher mean maximum morphine Cmax, Tmax, and Abuse quotient (Cmax/Tmax) were positively correlated with maximum effect for drug liking (R2 ≥ 0.9795). Conclusion. These data suggest that Morphine ARER maintains its ER profile despite physical manipulation and intranasal administration, which may be predictive of a lower intranasal Abuse potential compared with ER morphine.
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A Randomized, Double-Blind, Double-Dummy, Placebo-Controlled, Intranasal Drug Liking Study on a Novel Abuse-Deterrent Formulation of Morphine—Morphine ARER
Pain Medicine, 2016Co-Authors: Lynn R. Webster, Eric R. Kinzler, Carmela Pantaleon, Matthew Iverson, Michael D. Smith, Manish S. Shah, Ray J. Difalco, Stefan AignerAbstract:Objective. Misuse and Abuse of prescription opioids remains a major healthcare concern despite considerable efforts to increase public awareness. Abuse-Deterrent Formulations of prescription opioids are designed to reduce intentional misuse, Abuse, and prescription opioid–related death. A novel extended-release (ER) Formulation of morphine (Morphine ARER; MorphaBond™) resists physical manipulation and retains the drug’s ER characteristics, even if attempts are made to manipulate the Formulation. Design. This randomized, double-blind, double-dummy, placebo-controlled, four-way crossover study investigated the Abuse potential and safety of crushed intranasal and intact oral Morphine ARER compared with commercially available crushed intranasal ER morphine sulfate (ER morphine). Outcome Measures. Endpoints included maximum mean drug liking (Emax) as measured by subjects on a bipolar 100 mm visual analog scale (primary), a subject’s desire to take the drug again, good effects of the drug, and drug high. Results. Twenty-five subjects completed the treatment phase. There was a 40% reduction in Emax for crushed intranasal Morphine ARER compared with crushed intranasal ER morphine ( P
