A nasal abuse potential randomized clinical trial of REMOXY® ER, a high-viscosity extended-release oxycodone formulation

2018 ◽  
Vol 14 (6) ◽  
pp. 437-443 ◽  
Author(s):  
Nadav Friedmann, PhD, MD ◽  
Michael R. Marsman, PharmD ◽  
Annelies W. De Kater, PhD ◽  
Lindsay H. Burns, PhD ◽  
Lynn R. Webster, MD
Keyword(s):  
Clinical Trial ◽  
Extended Release ◽  
High Viscosity ◽  
Abuse Potential ◽  
Maximum Effect ◽  
Self Administration ◽  
Open Label ◽  
Secondary Endpoints ◽  
Opioid Users ◽  
Drug Liking

Objective: This study examined the nasal abuse deterrence of REMOXY ER, a novel high-viscosity extended-release oxycodone formulation.Design: An Institutional Review Board-approved, single-center, randomized, double-blind, placebo, and active-controlled, four-way crossover study of intranasal REMOXY ER gel, manipulated or intact, and ground oxycodone immediate-release (IR). An open label extension examined pharmacokinetics of OxyContin® ER in the first 20 subjects.Participants: Healthy, adult nondependent recreational opioid users with a history of intranasal abuse. Thirty-eight subjects enrolled; 36 completed.Setting: A clinical research in-patient unit.Interventions: Cross-over arms included nasal self-administration of the entire contents of REMOXY ER 40 mg capsules (manipulated or intact), ground oxycodone IR 40 mg tablets, and placebo. The open-label arm was ground OxyContin ER.Main outcome measures: The primary endpoint was the maximum effect (Emax) of visual analog scale ratings of Drug Liking. Secondary endpoints included Take Drug Again (12 and 24 hours), Drug High Emax, area under effect curves through 12 hours, pupillometry, peak oxycodone concentrations (Cmax), time to maximum concentration (Tmax), and Abuse Quotient (Cmax/Tmax).Results: Intranasal REMOXY ER (manipulated or intact) elicited lower Drug Liking and Drug High compared to ground oxycodone IR. Secondary endpoints also reflected reduced Abuse Potential. Intranasal REMOXY ER (manipulated or intact) led to fourfold lower Cmax, a 57 to 128 percent longer Tmax, a 10-fold lower Abuse Quotient and lower Take Drug Again scores compared to both OxyContin ER and oxycodone IR.Conclusion: In this study, REMOXY ER demonstrated significantly lower nasal abuse potential compared to oxycodone IR or OxyContin ER.Perspective: Abuse-deterrent drugs are intended to help fight opioid abuse. Yet the persistence of the opioid epidemic indicates that vast improvements in abuse-deterrent technology are needed. A new, high-viscosity, extended-release oxycodone formulation showed robust abuse-deterrence against the nasal route of abuse in an Food and Drug Administration-advised clinical trial in recreational opioid users.

scholarly journals 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

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Lynn R. Webster ◽  
Carmela Pantaleon ◽  
Matthew Iverson ◽  
Michael D. Smith ◽  
Eric R. Kinzler ◽  
...  
Keyword(s):  
Crossover Study ◽  
Intranasal Administration ◽  
Extended Release ◽  
Oral Morphine ◽  
Abuse Potential ◽  
Maximum Effect ◽  
Double Blind ◽  
Opioid Users ◽  
Physical Manipulation ◽  
Drug Liking

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.

scholarly journals Evaluation of the oral human abuse potential of Oxycodone DETERx® formulation (Xtampza® ER)

2018 ◽  
Vol 14 (5) ◽  
pp. 359-372 ◽  
Author(s):  
Diana Meske, PhD ◽  
Ernest A. Kopecky, PhD ◽  
Steven Passik, PhD ◽  
Megan J. Shram, PhD
Keyword(s):  
Immediate Release ◽  
Oral Route ◽  
Abuse Potential ◽  
Maximum Effect ◽  
Double Blind ◽  
Visual Analog Scales ◽  
The Mean ◽  
Opioid Users ◽  
Primary Measure ◽  
Drug Liking

Objective: To further characterize the human abuse potential and pharmacokinetics (PK) of Oxycodone DETERx (Xtampza® ER) after intact and chewed oral administration.Design: Randomized, double-blind, triple-dummy, active- and placebo-controlled, single-dose, six-period, crossover comparison study.Setting: Clinical research unit.Subjects: Adult, nondependent recreational opioid users who liked the effects of crushed immediate-release (IR) oxycodone in solution and were able to differentiate the effects from placebo solution.Interventions: Oral administration of intact Oxycodone DETERx (fasted and fed), chewed Oxycodone DETERx (fasted and fed), crushed IR oxycodone (fasted), and placebo (fed).Main Outcome Measures: Subject ratings (100-point visual analog scales) of Drug Liking (primary measure) and Take Drug Again (key secondary measure).Results: The pharmacodynamic (PD) analysis included 52 subjects who completed the study; the PK analysis included 71 subjects. Compared with crushed IR oxycodone fasted, the least-squares mean maximum effect (Emax) was statistically significant (p 0.01) for Drug Liking and Take Drug Again, respectively, for chewed Oxycodone DETERx fasted (LS mean difference ± standard error of the mean: 13.1 ± 2.2 and 10.0 ± 3.2 points) and fed (10.9 ± 2.2 and 9.7 ± 3.3 points) and intact Oxycodone DETERx fasted (12.2 ± 2.2 and 9.3 ± 3.3 points) and fed (10.3 ± 2.2 and 9.2 ± 3.3 points). Results were consistent for other PD measures (Good Effects, Feeling High). Chewed Oxycodone DETERx fasted and fed treatments were bioequivalent to the respective intact treatments based on PK parameters. Conclusions: This study showed that when chewed or swallowed intact, under fasted or fed conditions, Oxycodone DETERx had statistically significantly lower abuse potential via the oral route compared with IR oxycodone.

scholarly journals Evaluation of the Relative Intranasal Abuse Potential of a Hydrocodone Extended-Release Tablet Formulated with Abuse-Deterrence Technology in Nondependent, Recreational Opioid Users

Pain Medicine ◽  
2017 ◽  
Vol 19 (8) ◽  
pp. 1597-1612
Author(s):  
Mary Bond ◽  
Kerri A Schoedel ◽  
Laura Rabinovich-Guilatt ◽  
Maciej Gasior ◽  
William Tracewell ◽  
...  
Keyword(s):  
Extended Release ◽  
Abuse Potential ◽  
Opioid Users ◽  
Extended Release Tablet ◽  
Release Tablet

scholarly journals Evaluation of the abuse potential of pitolisant, a selective H3-receptor antagonist/inverse agonist, for the treatment of adult patients with narcolepsy with or without cataplexy

SLEEP ◽  
2019 ◽  
Vol 43 (4) ◽  
Author(s):  
Beatrice Setnik ◽  
Michael McDonnell ◽  
Catherine Mills ◽  
Catherine Scart-Grès ◽  
Philippe Robert ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Inverse Agonist ◽  
Mean Difference ◽  
Abuse Potential ◽  
Adult Patients ◽  
Maximum Effect ◽  
Double Blind ◽  
Clinical Trial Registration ◽  
H3 Receptor ◽  
Drug Liking

Abstract Objectives To evaluate the human abuse potential of pitolisant, a selective histamine 3 (H3)-receptor antagonist/inverse agonist recently approved by the US Food and Drug Administration for the treatment of excessive daytime sleepiness in adult patients with narcolepsy. Methods Nondependent, recreational stimulant users able to distinguish phentermine HCl 60 mg from placebo in a drug discrimination test were randomized in a four-period, double-blind, crossover design to receive single doses of pitolisant 35.6 mg (therapeutic dose), pitolisant 213.6 mg (supratherapeutic dose), phentermine HCl 60 mg, and placebo. The primary endpoint was maximum effect (Emax) on the 100-point Drug Liking (“at this moment”) visual analog scale. Results In 38 study completers (73.7% male; 65.8% white; mean age, 33.3 years), mean Drug Liking Emax was significantly greater for phentermine versus pitolisant 35.6 mg (mean difference, 21.4; p < 0.0001) and pitolisant 213.6 mg (mean difference, 19.7; p < 0.0001). Drug Liking Emax was similar for pitolisant (both doses) and placebo. Similarly, for key secondary measures of Overall Drug Liking and willingness to Take Drug Again, mean Emax scores were significantly greater for phentermine versus pitolisant (both doses) and similar for pitolisant (both doses) versus placebo. The incidence of adverse events was 82.1% after phentermine HCl 60 mg, 72.5% after pitolisant 213.6 mg, 47.5% after pitolisant 35.6 mg, and 48.8% after placebo administration. Conclusions In this study, pitolisant demonstrated significantly lower potential for abuse compared with phentermine and an overall profile similar to placebo; this suggests a low risk of abuse for pitolisant. Clinical Trial Registration ClinicalTrials.gov NCT03152123. Determination of the abuse potential of pitolisant in healthy, nondependent recreational stimulant users. https://clinicaltrials.gov/ct2/show/NCT03152123.

scholarly journals 5 Clinical Evaluation of the Abuse Potential of Buprenorphine/Samidorphan Combination

CNS Spectrums ◽  
2019 ◽  
Vol 24 (1) ◽  
pp. 176-176
Author(s):  
Andrew J. Cutler ◽  
Sanjay J. Mathew ◽  
Michael E. DeBakey ◽  
Beatrice Setnik ◽  
Narinder Nangia ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Opioid Receptor ◽  
Safety Data ◽  
Abuse Potential ◽  
Fixed Dose ◽  
Maximum Effect ◽  
Study Objective ◽  
Opioid Receptor Antagonist ◽  
Vas Scores ◽  
Drug Liking

AbstractIntroductionBuprenorphine (BUP)/samidorphan (SAM) combination is an opioid system modulator being investigated as an adjunctive treatment for major depressive disorder (MDD). BUP/SAM is a fixed-dose combination of BUP, a partial µ-opioid receptor agonist and κ-opioid receptor antagonist, and SAM, a µ-opioid receptor antagonist added to address the abuse and dependence potential of BUP.1,2Study ObjectiveWe assessed the effects of SAM on the abuse potential of BUP in the BUP/SAM combination in two ways: (1) a human abuse potential (HAP) study in volunteers; and (2) an evaluation of the clinical experience across studies of patients with MDD.MethodsStudy 212 (ClinicalTrials.gov ID: NCT02413281) was a HAP study in nondependent, recreational, adult opioid users. Following a qualification period, participants were randomized to 6 treatments in a blinded, crossover design: placebo (PBO), BUP/SAM at the target therapeutic dose (BUP/SAM 2mg/2mg), at 8mg/8mg and 16mg/16mg , and BUP alone (8mg and 16mg). The primary endpoint was maximum effect (Emax) for “At The Moment” Drug Liking Visual Analog Scale (VAS).The clinical program for BUP/SAM included 4 PBO-controlled studies of patients with MDD (n=961). Pooled safety data were evaluated for adverse events (AEs) that may be associated with abuse, dependence, or withdrawal, as well as for objective signs of withdrawal with the Clinical Opioid Withdrawal Scale (COWS).ResultsIn Study 212 (n=38), Emax Drug Liking VAS scores for the BUP/SAM 2mg/2mg dose were similar to those for PBO (median within-subject difference [90% CI]: 2.5 [0.0–9.0]). Emax Drug Liking VAS scores for all BUP/SAM dose groups, including supratherapeutic doses, were significantly lower than those observed for either of the BUP doses. The supratherapeutic doses of BUP/SAM (8mg/8mg and 16mg/16mg) had higher Emax Drug Liking VAS scores than PBO, but the differences were small.In the MDD controlled studies, the incidence of euphoria-related AEs was low for BUP/SAM 2mg/2mg and PBO (1.6% vs 0.2%, respectively) and there was no evidence of abuse or dependence behavior. Euphoria-related events typically occurred with treatment initiation and resolved with continued treatment. There was minimal evidence of withdrawal by reported AEs or COWS assessment.ConclusionsThese findings indicate that SAM mitigates the abuse potential of BUP in the BUP/SAM combination.Funding Acknowledgements: Alkermes, Inc.

Microsphere oxycodone for pain management in head and neck cancer (HNC) patients receiving radiotherapy.

2019 ◽  
Vol 37 (31_suppl) ◽  
pp. 123-123
Author(s):  
Andrew Michael McDonald ◽  
Sharon Spencer ◽  
Christopher Douglas Willey ◽  
James A. Bonner ◽  
Thomas A Swain ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Extended Release ◽  
Common Adverse Effect ◽  
Immediate Release ◽  
Gastrostomy Tube ◽  
World Health ◽  
Future Research ◽  
Transdermal Fentanyl ◽  
Open Label ◽  
Opioid Dose

123 Background: Pain is a common adverse effect of RT in patients with HNC, and extended release analgesic options are limited due to high rates of dysphagia. Wax microsphere bound oxycodone was developed as an abuse-deterrent opioid and maintains a similar pharmacokinetic profile whether administered with or without an intact capsule. We hypothesized that microsphere oxycodone could be used for extended release analgesia in patients undergoing RT for HNC and would not need to be discontinued due to dysphagia or gastrostomy tube dependence. Methods: We performed an open-label prospective clinical trial (NCT03317730) to assess the feasibility of microsphere oxycodone for extended release analgesia during RT for HNC. Participants were > 18y, had histologically confirmed HNC, and were to receive > 50 Gy of RT. Analgesia was prescribed in accordance with the World Health Organization pain ladder. Non-opioid and immediate release opioids were used at the discretion of the treating physicians. Microsphere oxycodone was initiated when total daily opioid dose exceeded 30mg morphine sulfate equivalent and was titrated weekly during RT. The primary feasibility endpoint was frequency of microsphere oxycodone discontinuation within 3 months of RT for reasons other than pain resolution. Secondary endpoints included pain level during RT. Results: Twenty-six eligible patients were enrolled between June and November, 2018. Microsphere oxycodone was initiated in 13 (50%) patients at a median of 5 weeks after beginning RT (range: 0 – 7 weeks). The mean Brief Pain Index Severity composite score at time of microsphere oxycodone initiation was 5.4 (SD ±2.0) and was 4.8 (SD ±1.5) during the final week of RT ( p= 0.21). Six patients utilized a gastrostomy tube to administer microsphere oxycodone for all or part of RT. Microsphere oxycodone was discontinued in 1 (7.6%) patient due to perceived inefficacy, 0 patients due to toxicity, and 0 patients due to difficulty with administration. Conclusions: These results support the feasibility and safety of microsphere oxycodone for extended release analgesia in patients with HNC undergoing RT. Future research should compare microsphere oxycodone and transdermal fentanyl in this population. Clinical trial information: NCT03317730.

Pressurized intraperitoneal aerosol chemotherapy with low-dose cisplatin and doxorubicin (PIPAC C/D) in patients with gastric cancer and peritoneal metastasis (PIPAC-GA1).

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 99-99 ◽  
Author(s):  
Florian Struller ◽  
Philipp Horvath ◽  
Wiebke Solass ◽  
Frank Jurgen Weinreich ◽  
Alfred Konigsrainer ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Clinical Trial ◽  
Overall Survival ◽  
Peritoneal Metastasis ◽  
Low Dose ◽  
Tumor Regression ◽  
Open Label ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
Clinical Trial Information

99 Background: Efficacy of 2nd and 3rdline chemotherapy in recurrent gastric cancer with peritoneal metastasis (RGCPM) is limited. We assessed the feasibility, safety and activity of intraperitoneal chemotherapy as PIPAC C/D in RGCPM after > 1 line of intravenous chemotherapy. Methods: Open-label, single-arm, Phase II ICH-GCP Clinical Trial (NCT01854255) Patients were scheduled for 3 courses q42 days of low-dose PIPAC with doxorubicin 1.5 mg/m2 and cisplatin 7.5 mg/m2. Primary endpoint was objective tumor response (RECIST 1.1). Secondary endpoints were safety (CTCAE 4.0), histological tumor regression (PRGS) and overall survival. Results: 25 patients were enrolled. 10/25 (40 %, ITT) patients had an OTR. Complete or major regression on histology was observed in 9/12 (75 %) patients who underwent at least 2 PIPAC cycles. Mean overall survival was 8.4 months (13.1 months in patients with PCI < 12). There were no treatment-related deaths, no grade 4 toxicity and four (16%) grade 3 toxicities. Conclusions: PIPAC C/D is well tolerated and active in patients with RGCPM. Survival is encouraging. Randomized controlled trials should now be designed. Clinical trial information: NCT01854255. [Table: see text]

Sign in / Sign up

Export Citation Format

Share Document