Caitlin E. Martin , James M. Bjork , Lori Keyser-Marcus , Roy T. Sabo , Tiffany Pignatello , Kameron Simmons , Christina La Rosa , Albert J. Arias , Tatiana Ramey , F. Gerard Moeller
{"title":"leleborexant辅助治疗失眠与丁丙诺啡-纳洛酮治疗阿片类药物使用障碍的1b/2a期安全性研究:一项随机对照试验","authors":"Caitlin E. Martin , James M. Bjork , Lori Keyser-Marcus , Roy T. Sabo , Tiffany Pignatello , Kameron Simmons , Christina La Rosa , Albert J. Arias , Tatiana Ramey , F. Gerard Moeller","doi":"10.1016/j.dadr.2024.100304","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Evidence supports the common incidence of sleep disturbance in opioid use disorder (OUD) as a potential marker of disrupted orexin system functioning. This study evaluated the initial safety and tolerability of a challenge dose of lemborexant, a dual orexin antagonist, as an adjunct to buprenorphine/naloxone.</div></div><div><h3>Methods</h3><div>Patients (18–65 years old) with OUD receiving sublingual buprenorphine/naloxone, with a Pittsburgh Sleep Quality Index total score of 6 or higher, were recruited from outpatient clinics. After randomization, while being monitored on an inpatient research unit over two 10-hour daytime periods, participants received a placebo or lemborexant (5<!--> <!-->mg on day one and 10<!--> <!-->mg on day two) along with buprenorphine/naloxone. Primary outcomes included safety and tolerability: adverse events, physiologic measures, sedation level assessments. Generalized linear mixed model analysis assessed the effect of study drug and time on outcomes.</div></div><div><h3>Results</h3><div>N=18 (14=male, 4=female) were randomized to lemborexant (n=12) or placebo (n=6). No unanticipated problems occurred; five adverse events occurred in the lemborexant group and two in the placebo group with no serious adverse events. None of the physiologic measures showed a significant interaction of time and placebo vs. lemborexant (5 or 10<!--> <!-->mg): Pulse oximetry (F=0.6; p=0.84), End-tidal CO2 (F=0.5; p=0.91), Heart rate (F=0.6; p=0.82), Systolic blood pressure (F=0.7; p=0.73), Diastolic blood pressure (F=2.0; p=0.06). At 9<!--> <!-->hours after study drug administration, all participants returned to baseline sedation levels and were discharged.</div></div><div><h3>Conclusions</h3><div>Findings support the initial safety and tolerability of lemborexant as an adjunctive treatment for insomnia in humans receiving buprenorphine for OUD. Future longitudinal work is warranted with larger samples.</div></div>","PeriodicalId":72841,"journal":{"name":"Drug and alcohol dependence reports","volume":"14 ","pages":"Article 100304"},"PeriodicalIF":0.0000,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11728975/pdf/","citationCount":"0","resultStr":"{\"title\":\"Phase 1b/2a safety study of lemborexant as an adjunctive treatment for insomnia to buprenorphine-naloxone for opioid use disorder: A randomized controlled trial\",\"authors\":\"Caitlin E. Martin , James M. Bjork , Lori Keyser-Marcus , Roy T. Sabo , Tiffany Pignatello , Kameron Simmons , Christina La Rosa , Albert J. Arias , Tatiana Ramey , F. Gerard Moeller\",\"doi\":\"10.1016/j.dadr.2024.100304\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><div>Evidence supports the common incidence of sleep disturbance in opioid use disorder (OUD) as a potential marker of disrupted orexin system functioning. This study evaluated the initial safety and tolerability of a challenge dose of lemborexant, a dual orexin antagonist, as an adjunct to buprenorphine/naloxone.</div></div><div><h3>Methods</h3><div>Patients (18–65 years old) with OUD receiving sublingual buprenorphine/naloxone, with a Pittsburgh Sleep Quality Index total score of 6 or higher, were recruited from outpatient clinics. After randomization, while being monitored on an inpatient research unit over two 10-hour daytime periods, participants received a placebo or lemborexant (5<!--> <!-->mg on day one and 10<!--> <!-->mg on day two) along with buprenorphine/naloxone. Primary outcomes included safety and tolerability: adverse events, physiologic measures, sedation level assessments. Generalized linear mixed model analysis assessed the effect of study drug and time on outcomes.</div></div><div><h3>Results</h3><div>N=18 (14=male, 4=female) were randomized to lemborexant (n=12) or placebo (n=6). No unanticipated problems occurred; five adverse events occurred in the lemborexant group and two in the placebo group with no serious adverse events. None of the physiologic measures showed a significant interaction of time and placebo vs. lemborexant (5 or 10<!--> <!-->mg): Pulse oximetry (F=0.6; p=0.84), End-tidal CO2 (F=0.5; p=0.91), Heart rate (F=0.6; p=0.82), Systolic blood pressure (F=0.7; p=0.73), Diastolic blood pressure (F=2.0; p=0.06). At 9<!--> <!-->hours after study drug administration, all participants returned to baseline sedation levels and were discharged.</div></div><div><h3>Conclusions</h3><div>Findings support the initial safety and tolerability of lemborexant as an adjunctive treatment for insomnia in humans receiving buprenorphine for OUD. Future longitudinal work is warranted with larger samples.</div></div>\",\"PeriodicalId\":72841,\"journal\":{\"name\":\"Drug and alcohol dependence reports\",\"volume\":\"14 \",\"pages\":\"Article 100304\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-11-22\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11728975/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Drug and alcohol dependence reports\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S277272462400088X\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Drug and alcohol dependence reports","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S277272462400088X","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Phase 1b/2a safety study of lemborexant as an adjunctive treatment for insomnia to buprenorphine-naloxone for opioid use disorder: A randomized controlled trial
Background
Evidence supports the common incidence of sleep disturbance in opioid use disorder (OUD) as a potential marker of disrupted orexin system functioning. This study evaluated the initial safety and tolerability of a challenge dose of lemborexant, a dual orexin antagonist, as an adjunct to buprenorphine/naloxone.
Methods
Patients (18–65 years old) with OUD receiving sublingual buprenorphine/naloxone, with a Pittsburgh Sleep Quality Index total score of 6 or higher, were recruited from outpatient clinics. After randomization, while being monitored on an inpatient research unit over two 10-hour daytime periods, participants received a placebo or lemborexant (5 mg on day one and 10 mg on day two) along with buprenorphine/naloxone. Primary outcomes included safety and tolerability: adverse events, physiologic measures, sedation level assessments. Generalized linear mixed model analysis assessed the effect of study drug and time on outcomes.
Results
N=18 (14=male, 4=female) were randomized to lemborexant (n=12) or placebo (n=6). No unanticipated problems occurred; five adverse events occurred in the lemborexant group and two in the placebo group with no serious adverse events. None of the physiologic measures showed a significant interaction of time and placebo vs. lemborexant (5 or 10 mg): Pulse oximetry (F=0.6; p=0.84), End-tidal CO2 (F=0.5; p=0.91), Heart rate (F=0.6; p=0.82), Systolic blood pressure (F=0.7; p=0.73), Diastolic blood pressure (F=2.0; p=0.06). At 9 hours after study drug administration, all participants returned to baseline sedation levels and were discharged.
Conclusions
Findings support the initial safety and tolerability of lemborexant as an adjunctive treatment for insomnia in humans receiving buprenorphine for OUD. Future longitudinal work is warranted with larger samples.