Exploring Opioid Use Disorder Outcomes by Quantitative Urinalysis: Post Hoc Analysis of a Phase 3 Randomized Clinical Trial.

IF 4.2 3区医学 Q1 SUBSTANCE ABUSE

Journal of Addiction Medicine Pub Date : 2024-12-10 DOI:10.1097/ADM.0000000000001405

Stefan Peterson, Edward V Nunes, Michelle R Lofwall, Sharon L Walsh, Fredrik Tiberg

{"title":"Exploring Opioid Use Disorder Outcomes by Quantitative Urinalysis: Post Hoc Analysis of a Phase 3 Randomized Clinical Trial.","authors":"Stefan Peterson, Edward V Nunes, Michelle R Lofwall, Sharon L Walsh, Fredrik Tiberg","doi":"10.1097/ADM.0000000000001405","DOIUrl":null,"url":null,"abstract":"Objectives: Opioid use disorder (OUD) is a global concern. Urine drug screening uses opioid immunoassays to monitor OUD treatment response but is limited to yes/no results. Analytical cutoff variation complicates interstudy comparisons. This study investigated whether quantitative urinalysis can provide additional clinically meaningful treatment efficacy information and assessed the impact of different cutoffs on treatment differences.Methods: Quantitative urine drug test data were analyzed from a randomized, active-controlled, parallel-group, double-blind, 31-week phase 3 trial (N = 428; December 29, 2015, to October 19, 2016) assessing CAM2038 subcutaneous (SC) buprenorphine (BPN) extended-release injections compared to daily sublingual (SL) BPN/naloxone (BPN/NX) tablets, and equivalent placebos, in OUD treatment (NCT02651584). Urine samples were analyzed by gas or liquid chromatography with mass spectrometry. The European Medicines Agency (EMA)-directed primary endpoint, based on opioid detection above the lower limit of quantification (LLOQ), was explored using different cutoffs.Results: Using the LLOQ, the mean percentage of opioid-negative samples was 35.1% and 28.4% for CAM2038 and SL BPN/NX, respectively (mean difference [95% confidence interval], 6.7% [-0.1% to 13.6%]). Using standard cutoffs (1 ng/mg creatinine [fentanyl/norfentanyl], 300 ng/mg creatinine [other opioids]), results were 41.2% and 32.2% (9.0% [1.8%-16.1%]). Increasing cutoffs led to greater differences favoring CAM2038. Significant differences in mean concentrations over time and cumulative distribution of exposure to different opioids also favored CAM2038. The difference in fentanyl exposure between treatments was nonsignificant.Conclusions: Quantitative urinalysis provides insights into opioid use beyond assessment of abstinence. Study outcomes are impacted by analytical thresholds, which should be carefully considered when designing, interpreting, and comparing clinical trial results.","PeriodicalId":14744,"journal":{"name":"Journal of Addiction Medicine","volume":" ","pages":""},"PeriodicalIF":4.2000,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Addiction Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/ADM.0000000000001405","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"SUBSTANCE ABUSE","Score":null,"Total":0}

引用次数: 0

Abstract

Objectives: Opioid use disorder (OUD) is a global concern. Urine drug screening uses opioid immunoassays to monitor OUD treatment response but is limited to yes/no results. Analytical cutoff variation complicates interstudy comparisons. This study investigated whether quantitative urinalysis can provide additional clinically meaningful treatment efficacy information and assessed the impact of different cutoffs on treatment differences.

Methods: Quantitative urine drug test data were analyzed from a randomized, active-controlled, parallel-group, double-blind, 31-week phase 3 trial (N = 428; December 29, 2015, to October 19, 2016) assessing CAM2038 subcutaneous (SC) buprenorphine (BPN) extended-release injections compared to daily sublingual (SL) BPN/naloxone (BPN/NX) tablets, and equivalent placebos, in OUD treatment (NCT02651584). Urine samples were analyzed by gas or liquid chromatography with mass spectrometry. The European Medicines Agency (EMA)-directed primary endpoint, based on opioid detection above the lower limit of quantification (LLOQ), was explored using different cutoffs.

Results: Using the LLOQ, the mean percentage of opioid-negative samples was 35.1% and 28.4% for CAM2038 and SL BPN/NX, respectively (mean difference [95% confidence interval], 6.7% [-0.1% to 13.6%]). Using standard cutoffs (1 ng/mg creatinine [fentanyl/norfentanyl], 300 ng/mg creatinine [other opioids]), results were 41.2% and 32.2% (9.0% [1.8%-16.1%]). Increasing cutoffs led to greater differences favoring CAM2038. Significant differences in mean concentrations over time and cumulative distribution of exposure to different opioids also favored CAM2038. The difference in fentanyl exposure between treatments was nonsignificant.

Conclusions: Quantitative urinalysis provides insights into opioid use beyond assessment of abstinence. Study outcomes are impacted by analytical thresholds, which should be carefully considered when designing, interpreting, and comparing clinical trial results.

查看原文本刊更多论文

通过定量尿液分析探索阿片类药物使用障碍的结果：一项3期随机临床试验的事后分析。

目的：阿片类药物使用障碍（OUD）是一个全球关注的问题。尿药物筛查使用阿片类免疫测定来监测OUD治疗反应，但仅限于是/否结果。分析截止变异使研究间比较复杂化。本研究探讨了尿液定量分析是否可以提供额外的临床有意义的治疗疗效信息，并评估了不同的截止点对治疗差异的影响。方法：采用随机、主动对照、平行组、双盲、31周的3期临床试验(N = 428；2015年12月29日至2016年10月19日)，评估CAM2038皮下（SC）丁丙诺啡（BPN）缓释注射与每日舌下（SL）丁丙诺啡/纳洛酮（BPN/NX）片剂和等效安慰剂在OUD治疗中的比较（NCT02651584）。尿样采用气相或液相色谱联用质谱法进行分析。欧洲药品管理局（EMA）指导的主要终点，基于阿片类药物检测高于定量下限（LLOQ），使用不同的截止点进行了探索。结果：使用定量限，CAM2038和SL BPN/NX的阿片类药物阴性样品的平均百分比分别为35.1%和28.4%（平均差值[95%置信区间]，6.7%[-0.1% ~ 13.6%]）。采用标准截止值（1 ng/mg肌酐[芬太尼/去芬太尼]，300 ng/mg肌酐[其他阿片类药物]），结果分别为41.2%和32.2%（9.0%[1.8% ~ 16.1%]）。随着截止值的增加，有利于CAM2038的差异更大。平均浓度随时间的显著差异和暴露于不同阿片类药物的累积分布也有利于CAM2038。不同治疗组芬太尼暴露量差异不显著。结论：定量尿液分析提供了阿片类药物使用评估之外的见解。研究结果受到分析阈值的影响，在设计、解释和比较临床试验结果时应仔细考虑分析阈值。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Journal of Addiction Medicine 医学-药物滥用

CiteScore

6.10

自引率

9.10%

发文量

260

审稿时长

>12 weeks

期刊介绍： The mission of Journal of Addiction Medicine, the official peer-reviewed journal of the American Society of Addiction Medicine, is to promote excellence in the practice of addiction medicine and in clinical research as well as to support Addiction Medicine as a mainstream medical sub-specialty. Under the guidance of an esteemed Editorial Board, peer-reviewed articles published in the Journal focus on developments in addiction medicine as well as on treatment innovations and ethical, economic, forensic, and social topics including: •addiction and substance use in pregnancy •adolescent addiction and at-risk use •the drug-exposed neonate •pharmacology •all psychoactive substances relevant to addiction, including alcohol, nicotine, caffeine, marijuana, opioids, stimulants and other prescription and illicit substances •diagnosis •neuroimaging techniques •treatment of special populations •treatment, early intervention and prevention of alcohol and drug use disorders •methodological issues in addiction research •pain and addiction, prescription drug use disorder •co-occurring addiction, medical and psychiatric disorders •pathological gambling disorder, sexual and other behavioral addictions •pathophysiology of addiction •behavioral and pharmacological treatments •issues in graduate medical education •recovery •health services delivery •ethical, legal and liability issues in addiction medicine practice •drug testing •self- and mutual-help.