Safety of a Rapidly Dissolving Buprenorphine/Naloxone Sublingual Tablet (BNX-RDT) for Treatment of Opioid Dependence: A Multicenter, Open-label Extension Study

Hoffman, Kent Steven; Peyton, Marvin; Sumner, Michael

doi:10.1097/adm.0000000000000301

Cited by 10 publications

(20 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Retention and illicit opioid use in relation to buprenorphine dose There were 15 randomized controlled trials included in the systematic review (Table 2) [29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44]. The definition of retention varied across the studies.…”

Section: Opioid Blockade In Relation To Buprenorphine Dosementioning

confidence: 99%

Optimal dose of buprenorphine in opioid use disorder treatment: a review of pharmacodynamic and efficacy data

Hjelmström¹,

Nordbeck²,

Tiberg³

2020

Drug Development and Industrial Pharmacy

View full text Add to dashboard Cite

Context: There is currently no consensus regarding optimal dose or dose-range of buprenorphine (BUP) for treatment of opioid use disorder (OUD). Objective: To elucidate the relationship between BUP dose and opioid receptor blockade, retention in treatment and illicit opioid drug use. Methods: Systematic review of the scientific literature through searches in the databases MEDLINE and PubMed. Results: The review of the opioid receptor blockade studies did not find evidence that a daily sublingual (SL) BUP tablet dose higher than 16 mg confers added blockade benefit, while doses under 8 mg are insufficient to produce opioid receptor blockade. The data are inconclusive regarding the relative effectiveness of an 8 mg SL BUP tablet dose versus a 16 mg SL BUP tablet dose in terms of opioid receptor blockade. The review did not establish any clear relationship between BUP dose and treatment retention or illicit opioid use. Conclusions: The BUP dose in treatment of OUD should be individualized based on a continuous clinical benefit-risk assessment. Further research is needed to better understand the relationship between dose and efficacy over time in patients with this complex disorder.

show abstract

Section: Opioid Blockade In Relation To Buprenorphine Dosementioning

confidence: 99%

Optimal dose of buprenorphine in opioid use disorder treatment: a review of pharmacodynamic and efficacy data

Hjelmström¹,

Nordbeck²,

Tiberg³

2020

Drug Development and Industrial Pharmacy

View full text Add to dashboard Cite

show abstract

“…Based on robust randomized clinical trials, buprenorphine/naloxone (SUBOXONE ® ) sublingual film and sublingual tablets have been approved in more than 40 countries worldwide for the treatment of OUD, but are not yet approved in China [13–17]. Buprenorphine is a partial agonist at the µ-opioid receptor that can attenuate withdrawal symptoms while lowering the risk of respiratory depression and fatal overdose associated with full agonists [16].…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics of Sublingual Buprenorphine Tablets Following Single and Multiple Doses in Chinese Participants With and Without Opioid Use Disorder

Dong

Wang

et al. 2019

Drugs R D

View full text Add to dashboard Cite

BackgroundTwo phase I studies assessed the pharmacokinetics of buprenorphine, its metabolite norbuprenorphine, and naloxone following administration of buprenorphine/naloxone sublingual tablets in Chinese participants.MethodsIn the first phase I, open-label, single ascending-dose (SAD) study, 82 opioid-naïve volunteers received a single buprenorphine/naloxone dose ranging from 2 mg/0.5 mg to 24 mg/6 mg while under naltrexone block. In a second phase I, open-label, multiple ascending-dose (MAD) study, 27 patients with opioid dependence in withdrawal received buprenorphine/naloxone doses of either 16 mg/4 mg or 24 mg/6 mg for 9 consecutive days. Serial blood samples were collected after a single dose (SAD study) and at steady-state (MAD study). Pharmacokinetic parameters were calculated using non-compartmental analysis. Safety assessments included adverse events monitoring and laboratory tests.ResultsThe pharmacokinetic profiles of buprenorphine and naloxone were consistent between single- and multiple-dose studies. Peak plasma concentrations (Cmax) were reached early for buprenorphine (0.75–1.0 h) and naloxone (0.5 h), supporting rapid absorption. In the SAD study, increases in plasma exposures to buprenorphine and naloxone were less than dose proportional, in line with previous observations in Western populations. Buprenorphine-to-naloxone ratios for Cmax and area under the curve (AUC) were constant over the dose range investigated and also consistent with Western populations data. Steady state was reached within 7 days of daily dosing, with slight accumulation over repeated doses. No serious adverse events were observed.ConclusionsThe present data suggest that buprenorphine/naloxone pharmacokinetic profiles in Chinese participants are consistent, overall, with those in Western populations, supporting no differences in dosing.Clinical Trial RegistrationThe protocols were registered on the official website of the China Food and Drug Administration (CFDA): http://www.chinadrugtrials.org.cn/; Registration numbers CTR20132963 (RB-CN-10-0012), CTR20140153 (RB-CN-10-0015).Electronic supplementary materialThe online version of this article (10.1007/s40268-019-0277-9) contains supplementary material, which is available to authorized users.

show abstract

“…Naloxone was added to buprenorphine to deter intravenous abuse without affecting the efficacy of the treatment. Studies in Western countries have demonstrated its efficacy in opioid‐dependent patients and reduction of intravenous misuse of buprenorphine; limited information exists among the Chinese population (Schottenfeld, Chawarski, & Mazlan, ; HIV Prevention Trials Network, ; Hoffman, Peyton, & Sumner, ; Woody, ).…”

Section: Introductionmentioning

confidence: 99%

Treatment of opioid dependence with buprenorphine/naloxone sublingual tablets: A phase 3 randomized, double‐blind, placebo‐controlled trial

Wang

Jiang

Zhao

et al. 2018

Asia-Pacific Psychiatry

View full text Add to dashboard Cite

Introduction The purpose of the study is to evaluate the efficacy and safety of buprenorphine/naloxone sublingual tablets for the treatment of opioid dependence in Chinese adults. Methods This multicenter, double‐blind, placebo‐controlled study included four periods: induction (3‐5 days), stabilization (7‐21 days), randomization/treatment (6 weeks), and postmedication follow‐up (1 week). A total of 442 participants with opioid dependence were enrolled; 260 were randomized to buprenorphine/naloxone or placebo. The primary outcome was retention in treatment, defined as the time from randomization to treatment completion or treatment failure. Secondary outcomes included maximum consecutive days of abstinence from opioids, self‐reported craving and opioid withdrawal symptoms, and urine drug screen results. Safety assessments included adverse event reporting, electrocardiograms, clinical laboratory tests, vital signs, and prior/concomitant medications. Results The median treatment retention time (95% confidence internal) with buprenorphine/naloxone was 32 days (26‐38) versus 6 days (5‐8) for placebo, with a Cox hazard ratio of 0.28 (95% confidence interval, 0.21‐0.38; P < 0.0001). The median maximum consecutive days of abstinence (95% confidence interval) was: buprenorphine/naloxone, 21 days (26‐38); placebo, 5 days (5‐8) with a Cox hazard ratio of 0.38 (95% confidence interval, 0.25‐0.60; P < 0.0001). Withdrawal and craving symptoms were significantly milder with buprenorphine/naloxone versus placebo (P < 0.001). Urine drug screen results indicated significantly lower opioid usage in the buprenorphine/naloxone group compared with placebo (P < 0.001). The most commonly reported adverse events in the buprenorphine/naloxone group during treatment were aspartate aminotransferase increased and nasopharyngitis. Discussion Efficacy and safety results from this clinical trial support a positive benefit‐risk ratio for buprenorphine/naloxone sublingual tablet use in the treatment of an opioid‐dependent Chinese population.

show abstract

Safety of a Rapidly Dissolving Buprenorphine/Naloxone Sublingual Tablet (BNX-RDT) for Treatment of Opioid Dependence: A Multicenter, Open-label Extension Study

Cited by 10 publications

References 20 publications

Optimal dose of buprenorphine in opioid use disorder treatment: a review of pharmacodynamic and efficacy data

Optimal dose of buprenorphine in opioid use disorder treatment: a review of pharmacodynamic and efficacy data

Pharmacokinetics of Sublingual Buprenorphine Tablets Following Single and Multiple Doses in Chinese Participants With and Without Opioid Use Disorder

Treatment of opioid dependence with buprenorphine/naloxone sublingual tablets: A phase 3 randomized, double‐blind, placebo‐controlled trial

Contact Info

Product

Resources

About