title: Sustained-Release Buprenorphine (RBP-6000) Blocks the Effects of Opioid Challenge With Hydromorphone in Subjects With Opioid Use Disorder.
abstract: A major goal for the treatment of opioid use disorder is to reduce or eliminate the use of illicit opioids. Buprenorphine, a μ-opioid receptor partial agonist and kappa opioid receptor antagonist, is now being developed as a monthly, sustained-release formulation (RBP-6000). The objective of this study was to demonstrate that RBP-6000 blocks the subjective effects and reinforcing efficacy of the μ-opioid receptor agonist hydromorphone (intramuscularly administered) in subjects with moderate or severe opioid use disorder. Subjects were first inducted and dose stabilized on sublingual buprenorphine/naloxone (8-24 mg daily; dose expressed as the buprenorphine component), then received two subcutaneous injections of RBP-6000 (300 mg) on Day 1 and Day 29. Hydromorphone challenges (6 mg, 18 mg or placebo administered in randomized order) occurred on 3 consecutive days of each study week before and after receiving RBP-6000. Subjects reported their responses to each challenge on various 100-mm Visual Analogue Scales (VAS). Subjects also completed a choice task to assess the reinforcing efficacy of each hydromorphone dose relative to money. At baseline, mean "drug liking" VAS scores for hydromorphone 18 mg and 6 mg versus placebo were 61 mm (95% confidence interval, 52.3-68.9) and 45 mm (95% confidence interval, 37.2-53.6), respectively. After 300 mg RBP-6000 was administered, mean VAS score differences from placebo were less than 10 mm through week 12. The reinforcing efficacy of hydromorphone decreased in a parallel manner. This study demonstrated that RBP-6000 at a 300 mg dose provides durable and potent blockade of the subjective effects and reinforcing efficacy of hydromorphone in subjects with moderate or severe opioid use disorder.
authors.affiliation: From *Indivior Inc., Richmond, VA; †the Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI; and ‡Vince & Associates Clinical Research, Inc., Overland Park, KS.
authors.forename: Azmi F
authors.initials: AF
authors.lastname: Nasser
authors.forename: Mark K
authors.initials: MK
authors.lastname: Greenwald
authors.forename: Bradley
authors.initials: B
authors.lastname: Vince
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Fudala
authors.forename: Philip
authors.initials: P
authors.lastname: Twumasi-Ankrah
authors.forename: Yongzhen
authors.initials: Y
authors.lastname: Liu
authors.forename: J P
authors.initials: JP
authors.lastname: Jones
authors.forename: Christian
authors.initials: C
authors.lastname: Heidbreder
mesh_terms: D000328:Adult; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology; D002047:Buprenorphine / Q000008:administration & dosage* / Q000494:pharmacology; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D004091:Hydromorphone / Q000008:administration & dosage* / Q000494:pharmacology; D007273:Injections, Intramuscular; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D009292:Narcotic Antagonists / Q000008:administration & dosage* / Q000494:pharmacology; D009293:Opioid-Related Disorders / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D000701:Analgesics, Opioid; D003692:Delayed-Action Preparations; D009292:Narcotic Antagonists; D002047:Buprenorphine; D004091:Hydromorphone