title: Randomised Comparison of a Novel Buprenorphine Oral Lyophilisate versus Existing Buprenorphine Sublingual Tablets in Opioid-Dependent Patients: A First-in-Patient Phase II Randomised Open Label Safety Study.
abstract: OBJECTIVE
  To test the safety of new buprenorphine oral lyophilisate wafer ("bup-lyo") versus standard sub-lingual buprenorphine ("bup-SL").
  
  
  METHODS
  Randomised (2:1) open-label study; opioid-dependent subjects; subsequent partial cross-over.
  
  
  METHODS
  Specialised clinical trials facility and addictions treatment facility.
  
  
  METHODS
  Opioid-dependent subjects (n = 36) commencing buprenorphine maintenance (personalised dose-titration) including patients co-using alcohol, cocaine and benzodiazepines (below thresholds).
  
  
  METHODS
  Respiratory function (respiratory rate, pulse-oximetry); medication hold and dose adequacy; opiate withdrawal signs and symptoms; tablet disintegration times; treatment retention. Pharmacokinetics (PK) for plasma buprenorphine and norbuprenorphine (n = 11).
  
  
  RESULTS
  Oral lyophilised buprenorphine ("bup-lyo") completely dissolved within 2 min for 58 vs. 5% for "bup-SL." Dose titration resulted in similar maintenance dosing (10.8 vs. 9.6 mg). There were no significant between-group differences in opiate-withdrawal phenomena, craving, adequacy of "hold," respiratory function. No serious adverse events (AEs), nor "severe" AEs, although more AEs and Treatment-Emergent AEs with "bup-lyo" (mostly "mild"). PK found greater bioavailability of buprenorphine with "bup-lyo" (but not norbuprenorphine).
  
  
  CONCLUSIONS
  Orally disintegrating buprenorphine oral lyophilisate wafer disintegrated rapidly. No increased respiratory depression was found and clinically no difference between medications was observed. PK found substantially increased bioavailability of buprenorphine (but not of nor-buprenorphine) with "bup-lyo" relative to "bup-SL." In supervised dosing contexts, rapidly disintegrating formulations may enable wider buprenorphine prescribing.
authors.affiliation: King's College London, National Addiction Centre, Institute of Psychiatry, Psychology and Neuroscience, London, UK.
authors.forename: John
authors.initials: J
authors.lastname: Strang
authors.forename: Kylie
authors.initials: K
authors.lastname: Reed
authors.forename: Karolina
authors.initials: K
authors.lastname: Bogdanowicz
authors.forename: James
authors.initials: J
authors.lastname: Bell
authors.forename: Rob
authors.initials: R
authors.lastname: van der Waal
authors.forename: Jenny
authors.initials: J
authors.lastname: Keen
authors.forename: Pete
authors.initials: P
authors.lastname: Beavan
authors.forename: Shelagh
authors.initials: S
authors.lastname: Baillie
authors.forename: Alastair
authors.initials: A
authors.lastname: Knight
mesh_terms: D000701:Analgesics, Opioid / Q000009:adverse effects; D002047:Buprenorphine / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D004333:Drug Administration Routes; D005260:Female; D006801:Humans; D058850:Opiate Substitution Treatment / Q000379:methods*; D009293:Opioid-Related Disorders / Q000188:drug therapy*; D013607:Tablets
chemical_list: D000701:Analgesics, Opioid; D013607:Tablets; D002047:Buprenorphine; C043585:norbuprenorphine
keywords: Buprenorphine; Lyophilised; New treatment; Opiate addiction; Opioid substitute therapy; Phase II trial; Randomised trial; Rapidly-disintegrating buprenorphine; Safety study