title: Pharmacokinetic Evaluation of Once-Weekly and Once-Monthly Buprenorphine Subcutaneous Injection Depots (CAM2038) Versus Intravenous and Sublingual Buprenorphine in Healthy Volunteers Under Naltrexone Blockade: An Open-Label Phase 1 Study.
abstract: CAM2038 q1w (once weekly) and q4w (once monthly) are investigational buprenorphine subcutaneous (SC) formulations based on FluidCrystal®injection depot technology. These two drug products are being developed for opioid dependence treatment, with a target for once-weekly and once-monthly SC dosing. The rationale for developing two products with different dosing frequencies is that treatment strategies/routines, and hence different treatment preferences, can vary between patients, different stages of opioid maintenance treatment, and countries. This study evaluated the pharmacokinetics and safety of buprenorphine and norbuprenorphine following administration of CAM2038 q1w or q4w versus active controls.
  
  
  
  Healthy volunteers were randomized to five treatment groups. All received a single intravenous dose of buprenorphine 600 µg, followed post-washout by a single dose of CAM2038 q4w 96 mg, a single dose of CAM2038 q4w 192 mg, or sublingual buprenorphine 8, 16, or 24 mg daily for 7 days, followed post-washout by a single dose of CAM2038 q4w 64 or 128 mg or four repeated weekly doses of CAM2038 q1w 16 mg. All subjects received daily naltrexone.
  
  
  
  Eighty-seven subjects were randomized. Median buprenorphine tmaxafter CAM2038 q4w was 4-10 h (24 h for CAM2038 q1w); mean terminal half-life was 19-25 days (5 days for CAM2038 q1w). CAM2038 q4w showed dose-proportional buprenorphine release, with similar exposure to repeat-dose CAM2038 q1w at comparable monthly dose level. Both CAM2038 formulations showed complete absolute bioavailability of buprenorphine and 5.7- to 7.7-fold greater buprenorphine bioavailability versus sublingual buprenorphine. CAM2038 q1w and q4w were well tolerated; subjects' acceptance was higher for CAM2038 than for sublingual buprenorphine 1 h post-dose.
  
  
  
  The pharmacokinetic profiles of CAM2038 q1w and q4w versus sublingual buprenorphine support expected treatment efficacy with once-weekly and once-monthly dosing, respectively. CAM2038 formulations were safe and showed good local tolerability.
  
  
  
  ISRCTN24987553.
  
  
  
  Camurus AB.
authors.affiliation: Parexel Early Phase Clinical Unit Level 7, Northwick Park Hospital, Watford Road, Harrow, Middlesex, London, UK.
authors.forename: Muna
authors.initials: M
authors.lastname: Albayaty
authors.affiliation: Camurus AB, Ideon Science Park, 223 70, Lund, Sweden.
authors.forename: Margareta
authors.initials: M
authors.lastname: Linden
authors.affiliation: Camurus AB, Ideon Science Park, 223 70, Lund, Sweden.
authors.forename: Håkan
authors.initials: H
authors.lastname: Olsson
authors.affiliation: Camurus AB, Ideon Science Park, 223 70, Lund, Sweden.
authors.forename: Markus
authors.initials: M
authors.lastname: Johnsson
authors.affiliation: Camurus AB, Ideon Science Park, 223 70, Lund, Sweden.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Strandgården
authors.affiliation: Camurus AB, Ideon Science Park, 223 70, Lund, Sweden. fredrik.tiberg@camurus.com.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Tiberg
mesh_terms: D000286:Administration, Sublingual; D000328:Adult; D001682:Biological Availability; D002047:Buprenorphine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000493:pharmacokinetics; D016903:Drug Monitoring; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics; D058850:Opiate Substitution Treatment / Q000379:methods*; D009293:Opioid-Related Disorders / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D003692:Delayed-Action Preparations; D009292:Narcotic Antagonists; D002047:Buprenorphine; C043585:norbuprenorphine
keywords: Buprenorphine; CAM2038; Opioid dependence; Opioid use disorder; Pharmacokinetics; Sustained release