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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

Albayaty, Muna; Linden, Margareta; Olsson, Håkan LU ; Johnsson, Markus LU ; Strandgården, Kerstin and Tiberg, Fredrik LU (2017) In Advances in Therapy 34(2). p.560-575
Abstract

Introduction: 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. Methods:... (More)

Introduction: 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. Methods: 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. Results: Eighty-seven subjects were randomized. Median buprenorphine tmax after 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. Conclusions: 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. Trial registration: ISRCTN24987553. Funding: Camurus AB.

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author
publishing date
type
Contribution to journal
publication status
published
keywords
Buprenorphine, CAM2038, Opioid dependence, Opioid use disorder, Pharmacokinetics, Sustained release
in
Advances in Therapy
volume
34
issue
2
pages
16 pages
publisher
Health Communications Inc.
external identifiers
  • scopus:85008640776
ISSN
0741-238X
DOI
10.1007/s12325-016-0472-9
language
English
LU publication?
no
id
d44ca8bb-da1b-4335-93dd-753584cf696b
date added to LUP
2017-02-13 10:19:30
date last changed
2018-03-18 05:09:21
@article{d44ca8bb-da1b-4335-93dd-753584cf696b,
  abstract     = {<p>Introduction: CAM2038 q1w (once weekly) and q4w (once monthly) are investigational buprenorphine subcutaneous (SC) formulations based on FluidCrystal<sup>®</sup> 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. Methods: 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. Results: Eighty-seven subjects were randomized. Median buprenorphine t<sub>max</sub> after 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. Conclusions: 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. Trial registration: ISRCTN24987553. Funding: Camurus AB.</p>},
  author       = {Albayaty, Muna and Linden, Margareta and Olsson, Håkan and Johnsson, Markus and Strandgården, Kerstin and Tiberg, Fredrik},
  issn         = {0741-238X},
  keyword      = {Buprenorphine,CAM2038,Opioid dependence,Opioid use disorder,Pharmacokinetics,Sustained release},
  language     = {eng},
  month        = {01},
  number       = {2},
  pages        = {560--575},
  publisher    = {Health Communications Inc.},
  series       = {Advances in Therapy},
  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},
  url          = {http://dx.doi.org/10.1007/s12325-016-0472-9},
  volume       = {34},
  year         = {2017},
}