TY - JOUR KW - Administration, Sublingual KW - Adult KW - Biological Availability KW - Buprenorphine/administration & dosage/analogs & derivatives/pharmacokinetics KW - Delayed-Action Preparations/administration & dosage/pharmacokinetics KW - Drug Monitoring KW - Female KW - Healthy Volunteers KW - Humans KW - Injections, Subcutaneous KW - Male KW - Middle Aged KW - Narcotic Antagonists/administration & dosage/pharmacokinetics KW - Opiate Substitution Treatment/methods KW - Opioid-Related Disorders/drug therapy KW - Treatment Outcome KW - buprenorphine KW - CAM2038 KW - opioid dependence KW - opioid use disorder KW - Pharmacokinetics KW - Sustained release AU - M. Albayaty AU - M. Linden AU - H. Olsson AU - M. Johnsson AU - K. Strandgarden AU - F. Tiberg A1 - AB - INTRODUCTION: CAM2038 q1w (once weekly) and q4w (once monthly) are investigational buprenorphine subcutaneous (SC) formulations based on FluidCrystal((R)) 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 microg, 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 max 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. AD - Parexel Early Phase Clinical Unit Level 7, Northwick Park Hospital, Watford Road, Harrow, Middlesex, London, UK.; Camurus AB, Ideon Science Park, 223 70, Lund, Sweden.; Camurus AB, Ideon Science Park, 223 70, Lund, Sweden.; Camurus AB, Ideon Science Park, 223 70, Lund, Sweden.; Camurus AB, Ideon Science Park, 223 70, Lund, Sweden.; Camurus AB, Ideon Science Park, 223 70, Lund, Sweden. fredrik.tiberg@camurus.com. BT - Advances in Therapy C5 - Opioids & Substance Use CP - 2 CY - United States DO - 10.1007/s12325-016-0472-9 IS - 2 JF - Advances in Therapy M1 - Journal Article N2 - INTRODUCTION: CAM2038 q1w (once weekly) and q4w (once monthly) are investigational buprenorphine subcutaneous (SC) formulations based on FluidCrystal((R)) 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 microg, 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 max 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. PP - United States PY - 2017 SN - 1865-8652; 0741-238X SP - 560 EP - 575 EP - T1 - 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 T2 - Advances in Therapy TI - 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 U1 - Opioids & Substance Use U2 - 28070862 U3 - 10.1007/s12325-016-0472-9 VL - 34 VO - 1865-8652; 0741-238X Y1 - 2017 Y2 - Feb ER -