Haasen Christian, Linden Margareta, Tiberg Fredrik
Clinical Trial Centre North, MediGate GmbH, University Medical Centre Hamburg Eppendorf, Martinistraße 52, Haus S10, 20246 Hamburg, Germany.
Camurus AB, Ideon Science Park, Gamma Building, Sölvegatan 41, 223 70 Lund, Sweden.
J Subst Abuse Treat. 2017 Jul;78:22-29. doi: 10.1016/j.jsat.2017.04.008. Epub 2017 Apr 14.
Sublingual buprenorphine is effective for opioid dependence treatment but associated with misuse, abuse, and diversion. The present Phase I/II study evaluated a novel buprenorphine subcutaneous depot formulation for once-weekly dosing (CAM2038 q1w) in patients receiving maintenance treatment for opioid use disorder with daily sublingual buprenorphine.
After discontinuation of buprenorphine for 48h, patients received a single CAM2038 q1w dose based on their pre-study daily sublingual maintenance dose. CAM2038 q1w doses of 7.5, 15, 22.5, and 30mg were administered in a sequential dose-escalating design. The following assessments were performed: pharmacokinetics of buprenorphine and norbuprenorphine, pharmacodynamics (evaluated using the Subjective and Clinical Opiate Withdrawal Scales), and time to intake of rescue sublingual buprenorphine medication.
Single doses of CAM2038 q1w indicated dose-proportional buprenorphine pharmacokinetics (C and AUC), with time to C ~20h and an apparent terminal half-life of 3-5days, supporting once-weekly dosing. On average, patients showed a rapid and extended decrease in opiate-withdrawal symptoms from baseline, with zero or very low SOWS and COWS values measured at least up to 7days after dosing of CAM2038 q1w. The median time to first use of rescue buprenorphine was 10days. No dose dependence was seen in the pharmacodynamics, attributable to the selection of CAM2038 q1w doses based on patients' pre-study maintenance doses. CAM2038 q1w was safe and generally well tolerated.
Pharmacokinetics and pharmacodynamics of a novel buprenorphine subcutaneous depot formulation for once-weekly dosing was evaluated, suggesting utility in maintenance treatment of patients with opioid use disorder.
舌下含服丁丙诺啡对阿片类药物依赖治疗有效，但存在误用、滥用和转移的问题。本I/II期研究评估了一种新型丁丙诺啡皮下长效注射制剂，用于接受每日舌下含服丁丙诺啡维持治疗的阿片类药物使用障碍患者，每周给药一次（CAM2038 q1w）。
在丁丙诺啡停药48小时后，患者根据其研究前每日舌下维持剂量接受单次CAM2038 q1w剂量。采用序贯剂量递增设计，给予7.5、15、22.5和30mg的CAM2038 q1w剂量。进行了以下评估：丁丙诺啡和去甲丁丙诺啡的药代动力学、药效学（使用主观和临床阿片类药物戒断量表进行评估）以及使用舌下含服丁丙诺啡急救药物的时间。
单次CAM2038 q1w剂量显示丁丙诺啡药代动力学（C和AUC）呈剂量比例关系，达到C的时间约为20小时，表观终末半衰期为3至5天，支持每周给药一次。平均而言，患者的阿片类药物戒断症状从基线开始迅速且持续下降，在给予CAM2038 q1w剂量后至少7天内，主观和临床阿片类药物戒断量表（SOWS和COWS）值为零或非常低。首次使用丁丙诺啡急救药物的中位时间为10天。由于根据患者研究前的维持剂量选择CAM2038 q1w剂量，因此在药效学方面未观察到剂量依赖性。CAM2038 q1w安全且耐受性良好。
评估了一种新型丁丙诺啡皮下长效注射制剂每周给药一次的药代动力学和药效学，表明其在阿片类药物使用障碍患者维持治疗中的效用。
