Albayaty Muna, Linden Margareta, Olsson Håkan, Johnsson Markus, Strandgården Kerstin, Tiberg Fredrik
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.
Adv Ther. 2017 Feb;34(2):560-575. doi: 10.1007/s12325-016-0472-9. Epub 2017 Jan 9.
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 t 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.
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.
CAM2038每1周1次（每周一次）和每4周1次（每月一次）是基于液晶体注射储库技术的丁丙诺啡皮下注射用制剂。这两种药品正用于阿片类药物依赖治疗的研发，目标是实现每周一次和每月一次的皮下给药。研发两种给药频率不同的产品的理由是，治疗策略/方案，以及不同的治疗偏好，在患者、阿片类药物维持治疗的不同阶段和不同国家之间可能存在差异。本研究评估了CAM2038每1周1次或每4周1次给药与活性对照相比后丁丙诺啡和去甲丁丙诺啡的药代动力学和安全性。
健康志愿者被随机分为五个治疗组。所有人均接受单次静脉注射600 μg丁丙诺啡，洗脱期后接受单次剂量的CAM2038每4周1次96 mg、单次剂量的CAM2038每4周1次192 mg，或每日舌下含服丁丙诺啡8、16或24 mg，持续7天，洗脱期后接受单次剂量的CAM2038每4周1次64或128 mg，或CAM2038每1周1次16 mg重复给药4次。所有受试者均每日服用纳曲酮。
87名受试者被随机分组。CAM2038每4周1次给药后丁丙诺啡的中位达峰时间为4 - 10小时（CAM2038每1周1次给药后为24小时）；平均终末半衰期为19 - 25天（CAM2038每1周1次给药后为5天）。CAM2038每4周1次给药显示出丁丙诺啡剂量成比例释放，在相当的每月剂量水平下与CAM2038每1周1次重复给药的暴露量相似。两种CAM2038制剂均显示丁丙诺啡具有完全绝对生物利用度，且丁丙诺啡生物利用度比舌下含服丁丙诺啡高5.7至7.7倍。CAM2038每1周1次和每4周1次给药耐受性良好；给药后1小时，受试者对CAM2038的接受度高于舌下含服丁丙诺啡。
CAM2038每1周1次和每4周1次给药与舌下含服丁丙诺啡相比的药代动力学特征分别支持每周一次和每月一次给药预期的治疗效果。CAM2038制剂安全且显示出良好的局部耐受性。
ISRCTN24987553。
卡穆鲁斯公司。
