Parathyroid Hormone (1-34)-Coated Microneedle Patch System: Clinical Pharmacokinetics and Pharmacodynamics for Treatment of Osteoporosis
Parathyroid Hormone (1-34)-Coated Microneedle Patch System: Clinical Pharmacokinetics and Pharmacodynamics for Treatment of Osteoporosis
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DOI：
10.1007/s11095-010-0192-9
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发表时间：
2011-01-01
影响因子：
3.7
通讯作者：
Maa, Yuh-Fun
中科院分区：
文献类型：
--
作者：
Daddona, Peter E.;Matriano, James. A.;Maa, Yuh-Fun
目的评价新型经皮药物包被微针贴片系统（ZP-PTH）治疗骨质疏松症的PTH（1-34）的临床PK/PD。方法在40-85岁的正常志愿者中进行一期PK研究，评估给药部位、贴片佩戴时间和剂量的影响。二期研究在绝经后骨质疏松症妇女中进行，以确定与安慰剂贴片和FORTEO (R)注射相比贴片剂量的反应。结果1期ZP-PTH贴片给药后PTH等离子体脉冲谱快速，T-max缩短3倍，表观T-1/2缩短2倍。在第二阶段，ZP-PTH 20、30和40 μ g剂量显示血浆PTH AUC成比例增加。所有贴片剂量的受试者间和受试者内AUC变异性相似，与注射相当。所有贴片剂量均显著增加脊柱骨矿物质密度。出乎意料的是，ZP-PTH还产生了髋部骨矿物质密度的早期增加，注射时没有观察到这种效果。这些研究表明，这种新型的ZP-PTH贴片系统可以提供一致的、与治疗相关的PTH PK谱。基于令人鼓舞的2期安全性和有效性数据，该项目正在推进关键的3期临床研究。
Objectives To evaluate the clinical PK/PD of PTH(1-34) delivered by a novel transdermal drug-coated microneedle patch system (ZP-PTH) for the treatment of osteoporosis.Methods Phase 1 PK studies evaluated the effect of site of administration, patch wear time and dose in normal volunteers, ages 40-85 yrs. Phase 2 was conducted in post-menopausal women with osteoporosis to determine the patch dose response compared to placebo patch and FORTEO (R) injection.Results Phase 1 ZP-PTH patch delivery demonstrated a rapid PTH plasma pulse profile with T-max 3 times shorter and apparent T-1/2 2 times shorter than FORTEO (R). In Phase 2, ZP-PTH 20, 30 and 40 mu g doses showed a proportional increase in plasma PTH AUC. Inter-subject and intra-subject AUC variability was similar for all patch doses and comparable to injection. All patch doses produced a significant increase in spine bone mineral density. Unexpectedly, ZP-PTH also produced an early increase in hip bone mineral density, an effect not observed with the injection.Conclusions These studies suggest that this novel ZP-PTH patch system can deliver a consistent and therapeutically relevant PTH PK profile. Based on encouraging Phase 2 safety and efficacy data, the program is advancing into a pivotal Phase 3 clinical study.