Jost Wolfgang H, Wang Maggie, Wauer Gabriel, Dax Annika, Wedemeyer Ralph-Steven, Schug Barbara, Warnke André, Leblanc Ana, Schurad Bjoern
Int J Clin Pharmacol Ther. 2025 Feb;63(2):77-86. doi: 10.5414/CP204672.
To demonstrate adequate skin adhesion of a new once-daily rotigotine transdermal patch (ROT-TDS) compared to the originator product (reference) in patients with Parkinson's disease (PD).
Pharmacokinetic bioequivalence (PK BE) was assessed with the 4 mg/24h patches in healthy adults in a single-/multiple-dose, crossover trial. The trial investigating skin adhesion in PD patients (stable dose ≥ 8 mg/day rotigotine) was performed with the 8 mg/24h patches as a multiple-dose, crossover trial (4 alternating once-daily patch applications). Skin status (seborrhea, sweating) was characterized at screening. Adhesion was assessed 5 minutes after application and 5 minutes before removal of each patch. Systemic safety and skin irritation/sensitization were monitored.
ROT-TDS was bioequivalent to the reference product in the PK BE trial in 48 randomized healthy subjects. In the skin adhesion trial in 43 randomized PD patients, the cumulative mean percentage of adhesion (90% CI) at the end-of-dosing interval was 92.948% (90.156 - 95.740%) for ROT-TDS and 90.471% (87.574 - 93.367%) for the reference. For ROT-TDS, 80.23% of patches were ≥ 90% adhered at the end-of-dosing interval, while this was the case for 67.44% of the reference patches. Safety and skin tolerability of both products were comparable; the most frequent treatment-related adverse event was application-site pruritus for both treatments at comparable extent.
ROT-TDS - with shown BE to the originator reference product - displayed similar safety and local tolerability as the reference product in patients with PD. The results show a trend to improved skin adhesion of the new patch compared to the reference in the target population.
在帕金森病（PD）患者中，证明一种新型每日一次的罗替戈汀透皮贴剂（ROT - TDS）与原研产品（参比制剂）相比具有足够的皮肤黏附性。
在一项单剂量/多剂量交叉试验中，对健康成年人使用4 mg/24h的贴剂评估药代动力学生物等效性（PK BE）。在PD患者（罗替戈汀稳定剂量≥8 mg/天）中进行的皮肤黏附性研究，使用8 mg/24h的贴剂作为多剂量交叉试验（4次每日交替贴敷）。在筛选时对皮肤状况（皮脂溢、出汗）进行特征描述。在每次贴剂应用后5分钟和移除前5分钟评估黏附性。监测全身安全性以及皮肤刺激/致敏情况。
在48名随机分组的健康受试者中进行的PK BE试验中，ROT - TDS与参比产品生物等效。在43名随机分组的PD患者中进行的皮肤黏附性试验中，给药间隔结束时，ROT - TDS的累积平均黏附百分比（90% CI）为92.948%（90.156 - 95.740%），参比制剂为90.471%（87.574 - 93.367%）。对于ROT - TDS，80.23%的贴剂在给药间隔结束时黏附率≥90%，而参比贴剂的这一比例为67.44%。两种产品的安全性和皮肤耐受性相当；两种治疗中最常见的与治疗相关的不良事件均为应用部位瘙痒，程度相当。
ROT - TDS与原研参比产品显示生物等效，在PD患者中表现出与参比产品相似的安全性和局部耐受性。结果表明，在目标人群中，新型贴剂与参比制剂相比有皮肤黏附性改善的趋势。
