Hauser Robert A, Favit Antonella, Hewitt L Arthur, Lindsten Annika, Gorny Stephen, Kymes Steven, Isaacson Stuart H
Parkinson Foundation Center of Excellence, University of South Florida Parkinson's Disease and Movement Disorders Center, 4001 E Fletcher Avenue, Tampa, FL, 33613, USA.
Lundbeck, Deerfield, IL, 60015, USA.
Neurol Ther. 2022 Mar;11(1):459-469. doi: 10.1007/s40120-021-00317-5. Epub 2022 Feb 2.
Droxidopa is approved to treat neurogenic orthostatic hypotension (nOH) symptoms in patients with autonomic failure based on short-term clinical trial data. Additional data on the long-term efficacy of droxidopa are needed. We have evaluated the 12-week efficacy and tolerability of droxidopa in patients with nOH in an open-label period of an ongoing phase 4 study .
Patients received 12 weeks of open-label treatment with an individually optimized droxidopa dose (100-600 mg, 3 times daily) as identified during a preceding titration period. Patient-reported outcomes included the Orthostatic Hypotension Symptom Assessment (OHSA), Orthostatic Hypotension Daily Activity Scale (OHDAS), and clinician- and patient-rated Clinical Global Impression-Severity (CGI-S) scales. Supine blood pressure (BP) and adverse events (AEs) were recorded.
Data from 114 patients enrolled into the 12-week open-label period were available for analyses. After 12 weeks of droxidopa treatment, patients reported significant (P < 0.0001) improvements from baseline in OHSA and OHDAS composite and individual item scores and on clinician and patient CGI-S scores. Mean ± SD supine systolic and diastolic BP at week 12 increased by 15.5 ± 22.9 and 7.8 ± 11.7 mmHg from baseline, respectively (P < 0.0001 for both). The most frequently reported AEs were falls (17%), headache (13%), and dizziness (9%); one (0.9%) patient reported an AE of supine hypertension.
During 12 weeks of open-label treatment, droxidopa was associated with significant improvement from baseline in nOH symptoms and activities of daily living. No clinically important changes in supine hypertension or AEs of concern were observed. These results support the efficacy of droxidopa beyond 2 weeks of treatment.
NCT02586623.
基于短期临床试验数据，屈昔多巴已获批用于治疗自主神经功能衰竭患者的神经源性直立性低血压（nOH）症状。尚需有关屈昔多巴长期疗效的更多数据。我们在一项正在进行的4期研究的开放标签阶段，评估了屈昔多巴对nOH患者的12周疗效和耐受性。
患者接受为期12周的开放标签治疗，使用在前一滴定期确定的个体化优化屈昔多巴剂量（100 - 600毫克，每日3次）。患者报告的结局包括直立性低血压症状评估（OHSA）、直立性低血压日常活动量表（OHDAS）以及临床医生和患者评定的临床总体印象-严重程度（CGI-S）量表。记录仰卧位血压（BP）和不良事件（AE）。
纳入12周开放标签阶段的114例患者的数据可用于分析。屈昔多巴治疗12周后，患者报告OHSA和OHDAS综合及单项评分以及临床医生和患者CGI-S评分较基线有显著改善（P < 0.0001）。第12周时，仰卧位收缩压和舒张压的均值±标准差较基线分别升高15.5±22.9和7.8±11.7毫米汞柱（两者P均< 0.0001）。最常报告的不良事件为跌倒（17%）、头痛（13%）和头晕（9%）；1例（0.9%）患者报告了仰卧位高血压不良事件。
在12周的开放标签治疗期间，屈昔多巴与nOH症状和日常生活活动较基线相比有显著改善相关。未观察到仰卧位高血压或其他相关不良事件有临床意义的变化。这些结果支持屈昔多巴治疗超过2周的疗效。
NCT02586623。
