Durability of the Clinical Benefit of Droxidopa for Neurogenic Orthostatic Hypotension During 12 Weeks of Open-Label Treatment

Robert A Hauser, Antonella Favit, L Arthur Hewitt, Annika Lindsten, Stephen Gorny, Steven Kymes, Stuart H Isaacson, Robert A Hauser, Antonella Favit, L Arthur Hewitt, Annika Lindsten, Stephen Gorny, Steven Kymes, Stuart H Isaacson

Abstract

Introduction: 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 .

Methods: 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.

Results: 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.

Conclusion: 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.

Trial registration: NCT02586623.

Keywords: Droxidopa; Durability; Efficacy; Neurogenic orthostatic hypotension; Safety; Treatment.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Flow diagram of study disposition. Asterisk indicates that the dataset was not complete as of the cutoff date for analyses. Dagger indicates that the complete dataset was available as of the cutoff date for analyses
Fig. 2
Fig. 2
Mean (SD) OHSA (a) and OHDAS (b) scores are shown, with the SD for each data point indicated in the tables beneath the figure panels. Note: Score reductions for OHSA and OHDAS indicate decreased symptom burden on a rating scale from 0 (no symptoms/no interference) to 10 (worst possible symptoms/complete interference). OHDAS Orthostatic Hypotension Daily Activity Scale, OHSA Orthostatic Hypotension Symptom Assessment, SD standard deviation
Fig. 3
Fig. 3
Mean CGI-S* scores. CGI-S Clinical Global Impression–Severity scale. Note: Score reductions indicate decreased symptom burden on a rating scale from 1 (no symptoms) to 7 (severe symptoms)
Fig. 4
Fig. 4
Mean (SD) supine BP. BP Blood pressure

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