Abstract Details

Title An Open-Label Phase 2 Study to Explore the Durability of Effect, and Safety of Once-Daily Oral Ampreloxetine (TD-9855), a Norepinephrine Reuptake Inhibitor, for the Symptomatic Treatment of Neurogenic Orthostatic Hypotension in Subjects With Synucleinopathies

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) P5 - Poster Session 5 (8:00 AM-9:00 AM)

Poster/Presentation
Number 1-001

Objective To explore the durability of effect and safety of once-daily oral ampreloxetine for the symptomatic treatment of neurogenic orthostatic hypotension (nOH) in subjects with synucleinopathies.

Background Inadequate norepinephrine (NE) release in nOH causes blood pressure to fall on standing and debilitating symptoms of cerebral hypoperfusion. Ampreloxetine, a novel, longer-acting, NE reuptake inhibitor, potentiates the effects of endogenous NE, and may improve symptoms of nOH.

Design/Methods In an open-label, phase 2, exploratory, multicenter study, subjects received open-label ampreloxetine (3-20 mg) once-daily for up to 20 weeks, with 4-week follow-up after stopping ampreloxetine and restarting alternative pressor agents. Assessments included Orthostatic Hypotension Symptom Assessment Item 1 (OHSA#1; dizziness, lightheadedness, feeling faint; OHSA and Orthostatic Hypotension Daily Activities Scale (OHDAS) composite scores, and Patient Global Impression of Severity and Change (PGI-S, PGI-C, respectively).

Results Seventeen symptomatic subjects (baseline OHSA#1 score >4) were enrolled (mean age, 65 years). At Week 4, mean (SD) improvement on OHSA#1 was -3.8 (3.1) points; ~77% of subjects reported ≥1-point improvement (minimal clinically important difference). At Week 20, mean improvement was -3.1 (3.0) points; ~86% reported ≥1-point improvement. Symptom improvement was observed as early as Week 1 and was sustained throughout the study. Deterioration to baseline symptom severity was seen by the end of the 4-week follow-up period. Similar trends were seen in OHSA and OHDAS composite scores, PGI-S, and PGI-C. Most common adverse events were urinary tract infection (24%), hypertension (19%), and headache (14%), with no study-drug related serious adverse events.

Conclusions Ampreloxetine showed durable symptom improvement in symptomatic subjects with nOH over 20 weeks, with return to baseline symptom severity after stopping ampreloxetine. Ampreloxetine was well tolerated with a favorable safety profile. These encouraging open label findings are being evaluated further in ongoing Phase 3, double blind, confirmatory studies in subjects with nOH and synucleinopathies.

Authors/Disclosures
Horacio C. Kaufmann, MD, F�鶹��ýӳ�� (NYU Langone Health - NYU Dysautonomia Center) PRESENTER	Dr. Kaufmann has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Theravance. Dr. Kaufmann has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Teva Pharmaceuticals. Dr. Kaufmann has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Curasen Therapeutics. Dr. Kaufmann has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Lundbeck. Dr. Kaufmann has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for AskBio. Dr. Kaufmann has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for BioArctic. Dr. Kaufmann has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sanofi. Dr. Kaufmann has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Spinger. The institution of Dr. Kaufmann has received research support from Biogen. The institution of Dr. Kaufmann has received research support from Vaxxinity. Dr. Kaufmann has received publishing royalties from a publication relating to health care.
	No disclosure on file
	No disclosure on file
	No disclosure on file
Ross Vickery	Ross Vickery has nothing to disclose.

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