Abstract Details

Title Effects of Once-Daily Ampreloxetine (TD-9855), a Norepinephrine Reuptake Inhibitor, on Blood Pressure in Subjects With Symptomatic Neurogenic Orthostatic Hypotension

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) S19 - Autonomic Disorders (3:42 PM-3:54 PM)

Poster/Presentation
Number 002

Objective To evaluate objective measures of blood pressure (BP) regulation in subjects with symptomatic neurogenic orthostatic hypotension (nOH) treated with open-label ampreloxetine.

Background In nOH, BP falls due to inadequate norepinephrine (NE) release when upright. Ampreloxetine, a novel, longer-acting, NE reuptake inhibitor, potentiates effects of endogenous NE and has shown durable symptom improvement in subjects with nOH associated with synucleinopathies.

Design/Methods In a phase 2, multicenter, exploratory study, subjects received ampreloxetine once-daily (3–20 mg) for up to 20 weeks, with 4-week follow-up after stopping ampreloxetine and restarting other pressor agents. Assessments included Orthostatic Hypotension Symptom Assessment Item 1 score (OHSA#1; dizziness, lightheadedness, feeling faint;); standing, sitting, supine systolic BP (SBP); standing duration; and plasma NE.

Results Seventeen symptomatic subjects (baseline OHSA#1 score >4) were enrolled (mean age, 65 years). Standing and sitting SBP, standing duration, plasma NE, and symptoms improved from Weeks 1 to 20. Mean increase in 3-minute standing SBP from baseline was 9.0 mmHg at Week 4 and 10.8 mmHg at Week 20; >50% of subjects maintained SBP >80 mmHg. Sitting SBP changes were less, with little change in supine SBP. At Week 4, 67% of subjects could stand for >5 mins, 31% improvement from baseline. NE plasma levels rose from pre-dose to Week 4 (1664.93–2231.67 pmol/l). After stopping ampreloxetine and restarting other pressor agents, standing SBP remained increased; however, nOH symptoms deteriorated to baseline. Ampreloxetine was well tolerated.

Conclusions Ampreloxetine has previously demonstrated durable symptom improvement in nOH. Symptom improvement was accompanied by increase in standing and sitting SBP, standing duration, and NE plasma levels, with little effect on supine SBP. These encouraging findings are being evaluated further in ongoing Phase 3 confirmatory studies in subjects with nOH and synucleinopathies.

Authors/Disclosures
Horacio C. Kaufmann, MD, FAAN (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 $500-$4,999 for serving as a Consultant for Parexel. 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 $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Takeda Pharmaceuticals. 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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