Neurology. 2025 Apr 8;104(7_Supplement_1):4987. doi: 10.1212/WNL.0000000000212055. Epub 2025 Apr 7.
ABSTRACT
OBJECTIVE: To determine the impact of ampreloxetine (oral, 10 mg/day) on supine hypertension as assessed by ambulatory blood pressure (BP) monitoring.
BACKGROUND: In addition to neurogenic orthostatic hypotension (nOH), patients with alpha-synucleinopathies often have supine hypertension. Currently, all FDA-approved pressor agents for treating nOH carry black-boxed warnings that these drugs may exacerbate supine hypertension. Ampreloxetine is a novel, long-acting, norepinephrine reuptake inhibitor being tested as a treatment for nOH in phase III trials.
DESIGN/METHODS: Subjects with nOH due to alpha-synucleinopathies (n=186) were recruited into a 4-week double-blind placebo-controlled parallel-group trial (NCT03829657). Supine hypertension was assessed with two methods: 1) in-office after 10-mins supine rest and 2) throughout the night (nocturnal) using ambulatory BP monitoring at three time points: screening (pre-treatment) and day-7 and day-21 in the randomized phase; then graded as: absent <140, mild 140-159, moderate 160-179, or severe >180 mmHg.
RESULTS: Satisfactory ambulatory BP recordings at two or more timepoints were available in 80 subjects (n=48 Parkinson disease, n=22 multiple system atrophy, n=10 pure autonomic failure). Diagnostic subtype and age/sex were similar in the placebo (n=50) and ampreloxetine (n=30) groups. Mean pre-treatment nocturnal BP was not different (127.2±17.0 vs. 127.3±16.9 mmHg, respectively). In the randomized phase, nocturnal BP was unchanged from baseline in both the ampreloxetine-treated and placebo-treated groups at day-7 and day-21. Shift table analysis showed no worsening in the severity of supine hypertension on ampreloxetine. No significant differences were observed in office supine BP.
CONCLUSIONS: We saw no signal for worsening of supine hypertension on ampreloxetine in patients with alpha-synucleinopathies and nOH. This suggests that, if the ongoing phase 3 study confirms safety and efficacy, ampreloxetine may be the first drug to treat nOH without exacerbating supine hypertension, which should not worsen intravascular volume loss overnight or add to the risk of target organ damage. Disclaimer: Abstracts were not reviewed by Neurology® and do not reflect the views of Neurology® editors or staff. Disclosure: Prof. Norcliffe-Kaufmann has received personal compensation for serving as an employee of Theravance BioPharma. Prof. Norcliffe-Kaufmann has received personal compensation for serving as an employee of 23andMe. Alessandra Fanciulli, MD, PhD has received personal compensation in the range of $0-$499 for serving as a Consultant for Theravance Biopharma. Alessandra Fanciulli, MD, PhD has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. Alessandra Fanciulli, MD, PhD has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Theravance Biopharma. Alessandra Fanciulli, MD, PhD has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Healthware. Alessandra Fanciulli, MD, PhD has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Abbvie. Alessandra Fanciulli, MD, PhD has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Stopp-HSP. Alessandra Fanciulli, MD, PhD has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Otto Loewi Society. Alessandra Fanciulli, MD, PhD has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bial . Alessandra Fanciulli, MD, PhD has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. The institution of Alessandra Fanciulli, MD, PhD has received research support from Parkinson Fond. The institution of Alessandra Fanciulli, MD, PhD has received research support from Tuba Foundation. The institution of Alessandra Fanciulli, MD, PhD has received research support from MSA Coalition. The institution of Alessandra Fanciulli, MD, PhD has received research support from Austrian Exchange Programme. The institution of Alessandra Fanciulli, MD, PhD has received research support from Austrian Science Fund. Alessandra Fanciulli, MD, PhD has received publishing royalties from a publication relating to health care. Mr. Guerin has received personal compensation for serving as an employee of Theravance Biopharma. Ross Vickery has nothing to disclose. 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 on a Scientific Advisory or Data Safety Monitoring board for Lilly USA. 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 on a Scientific Advisory or Data Safety Monitoring board for Ono Pharma UK Ltd. Dr. Kaufmann has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Vaxxinity. 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. Dr. Kaufmann has received publishing royalties from a publication relating to health care. Dr. Biaggioni has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Theravance biopharma. Dr. Biaggioni has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Theravance biopharma. The institution of Dr. Biaggioni has received research support from Theravance biopharma. Dr. Freeman has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Regenacy. Dr. Freeman has received personal compensation in the range of $100,000-$499,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Neurobo. Dr. Freeman has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Vertex. Dr. Freeman has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eli-Lilly. Dr. Freeman has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Theravance. Dr. Freeman has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Inhibikase. Dr. Freeman has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. Dr. Freeman has stock in Neurobo. Dr. Freeman has stock in Cutaneous NeuroDiagnostics. The institution of Dr. Freeman has received research support from NIH. The institution of Dr. Freeman has received research support from Theravance. The institution of Dr. Freeman has received research support from Biohaven. The institution of Dr. Freeman has received research support from Lundbeck.
PMID:40193878 | DOI:10.1212/WNL.0000000000212055
