Safety and efficacy of ampreloxetine in symptomatic neurogenic orthostatic hypotension, 2021, Horacio Kaufmann et al

Phase 2 trial:

Abstract
Purpose
In neurogenic orthostatic hypotension, blood pressure falls when upright owing to impaired release of norepinephrine, leading to dizziness. Ampreloxetine, a selective norepinephrine reuptake inhibitor, increases circulating norepinephrine levels. This study explored the safety of ampreloxetine and its effect on blood pressure and symptoms in patients with neurogenic orthostatic hypotension.

Methods
A multicenter ascending-dose trial (range 1–20 mg, Part A) was followed by a 1 day, double-blind, randomized, placebo-controlled study (median dose 15 mg, Part B). Eligible patients then enrolled in a 20-week, open-label, steady-state extension phase (median dose 10 mg, Part C) followed by a 4-week withdrawal. Assessments included the Orthostatic Hypotension Symptom Assessment Scale (item 1), supine/seated/standing blood pressure, and safety.

Results
Thirty-four patients (age 66 ± 8 years, 22 men) were enrolled. Part A: The proportion of participants with a positive response (i.e., increase from baseline in seated systolic blood pressure of ≥ 10 mmHg) was greater with the 5 and 10 mg ampreloxetine doses than with placebo or other active ampreloxetine doses. Part B: Seated blood pressure increased 15.7 mmHg 4 h after ampreloxetine and decreased 14.2 mmHg after placebo [least squares mean difference (95% CI) 29.9 mmHg (7.6–52.3); P = 0.0112]. Part C: Symptoms of dizziness/lightheadedness improved 3.1 ± 3.0 points from baseline and standing systolic blood pressure increased 11 ± 12 mmHg. After 4 weeks of withdrawal, symptoms returned to pretreatment levels. The effect of ampreloxetine on supine blood pressure was minimal throughout treatment duration.

Conclusion
Ampreloxetine was well tolerated and improved orthostatic symptoms and seated/standing blood pressure with little change in supine blood pressure.

https://link.springer.com/article/10.1007/s10286-021-00827-0

 

Unfortunately the Phase III failed, and the company now faces making a lot of its staff redundant. I know that's how it sometimes goes with drug development, but it must be gutting to put that much effort in and end up with no drug and no job. You really have to feel for them.

 

@Kitty

Could you provide a link for this?

 

This was the company's news release on the phase III trial, published 15/9/21 on their website

https://investor.theravance.com/new...pharma-inc-announces-top-line-results-phase-3

 

Yes, sure:

https://www.biospace.com/article/th...vascular-asset-fails-to-hit-primary-endpoint/