First Patient Treated in Phase 3 Study of Ampreloxetine for Neurogenic Orthostatic Hypotension
The first patient has been dosed in a registrational phase 3 study (NCT03750552) of ampreloxetine (TD955; Theravance Biopharma, South San Francisco, CA) for treating symptomatic neurogenic orthostatic hypotension (nOH). The study will evaluate the novel, once-daily drug in patients with nOH in patients with multiple system atrophy, Parkinson's disease, or pure autonomic failure.
This phase 3 study is a multi-center, randomized, placebo-controlled study designed to evaluate the efficacy, safety, and tolerability of ampreloxetine in approximately 188 participants. Patients will be randomly assigned to receive a single 10mg dose of ampreloxetine or placebo once daily for 4 weeks. The primary endpoint of the study is change from baseline in dizziness severity, as measured by Orthostatic Hypotension Symptom Assessment.
Characterized by a sustained orthostatic fall in systolic blood pressure, nOH is defined as more than 20 mm Hg drop in systolic blood pressure or more than a 10 mm Hg drop in diastolic blood pressure within 3 minutes of standing. Severely affected patients with nOH are unable to stand for extended periods of time because of the decrease in blood pressure.
A majority of patients in a previous phase 2 trial (NCT02705755) of ampreloxetine showed durable improvements in nOH symptom severity. “Positive 4-week results achieved in our phase 2 study provide the basis for advancing ampreloxetine into this registrational phase 3 program,” said Brett Haumann, MD, Chief Medical Officer at Theravance Biopharma. "Given the limitations of currently available therapeutic options, we recognize a significant opportunity exists for a potentially safe and durable treatment for nOH.”
Ampreloxetine is an investigational norepinephrine reuptake inhibitor with high affinity for binding to norepinephrine transporters. By blocking the action of these transporters, ampreloxetine causes an increase in extracellular concentrations of norepinephrine.