Protocol 0169 - TD-9855 for Treating snOH

  • Research type

    Research Study

  • Full title

    Phase 3, 4-week, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study of TD-9855 in Treating Symptomatic Neurogenic Orthostatic Hypotension in Subjects With Primary Autonomic Failure

  • IRAS ID

    262263

  • Contact name

    Camille Carroll

  • Contact email

    camille.carroll@plymouth.ac.uk

  • Sponsor organisation

    Theravance Biopharma Ireland Limited

  • Eudract number

    2018-003289-15

  • Clinicaltrials.gov Identifier

    NCT03750552

  • Duration of Study in the UK

    1 years, 4 months, 1 days

  • Research summary

    Summary of Research

    This study will look at whether an investigational drug called TD-9855 works and how safe it is for treating symptomatic neurogenic orthostatic hypotension (snOH) in people with Parkinson’s disease (PD), multiple system atrophy (MSA) or pure autonomic failure (PAF).

    This is a Phase 3 study. This means that the study drug has already been given to a smaller group of people in other clinical research studies with snOH and other types of conditions including people with attention‑deficit hyperactivity disorder (ADHD) and fibromyalgia. In this study, it will be tested in a larger group of people with snOH and PD, MSA, or PAF.

    Currently, there are limited treatment options available for this patient population, and no treatment options that demonstrate durability of effect.

    Preclinical and clinical studies have demonstrated a moderate increase in heart rate and blood pressure, suggesting that TD-9855 has the potential to provide a novel treatment option for snOH

    Around 188 patients in approximately 100 study centres around the world will take part in this study.

    The study drug will be compared with a placebo, which looks the same as the study drug but does not contain any active ingredients. Participants will be randomly assigned (by chance) and will have a 50/50 chance of receiving either the study drug (10 mg per day) OR placebo. Participants will take a single tablet of the study medication (study drug or placebo) by mouth at the same time each morning with a glass of water. The study medication can be taken with or without food.

    This study is ‘double-blinded’, which means that neither the participant nor the study doctor will know which study medication the participant taking.

    The duration of study participation will be approximately 8 weeks.

    The study will also collect information on the experiences of the person caring for the participant. If applicable, the person who cares for the participant (‘caregiver’) will be asked to complete a questionnaire about how caring for the participant affects their life.

    Summary of Results

    Efficacy Results:
    Treatment with ampreloxetine did not show a statistically significant difference from placebo in change from baseline to Week 4 in OHSA#1.
    In addition, secondary endpoints including change in scores from baseline in OHSA, OHDAS, and PCG-C reflecting patient-reported symptom and activity scales did not show significant improvements after 4 weeks of ampreloxetine as compared to placebo.

    Safety Results
    Ampreloxetine was generally well-tolerated when administered orally once daily for 4 weeks; the majority of treatment-related adverse events were mild or moderate in severity. Serious adverse events occurred in two patients on placebo and four on ampreloxetine and none were considered related to the study drug; no deaths were reported. There was no signal for supine hypertension. Mean changes observed in vital signs (eg, an increase in heart rate following 4 weeks of treatment with ampreloxetine) are consistent with the mechanism of action of a norepinephrine uptake inhibitor and similar in magnitude to those observed in prior Phase1 and 2 ampreloxetine studies.

  • REC name

    Wales REC 1

  • REC reference

    19/WA/0104

  • Date of REC Opinion

    8 May 2019

  • REC opinion

    Further Information Favourable Opinion