Protocol 0170 - TD-9855 for Treating snOH
Research type
Research Study
Full title
A Phase 3, 22-week, Multi-center, Randomized Withdrawal Study of TD˗9855 in Treating Symptomatic Neurogenic Orthostatic Hypotension in Subjects with Primary Autonomic Failure
IRAS ID
264794
Contact name
Camille Carroll
Contact email
Sponsor organisation
Theravance Biopharma Ireland Limited
Eudract number
2018-003941-41
Clinicaltrials.gov Identifier
Duration of Study in the UK
1 years, 3 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 when taken over a longer period to treat symptomatic neurogenic orthostatic hypotension (snOH) in people with Parkinson’s disease (PD), multiple system atrophy (MSA), or pure autonomic failure (PAF).It will also look at the effects of TD-9855 on general well-being and whether it can improve symptoms of neurogenic OH (nOH).
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 the condition 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.
Participants can also enter this study if they completed study 0169 (Phase 3, 4-week, Multicentre, Randomised, Double-blind, Placebo-controlled, Parallel-group Study of TD-9855 in Treating Symptomatic Neurogenic Orthostatic Hypotension in Subjects With Primary Autonomic Failure).
Around 258 patients in approximately 120 study centres around the world will take part in this study.
In this study, participants will receive treatment for 22 weeks, split into two periods: a 16-week open-label period when all participants will receive the study drug 10mg per day, followed by a 6-week double-blind period. In the double-blind period, the study drug will be compared with a placebo. A placebo looks the same as the study drug but does not contain any active ingredients. Participants will have a 50/50% chance of receiving either the study drug (10 mg per day) or placebo.
The duration of study participation could be up to 24 weeks (for participants entering this study from Study 0169) or 27 weeks (for patients not entering this study from Study 0169).
Summary of Results
Efficacy Results:
During the open-label treatment period, subjects experienced a reduction in signs and symptoms as measured by OHSA#1, OHSA composite score, and OHDAS (patient-reported symptom and activity scales).
During the 6-week double-blind period, even though the study did not meet its primary endpoint, the primary and key secondary efficacy endpoints showed a trend in favor of ampreloxetine in the full analysis set, demonstrating that ampreloxetine has the potential to provide durable and stable benefit to patients with nOH. In a pre-planned analysis by disease type this trend was particularly strong and consistent in the MSA subjects, with large treatment effects across multiple endpoints, including OHSA composite, OHDAS composite, OHQ composite and OHSA #1, as well as blood pressure endpoints.Safety Results:
Overall, ampreloxetine administered as a 10-mg tablet QD for the duration of the study was generally safe and well tolerated by this population of subjects with primary autonomic failures; incidence of treatment-related adverse events was generally similar across treatment groups. While the overall incidence of adverse events was 52.5%, this high frequency of treatment emergent adverse events is consistent and not unexpected in a study population with progressing primary conditions of Parkinson’s, PAF, and MSA.Seven subjects died during the study; 4 males and 3 females ranging in age from 57 to 88 years, with primary disease of MSA (2 subjects), PAF (1 subject) and Parkinson’s (4 subjects). Five deaths occurred in the open-label treatment period and 2 deaths occurred in the double-blind treatment period. All 7 subjects received treatment with ampreloxetine prior to their deaths. None of the deaths reported in the open label treatment period were considered related to study drug.
Deaths during the double-blind treatment period were due to respiratory tract infection and unspecified cause. Both deaths occurred in the ampreloxetine group, and the death of unknown cause was imputed as related to study drug.REC name
North East - Newcastle & North Tyneside 1 Research Ethics Committee
REC reference
19/NE/0205
Date of REC Opinion
9 Aug 2019
REC opinion
Further Information Favourable Opinion