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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03829657




Registration number
NCT03829657
Ethics application status
Date submitted
10/01/2019
Date registered
4/02/2019
Date last updated
20/01/2023

Titles & IDs
Public title
Phase 3 Clinical Effect Durability of TD-9855 for Treating Symptomatic nOH in Subjects With Primary Autonomic Failure
Scientific 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
Secondary ID [1] 0 0
2018-003941-41
Secondary ID [2] 0 0
0170
Universal Trial Number (UTN)
Trial acronym
REDWOOD
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Symptomatic Neurogenic Orthostatic Hypotension 0 0
MSA 0 0
Parkinson's Disease (PD) 0 0
Pure Autonomic Failure (PAF) 0 0
Condition category
Condition code
Neurological 0 0 0 0
Parkinson's disease
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system
Neurological 0 0 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - ampreloxetine
Treatment: Drugs - Placebo

Experimental: ampreloxetine (Open Label (OL)) - Participants will receive ampreloxetine as a single, oral, daily dose of active drug for 16 weeks.

Experimental: ampreloxetine - After completing the OL, participants randomized to ampreloxetine will receive single, oral, daily dose of active drug for a further 6 weeks.

Placebo comparator: Placebo - After completing the OL, participants randomized to Placebo will receive single, oral, daily dose of placebo for 6 weeks.


Treatment: Drugs: ampreloxetine
Oral tablet, QD (Daily)

Treatment: Drugs: Placebo
Oral tablet, QD
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Proportion of Participants With Treatment Failure at Week 6 of RW Treatment Period
Timepoint [1] 0 0
6-week randomized withdrawal period (Week 16 to Week 22)

Eligibility
Key inclusion criteria
Inclusion Criteria (For 0169 Completers Group):

* Subject has completed 4 weeks of double blind treatment in Study 0169 (V6) and, in the opinion of the Investigator, could benefit from continued treatment with ampreloxetine. Only subjects with OHSA#1 score of =7 will be eligible for randomization for the double-blind treatment period.
* Subject has a minimum of 80% study medication compliance in Study 0169.

Inclusion Criteria (For De Novo Group):

* Subject is male or female and at least 30 years old.
* Subject must meet the diagnostic criteria of symptomatic nOH, as demonstrated by a sustained reduction in BP of =20 mm Hg (systolic) or =10 mm Hg (diastolic) within 3 min of being tilted-up =60o from a supine position as determined by a tilt-table test.
* Subject must score at least a 4 on the OHSA#1 at V1.
* For subjects with PD only: Subject has a diagnosis of PD according to the United Kingdom Parkinson's Disease Society (UKPDS) Brain Bank Criteria (1992).
* For subjects with MSA only: Subject has a diagnosis of possible or probable MSA of the Parkinsonian subtype (MSA-P) or cerebellar subtype (MSA-C) according to The Gilman Criteria (2008).
* For subjects with PAF only: Subject has documented impaired autonomic reflexes, including the Valsalva maneuver performed within 24 months from the date of randomization
* Subject has plasma Norepinephrine (NE) levels = 100 pg/mL after being in seated position for 30 minutes.
Minimum age
30 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria (For 0169 Completers Group):

* Subject has a medical, laboratory, or surgical issue(s) deemed by the investigator to be clinically significant.
* Subject has an uncooperative attitude or reasonable likelihood of non-compliance with the protocol.
* Subject has a concurrent disease or condition that, in the opinion of the investigator, would confound or interfere with study participation or evaluation of safety, tolerability, or pharmacokinetics of the study drug.

Exclusion Criteria (For De Novo Group):

* Subject has a known systemic illness known to produce autonomic neuropathy, including but not limited to amyloidosis, and autoimmune neuropathies.
* Subject has a known intolerance to other NRIs or serotonin norepinephrine reuptake inhibitors (SNRIs).
* Subject currently uses concomitant antihypertensive medication for the treatment of essential hypertension unrelated to autonomic dysfunction.
* Subject has used strong CYP1A2 inhibitors or inducers within 7 days or 5 half-lives, whichever is longer, prior to V1 or requires concomitant use until the follow-up visit.
* Subject has changed dose, frequency, or type of prescribed medication for orthostatic hypotension within 7 days prior to V1.

* Midodrine and droxidopa (if applicable) must be tapered off at least 7 days prior to V1.
* Subject has known or suspected alcohol or substance abuse within the past 12 months (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision [DSM-IV-TR®] definition of alcohol or substance abuse).
* Subject has a clinically unstable coronary artery disease, or has had a major cardiovascular or neurological event in the past 6 months.
* Subject has used any monoamine oxidase inhibitor (MAO-I) within 14 days prior to V1.
* Subject has a history of untreated closed angle glaucoma, or treated closed angle glaucoma that, in the opinion of an ophthalmologist, might result in an increased risk to the subject.
* Subject has any significant uncontrolled cardiac arrhythmia.
* Subject has a Montreal Cognitive Assessment (MoCA) =23.
* Subject is unable or unwilling to complete all protocol specified procedures including questionnaires.
* Subject had a myocardial infarction in the past 6 months or has current unstable angina.
* Subject has known congestive heart failure (New York Heart Association [NYHA] Class 3 or 4).
* Subject has a clinically significant abnormal laboratory finding (e.g., alanine aminotransferase [ALT] or aspartate aminotransferase [AST] >3.0 x upper limit of normal [ULN]; blood bilirubin [total] >1.5 x ULN; estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2, or any abnormal laboratory value that could interfere with safety of the subject).
* Subject has demonstrated a history of lifetime suicidal ideation and/or suicidal behavior, as outlined by the Columbia Suicide Severity Rating Scale (C-SSRS)(Baseline/Screening Version). Subject should be assessed by the rater for risk of suicide and the subject's appropriateness for inclusion in the study.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
22/02/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
10/11/2021
Sample size
Target
Accrual to date
Final
203
Recruitment in Australia
Recruitment state(s)
NSW,VIC,WA
Recruitment hospital [1] 0 0
Concord Hospital, Neurosciences Department - Concord
Recruitment hospital [2] 0 0
Clinical Trials Centre, Level 3 Monash Health Translational Precinct Building Monash Medical Centre - Clayton
Recruitment hospital [3] 0 0
The Royal Melbourne Hospital Neurology Department - Parkville
Recruitment hospital [4] 0 0
Perron Institute for Neurological and Translational Science - Nedlands
Recruitment postcode(s) [1] 0 0
02139 - Concord
Recruitment postcode(s) [2] 0 0
3168 - Clayton
Recruitment postcode(s) [3] 0 0
3050 - Parkville
Recruitment postcode(s) [4] 0 0
6009 - Nedlands
Recruitment outside Australia
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United States of America
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Arizona
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California
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Innsbruck
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Tulln
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Sofia
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Tartu
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Nîmes
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Gera
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Roma
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Italy
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Salerno
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Terni
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Christchurch
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Katowice
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Oswiecim
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Warszawa
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Portugal
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Guimarães
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Torres Vedras
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Russian Federation
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Sestroretsk
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Krasnoyarsk
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Kharkiv
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Lviv
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Ukraine
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Vinnytsia
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United Kingdom
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Devon
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United Kingdom
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Greater Manchester
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United Kingdom
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London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Theravance Biopharma
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
A Phase 3, 22-week, Multi-center, Randomized Withdrawal Study of ampreloxetine in Treating Symptomatic Neurogenic Orthostatic Hypotension in Subjects with Primary Autonomic Failure
Trial website
https://clinicaltrials.gov/study/NCT03829657
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Monitor
Address 0 0
Theravance Biopharma
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT03829657