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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT03829657
Ethics application status
Date submitted
10/01/2019
Date registered
4/02/2019
Date last updated
18/11/2020

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
Condition category
Condition code
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
Change (worsening) from baseline in OHSA#1 score of 1.0 point and worsening of disease severity as assessed by a 1 point change in PGI-S - Score change from baseline on Question 1 of the Orthostatic Hypotension Symptom Assessment (OHSA). Question #1 assesses dizziness, lightheadedness, feeling faint, or feeling like you might blackout and Score change from baseline on Patient Global Impression of Severity (PGI-S). PGI-S assesses patient's impression of disease severity.
Timepoint [1] 0 0
6-week randomized withdrawal period (Week 16 to Week 22)
Secondary outcome [1] 0 0
Change from baseline in OHSA#1 at Week 6 post randomization at Week 6 post randomization. - Score change from baseline on Question 1 of the Orthostatic Hypotension Symptom Assessment (OHSA). Question #1 assesses dizziness, lightheadedness, feeling faint, or feeling like you might blackout.
Timepoint [1] 0 0
6-week randomized withdrawal period (Week 16 to Week 22)
Secondary outcome [2] 0 0
Change from baseline in OHSA composite score at Week 6 post randomization - Orthostatic Hypotension Symptom Assessment (OHSA) is an assessment of the severity of symptoms from low blood pressure.
Timepoint [2] 0 0
6-week randomized withdrawal period (Week 16 to Week 22)
Secondary outcome [3] 0 0
Change from baseline in OHDAS composite score at Week 6 post randomization - Orthostatic Hypotension Daily Activities Scale (OHDAS) is an assessment of how low blood pressure symptoms affect daily life.
OHDAS is a 4 item assessment that uses an 11 point scale from 0 to 10, with 0 indicating no symptoms/no interference and 10 indicating the worst possible symptoms/complete interference.
Timepoint [3] 0 0
6-week randomized withdrawal period (Week 16 to Week 22)
Secondary outcome [4] 0 0
Change from baseline in PGI-S at Week 6 post randomization - Score change from baseline on Patient Global Impression of Severity (PGI-S). PGI-S assesses patient's impression of disease severity.
Timepoint [4] 0 0
6-week randomized withdrawal period (Week 16 to Week 22)
Secondary outcome [5] 0 0
Change from baseline in percent of time spent in standing position as measured by a wearable device at Week 6 post randomization - A wearable device, such as an activity monitor, that provides date- and time-stamped activity information will be used to collect raw motion data to measure the time spent in supine, sitting, and standing positions.
Timepoint [5] 0 0
6-week randomized withdrawal period (Week 16 to Week 22)
Secondary outcome [6] 0 0
Change from baseline in average number of steps taken as measured by a wearable device at Week 6 post randomization - A wearable device, such as an activity monitor, that provides date- and time-stamped activity information will be used to collect raw motion data to measure the time spent in supine, sitting, and standing positions.
Timepoint [6] 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. No minimum score of OHSA#1 is required to enter V1 of Study 0170.

- 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
Gender
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 assessing the outcomes
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
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC,WA
Recruitment hospital [1] 0 0
The Royal Melbourne Hospital Neurology Department - Parkville
Recruitment hospital [2] 0 0
Perron Institute for Neurological and Translational Science - Nedlands
Recruitment postcode(s) [1] 0 0
3050 - Parkville
Recruitment postcode(s) [2] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Kansas
Country [6] 0 0
United States of America
State/province [6] 0 0
Michigan
Country [7] 0 0
United States of America
State/province [7] 0 0
Minnesota
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
North Carolina
Country [10] 0 0
United States of America
State/province [10] 0 0
Ohio
Country [11] 0 0
United States of America
State/province [11] 0 0
Oregon
Country [12] 0 0
United States of America
State/province [12] 0 0
Tennessee
Country [13] 0 0
United States of America
State/province [13] 0 0
Texas
Country [14] 0 0
United States of America
State/province [14] 0 0
Washington
Country [15] 0 0
Austria
State/province [15] 0 0
Innsbruck
Country [16] 0 0
Austria
State/province [16] 0 0
Tulln
Country [17] 0 0
Bulgaria
State/province [17] 0 0
Sofia
Country [18] 0 0
Canada
State/province [18] 0 0
Alberta
Country [19] 0 0
Denmark
State/province [19] 0 0
Copenhagen
Country [20] 0 0
Denmark
State/province [20] 0 0
Odense
Country [21] 0 0
Estonia
State/province [21] 0 0
Tallinn
Country [22] 0 0
Estonia
State/province [22] 0 0
Tartu
Country [23] 0 0
France
State/province [23] 0 0
Nîmes
Country [24] 0 0
Germany
State/province [24] 0 0
Berlin
Country [25] 0 0
Germany
State/province [25] 0 0
Gera
Country [26] 0 0
Hungary
State/province [26] 0 0
Budapest
Country [27] 0 0
Israel
State/province [27] 0 0
Petah Tikva
Country [28] 0 0
Israel
State/province [28] 0 0
Rehovot
Country [29] 0 0
Italy
State/province [29] 0 0
Bologna
Country [30] 0 0
Italy
State/province [30] 0 0
Milano
Country [31] 0 0
Italy
State/province [31] 0 0
Salerno
Country [32] 0 0
New Zealand
State/province [32] 0 0
Christchurch
Country [33] 0 0
Poland
State/province [33] 0 0
Katowice
Country [34] 0 0
Poland
State/province [34] 0 0
Kraków
Country [35] 0 0
Poland
State/province [35] 0 0
Oswiecim
Country [36] 0 0
Poland
State/province [36] 0 0
Siemianowice Slaskie
Country [37] 0 0
Poland
State/province [37] 0 0
Warszawa
Country [38] 0 0
Portugal
State/province [38] 0 0
Torres Vedras
Country [39] 0 0
Russian Federation
State/province [39] 0 0
Krasnoyarsk
Country [40] 0 0
Russian Federation
State/province [40] 0 0
Moscow
Country [41] 0 0
Russian Federation
State/province [41] 0 0
Novosibirsk
Country [42] 0 0
Russian Federation
State/province [42] 0 0
Saint Petersburg
Country [43] 0 0
Spain
State/province [43] 0 0
Barcelona
Country [44] 0 0
Spain
State/province [44] 0 0
Madrid
Country [45] 0 0
Ukraine
State/province [45] 0 0
Kharkiv
Country [46] 0 0
Ukraine
State/province [46] 0 0
Lviv
Country [47] 0 0
Ukraine
State/province [47] 0 0
Vinnytsia
Country [48] 0 0
United Kingdom
State/province [48] 0 0
Devon
Country [49] 0 0
United Kingdom
State/province [49] 0 0
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/show/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
Theravance Biopharma Call Center
Address 0 0
Country 0 0
Phone 0 0
1-855-633-8479
Fax 0 0
Email 0 0
medinfo@theravance.com
Contact person for scientific queries

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