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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03750552




Registration number
NCT03750552
Ethics application status
Date submitted
20/11/2018
Date registered
23/11/2018
Date last updated
20/11/2020

Titles & IDs
Public title
Clinical Effect of Ampreloxetine (TD-9855) for Treating Symptomatic nOH in Subjects With Primary Autonomic Failure
Scientific title
A 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
Secondary ID [1] 0 0
2018-003289-15
Secondary ID [2] 0 0
0169
Universal Trial Number (UTN)
Trial acronym
SEQUOIA
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 - Participants randomized to ampreloxetine will receive a single, oral, daily dose of active drug for 4 weeks.

Placebo Comparator: Placebo - Participants randomized to Placebo will receive a single, oral, daily dose of placebo for 4 weeks.


Treatment: Drugs: ampreloxetine
Oral tablet, QD

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 from baseline in OHSA#1 at Week 4 - 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
Baseline to Week 4
Secondary outcome [1] 0 0
Change from baseline in OHSA composite score in Weeks 1 to 4 - Orthostatic Hypotension Symptom Assessment (OHSA ) is an assessment of the severity of symptoms from low blood pressure.
Timepoint [1] 0 0
Baseline, Week 1, Week 2, Week 3, Week 4
Secondary outcome [2] 0 0
Change from baseline in OHDAS composite score in Weeks 1 to 4 - 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 [2] 0 0
Baseline, Week 1, Week 2, Week 3, Week 4
Secondary outcome [3] 0 0
PGI-C at Week 4 - Using the Patient Global Impression of Change (PGI-C) scale, a subject rates their total improvement compared to baseline.
Timepoint [3] 0 0
Week 4
Secondary outcome [4] 0 0
Incidence of falls - Incidence of patient-reported falls.
Timepoint [4] 0 0
Week 4

Eligibility
Key inclusion criteria
- 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
minutes of being tilted-up to =60o from a supine position as determined by a
tilt-table test.

- Subject must score at least a 4 on the Orthostatic Hypotension Symptom Assessment
Question #1 at randomization visit.

- 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 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
- 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 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 randomization 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 a known or suspected alcohol or substance abuse within the past 12 months
(DSM-IV-TR® definition of alcohol or substance abuse).

- Subject has a clinically unstable coronary artery disease, or major cardiovascular or
neurological event in the past 6 months.

- Subject has used any monoamine oxidase inhibitor (MAO-I) within 14 days prior to
randomization.

- 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 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 findings (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/1.73m2, 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 C-SSRS (Columbia Suicide Severity Rating Scale)
(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)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Concord Hospital - Concord
Recruitment hospital [2] 0 0
Royal Brisbane and Women's Hospital - Herston
Recruitment hospital [3] 0 0
Monash Health - Clinical Trials Centre - Clayton
Recruitment hospital [4] 0 0
The Royal Melbourne Hospital - Parkville
Recruitment hospital [5] 0 0
Perron Institute for Neurological and Translational Science, QEII Medical Centre - Nedlands
Recruitment postcode(s) [1] 0 0
2139 - Concord
Recruitment postcode(s) [2] 0 0
4029 - Herston
Recruitment postcode(s) [3] 0 0
3168 - Clayton
Recruitment postcode(s) [4] 0 0
3050 - Parkville
Recruitment postcode(s) [5] 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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Salford

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

Ethics approval
Ethics application status

Summary
Brief summary
A Phase 3 study to evaluate efficacy, safety, and tolerability of ampreloxetine (TD-9855) in
subjects with primary autonomic failures (MSA, PD, or PAF) and symptomatic nOH with up to 4
weeks of treatment.
Trial website
https://clinicaltrials.gov/show/NCT03750552
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/NCT03750552