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Trial record 1 of 1 for:    NCT03750552
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Clinical Effect of Ampreloxetine (TD-9855) for Treating Symptomatic nOH in Subjects With Primary Autonomic Failure (SEQUOIA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03750552
Recruitment Status : Recruiting
First Posted : November 23, 2018
Last Update Posted : September 18, 2020
Information provided by (Responsible Party):
Theravance Biopharma

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 snOH with up to 4 weeks of treatment.

Condition or disease Intervention/treatment Phase
Symptomatic Neurogenic Orthostatic Hypotension Drug: ampreloxetine Drug: Placebo Phase 3

Detailed Description:
A Phase 3, randomized, double-blind, placebo-controlled, parallel-group, multicenter study to evaluate efficacy, safety, and tolerability of ampreloxetine (TD-9855) in subjects with primary autonomic failures (MSA, PD, or PAF) and snOH. The study consists of 3 periods: (i) 4-week screening, (ii) 4-week randomized treatment, and (iii) 2-week follow up.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 188 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Parallel assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official 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
Actual Study Start Date : January 24, 2019
Estimated Primary Completion Date : September 2020
Estimated Study Completion Date : September 2020

Arm Intervention/treatment
Experimental: ampreloxetine
Participants randomized to ampreloxetine will receive a single, oral, daily dose of active drug for 4 weeks.
Drug: ampreloxetine
Oral tablet, QD
Other Name: TD-9855

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

Primary Outcome Measures :
  1. Change from baseline in OHSA#1 at Week 4 [ Time Frame: Baseline to 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.

Secondary Outcome Measures :
  1. Change from baseline in OHSA composite score in Weeks 1 to 4 [ Time Frame: Baseline, Week 1, Week 2, Week 3, Week 4 ]
    Orthostatic Hypotension Symptom Assessment (OHSA ) is an assessment of the severity of symptoms from low blood pressure.

  2. Change from baseline in OHDAS composite score in Weeks 1 to 4 [ Time Frame: Baseline, Week 1, Week 2, Week 3, Week 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.

  3. PGI-C at Week 4 [ Time Frame: Week 4 ]
    Using the Patient Global Impression of Change (PGI-C) scale, a subject rates their total improvement compared to baseline.

  4. Incidence of falls [ Time Frame: Week 4 ]
    Incidence of patient-reported falls.

Information from the National Library of Medicine

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Ages Eligible for Study:   30 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Subject is male or female and at least 30 years old.
  • Subject must meet the diagnostic criteria of snOH, 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.

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03750552

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Contact: Theravance Biopharma Call Center 1-855-633-8479

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Sponsors and Collaborators
Theravance Biopharma
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Study Director: Medical Monitor Theravance Biopharma
Additional Information:
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Responsible Party: Theravance Biopharma Identifier: NCT03750552    
Other Study ID Numbers: 0169
2018-003289-15 ( EudraCT Number )
First Posted: November 23, 2018    Key Record Dates
Last Update Posted: September 18, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Theravance Biopharma, Inc. will not be sharing individual de-identified participant data or other relevant study documents.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Theravance Biopharma:
Symptomatic Neurogenic Orthostatic Hypotension
symptomatic nOH
multiple system atrophy
Parkinson's disease
pure autonomic failure
primary autonomic failure
low blood pressure
blacking out
Neurogenic Orthostatic Hypotension
Additional relevant MeSH terms:
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Hypotension, Orthostatic
Pure Autonomic Failure
Vascular Diseases
Cardiovascular Diseases
Orthostatic Intolerance
Primary Dysautonomias
Autonomic Nervous System Diseases
Nervous System Diseases