Trial record 1 of 1 for:
2018-003289-15
Clinical Effect of Ampreloxetine (TD-9855) for Treating Symptomatic nOH in Subjects With Primary Autonomic Failure (SEQUOIA)
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| ClinicalTrials.gov Identifier: NCT03750552 |
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Recruitment Status :
Completed
First Posted : November 23, 2018
Results First Posted : September 14, 2022
Last Update Posted : September 14, 2022
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Sponsor:
Theravance Biopharma
Information provided by (Responsible Party):
Theravance Biopharma
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Symptomatic Neurogenic Orthostatic Hypotension | Drug: ampreloxetine Drug: Placebo | Phase 3 |
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 symptomatic nOH. The study consists of 3 periods: (i) 4-week screening, (ii) 4-week randomized treatment, and (iii) 2-week follow up. The trial utilizes an operational design featuring the ability to conduct protocol required visits as either in clinic or remote visits (except Screening visit).
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 195 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 |
| Actual Primary Completion Date : | July 21, 2021 |
| Actual Study Completion Date : | July 21, 2021 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Orthostatic hypotension
MedlinePlus related topics:
Low Blood Pressure
| Arm | Intervention/treatment |
|---|---|
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Experimental: ampreloxetine
Participants randomized to ampreloxetine will receive a single, oral, daily dose of active drug for 4 weeks.
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Drug: ampreloxetine
Oral tablet, QD
Other Name: TD-9855 |
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Placebo Comparator: Placebo
Participants randomized to Placebo will receive a single, oral, daily dose of placebo for 4 weeks.
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Drug: Placebo
Oral tablet, QD |
Primary Outcome Measures :
- Change From Baseline in Orthostatic Hypotension Symptom Assessment (OHSA) Question #1 Score at Week 4 [ Time Frame: Baseline and Week 4 ]
OHSA is an assessment of the severity of symptoms from low blood pressure. OHSA is a 6 question symptom assessment scale where each question 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.
Question #1 assesses dizziness, lightheadedness, feeling faint, or feeling like you might blackout.
A mean negative change from baseline indicates a better outcome.
Secondary Outcome Measures :
- Change From Baseline in Orthostatic Hypotension Symptom Assessment (OHSA) Composite Score at Week 4 [ Time Frame: Baseline and Week 4 ]
OHSA is an assessment of the severity of symptoms from low blood pressure. OHSA is a 6 question symptom assessment scale in which the composite score 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.
A mean negative change from baseline indicates a better outcome.
- Change From Baseline in Orthostatic Hypotension Daily Activities Scale (OHDAS) Composite Score at Week 4 [ Time Frame: Baseline and Week 4 ]
OHDAS is an assessment of how low blood pressure symptoms affect daily life. OHDAS is a 4 item assessment in which the composite score 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.
A mean negative change from baseline indicates a better outcome.
- Number of Participants Who Experienced an Improvement From Baseline in Patient Global Impression of Change (PGI-C) Score at Week 4 [ Time Frame: Baseline and Week 4 ]PGI-C was assessed using a 5-point scale where participants were asked to compare their current condition to their condition at baseline from 1 to 5, with 1 indicating the condition is very much improved and 5 indicating the condition is very much worse. These scores were analyzed in 2 categories: better and no change/worse.
- Number of Participants Who Experienced at Least One Fall [ Time Frame: Up to Week 4 ]
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 |
Criteria
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.
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.
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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 ClinicalTrials.gov identifier (NCT number): NCT03750552
Locations
Show 125 study locations
Sponsors and Collaborators
Theravance Biopharma
Investigators
| Study Director: | Medical Monitor | Theravance Biopharma |
Study Documents (Full-Text)
Documents provided by Theravance Biopharma:
Documents provided by Theravance Biopharma:
Study Protocol [PDF] August 5, 2020
Statistical Analysis Plan [PDF] July 19, 2021
| Responsible Party: | Theravance Biopharma |
| ClinicalTrials.gov Identifier: | NCT03750552 |
| Other Study ID Numbers: |
0169 2018-003289-15 ( EudraCT Number ) |
| First Posted: | November 23, 2018 Key Record Dates |
| Results First Posted: | September 14, 2022 |
| Last Update Posted: | September 14, 2022 |
| Last Verified: | August 2022 |
| 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. |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Theravance Biopharma:
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Symptomatic Neurogenic Orthostatic Hypotension symptomatic nOH multiple system atrophy MSA Parkinson's disease PD pure autonomic failure PAF primary autonomic failure SEQUOIA ampreloxetine low blood pressure dizziness fainting |
blacking out lightheadedness norepinephrine hypotension Parkinsonism TD-9855 Neurogenic Orthostatic Hypotension nOH 0145 145 169 0169 TD9855 |
Additional relevant MeSH terms:
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Hypotension, Orthostatic Pure Autonomic Failure Hypotension Vascular Diseases Cardiovascular Diseases |
Orthostatic Intolerance Primary Dysautonomias Autonomic Nervous System Diseases Nervous System Diseases |