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Trial record 2 of 5 for:    ampreloxetine

Clinical Effect of Ampreloxetine (TD-9855) for Treating snOH in Subjects With Primary Autonomic Failure (SEQUOIA)

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ClinicalTrials.gov Identifier: NCT03750552
Recruitment Status : Recruiting
First Posted : November 23, 2018
Last Update Posted : May 29, 2020
Sponsor:
Information provided by (Responsible Party):
Theravance Biopharma

Tracking Information
First Submitted Date  ICMJE November 20, 2018
First Posted Date  ICMJE November 23, 2018
Last Update Posted Date May 29, 2020
Actual Study Start Date  ICMJE January 24, 2019
Estimated Primary Completion Date September 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 20, 2018)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 28, 2020)
  • 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.
  • 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.
  • 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.
  • Incidence of falls [ Time Frame: Week 4 ]
    Incidence of patient-reported falls.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 20, 2018)
  • 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.
  • 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.
  • 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.
  • Incidence of falls [ Time Frame: Week 4 ]
    Incidence of patient-reported falls.
  • Standing systolic blood pressure during orthostatic standing test [ Time Frame: Baseline, Week 1, Week 2, Week 3, Week 4 ]
    Systolic blood pressure taken during the standing portion of the orthostatic standing test.
  • Change from baseline in UPDRS at Week 4 [ Time Frame: Baseline to Week 4 ]
    Unified Parkinson's Disease Rating Scale (UPDRS) is a clinical rating scale for Parkinson's Disease (PD). Outcome measure only applies to subjects with PD.
  • Change from baseline in PDQ-8 at Week 4 [ Time Frame: Baseline to Week 4 ]
    Parkinson's Disease Questionnaire-8 (PDQ-8) is an assessment for Parkinson's Disease (PD) subjects. Outcome measure only applies to subjects with PD.
  • Change from baseline in COMPASS-31 at Week 4 [ Time Frame: Baseline to Week 4 ]
    Composite Autonomic Symptoms Score-31 (COMPASS-31) is an assessment that provides a quantitative measure of autonomic symptoms. Outcome measure only applies to subjects with Multiple System Atrophy (MSA).
  • Change from baseline in UMSARS at Week 4 [ Time Frame: Baseline to Week 4 ]
    Unified Multiple System Atrophy Rating Scale (UMSARS) is an assessment for Multiple System Atrophy (MSA) subjects. Outcome measure only applies to subjects with MSA.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Clinical Effect of Ampreloxetine (TD-9855) for Treating snOH in Subjects With Primary Autonomic Failure
Official Title  ICMJE 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
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.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Parallel assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Symptomatic Neurogenic Orthostatic Hypotension
Intervention  ICMJE
  • Drug: ampreloxetine
    Oral tablet, QD
    Other Name: TD-9855
  • Drug: Placebo
    Oral tablet, QD
Study Arms  ICMJE
  • Experimental: ampreloxetine
    Participants randomized to ampreloxetine will receive a single, oral, daily dose of active drug for 4 weeks.
    Intervention: Drug: ampreloxetine
  • Placebo Comparator: Placebo
    Participants randomized to Placebo will receive a single, oral, daily dose of placebo for 4 weeks.
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 20, 2018)
188
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 2020
Estimated Primary Completion Date September 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 30 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Theravance Biopharma Call Center 1-855-633-8479 medinfo@theravance.com
Listed Location Countries  ICMJE Australia,   Austria,   Bulgaria,   Canada,   Denmark,   Estonia,   France,   Germany,   Hungary,   Israel,   Italy,   New Zealand,   Poland,   Portugal,   Russian Federation,   Spain,   Ukraine,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03750552
Other Study ID Numbers  ICMJE 0169
2018-003289-15 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: Theravance Biopharma, Inc. will not be sharing individual de-identified participant data or other relevant study documents.
Responsible Party Theravance Biopharma
Study Sponsor  ICMJE Theravance Biopharma
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Monitor Theravance Biopharma
PRS Account Theravance Biopharma
Verification Date May 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP