Purpose

A Phase 3, 22-week, Multi-center, Randomized Withdrawal Study of ampreloxetine in Treating Symptomatic Neurogenic Orthostatic Hypotension in Subjects with Primary Autonomic Failure

Condition

Eligibility

Eligible Ages
Over 30 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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.

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

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Open Label Extension followed by Randomized Parallel Assignment
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
ampreloxetine (Open Label (OL))
Participants will receive ampreloxetine as a single, oral, daily dose of active drug for 16 weeks.
  • Drug: ampreloxetine
    Oral tablet, QD (Daily)
    Other names:
    • TD-9855
Experimental
ampreloxetine
After completing the OL, participants randomized to ampreloxetine will receive single, oral, daily dose of active drug for a further 6 weeks.
  • Drug: ampreloxetine
    Oral tablet, QD (Daily)
    Other names:
    • TD-9855
Placebo Comparator
Placebo
After completing the OL, participants randomized to Placebo will receive single, oral, daily dose of placebo for 6 weeks.
  • Drug: Placebo
    Oral tablet, QD

Recruiting Locations

University of Kansas Medical Center Research Institute, Inc.
Kansas City, Kansas 66160

More Details

Status
Recruiting
Sponsor
Theravance Biopharma

Study Contact

Theravance Biopharma Call Center
1-855-633-8479
medinfo@theravance.com

Detailed Description

Phase 3, multi-center, randomized withdrawal study to evaluate the sustained benefit in efficacy and safety of ampreloxetine in subjects with primary autonomic failures (MSA, PD, or PAF) and symptomatic nOH. The study consists of 3 periods: (i) 16-week open-label (OL) treatment with ampreloxetine, (ii) 6-week randomized placebo-controlled treatment, and (iii) 2-week follow-up (only for patients who do not enroll in Study 0171 (long-term extension safety study)).

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.