A Study to Evaluate TD-9855 to Treat Symptomatic Neurogenic Orthostatic Hypotension (snOH) in Subjects with Primary Autonomic Failure

Overview

About this study

The purpose of this study is to evaluate the effectiveness, safety, and tolerability of TD-9855 in subjects with primary autonomic failures (MSA, PD, or PAF) and Symptomatic Neurogenic Orthostatic Hypotension (snOH)with up to 4 weeks of treatment.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Subject is male or female.
  • Subject is at least 30 years old.
  • Subject is female and must be nonpregnant and nonlactating. A woman of childbearing potential must have a documented negative pregnancy test at screening.
    • NOTE: A woman is considered to be of childbearing potential unless she is postmenopausal (amenorrheic for at least 2 years) or documented to be surgically sterile (bilateral tubal ligation or total hysterectomy). A female subject may be admitted to the study on the basis of a negative urine pregnancy test. If the urine bHCG (beta human chorionic gonadotropin) test is positive, a serum bHCG test must be performed. The pregnancy test must be confirmed negative for a subject to be eligible for this study.
  • During the study and for 30 days after receiving the last dose of the study drug, females of childbearing potential or males capable of fathering children must agree to use highly effective birth control measures (failure rate <1% when used consistently and correctly) or agree to abstain from sexual intercourse.
  • Subject must meet the diagnostic criteria of nOH, as demonstrated by a sustained reduction in BP of ≥ 20 mmHg (systolic) or ≥ 10 mmHg (diastolic) within 3 min of being tilted up to ≥ 60° 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.
  • Subject is willing and able to provide signed and dated written informed consent to participate prior to initiation of any study related procedures.
  • Subject is able to communicate well with the investigator and clinic staff, understands the expectations of the study and is able to comply with the study procedures, requirements, and restrictions.

Exclusion Criteria: 

  • Subject has a known systemic illness known to produce autonomic neuropathy, including but not limited to amyloidosis and autoimmune neuropathies. Subject has diabetes mellitus and diagnosis of PAF. Subject with diabetes mellitus and either MSA or PD, will be evaluated on a case by case basis by the medical monitor and considered ineligible unless they meet all of the following criteria:
    • Well controlled type-2 DM in treatment with only oral medications and diet;
    • HgbA1C of ≤ 7.5% performed during screening or up to 12 weeks before screening;
    • No clinically evident peripheral neuropathy (e.g., normal sensory examination on peripheral extremities);
    • No known retinopathy (e.g., annual ophthalmic exam is sufficient);
    • No nephropathy (e.g., absence of albuminuria and GFR > 60).
  • Subject has a known intolerance to other NRIs or SNRIs.
  • Subject currently uses concomitant antihypertensive medication for the treatment of essential hypertension.
  • 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 randomization visit.
    •  Midodrine and droxidopa (if applicable) must be tapered off at least 7 days prior to randomization.
  • 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 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 any malignant disease other than carcinoma in situ of the cervix or basal cell carcinoma within the past 2 years prior to screening.
  • Subject has a known gastrointestinal (GI) condition, which in the investigator’s judgment, may affect the absorption of study medication (e.g., ulcerative colitis, gastric bypass).
  • Subject has psychiatric, neurological, or behavioral disorders that may interfere with the ability of the subject to give informed consent or interfere with the conduct of the study.
  • Subject is currently receiving any investigational drug or has received an investigational drug within 30 days of dosing. An investigational drug is defined as nonregulatory agency approved drug (e.g., Food and Drug Administration).
  • 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/1.73m^2, 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 (Baseline/Screening Version) subject should be assessed by the rater for risk of suicide and the subject’s appropriateness for inclusion in the study.
  • 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.
  • Subject has known hypersensitivity to TD-9855 (ampreloxetine hydrochloride), or any excipients in the formulation.
  • Subject has:
    • confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) documented with coronavirus disease 2019 [COVID-19] positive test result, OR (ii) is suspected of SARS-CoV-2 infection (clinical features without documented test results two weeks after resolution of symptoms and remains asymptomatic until Day 1); OR
    • has been in close contact with a person with known (or suspected) SARS-CoV-2 infection and remains asymptomatic until Day 1.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Phillip Low, M.D.

Open for enrollment

Contact information:

Raelene Martini

(507) 284-0336

adc.research@mayo.edu

More information

Publications

Publications are currently not available

Study Results Summary

Not yet available

Supplemental Study Information

Not yet available