This study will look at whether an investigational drug called TD-9855 works and how safe it is for treating symptomatic neurogenic orthostatic hypotension (snOH) in people with Parkinson’s disease (PD), multiple system atrophy (MSA) or pure autonomic failure (PAF)
- Conditions
- Symptomatic Neurogenic Orthostatic Hypotension in Subjects with Primary Autonomic FailureTherapeutic area: Diseases [C] - Nervous System Diseases [C10]
- Registration Number
- EUCTR2018-003289-15-EE
- Lead Sponsor
- Theravance Biopharma Ireland Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 188
*Subject is male or female and 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.
*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 minutes of being tilted-up to =60 degrees 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 impaired autonomic reflexes, as determined by absence of Phase IV BP overshoot after release of the Valsalva strain.
*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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 95
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 95
*Subject has a known systemic illness known to produce autonomic neuropathy, including but not limited to diabetes mellitus, diabetes insipidus, diabetic neuropathy, 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.
*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 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/1.73m², 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 (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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method