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-PL
- 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 thestudy 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 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.
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 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:
a. Well controlled type-2 DM in treatment with only oral medications and
diet
b. HgbA1C of =7.5% performed during screening or up to 12 weeks
before screening
c. No clinically evident peripheral neuropathy (e.g., normal sensory examination on peripheral extremities)
d. No known retinopathy (e.g., annual ophthalmic exam is sufficient)
e. 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/1.73m², or any abnormal laboratory value that could interfere with safety of the
subject).
*Subject has demonstrated a history of lifetime sui
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