A Phase 3, 22-week, Multi-center, Randomized Withdrawal Study of TD-9855 in Treating Symptomatic NeurogenicOrthostatic Hypotension in Subjects with Primary Autonomic Failure - Redwood
- Conditions
- Symptomatic Neurogenic Orthostatic Hypotension in Subjects with Primary Autonomic FailureTherapeutic area: Diseases [C] - Nervous System Diseases [C10]
- Registration Number
- EUCTR2018-003941-41-DK
- Lead Sponsor
- Theravance Biopharma Ireland Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 258
Inclusion Criteria (For 0169 Completers Group):
1. Completion of 4 weeks of double blind treatment in Study 0169 (V6) and, in the opinion of the Investigator, could benefit from continued treatment with TD-9855. No minimum score of OHSA#1 is required to enter V1 of Study 0170.
2. The subject has a minimum of 80% study medication compliance in Study 0169.
3. The subject must be able to understand the nature of the study and must provide written informed consent prior to the conduct of any study procedures (including an understanding that entry to Study 0170 may result in changes occurring in the subject’s current therapeutic regimen).
4. The subject must be willing to continue on treatment regardless of the possibility of randomization to either TD-9855 or PBO during the randomized withdrawal phase and must continue to meet the inclusion criteria for the preceding study (Study 0169) with the exception that tilt-table test, ESC review and approval of eligibility are not required for entry into Study 0170.
Inclusion Criteria (For De Novo Group):
1. Subject is male or female and at least 30 years old.
2. If subject is female, the subject must be non-pregnant and non-lactating. 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 beta human chorionic gonadotropin (bHCG) 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.
3. 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.
4. 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 =60 degrees from a supine position as determined by a tilt-table test.
5. Subject must score at least a 4 on the OHSA#1 at V1.
6. 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).
7. 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).
8. 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.
9. Subject has plasma NE levels = 100 pg/mL after being in seated position for 30 minutes.
10. Subject is willing and able to provide signed and dated written informed consent to participate prior to initiation of any study related procedures.
11. Subject is able to communicate well with the investigator and understand 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
Exclusion Criteria (For 0169 Completers Group):
1. Subject may not be enrolled in another clinical trial (other than exiting Study 0169).
2. Subject has psychiatric, neurological, or behavioral disorders that may interfere with the ability of subjects to give informed consent, or interfere with the conduct of the study.
3. Medical, laboratory, or surgical issues deemed by the investigator to be clinically significant.
4. Uncooperative attitude or reasonable likelihood of non-compliance with the protocol.
5. 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):
1. Subject has a known systemic illness known to produce autonomic neuropathy, including, but not limited to, diabetes mellitus, diabetes insipidus, diabetic neuropathy, amyloidosis, or autoimmune neuropathies.
2. Subject has a known intolerance to other NRIs or serotonin norepinephrine reuptake inhibitors (SNRIs).
3. Subject currently uses concomitant antihypertensive medication for the treatment of essential hypertension.
4. 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.
5. Subject has changed dose, frequency, or type of prescribed medication for orthostatic hypotension within 7 days prior to V1.
• Midodrine and droxidopa must be tapered off at least 7 days prior to V1.
6. 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).
7. Subject has a clinically unstable coronary artery disease, or has had a major cardiovascular or neurological event in the past 6 months.
8. Subject has used any monoamine oxidase inhibitor (MAO-I) within 14 days prior to V1.
9. 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.
10. Subject has any significant uncontrolled cardiac arrhythmia.
11. Subject has a Montreal Cognitive Assessment (MoCA) =23.
12. Subject is unable or unwilling to complete all protocol specified procedures including questionnaires.
13. Subject had a myocardial infarction in the past 6 months or has current unstable angina.
14. Subject has known congestive heart failure (New York Heart Association [NYHA]
Class 3 or 4).
15. Subject has had any malignant disease, other than carcinoma in situ of the cervix or basal cell carcinoma, within the past 2 years prior to screening.
16. 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).
17. 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.
18. Subject is currently receiving any investigational drug or has received an investigational drug within 30 days of dosing. An investigational drug is defined as drug that is not approved by a regulatory agency (e.g., Food and Drug Administration [FDA]).
19. Subject has a clinically sig
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