TD-9855 Phase 2 in Neurogenic Orthostatic Hypotension (nOH)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02705755
Recruitment Status : Active, not recruiting
First Posted : March 10, 2016
Last Update Posted : September 7, 2018
Information provided by (Responsible Party):
Theravance Biopharma

Brief Summary:
This multiple-center, 3-part, single-blind dose escalation (Part A), randomized, double-blind (Part B), and open-label multiple dose extension (Part C) study will be conducted in male and female subjects with neurogenic orthostatic hypotension to evaluate the effect of TD-9855 in improving symptoms of orthostatic intolerance.

Condition or disease Intervention/treatment Phase
Neurogenic Orthostatic Hypotension Multiple System Atrophy (MSA) With Orthostatic Hypotension Pure Autonomic Failure Parkinson Disease Hypotension, Orthostatic Orthostatic Hypotension Pure Autonomic Failure With Orthostatic Hypotension Parkinson Disease With Orthostatic Hypotension Drug: TD-9855 Drug: Placebo Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 34 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Official Title: A Phase 2 Study to Assess the Effect of TD-9855 in Subjects With Neurogenic Orthostatic Hypotension
Actual Study Start Date : May 2016
Actual Primary Completion Date : July 2018
Estimated Study Completion Date : December 2018

Arm Intervention/treatment
Experimental: TD-9855: Part A
Subjects will receive placebo and escalating single doses of TD-9855
Drug: TD-9855
Drug: Placebo
Experimental: TD-9855: Part B
Subjects will receive a single dose of TD-9855 or placebo
Drug: TD-9855
Drug: Placebo
Experimental: TD-9855: Part C
Subjects will receive once daily doses of TD-9855 for up to 5 months as part of an optional outpatient open-label extension arm.
Drug: TD-9855

Primary Outcome Measures :
  1. Seated systolic blood pressure [ Time Frame: 6 to 8 hours after drug administration ]

Secondary Outcome Measures :
  1. Adverse Events [ Time Frame: Up to approximately 36 days for Part A ]
  2. Adverse Events [ Time Frame: Up to approximately 57 days for Part B ]
  3. Adverse Events [ Time Frame: Up to approximately 168 days for Part C ]
  4. Orthostatic hypotension symptoms [ Time Frame: Up to approximately 168 days for Part C ]

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Ages Eligible for Study:   40 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Diagnosed with symptomatic orthostatic hypotension due to Parkinson's disease, multiple system atrophy, or pure autonomic failure, (i.e. neurogenic orthostatic hypotension).
  • At screening, subject must meet the diagnostic criteria of neurogenic orthostatic hypotension, as demonstrated by a ≥ 30 mm Hg drop in systolic blood pressure (SBP) within 5 minutes of standing.
  • Impaired autonomic reflexes, as determined by absence of BP overshoot during phase IV of the Valsalva maneuver, in subjects where Valsalva is performed, as appropriate.
  • For the optional open-label extension study subjects must have demonstrated a pressor effect and completed dosing in Part A.

Exclusion Criteria:

  • Systemic illnesses known to produce autonomic neuropathy, including but not limited to diabetes mellitus, amyloidosis, monoclonal gammopathy of unknown significance, and autoimmune neuropathies.
  • Concomitant use of vasoconstricting agents for the purpose of increasing BP such as ephedrine, dihydroergotamine, or midodrine must be stopped at least 2 days or five half lives (whichever is longer) prior to dosing on Day 1 of Part A and C, and throughout the duration of Part C. Subjects previously enrolled in Part A under previous versions of the protocol will continue taking fludrocortisone during the washout period and in Part C at the dose and regimen used in Part A. For new subjects enrolling in Part A under Amendment 3, fludrocortisone use in both Parts of the study and during the washout period will be limited to 0.1 mg QD.
  • Concomitant use of anti-hypertensive medication for the treatment of essential hypertension unrelated to autonomic dysfunction.
  • Known or suspected alcohol or substance abuse within the past 12 months.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02705755

United States, California
Collaborative Neuroscience Network, LLC.
Long Beach, California, United States, 90806
United States, Michigan
Quest Research Institute
Farmington Hills, Michigan, United States, 48334
United States, New Jersey
Hassman Research Institute
Berlin, New Jersey, United States, 08009
United States, New York
NYU Langone Medical Center
New York, New York, United States, 10016
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232
United States, Texas
University of Texas Southwestern Medical Center
Dallas, Texas, United States, 75390
Sponsors and Collaborators
Theravance Biopharma
Study Director: Ross Vickery, Ph.D. Theravance Biopharma, US, Inc.

Responsible Party: Theravance Biopharma Identifier: NCT02705755     History of Changes
Other Study ID Numbers: 0145
First Posted: March 10, 2016    Key Record Dates
Last Update Posted: September 7, 2018
Last Verified: September 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Theravance Biopharma:
Neurogenic Orthostatic Hypotension (nOH)
Multiple System Atrophy (MSA)
Pure Autonomic Failure
Parkinson Disease(PD)
Orthostatic Hypotension

Additional relevant MeSH terms:
Parkinson Disease
Hypotension, Orthostatic
Multiple System Atrophy
Shy-Drager Syndrome
Pure Autonomic Failure
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Pathological Conditions, Anatomical
Vascular Diseases
Cardiovascular Diseases
Orthostatic Intolerance
Primary Dysautonomias
Autonomic Nervous System Diseases