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

Sponsor

Theravance Biopharma (Industry)

Overall Status

Completed

CT.gov ID

NCT02705755

Collaborator

(none)

Enrollment

Locations

Arms

Actual Duration (Months)

5.7

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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 Design

Study Type:

Interventional

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 1, 2016

Actual Primary Completion Date :

Jul 1, 2018

Actual Study Completion Date :

Dec 1, 2018

Arms and Interventions

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
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

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

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

Outcome Measures

Primary Outcome Measures

Seated systolic blood pressure [6 to 8 hours after drug administration]

Secondary Outcome Measures

Adverse Events [Up to approximately 36 days for Part A]
Adverse Events [Up to approximately 57 days for Part B]
Adverse Events [Up to approximately 168 days for Part C]
Orthostatic hypotension symptoms [Up to approximately 168 days for Part C]

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Theravance Biopharma Investigational Site	Long Beach	California	United States	90806
2	Theravance Biopharma Investigational Site	Farmington Hills	Michigan	United States	48334
3	Theravance Biopharma Investigational Site	Berlin	New Jersey	United States	08009
4	Theravance Biopharma Investigational Site	New York	New York	United States	10016
5	Theravance Biopharma Investigational Site	Nashville	Tennessee	United States	37232
6	Theravance Biopharma Investigational Site	Dallas	Texas	United States	75390