Extension Study of Ampreloxetine (TD-9855) for Treating snOH in Subjects With Primary Autonomic Failure (OAK)

• ClinicalTrials.gov Identifier: NCT04095793
• Recruitment Status: Recruiting
• First Posted: September 19, 2019
• Last Update Posted: June 11, 2020
• Sponsor: Theravance Biopharma
• Information provided by (Responsible Party): Theravance Biopharma

Study Description

Brief Summary:

A Phase 3, multi-center, open-label study to evaluate the safety and tolerability of ampreloxetine in subjects with primary autonomic failures (MSA, PD, and PAF) and snOH over 182 weeks.

Condition or disease	Intervention/treatment	Phase
Symptomatic Neurogenic Orthostatic Hypotension	Drug: ampreloxetine	Phase 3

Detailed Description:

This is a Phase 3, multi-center, open-label study to evaluate the safety and tolerability of ampreloxetine in subjects with primary autonomic failures (MSA, PD, and PAF) and snOH. The study consists of 3 periods: (i) 26-week treatment, (ii) 156-week treatment extension, and (iii) 2-week follow-up.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 80 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 3, 182-week, Open-Label, Safety and Tolerability Study of TD-9855 in Treating Symptomatic Neurogenic Orthostatic Hypotension (snOH) in Subjects With Primary Autonomic Failure
• Actual Study Start Date: September 19, 2019
• Estimated Primary Completion Date: February 2022
• Estimated Study Completion Date: March 2025

Arms and Interventions

Arm	Intervention/treatment
Experimental: ampreloxetine; Participants will receive a single, oral, daily dose of active drug (TD-9855) for 182 weeks.	Drug: ampreloxetine; Oral tablet, QD; Other Name: TD-9855

Outcome Measures

Primary Outcome Measures :

1. Physical examination [ Time Frame: Baseline to Week 26 ]
   Number of subjects with new abnormalities reported on their physical exam.
2. Neurological Examination [ Time Frame: Baseline to Week 26 ]
   Number of subjects with new abnormalities reported on their neurological exam.
3. Vital Signs [ Time Frame: Baseline to Week 26 ]
   Number of subjects with clinically significant vital sign abnormalities.
4. ECGs [ Time Frame: Baseline to Week 26 ]
   Number of subjects with clinically significant ECG findings.
5. Clinical Laboratory Tests [ Time Frame: Baseline to Week 26 ]
   Number of subjects with laboratory test abnormalities.
6. Concomitant Medications [ Time Frame: Baseline to Week 26 ]
   Changes in concomitant medications
7. Adverse Events (AEs) [ Time Frame: Baseline to Week 26 ]
   Incidence and severity of treatment-emergent adverse events
8. Subject compliance to study treatment [ Time Frame: Baseline to Week 26 ]
   Number of subjects determined to be compliant with study medications.
9. Incidence of Falls [ Time Frame: Baseline to Week 26 ]
   Changes in incidence of falls
10. Changes from baseline in Columbia Suicide Severity Rating Scale (C-SSRS) [ Time Frame: Baseline to Week 26 ]
    The C-SSRS is a tool designed to systematically assess and track suicidal AEs (suicidal behavior and suicidal ideation) and will be used for all visits.

Eligibility Criteria

• Ages Eligible for Study: 30 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Completion of Study 0170 and, in the opinion of the Investigator, would benefit from long-term treatment with ampreloxetine.
• 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 any changes occurring in the subject's current therapeutic regimen).
• The subject must be willing to continue on treatment and must continue to meet all the inclusion criteria for the preceding study (Study 0170) except, a score of >4 in OHSA#1.

Exclusion Criteria:

• Subjects may not be enrolled in another clinical trial.
• 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.
• Medical, laboratory, or surgical issues deemed by the Investigator to be clinically significant.
• Hypersensitivity to ampreloxetine or the formulation excipients.

Contacts and Locations

Contacts

Contact: Theravance Biopharma Call Center; 1-855-633-8479; medinfo@theravance.com

Locations

United States, Florida

Neurostudies, Inc.; Recruiting

Port Charlotte, Florida, United States, 33952

United States, Illinois

NorthShore University HealthSystem; Active, not recruiting

Glenview, Illinois, United States, 60026

United States, Kansas

University of Kansas Medical Center; Recruiting

Kansas City, Kansas, United States, 66160

United States, Minnesota

Mayo Clinic - Rochester; Active, not recruiting

Rochester, Minnesota, United States, 55905

United States, Tennessee

Vanderbilt University Medical Center; Recruiting

Nashville, Tennessee, United States, 37232

United States, Texas

University of Texas Southwestern Medical Center; Recruiting

Dallas, Texas, United States, 75390

United States, Washington

Inland Northwest Research; Recruiting

Spokane, Washington, United States, 99202

Denmark

Bispebjerg Hospital; Recruiting

Copenhagen, Denmark, 2400

Estonia

Tartu University Hospital; Active, not recruiting

Tartu, Estonia, 50406

Poland

Instytut Zdrowia Dr Boczarska-Jedynak SP. Z 0.0., SP. K.; Recruiting

Oswiecim, Poland, 32-600

Spain

Hospital del Mar; Active, not recruiting

Barcelona, Spain, 8003

Hospital Universitario de La Princesa; Recruiting

Madrid, Spain, 28006

Ukraine

Municipal Instituion of Health: Kharkiv Public Outpatient Clinic 9, Kharkiv Medical Academy of Post-Graduate Education, Department of General Practice - Family Medicine; Recruiting

Kharkiv, Ukraine, 61172

Lviv Regional Clinical Hospital; Recruiting

Lviv, Ukraine, 79010

United Kingdom

The National Hospital for Neurology & Neurosurgery; Active, not recruiting

London, Greater London, United Kingdom, WC1N 3BG

Sponsors and Collaborators

Theravance Biopharma

Investigators

• Study Director: Medical Monitor; Theravance Biopharma

More Information

• Responsible Party: Theravance Biopharma
• ClinicalTrials.gov Identifier: NCT04095793
• Other Study ID Numbers: 0171
• First Posted: September 19, 2019
• Last Update Posted: June 11, 2020
• Last Verified: June 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: Theravance Biopharma, Inc. will not be sharing individual de-identified participant data or other relevant study documents.

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

Keywords provided by Theravance Biopharma:

ampreloxetine; Symptomatic Neurogenic Orthostatic Hypotension; snOH; multiple symptom atrophy; MSA; Parkinson's disease; PD; pure autonomic failure; PAF; orthostatic hypotension; OH; 171; low blood pressure; dizziness; fainting; blacking out; lightheadedness; norepinephrine; hypotension; OAK

Additional relevant MeSH terms:

Hypotension, Orthostatic; Pure Autonomic Failure; Hypotension; Vascular Diseases; Cardiovascular Diseases; Orthostatic Intolerance; Primary Dysautonomias; Autonomic Nervous System Diseases; Nervous System Diseases