Phase 3 Open-Label Extension Study of TD-9855 for Treating Symptomatic nOH in Subjects With Primary Autonomic Failure (OAK)

• ClinicalTrials.gov Identifier: NCT04095793
• Recruitment Status: Terminated
• First Posted: September 19, 2019
• Results First Posted: November 30, 2022
• Last Update Posted: November 30, 2022
• Sponsor: Theravance Biopharma
• Information provided by (Responsible Party): Theravance Biopharma

Tracking Information

• First Submitted Date: August 1, 2019
• First Posted Date: September 19, 2019
• Results First Submitted Date: November 7, 2022
• Results First Posted Date: November 30, 2022
• Last Update Posted Date: November 30, 2022
• Actual Study Start Date: September 19, 2019
• Actual Primary Completion Date: November 12, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 7, 2022)

Number of Participants With Treatment-emergent Adverse Events (TEAEs) [ Time Frame: Day 1 up to a maximum of 749 days ]

An adverse event (AE) was any untoward medical occurrence in a patient or clinical study participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. A TEAE was defined as any AE that begins on or after the date of first dose of study drug up to the date of last dose of study drug plus the number of days in the follow-up period. Clinically significant abnormalities in physical and neurological examinations, vital signs, resting 12-lead electrocardiograms, and clinical laboratory evaluations, in addition to incidence of fall, suicidal ideation, and suicidal behavior, were reported as AEs.

Original Primary Outcome Measures (submitted: September 17, 2019)

• Physical examination [ Time Frame: Baseline to Day 197 (over a 26 week period) ]
  Number of subjects with new abnormalities reported on their physical exam.
• Neurological Examination [ Time Frame: Baseline to Day 197 (over a 26 week period) ]
  Number of subjects with new abnormalities reported on their neurological exam.
• Vital Signs [ Time Frame: Baseline to Day 197 (over a 26 week period) ]
  Number of subjects with clinically significant vital sign abnormalities.
• ECGs [ Time Frame: Baseline to Day 197 (over a 26 week period) ]
  Number of subjects with clinically significant ECG findings.
• Clinical Laboratory Tests [ Time Frame: Baseline to Day 197 (over a 26 week period) ]
  Number of subjects with laboratory test abnormalities.
• Concomitant Medications [ Time Frame: Baseline to Day 197 (over a 26 week period) ]
  Changes in concomitant medications
• Adverse Events (AEs) [ Time Frame: Baseline to Day 197 (over a 26 week period) ]
  Incidence and severity of treatment-emergent adverse events
• Subject compliance to study treatment [ Time Frame: Baseline to Day 197 (over a 26 week period) ]
  Number of subjects determined to be compliant with study medications.
• Incidence of Falls [ Time Frame: Baseline to Day 197 (over a 26 week period) ]
  Changes in incidence of falls
• Changes from baseline in Columbia Suicide Severity Rating Scale (C-SSRS) [ Time Frame: Baseline to Day 197 (over a 26 week period) ]
  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.

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Phase 3 Open-Label Extension Study of TD-9855 for Treating Symptomatic nOH in Subjects With Primary Autonomic Failure
• Official Title: A Phase 3, 182-week, Open-Label, Extension Study to Investigate the Safety and Tolerability of TD-9855 in Treating Symptomatic Neurogenic Orthostatic Hypotension (Symptomatic nOH) in Subjects With Primary Autonomic Failure
• 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 symptomatic nOH over 182 weeks.
• 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 symptomatic nOH. The study consists of 3 periods: (i) 26-week treatment, (ii) 156-week treatment extension, and (iii) 2-week follow-up.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Symptomatic Neurogenic Orthostatic Hypotension

Intervention

Drug: ampreloxetine

Oral tablet, QD

Other Name: TD-9855

Study Arms

Experimental: ampreloxetine

Participants will receive a single, oral, daily dose of active drug (TD-9855) for 182 weeks.

Intervention: Drug: ampreloxetine

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: October 15, 2021): 110
• Original Estimated Enrollment (submitted: September 17, 2019): 80
• Actual Study Completion Date: November 12, 2021
• Actual Primary Completion Date: November 12, 2021 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 30 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Austria, Bulgaria, Canada, Denmark, Estonia, France, Germany, Israel, Italy, New Zealand, Poland, Portugal, Russian Federation, Spain, Ukraine, United Kingdom, United States

Administrative Information

• NCT Number: NCT04095793
• Other Study ID Numbers: 0171; 2019-002425-30 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

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.

• Current Responsible Party: Theravance Biopharma
• Original Responsible Party: Same as current
• Current Study Sponsor: Theravance Biopharma
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Medical Monitor; Theravance Biopharma

• PRS Account: Theravance Biopharma
• Verification Date: November 2022