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

• Study Type: Interventional
• 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
• Enrollment: 110

Participant Flow

Recruitment Details	A total of 110 participants who completed Study 0170 rolled over into Study 0171. The study was performed in Europe, Asia/Pacific, and the United States between 19 September 2019 and 12 November 2021.
Pre-assignment Details	The study was planned to consist of 3 periods: 26-week treatment,156-week treatment extension, and 2-week follow-up.

Arm/Group Title	Ampreloxetine
Arm/Group Description	Participants received a single dose of 10 mg ampreloxetine once daily (QD) for a planned duration of up to 182 weeks.
Period Title: Overall Study
Started	110
Completed	0
Not Completed	110
Reason Not Completed
Adverse Event	3
Study Terminated by Sponsor	103
Withdrawal by Subject	4

Baseline Characteristics

Arm/Group Title		Ampreloxetine
Arm/Group Description		Participants received a single dose of 10 mg ampreloxetine QD for a planned duration of up to 182 weeks.
Overall Number of Baseline Participants		110
Baseline Analysis Population Description		The safety analysis set was defined as all enrolled participants who have received at least one dose of ampreloxetine in this study.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	110 participants
		68.4 (8.29)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	110 participants
	Female	31 28.2%
	Male	79 71.8%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	110 participants
	Hispanic or Latino	2 1.8%
	Not Hispanic or Latino	105 95.5%
	Unknown or Not Reported	3 2.7%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	110 participants
	American Indian or Alaska Native	0 0.0%
	Asian	1 0.9%
	Native Hawaiian or Other Pacific Islander	0 0.0%
	Black or African American	1 0.9%
	White	108 98.2%
	More than one race	0 0.0%
	Unknown or Not Reported	0 0.0%
Primary Diagnosis; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	110 participants
	Multiple System Atrophy	34 30.9%
	Parkinson's Disease	58 52.7%
	Pure Autonomic Failure	18 16.4%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Description	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.
Time Frame	Day 1 up to a maximum of 749 days

Outcome Measure Data

Analysis Population Description

The safety set was defined as all enrolled participants who received at least 1 dose of ampreloxetine in the study.

Arm/Group Title	Ampreloxetine
Arm/Group Description:	Participants received a single dose of 10 mg ampreloxetine QD for a planned duration of up to 182 weeks.
Overall Number of Participants Analyzed	110
Measure Type: Count of Participants; Unit of Measure: Participants
	61 55.5%

Adverse Events

Time Frame	Day 1 up to a maximum of 749 days
Adverse Event Reporting Description	The safety set was defined as all enrolled participants who received at least 1 dose of ampreloxetine in the study.
Arm/Group Title	Ampreloxetine
Arm/Group Description	Participants received a single dose of 10 mg ampreloxetine QD for a planned duration of up to 182 weeks.
All-Cause Mortality
	Ampreloxetine
	Affected / at Risk (%)
Total	1/110 (0.91%)
Serious Adverse Events
	Ampreloxetine
	Affected / at Risk (%)	# Events
Total	14/110 (12.73%)
Cardiac disorders
Atrial fibrillation † 1	1/110 (0.91%)	1
General disorders
Chest pain † 1	2/110 (1.82%)	2
Infections and infestations
Cystitis † 1	1/110 (0.91%)	1
Pneumonia † 1	1/110 (0.91%)	1
Urinary tract infection † 1	2/110 (1.82%)	5
Sepsis † 1	1/110 (0.91%)	1
Musculoskeletal and connective tissue disorders
Flank pain † 1	1/110 (0.91%)	1
Nervous system disorders
Loss of consciousness † 1	1/110 (0.91%)	1
Paraparesis † 1	1/110 (0.91%)	1
Lethargy † 1	1/110 (0.91%)	1
Sciatica † 1	1/110 (0.91%)	1
Syncope † 1	1/110 (0.91%)	1
Dizziness † 1	1/110 (0.91%)	1
Reproductive system and breast disorders
Prostatitis † 1	1/110 (0.91%)	2
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism † 1	2/110 (1.82%)	2
Skin and subcutaneous tissue disorders
Decubitus ulcer † 1	1/110 (0.91%)	1
Vascular disorders
Orthostatic hypotension † 1	1/110 (0.91%)	1
Deep vein thrombosis † 1	1/110 (0.91%)	1
1 Term from vocabulary, MedDRA (24.1); † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	3%
	Ampreloxetine
	Affected / at Risk (%)	# Events
Total	24/110 (21.82%)
Gastrointestinal disorders
Diarrhoea † 1	4/110 (3.64%)
General disorders
Fatigue † 1	4/110 (3.64%)
Infections and infestations
Urinary tract infection † 1	8/110 (7.27%)
Musculoskeletal and connective tissue disorders
Arthralgia † 1	5/110 (4.55%)
Nervous system disorders
Headache † 1	6/110 (5.45%)
Reproductive system and breast disorders
Benign prostatic hyperplasia † 1	4/110 (3.64%)
1 Term from vocabulary, MedDRA (24.1); † Indicates events were collected by systematic assessment

Limitations and Caveats

Because the study was terminated early by the Sponsor, the latest scheduled study visit completed by any participant was at Week 98.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Medical Monitor
• Organization: Theravance Biopharma
• Phone: 855 633 8479 ext +1
• EMail: medinfo@theravance.com

• Responsible Party: Theravance Biopharma
• ClinicalTrials.gov Identifier: NCT04095793
• Other Study ID Numbers: 0171; 2019-002425-30 ( EudraCT Number )
• First Submitted: August 1, 2019
• First Posted: September 19, 2019
• Results First Submitted: November 7, 2022
• Results First Posted: November 30, 2022
• Last Update Posted: November 30, 2022