Trial Outcomes & Findings for Phase 3 Open-Label Extension Study of TD-9855 for Treating Symptomatic nOH in Subjects With Primary Autonomic Failure (NCT NCT04095793)

Last Updated: 2022-11-30

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

110 participants

Primary outcome timeframe

Day 1 up to a maximum of 749 days

Results posted on

2022-11-30

Participant Flow

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.

The study was planned to consist of 3 periods: 26-week treatment,156-week treatment extension, and 2-week follow-up.

Participant milestones

Participant milestones
Measure	Ampreloxetine Participants received a single dose of 10 mg ampreloxetine once daily (QD) for a planned duration of up to 182 weeks.
Overall Study STARTED	110
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	110

Reasons for withdrawal

Reasons for withdrawal
Measure	Ampreloxetine Participants received a single dose of 10 mg ampreloxetine once daily (QD) for a planned duration of up to 182 weeks.
Overall Study Adverse Event	3
Overall Study Study Terminated by Sponsor	103
Overall Study Withdrawal by Subject	4

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ampreloxetine n=110 Participants Participants received a single dose of 10 mg ampreloxetine QD for a planned duration of up to 182 weeks.
Age, Continuous	68.4 years STANDARD_DEVIATION 8.29 • n=5 Participants
Sex: Female, Male Female	31 Participants n=5 Participants
Sex: Female, Male Male	79 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	105 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants
Race (NIH/OMB) White	108 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Primary Diagnosis Multiple System Atrophy	34 Participants n=5 Participants
Primary Diagnosis Parkinson's Disease	58 Participants n=5 Participants
Primary Diagnosis Pure Autonomic Failure	18 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 1 up to a maximum of 749 days

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

Outcome measures

Outcome measures
Measure	Ampreloxetine n=110 Participants Participants received a single dose of 10 mg ampreloxetine QD for a planned duration of up to 182 weeks.
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	61 Participants

Adverse Events

Ampreloxetine

Serious events: 14 serious events

Other events: 24 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Ampreloxetine n=110 participants at risk Participants received a single dose of 10 mg ampreloxetine QD for a planned duration of up to 182 weeks.
Vascular disorders Orthostatic hypotension	0.91% 1/110 • Number of events 1 • Day 1 up to a maximum of 749 days The safety set was defined as all enrolled participants who received at least 1 dose of ampreloxetine in the study.
Infections and infestations Cystitis	0.91% 1/110 • Number of events 1 • Day 1 up to a maximum of 749 days The safety set was defined as all enrolled participants who received at least 1 dose of ampreloxetine in the study.
Skin and subcutaneous tissue disorders Decubitus ulcer	0.91% 1/110 • Number of events 1 • Day 1 up to a maximum of 749 days The safety set was defined as all enrolled participants who received at least 1 dose of ampreloxetine in the study.
Infections and infestations Pneumonia	0.91% 1/110 • Number of events 1 • Day 1 up to a maximum of 749 days The safety set was defined as all enrolled participants who received at least 1 dose of ampreloxetine in the study.
Nervous system disorders Loss of consciousness	0.91% 1/110 • Number of events 1 • Day 1 up to a maximum of 749 days The safety set was defined as all enrolled participants who received at least 1 dose of ampreloxetine in the study.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	1.8% 2/110 • Number of events 2 • Day 1 up to a maximum of 749 days The safety set was defined as all enrolled participants who received at least 1 dose of ampreloxetine in the study.
Nervous system disorders Paraparesis	0.91% 1/110 • Number of events 1 • Day 1 up to a maximum of 749 days The safety set was defined as all enrolled participants who received at least 1 dose of ampreloxetine in the study.
Reproductive system and breast disorders Prostatitis	0.91% 1/110 • Number of events 2 • Day 1 up to a maximum of 749 days The safety set was defined as all enrolled participants who received at least 1 dose of ampreloxetine in the study.
Vascular disorders Deep vein thrombosis	0.91% 1/110 • Number of events 1 • Day 1 up to a maximum of 749 days The safety set was defined as all enrolled participants who received at least 1 dose of ampreloxetine in the study.
Infections and infestations Urinary tract infection	1.8% 2/110 • Number of events 5 • Day 1 up to a maximum of 749 days The safety set was defined as all enrolled participants who received at least 1 dose of ampreloxetine in the study.
Musculoskeletal and connective tissue disorders Flank pain	0.91% 1/110 • Number of events 1 • Day 1 up to a maximum of 749 days The safety set was defined as all enrolled participants who received at least 1 dose of ampreloxetine in the study.
Nervous system disorders Lethargy	0.91% 1/110 • Number of events 1 • Day 1 up to a maximum of 749 days The safety set was defined as all enrolled participants who received at least 1 dose of ampreloxetine in the study.
General disorders Chest pain	1.8% 2/110 • Number of events 2 • Day 1 up to a maximum of 749 days The safety set was defined as all enrolled participants who received at least 1 dose of ampreloxetine in the study.
Nervous system disorders Sciatica	0.91% 1/110 • Number of events 1 • Day 1 up to a maximum of 749 days The safety set was defined as all enrolled participants who received at least 1 dose of ampreloxetine in the study.
Cardiac disorders Atrial fibrillation	0.91% 1/110 • Number of events 1 • Day 1 up to a maximum of 749 days The safety set was defined as all enrolled participants who received at least 1 dose of ampreloxetine in the study.
Nervous system disorders Syncope	0.91% 1/110 • Number of events 1 • Day 1 up to a maximum of 749 days The safety set was defined as all enrolled participants who received at least 1 dose of ampreloxetine in the study.
Nervous system disorders Dizziness	0.91% 1/110 • Number of events 1 • Day 1 up to a maximum of 749 days The safety set was defined as all enrolled participants who received at least 1 dose of ampreloxetine in the study.
Infections and infestations Sepsis	0.91% 1/110 • Number of events 1 • Day 1 up to a maximum of 749 days The safety set was defined as all enrolled participants who received at least 1 dose of ampreloxetine in the study.

Other adverse events

Other adverse events
Measure	Ampreloxetine n=110 participants at risk Participants received a single dose of 10 mg ampreloxetine QD for a planned duration of up to 182 weeks.
Infections and infestations Urinary tract infection	7.3% 8/110 • Day 1 up to a maximum of 749 days The safety set was defined as all enrolled participants who received at least 1 dose of ampreloxetine in the study.
Nervous system disorders Headache	5.5% 6/110 • Day 1 up to a maximum of 749 days The safety set was defined as all enrolled participants who received at least 1 dose of ampreloxetine in the study.
Musculoskeletal and connective tissue disorders Arthralgia	4.5% 5/110 • Day 1 up to a maximum of 749 days The safety set was defined as all enrolled participants who received at least 1 dose of ampreloxetine in the study.
Reproductive system and breast disorders Benign prostatic hyperplasia	3.6% 4/110 • Day 1 up to a maximum of 749 days The safety set was defined as all enrolled participants who received at least 1 dose of ampreloxetine in the study.
Gastrointestinal disorders Diarrhoea	3.6% 4/110 • Day 1 up to a maximum of 749 days The safety set was defined as all enrolled participants who received at least 1 dose of ampreloxetine in the study.
General disorders Fatigue	3.6% 4/110 • Day 1 up to a maximum of 749 days The safety set was defined as all enrolled participants who received at least 1 dose of ampreloxetine in the study.

Additional Information

Medical Monitor

Theravance Biopharma

Phone: 855 633 8479

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place