Symptomatic Neurogenic Orthostatic Hypotension
Conditions
Keywords
Symptomatic Neurogenic Orthostatic Hypotension, sympomatic nOH, multiple symptom atrophy, MSA, Parkinson's disease, PD, pure autonomic failure, PAF, orthostatic hypotension, OH, ampreloxetine, 171, low blood pressure, dizziness, fainting, blacking out, lightheadedness, norepinephrine, hypotension, OAK
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.
Interventions
DRUGampreloxetine
Oral tablet, QD
Sponsors
Theravance Biopharma
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
30 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 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. |
Countries
Australia, Austria, Bulgaria, Canada, Denmark, Estonia, France, Germany, Israel, Italy, New Zealand, Poland, Portugal, Russia, Spain, Ukraine, United Kingdom, United States
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.
Participants by arm
| Arm | Count |
|---|---|
| Ampreloxetine Participants received a single dose of 10 mg ampreloxetine QD for a planned duration of up to 182 weeks. | 110 |
| Total | 110 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 3 |
| Overall Study | Study Terminated by Sponsor | 103 |
| Overall Study | Withdrawal by Subject | 4 |
Baseline characteristics
| Characteristic | Ampreloxetine |
|---|---|
| Age, Continuous | 68.4 years STANDARD_DEVIATION 8.29 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 105 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Primary Diagnosis Multiple System Atrophy | 34 Participants |
| Primary Diagnosis Parkinson's Disease | 58 Participants |
| Primary Diagnosis Pure Autonomic Failure | 18 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 108 Participants |
| Sex: Female, Male Female | 31 Participants |
| Sex: Female, Male Male | 79 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 110 |
| other Total, other adverse events | 24 / 110 |
| serious Total, serious adverse events | 14 / 110 |
Outcome results
Primary
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
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
Population: The safety set was defined as all enrolled participants who received at least 1 dose of ampreloxetine in the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ampreloxetine | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 61 Participants |