Trial Outcomes & Findings for Phase 3 Clinical Effect Durability of TD-9855 for Treating Symptomatic nOH in Subjects With Primary Autonomic Failure (NCT NCT03829657)

Last Updated: 2023-01-20

Results Overview

Treatment failure was defined as proportion of participants who met the following criteria at Week 6 following randomization: Change (worsening) from baseline in Question 1 of the Orthostatic Hypotension Symptom Assessment (OHSA#1) score of 1.0 point and worsening of disease severity as assessed by a 1-point change in Patient Global Impression of Severity (PGI-S). OHSA Question #1 assessed dizziness, lightheadedness, feeling faint, or feeling like you might blackout. PGI-S assessed patient's impression of disease severity. Least squares mean here is the model-based proportion of participants with treatment failure using logistic regression.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

203 participants

Primary outcome timeframe

6-week randomized withdrawal period (Week 16 to Week 22)

Results posted on

2023-01-20

Participant Flow

Participants were enrolled from February 2019 to November 2021. 203 participants were enrolled in the open label (OL) treatment period, including 170 participants from the 0169 study (NCT number: NCT03750552). 128 participants who completed the OL treatment period continued in the randomized withdrawal (RW) treatment period.

Participant milestones

Participant milestones
Measure	OL Treatment Period: 0169 Placebo Rollover Participants who received the placebo in study 0169, received 10 mg oral ampreloxetine once a day (QD) for up to 16 weeks.	OL Treatment Period: 0169 Ampreloxetine Rollover Participants who received ampreloxetine in study 0169, received 10 mg oral ampreloxetine QD for up to 16 weeks.	OL Treatment Period: De Novo Participants with symptomatic neurogenic orthostatic hypotension (nOH) who met all applicable study inclusion criteria and none of the applicable exclusion criteria, received 10 mg oral ampreloxetine QD for up to 16 weeks. These participants did not roll over from the 0169 study.	RW Treatment Period: Placebo Participants who completed the OL treatment period and were randomized to receive oral placebo QD for a further 6 weeks in the RW treatment period.	RW Treatment Period: Ampreloxetine Participants who completed the OL treatment period and were randomized to receive 10 mg oral ampreloxetine QD for a further 6 weeks in the RW treatment period.
OL Treatment Period (Week 1 to Week 16) STARTED	85	85	33	0	0
OL Treatment Period (Week 1 to Week 16) COMPLETED	52	64	12	0	0
OL Treatment Period (Week 1 to Week 16) NOT COMPLETED	33	21	21	0	0
RW Treatment Period (Week 16 to Week 24) STARTED	0	0	0	64	64
RW Treatment Period (Week 16 to Week 24) COMPLETED	0	0	0	61	58
RW Treatment Period (Week 16 to Week 24) NOT COMPLETED	0	0	0	3	6

Reasons for withdrawal

Reasons for withdrawal
Measure	OL Treatment Period: 0169 Placebo Rollover Participants who received the placebo in study 0169, received 10 mg oral ampreloxetine once a day (QD) for up to 16 weeks.	OL Treatment Period: 0169 Ampreloxetine Rollover Participants who received ampreloxetine in study 0169, received 10 mg oral ampreloxetine QD for up to 16 weeks.	OL Treatment Period: De Novo Participants with symptomatic neurogenic orthostatic hypotension (nOH) who met all applicable study inclusion criteria and none of the applicable exclusion criteria, received 10 mg oral ampreloxetine QD for up to 16 weeks. These participants did not roll over from the 0169 study.	RW Treatment Period: Placebo Participants who completed the OL treatment period and were randomized to receive oral placebo QD for a further 6 weeks in the RW treatment period.	RW Treatment Period: Ampreloxetine Participants who completed the OL treatment period and were randomized to receive 10 mg oral ampreloxetine QD for a further 6 weeks in the RW treatment period.
OL Treatment Period (Week 1 to Week 16) Adverse Event	12	4	2	0	0
OL Treatment Period (Week 1 to Week 16) Physician Decision	1	0	0	0	0
OL Treatment Period (Week 1 to Week 16) Study Terminated by Sponsor	1	3	9	0	0
OL Treatment Period (Week 1 to Week 16) Withdrawal by Subject	6	7	5	0	0
OL Treatment Period (Week 1 to Week 16) Failure to Meet Day 29 Continuation Criterion	10	6	4	0	0
OL Treatment Period (Week 1 to Week 16) Miscellaneous	3	1	1	0	0
RW Treatment Period (Week 16 to Week 24) Adverse Event	0	0	0	0	1
RW Treatment Period (Week 16 to Week 24) Study Terminated by Sponsor	0	0	0	2	3
RW Treatment Period (Week 16 to Week 24) Withdrawal by Subject	0	0	0	1	1
RW Treatment Period (Week 16 to Week 24) Miscellaneous	0	0	0	0	1

Baseline Characteristics

Phase 3 Clinical Effect Durability of TD-9855 for Treating Symptomatic nOH in Subjects With Primary Autonomic Failure

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	OL Treatment Period: 0169 Placebo Rollover n=83 Participants Participants who received the placebo in study 0169, received 10 mg oral ampreloxetine once a day (QD) for up to 16 weeks.	OL Treatment Period: 0169 Ampreloxetine Rollover n=85 Participants Participants who received ampreloxetine in study 0169, received 10 mg oral ampreloxetine QD for up to 16 weeks.	OL Treatment Period: De Novo n=32 Participants Participants with symptomatic neurogenic orthostatic hypotension (nOH) who met all applicable study inclusion criteria and none of the applicable exclusion criteria, received 10 mg oral ampreloxetine QD for up to 16 weeks. These participants did not roll over from the 0169 study.	Total n=200 Participants Total of all reporting groups
Age, Continuous	68.2 years STANDARD_DEVIATION 9.35 • n=93 Participants	68.2 years STANDARD_DEVIATION 9.00 • n=4 Participants	69.0 years STANDARD_DEVIATION 7.97 • n=27 Participants	68.4 years STANDARD_DEVIATION 8.96 • n=483 Participants
Sex: Female, Male Female	22 Participants n=93 Participants	30 Participants n=4 Participants	8 Participants n=27 Participants	60 Participants n=483 Participants
Sex: Female, Male Male	61 Participants n=93 Participants	55 Participants n=4 Participants	24 Participants n=27 Participants	140 Participants n=483 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=93 Participants	4 Participants n=4 Participants	0 Participants n=27 Participants	6 Participants n=483 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	77 Participants n=93 Participants	76 Participants n=4 Participants	32 Participants n=27 Participants	185 Participants n=483 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	4 Participants n=93 Participants	5 Participants n=4 Participants	0 Participants n=27 Participants	9 Participants n=483 Participants
Race/Ethnicity, Customized White	80 Participants n=93 Participants	83 Participants n=4 Participants	31 Participants n=27 Participants	194 Participants n=483 Participants
Race/Ethnicity, Customized Black or African American	0 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants	2 Participants n=483 Participants
Race/Ethnicity, Customized Asian	2 Participants n=93 Participants	1 Participants n=4 Participants	0 Participants n=27 Participants	3 Participants n=483 Participants
Race/Ethnicity, Customized Other	1 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	1 Participants n=483 Participants

PRIMARY outcome

Timeframe: 6-week randomized withdrawal period (Week 16 to Week 22)

Population: RW Treatment Period Full Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization.

Outcome measures

Outcome measures
Measure	RW Treatment Period: Placebo n=64 Participants Participants who completed the OL treatment period and were randomized to receive oral placebo QD for a further 6 weeks in the RW treatment period.	RW Treatment Period: Ampreloxetine n=64 Participants Participants who completed the OL treatment period and were randomized to receive 10 mg oral ampreloxetine QD for a further 6 weeks in the RW treatment period.
Proportion of Participants With Treatment Failure at Week 6 of RW Treatment Period	0.42 Proportion of participants Standard Error 0.068	0.30 Proportion of participants Standard Error 0.065

Adverse Events

OL Treatment Period: 0169 Placebo Rollover

Serious events: 7 serious events

Other events: 41 other events

Deaths: 2 deaths

OL Treatment Period: 0169 Ampreloxetine Rollover

Serious events: 8 serious events

Other events: 48 other events

Deaths: 3 deaths

OL Treatment Period: De Novo

Serious events: 1 serious events

Other events: 16 other events

Deaths: 0 deaths

RW Treatment Period: Placebo

Serious events: 2 serious events

Other events: 16 other events

Deaths: 0 deaths

RW Treatment Period: Ampreloxetine

Serious events: 4 serious events

Other events: 17 other events

Deaths: 2 deaths

Serious adverse events

Serious adverse events
Measure	OL Treatment Period: 0169 Placebo Rollover n=83 participants at risk Participants who received the placebo in study 0169, received 10 mg oral ampreloxetine once a day (QD) for up to 16 weeks.	OL Treatment Period: 0169 Ampreloxetine Rollover n=85 participants at risk Participants who received ampreloxetine in study 0169, received 10 mg oral ampreloxetine QD for up to 16 weeks.	OL Treatment Period: De Novo n=32 participants at risk Participants with symptomatic neurogenic orthostatic hypotension (nOH) who met all applicable study inclusion criteria and none of the applicable exclusion criteria, received 10 mg oral ampreloxetine QD for up to 16 weeks. These participants did not roll over from the 0169 study.	RW Treatment Period: Placebo n=64 participants at risk Participants who completed the OL treatment period and were randomized to receive oral placebo QD for a further 6 weeks in the RW treatment period.	RW Treatment Period: Ampreloxetine n=64 participants at risk Participants who completed the OL treatment period and were randomized to receive 10 mg oral ampreloxetine QD for a further 6 weeks in the RW treatment period.
Infections and infestations COVID-19	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.2% 1/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Infections and infestations Pneumonia	1.2% 1/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Infections and infestations Pneumonia aspiration	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.2% 1/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Nervous system disorders Bulbar palsy	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.2% 1/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Nervous system disorders Loss of consciousness	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.2% 1/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Nervous system disorders Neurological decompensation	1.2% 1/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Nervous system disorders Parkinson's disease	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.2% 1/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Injury, poisoning and procedural complications Hip fracture	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	2.4% 2/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Injury, poisoning and procedural complications Femur fracture	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.2% 1/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Injury, poisoning and procedural complications Injury	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.2% 1/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Cardiac disorders Atrial flutter	1.2% 1/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Cardiac disorders Atrioventricular block	1.2% 1/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Cardiac disorders Bradycardia	1.2% 1/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Cardiac disorders Myocardial infarction	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.2% 1/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Gastrointestinal disorders Diarrhoea	1.2% 1/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Gastrointestinal disorders Enterocolitis	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	3.1% 1/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
General disorders Death	1.2% 1/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.6% 1/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.2% 1/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Renal and urinary disorders Subcapsular renal haematoma	1.2% 1/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.2% 1/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Surgical and medical procedures Hip arthroplasty	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.2% 1/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Vascular disorders Orthostatic hypotension	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.2% 1/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.6% 1/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.6% 1/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Infections and infestations Respiratory tract infection	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.6% 1/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Injury, poisoning and procedural complications Spinal column injury	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.6% 1/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Infections and infestations Urinary tract infection	1.2% 1/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.2% 1/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.6% 1/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.

Other adverse events

Other adverse events
Measure	OL Treatment Period: 0169 Placebo Rollover n=83 participants at risk Participants who received the placebo in study 0169, received 10 mg oral ampreloxetine once a day (QD) for up to 16 weeks.	OL Treatment Period: 0169 Ampreloxetine Rollover n=85 participants at risk Participants who received ampreloxetine in study 0169, received 10 mg oral ampreloxetine QD for up to 16 weeks.	OL Treatment Period: De Novo n=32 participants at risk Participants with symptomatic neurogenic orthostatic hypotension (nOH) who met all applicable study inclusion criteria and none of the applicable exclusion criteria, received 10 mg oral ampreloxetine QD for up to 16 weeks. These participants did not roll over from the 0169 study.	RW Treatment Period: Placebo n=64 participants at risk Participants who completed the OL treatment period and were randomized to receive oral placebo QD for a further 6 weeks in the RW treatment period.	RW Treatment Period: Ampreloxetine n=64 participants at risk Participants who completed the OL treatment period and were randomized to receive 10 mg oral ampreloxetine QD for a further 6 weeks in the RW treatment period.
Infections and infestations Urinary tract infection	2.4% 2/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	9.4% 8/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	6.2% 2/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	4.7% 3/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	3.1% 2/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Nervous system disorders Headache	6.0% 5/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	3.5% 3/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	3.1% 2/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Nervous system disorders Dizziness	4.8% 4/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	3.5% 3/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.6% 1/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	3.1% 2/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Gastrointestinal disorders Nausea	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	5.9% 5/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	6.2% 2/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Nervous system disorders Syncope	2.4% 2/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	2.4% 2/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	3.1% 2/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Nervous system disorders Loss of consciousness	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.2% 1/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Nervous system disorders Memory impairment	1.2% 1/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.2% 1/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Nervous system disorders On and off phenomenon	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	2.4% 2/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Vascular disorders Supine hypertension	1.2% 1/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Nervous system disorders Balance disorder	1.2% 1/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Nervous system disorders Burning sensation	1.2% 1/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Nervous system disorders Dizziness exertional	1.2% 1/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Nervous system disorders Dizziness postural	1.2% 1/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Nervous system disorders Dyskinesia	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	3.1% 1/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Nervous system disorders Hypokinesia	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	3.1% 1/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Nervous system disorders Multiple system atrophy	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.2% 1/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Nervous system disorders Oromandibular dystonia	1.2% 1/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Nervous system disorders Presyncope	1.2% 1/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.6% 1/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Nervous system disorders Radial nerve palsy	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.2% 1/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Nervous system disorders Restless legs syndrome	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.2% 1/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Nervous system disorders Somnolence	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.2% 1/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Nervous system disorders Spasmodic dysphonia	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	3.1% 1/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Nervous system disorders Speech disorder	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.2% 1/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.6% 1/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Nervous system disorders Tremor	1.2% 1/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Infections and infestations COVID-19	1.2% 1/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.2% 1/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.6% 1/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Infections and infestations Nasopharyngitis	1.2% 1/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.2% 1/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	3.1% 1/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Infections and infestations Conjunctivitis	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.2% 1/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Infections and infestations Oral candidiasis	1.2% 1/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Infections and infestations Pharyngitis streptococcal	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.2% 1/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Infections and infestations Rhinitis	1.2% 1/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Infections and infestations Tooth abscess	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.2% 1/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Infections and infestations Urinary tract infection bacterial	1.2% 1/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Infections and infestations Viral upper respiratory tract infection	1.2% 1/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Gastrointestinal disorders Constipation	2.4% 2/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	4.7% 4/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.6% 1/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Gastrointestinal disorders Diarrhoea	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.2% 1/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.6% 1/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Gastrointestinal disorders Dry mouth	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.2% 1/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	3.1% 1/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Gastrointestinal disorders Flatulence	1.2% 1/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.2% 1/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.6% 1/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Gastrointestinal disorders Inguinal hernia	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.2% 1/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Gastrointestinal disorders Retching	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.2% 1/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Gastrointestinal disorders Toothache	1.2% 1/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Gastrointestinal disorders Vomiting	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.2% 1/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Psychiatric disorders Anxiety	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	3.5% 3/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Psychiatric disorders Depression	1.2% 1/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	2.4% 2/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Psychiatric disorders Insomnia	2.4% 2/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	3.1% 1/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Psychiatric disorders Hallucination	1.2% 1/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	3.1% 1/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Psychiatric disorders Agitation	1.2% 1/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Psychiatric disorders Bruxism	1.2% 1/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Psychiatric disorders Confusional state	1.2% 1/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Psychiatric disorders Hallucination, visual	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.2% 1/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Psychiatric disorders Hypomania	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.2% 1/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Psychiatric disorders Mental status changes	1.2% 1/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Psychiatric disorders Panic attack	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.2% 1/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Psychiatric disorders Sleep disorder	1.2% 1/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Skin and subcutaneous tissue disorders Hyperhidrosis	1.2% 1/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	3.5% 3/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.6% 1/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Skin and subcutaneous tissue disorders Pruritus	1.2% 1/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	2.4% 2/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Skin and subcutaneous tissue disorders Rash	1.2% 1/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.2% 1/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	3.1% 1/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Skin and subcutaneous tissue disorders Erythema	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.2% 1/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Skin and subcutaneous tissue disorders Hair growth rate abnormal	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.2% 1/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Skin and subcutaneous tissue disorders Hand dermatitis	1.2% 1/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Skin and subcutaneous tissue disorders Palmar erythema	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	3.1% 1/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Skin and subcutaneous tissue disorders Rash pruritic	1.2% 1/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
General disorders Oedema peripheral	1.2% 1/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	2.4% 2/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
General disorders Pyrexia	3.6% 3/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
General disorders Fatigue	1.2% 1/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.2% 1/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	3.1% 2/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
General disorders Chest pain	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.2% 1/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
General disorders Discomfort	1.2% 1/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
General disorders Gait disturbance	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.2% 1/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.6% 1/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
General disorders Malaise	1.2% 1/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
General disorders Pain	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	3.1% 1/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
General disorders Peripheral swelling	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.2% 1/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Injury, poisoning and procedural complications Contusion	1.2% 1/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.2% 1/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	3.1% 1/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Injury, poisoning and procedural complications Fall	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.2% 1/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	6.2% 2/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.6% 1/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.6% 1/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Injury, poisoning and procedural complications Arthropod bite	1.2% 1/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Injury, poisoning and procedural complications Hand fracture	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.2% 1/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Injury, poisoning and procedural complications Skin laceration	1.2% 1/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Investigations Blood creatine phosphokinase increased	1.2% 1/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	2.4% 2/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Investigations Blood creatinine increased	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	2.4% 2/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Investigations Blood lactate dehydrogenase increased	1.2% 1/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Investigations Blood pressure increased	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	3.1% 1/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Investigations Blood urea increased	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.2% 1/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Investigations Colonoscopy	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	3.1% 1/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Investigations Glomerular filtration rate abnormal	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	3.1% 1/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Investigations Glomerular filtration rate decreased	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.2% 1/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Investigations Haematocrit decreased	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.2% 1/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Investigations Platelet count decreased	1.2% 1/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Investigations Troponin increased	1.2% 1/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.2% 1/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	3.1% 1/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.2% 1/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	3.1% 1/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Musculoskeletal and connective tissue disorders Neck pain	1.2% 1/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.2% 1/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.6% 1/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Musculoskeletal and connective tissue disorders Arthralgia	1.2% 1/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Musculoskeletal and connective tissue disorders Groin pain	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.2% 1/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Musculoskeletal and connective tissue disorders Joint swelling	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	3.1% 1/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.2% 1/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.6% 1/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.2% 1/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Musculoskeletal and connective tissue disorders Osteoporosis	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.2% 1/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Musculoskeletal and connective tissue disorders Tendonitis	1.2% 1/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Vascular disorders Orthostatic hypotension	1.2% 1/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.2% 1/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Vascular disorders Hypertension	1.2% 1/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.2% 1/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Vascular disorders Flushing	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.2% 1/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Vascular disorders Hot flush	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.2% 1/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Vascular disorders White coat hypertension	1.2% 1/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.4% 2/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	2.4% 2/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Respiratory, thoracic and mediastinal disorders Cough	1.2% 1/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	3.1% 1/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Eye disorders Vision blurred	1.2% 1/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.2% 1/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Eye disorders Conjunctival haemorrhage	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.2% 1/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Eye disorders Diplopia	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.2% 1/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Eye disorders Hypermetropia	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.2% 1/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Eye disorders Open angle glaucoma	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.2% 1/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Eye disorders Vitreous floaters	1.2% 1/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Renal and urinary disorders Calculus urinary	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.2% 1/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Renal and urinary disorders Haematuria	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.2% 1/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Renal and urinary disorders Nocturia	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.2% 1/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Renal and urinary disorders Pollakiuria	1.2% 1/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Renal and urinary disorders Urinary hesitation	1.2% 1/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Renal and urinary disorders Urinary retention	1.2% 1/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.6% 1/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Blood and lymphatic system disorders Anaemia	2.4% 2/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.2% 1/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Blood and lymphatic system disorders Lymphopenia	1.2% 1/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.2% 1/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Cardiac disorders Atrioventricular block first degree	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.2% 1/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Cardiac disorders Bundle branch block left	1.2% 1/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Cardiac disorders Tachycardia	1.2% 1/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Metabolism and nutrition disorders Decreased appetite	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	2.4% 2/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Metabolism and nutrition disorders Hyperkalaemia	1.2% 1/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Metabolism and nutrition disorders Hypokalaemia	1.2% 1/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Metabolism and nutrition disorders Hypomagnesaemia	1.2% 1/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Metabolism and nutrition disorders Hyponatraemia	1.2% 1/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Metabolism and nutrition disorders Vitamin D deficiency	1.2% 1/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.6% 1/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Immune system disorders Allergy to vaccine	1.2% 1/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Immune system disorders Seasonal allergy	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	3.1% 1/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Reproductive system and breast disorders Gynaecomastia	1.2% 1/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Reproductive system and breast disorders Priapism	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.2% 1/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Hepatobiliary disorders Cholecystitis chronic	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	3.1% 1/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Haemangioma	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	3.1% 1/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Product Issues Device occlusion	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.2% 1/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Social circumstances Walking disability	1.2% 1/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Infections and infestations Bronchitis	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.6% 1/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.6% 1/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Infections and infestations Upper respiratory tract infection	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.6% 1/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Nervous system disorders Migraine with aura	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.6% 1/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Nervous system disorders Parkinson's disease	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.6% 1/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Nervous system disorders Radiculopathy	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.6% 1/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
General disorders Asthenia	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.6% 1/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
General disorders Hyperthermia	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.6% 1/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Injury, poisoning and procedural complications Back injury	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.6% 1/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Injury, poisoning and procedural complications Limb injury	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.6% 1/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Injury, poisoning and procedural complications Post procedural discomfort	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.6% 1/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Injury, poisoning and procedural complications Soft tissue injury	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.6% 1/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Gastrointestinal disorders Large intestine polyp	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.6% 1/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Gastrointestinal disorders Rectal haemorrhage	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.6% 1/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Musculoskeletal and connective tissue disorders Mobility decreased	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.6% 1/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.6% 1/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Vascular disorders Diastolic hypertension	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.6% 1/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Vascular disorders Hypotension	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.6% 1/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Renal and urinary disorders Calculus bladder	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.6% 1/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Blood and lymphatic system disorders Anaemia vitamin B12 deficiency	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.6% 1/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Cardiac disorders Myocardial infarction	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.6% 1/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Investigations Cystoscopy	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.6% 1/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Reproductive system and breast disorders Endometrial hyperplasia	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.6% 1/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Reproductive system and breast disorders Ovarian cyst	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.6% 1/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Reproductive system and breast disorders Uterine enlargement	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.6% 1/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.
Nervous system disorders Bulbar palsy	0.00% 0/83 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	1.2% 1/85 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/32 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.	0.00% 0/64 • OL Treatment Period: Day 1 to Week 16 (plus a 2 week follow-up period); RW Treatment Period: Week 16 to Week 24 (plus a 2 week follow-up period) OL Safety Analysis Set: all enrolled participants who received at least 1 dose of ampreloxetine during the OL period. RW Treatment Safety Analysis Set: all randomized participants who received at least 1 dose of study medication (ampreloxetine or placebo) following randomization. The Safety Analysis Set and FAS were identical for the RW treatment period.

Additional Information

Medical Monitor

Theravance Biopharma Ireland Limited

Phone: 855 633 8479

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
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