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Ampreloxetine

Phase 3

Symptomatic Neurogenic Orthostatic Hypotension | Small molecule | Neurology |Theravance Biopharma, Inc.|Last Updated: Sep 5, 2025

Target and mechanism

Molecular targetSLC6A2
Target classInhibitor
ModalitySmall molecule

Success Probability

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Market & Valuation

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Trial Design

RandomizedDouble-BlindPLACEBO_CONTROLLEDDMC
Total Trials2
Total Enrollment297

FDA Designations

ORPHAN_DRUG

Clinical trial landscape

Ampreloxetine · 3 trials · 4 indications

Phase 3 2Phase 1 1
NCT05696717Phase 3 Efficacy and Durability of Ampreloxetine for the Treatment of Symptomatic nOH in Participants With Multiple System AtrophySymptomatic Neurogenic Orthostatic Hypotension
ACTIVE NOT_RECRUITING102 Analytics
NCT03750552Clinical Effect of Ampreloxetine (TD-9855) for Treating Symptomatic nOH in Subjects With Primary Autonomic FailureSymptomatic Neurogenic Orthostatic Hypotension
COMPLETED195 Analytics
PHASE3ACTIVE NOT_RECRUITING
Phase 3 Efficacy and Durability of Ampreloxetine for the Treatment of Symptomatic nOH in Participants With Multiple System Atrophy
Symptomatic Neurogenic Orthostatic HypotensionUnlock trial analytics
PHASE3COMPLETED
Clinical Effect of Ampreloxetine (TD-9855) for Treating Symptomatic nOH in Subjects With Primary Autonomic Failure
Symptomatic Neurogenic Orthostatic HypotensionUnlock trial analytics

Study Endpoints

Primary Endpoints

Change in OHSA composite score at Week 8 during the double-blind RW period
8-week randomized withdrawal period (Week 12 to Week 20)

Score change from baseline on the composite of Questions 1 - 6 of the Orthostatic Hypotension Symptom Assessment (OHSA).

Change From Baseline in Orthostatic Hypotension Symptom Assessment (OHSA) Question #1 Score at Week 4
Baseline and Week 4

OHSA is an assessment of the severity of symptoms from low blood pressure. OHSA is a 6 question symptom assessment scale where each question uses an 11 point scale from 0 to 10, with 0 indicating no symptoms/no interference and 10 indicating the worst possible symptoms/complete interference. Question #1 assesses dizziness, lightheadedness, feeling faint, or feeling like you might blackout. A mean negative change from baseline indicates a better outcome.

Plasma AUC0-t
Plasma AUC0-t will be measured Day 1 to Day 15

Estimation of Area under the concentration-time curve, from time zero to the last measured time point

Plasma AUC0-inf
Plasma AUC0-inf will be measured from Day 1 to Day 15

Estimation of AUC from time zero extrapolated to infinity

Plasma Cmax
up to Day 21

Estimation of maximum observed plasma concentration

Secondary Endpoints

Change from baseline in OHDAS item 1 (activities that require standing for a short time) at Week 8 post randomization
8-week randomized withdrawal period (Week 12 to Week 20)
Change from baseline in OHDAS item 3 (activities that require walking for a short time) at Week 8 post randomization
8-week randomized withdrawal period (Week 12 to Week 20)
Change From Baseline in Orthostatic Hypotension Symptom Assessment (OHSA) Composite Score at Week 4
Baseline and Week 4
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Study Design & Arms

AllocationRANDOMIZED
MaskingQUADRUPLE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
Ampreloxetine (Open Label)ACTIVE_COMPARATORParticipants will receive ampreloxetine as a single, oral, daily dose of active drug for 12 weeks.
Ampreloxetine (Randomized Withdrawal)PLACEBO_COMPARATORAfter completing the open label, participants are randomized to either ampreloxetine or placebo receiving a single, oral, daily dose of active drug or placebo for a further 8 weeks.
Long-Term Extension PeriodACTIVE_COMPARATORParticipants will receive ampreloxetine as a single, oral, daily dose of active drug for 104 weeks.
ampreloxetineEXPERIMENTALParticipants randomized to ampreloxetine will receive a single, oral, daily dose of active drug for 4 weeks.
PlaceboPLACEBO_COMPARATORParticipants randomized to Placebo will receive a single, oral, daily dose of placebo for 4 weeks.
Normal Hepatic FunctionEXPERIMENTALAmpreloxetine Dose A single dose administration to subjects with normal hepatic function
Mild Hepatic FunctionEXPERIMENTALAmpreloxetine Dose A single dose administration to subjects with mild hepatic impairment
Moderate Hepatic FunctionEXPERIMENTALAmpreloxetine Dose A single dose administration to subjects with moderate hepatic impairment
Severe Hepatic FunctionEXPERIMENTALAmpreloxetine Dose A single dose administration to subjects with severe hepatic impairment

Interventions

NameTypeDescription
AmpreloxetineDRUGOral tablet, QD
PlaceboDRUGOral tablet, QD
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Eligibility Criteria

Age Range30 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites79

Inclusion Criteria: * Participant is male or female and at least 30 years old. * Participant has a diagnosis of possible or probable MSA of the Parkinsonian subtype (MSA-P) or cerebellar subtype (MSA-C) according to The Gilman Criteria (2008). * Participant has a diagnosis of possible or probable M...

Countries:United StatesArgentinaAustraliaAustriaBrazilCanadaDenmarkEstoniaFranceGermanyHungaryIsraelItalyNew ZealandPolandPortugalSerbiaSpainTaiwanUnited KingdomBulgariaRussiaUkraine
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Frequently asked questions about Ampreloxetine

What is Ampreloxetine used for?

Ampreloxetine is an investigational small molecule being developed for symptomatic neurogenic orthostatic hypotension (nOH), a condition of low blood pressure upon standing. It is also being studied in symptomatic neurogenic orthostatic hypertension. The drug is in clinical development and has not been approved by the FDA.

Who is developing Ampreloxetine?

Ampreloxetine is being developed by Theravance Biopharma, Inc., a biopharmaceutical company traded on the Nasdaq under the ticker TBPH. The company is conducting clinical trials to evaluate the drug for symptomatic neurogenic orthostatic hypotension.

What phase is Ampreloxetine in?

Ampreloxetine is in Phase 3 clinical development for symptomatic neurogenic orthostatic hypotension. It has also completed a Phase 1 study. The drug is investigational and has not received FDA approval.

What clinical trials is Ampreloxetine in?

Ampreloxetine has been studied in several trials. NCT03750552, a completed Phase 3 study, evaluated the drug in 195 participants with symptomatic neurogenic orthostatic hypotension. NCT04200573, a completed Phase 1 study, assessed its pharmacokinetics in 31 participants. NCT05696717, an active Phase 3 trial, is studying the drug in 102 participants with multiple system atrophy.

Does Ampreloxetine have FDA orphan drug designation?

Yes, Ampreloxetine has received orphan drug designation from the FDA. This designation is granted to drugs intended to treat rare diseases, which can provide certain development incentives.

Is Ampreloxetine the same as TD-9855?

Yes, Ampreloxetine is also known as TD-9855. Clinical trial records refer to the drug by both names, with TD-9855 appearing in earlier study titles and Ampreloxetine used in later ones.