Clinical Trials/NCT05696717

NCT05696717

Active, not recruiting

Phase 3

A Phase 3, Multi-center, Randomized Withdrawal and Long Term Extension Study of Ampreloxetine for the Treatment of Symptomatic Neurogenic Orthostatic Hypotension in Participants With Multiple System Atrophy

Theravance Biopharma77 sites in 11 countries102 target enrollmentJune 27, 2023

ConditionsSymptomatic Neurogenic Orthostatic Hypotension MSA - Multiple System Atrophy

InterventionsAmpreloxetine Placebo

DrugsAmpreloxetine Placebo

Overview

Phase: Phase 3
Intervention: Ampreloxetine
Conditions: Symptomatic Neurogenic Orthostatic Hypotension
Sponsor: Theravance Biopharma
Enrollment: 102
Locations: 77
Primary Endpoint: Change in OHSA composite score at Week 8 during the double-blind RW period
Status: Active, not recruiting
Last Updated: 7 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials Related News

Overview

Brief Summary

This is a Phase 3, multi-center, randomized withdrawal study to evaluate the efficacy and durability of ampreloxetine in participants with MSA and symptomatic nOH after 20 weeks of treatment. This study includes 4 periods: Screening, open label, randomized withdrawal, and long-term treatment extension (LTE).

Registry

clinicaltrials.gov

Start Date

June 27, 2023

End Date

January 1, 2028

Last Updated

7 months ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Theravance Biopharma

Responsible Party

Sponsor

Eligibility Criteria

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 MSA of the Parkinsonian subtype (MSA-P) or cerebellar subtype (MSA-C) confirmed by the Enrollment Steering Committee (ESC).
•Participant must meet the diagnostic criteria of nOH, as demonstrated by a sustained reduction in BP of ≥20 mmHg (systolic) or ≥10 mmHg (diastolic) within 3 min of standing as part of orthostatic standing test or being tilted up ≥60o from a supine position as determined by a tilt-table test.
•Participant must score ≤4 on UMSARS Part IV at Visit 1 (Screening).
•Participant must score at least a 4 on the OHSA item 1 at Visit 2 (Day 1).
•Participant must be willing to not take any prohibited medications during the study.
•If participant is female, the participant must not be pregnant, breastfeeding, or planning a pregnancy during the course of the study. A woman of childbearing potential must have a documented negative pregnancy test at screening.
•During the study and for 30 days after receiving the last dose of the study drug, females of childbearing potential or males capable of fathering children must agree to use highly effective birth control measures (failure rate \<1% when used consistently and correctly) or agree to abstain from sexual intercourse.
•Participant is willing and able to provide signed and dated written informed consent to -participate prior to initiation of any study related procedures.

Exclusion Criteria

•Participant has a systemic illness known to produce autonomic neuropathy, including, but not limited to, amyloidosis and autoimmune neuropathies. Participant with diabetes mellitus (DM) will be evaluated on a case-by-case basis by the medical monitor and considered ineligible unless they meet all of the following criteria:
•Well controlled type-2 DM in treatment with only oral medications and diet
•HbA1C of ≤7.5% performed during screening or up to 12 weeks before screening
•No clinically evident peripheral neuropathy (e.g., normal sensory examination on peripheral extremities)
•No known retinopathy (e.g., annual ophthalmic exam is sufficient)
•No nephropathy (e.g., absence of albuminuria and GFR \>60).
•Participant has a known intolerance to other NRIs or SNRIs.
•Participant currently uses concomitant antihypertensive medication for the treatment of essential hypertension.
•Participant has used strong CYP1A2 inhibitors or inducers within 7 days or 5 half lives, whichever is longer, prior to Visit 2 (Day 1) or requires concomitant use until the Safety follow-up Visit.
•Participant has changed dose, frequency, or type of prescribed medication for orthostatic hypotension within 7 days prior to Visit 2 (Day 1).

Arms & Interventions

Ampreloxetine (Randomized Withdrawal)

After 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.

Intervention: Ampreloxetine

Ampreloxetine (Open Label)

Participants will receive ampreloxetine as a single, oral, daily dose of active drug for 12 weeks.

Intervention: Ampreloxetine

Ampreloxetine (Randomized Withdrawal)

After 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.

Intervention: Placebo

Long-Term Extension Period

Participants will receive ampreloxetine as a single, oral, daily dose of active drug for 104 weeks.

Intervention: Ampreloxetine

Outcomes

Primary Outcomes

Change in OHSA composite score at Week 8 during the double-blind RW period

Time Frame: 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).

Secondary Outcomes

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))