Delving into the Latest Updates on Ampreloxetine hydrochloride with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Ampreloxetine (USAN/INN), TD 9855, TD-9855

+ [1]

Target

NET x SERT

Mechanism

NET inhibitors(Norepinephrine transporter inhibitors), SERT inhibitors(Serotonin transporter inhibitors)

Therapeutic Areas

Nervous System DiseasesCardiovascular DiseasesEndocrinology and Metabolic Disease+ [1]

Active Indication

Multiple System AtrophyNeurogenic Orthostatic Hypotension

Inactive Indication

Attention Deficit Disorder With HyperactivityFibromyalgiaMultiple System Atrophy (MSA) With Orthostatic Hypotension+ [3]

Originator Organization

Theravance Biopharma, Inc.

Active Organization

Theravance Biopharma, Inc.

Inactive Organization-

Drug Highest PhasePhase 3

First Approval Date-

RegulationOrphan Drug (US)

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Structure

Molecular FormulaC18H19ClF3NO

InChIKeyRVUPIJWDTBFULZ-UHFFFAOYSA-N

CAS Registry1227056-87-2

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).

Start Date27 Jun 2023

Sponsor / Collaborator

Theravance Biopharma, Inc.

NCT04688632 / CompletedPhase 1

A Phase 1, Randomized, Double-Blind, Placebo- and Positive-Controlled, Thorough QT Study to Evaluate the Effect of Ampreloxetine on Cardiac Repolarization in Healthy Subjects

A double-blind study to characterize the effect of ampreloxetine on cardiac repolarization in healthy subjects.

Start Date18 Jan 2021

Sponsor / Collaborator

Theravance Biopharma, Inc.

NCT04200573 / CompletedPhase 1

A Phase 1, Open-Label, Single Dose Study to Evaluate the Pharmacokinetics of Ampreloxetine Following a Single-dose in Subjects With Mild, Moderate, and Severe Hepatic Impairment and in Matching Healthy Subjects

An open-label study to characterize the effects of mild, moderate, and severe Hepatic Impairment (HI) on the pharmacokinetics (PK) of ampreloxetine following a single oral dose in comparison with healthy volunteers with normal hepatic function.

Start Date13 Jan 2020

Sponsor / Collaborator

Theravance Biopharma, Inc.

100 Clinical Results associated with Ampreloxetine hydrochloride

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100 Translational Medicine associated with Ampreloxetine hydrochloride

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100 Patents (Medical) associated with Ampreloxetine hydrochloride

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7

Literatures (Medical) associated with Ampreloxetine hydrochloride

01 Jul 2024·Clinical pharmacology and therapeutics

Hepatic Dysfunction Quantified by HepQuant DuO Outperforms Child‐Pugh Classification in Predicting the Pharmacokinetics of Ampreloxetine

Article

Author: McRae, Michael P. ; Everson, Gregory T. ; Giovinazzo, Hugh ; Bourdet, David L. ; Kanodia, Jitendra ; Helmke, Steve M. ; Yates, Wayne

HepQuant tests quantify liver function from clearance of deuterium‐ and 13C‐labeled cholates administered either intravenously and orally (SHUNT) or orally (DuO). Hepatic impairment studies have relied on clinical or laboratory criteria like Child‐Pugh classification to categorize the degree of hepatic dysfunction. We compared HepQuant tests with Child‐Pugh classification in predicting the pharmacokinetics of ampreloxetine. Twenty‐one subjects with hepatic impairment (8 Child‐Pugh A, 7 Child‐Pugh B, and 6 Child‐Pugh C), and 10 age‐ and sex‐matched controls were studied. The pharmacokinetics of ampreloxetine were measured after oral administration of a single dose of 10 mg. Disease severity index (DSI), portal‐systemic shunting (SHUNT%), hepatic reserve, and hepatic filtration rates (HFRs) were measured from serum samples obtained after intravenous administration of [24‐13C]‐cholate and oral administration of [2,2,4,4‐2H]cholate. Ampreloxetine plasma exposure (AUC0‐inf) was similar to controls in Child‐Pugh A, increased 1.7‐fold in subjects with Child‐Pugh B, and 2.5‐fold in subjects with Child‐Pugh C and correlated with both Child‐Pugh score and HepQuant parameters. The variability observed in ampreloxetine exposure (AUC0‐inf) in subjects with moderate (Child‐Pugh B) and severe hepatic impairment (Child‐Pugh C) was explained by HepQuant parameters. Multivariable regression models demonstrated that DSI, SHUNT%, and Hepatic Reserve from SHUNT and DuO were superior predictors of ampreloxetine exposure (AUC0‐inf) compared to Child‐Pugh score. HepQuant DSI, SHUNT%, and hepatic reserve were more useful predictors of drug exposure than Child‐Pugh class for ampreloxetine and thus may better optimize dose recommendations in patients with liver disease. The simple‐to‐administer, oral‐only DuO version of the HepQuant test could enhance clinical utility.

11 May 2023·Cureus

Ampreloxetine Versus Droxidopa in Neurogenic Orthostatic Hypotension: A Comparative Review

Review

Author: Hoxhaj, Pranvera ; Goyal, Abhishek ; Razzaq, Waleed ; Khawaja, Imran ; Gupta, Ishita ; Khan, Wajiha ; Botlaguduru, Deepti ; Shah, Shruti ; Collado, Gaudy F ; Sadeghzadegan, Amirali ; Abdin, Zain U ; Singh, Saumya ; Muyolema Arce, Veronica E

Neurogenic orthostatic hypotension (nOH) is a disabling problem of autonomic dysfunction in patients with Parkinson's disease, which is associated with poor quality of life and higher mortality rates. The purpose of this literature review was to explore and compare the efficacy and safety of droxidopa (an existing treatment) and ampreloxetine (a newer medication) in the treatment of nOH. We used a mixed-method literature review that addresses the epidemiology, pathophysiology, and pharmacological and non-pharmacological management of nOH in Parkinson's disease in a general way, with a more exploratory approach to droxidopa- and ampreloxetine-controlled trial studies. We included a total of 10 studies of randomized controlled trials with eight studies focused on droxidopaand two studies focused on ampreloxetine. These two drugs were analyzed and compared based on the collected individual study results. Treatment of nOH in Parkinson's disease patients with droxidopa or ampreloxetine showed clinically meaningful and statistically significant improvements relative to placebo on the components of the OHSA (Orthostatic Hypotension Symptom Assessment) composite score and OHDAS (Orthostatic Hypotension Daily Activity Scale composite scores) composite score. Droxidopa had an improved effect on daily activities, with an associated increase in standing systolic blood pressure (BP), but the long-term efficacy of droxidopa has not been documented. Standing systolic BP was maintained by ampreloxetine and worsened after the withdrawal phase. This highlights the importance of conducting further research which will help us to improve the therapeutic approach for patients with nOH and Parkinson's disease.

01 Dec 2021·Clinical autonomic research : official journal of the Clinical Autonomic Research SocietyQ3 · MEDICINE

Safety and efficacy of ampreloxetine in symptomatic neurogenic orthostatic hypotension: a phase 2 trial

Q3 · MEDICINE

Article

Author: Norcliffe-Kaufmann, Lucy ; Shibao, Cyndya A ; Kanodia, Jitendra ; Haumann, Brett ; Wang, Whedy ; Biaggioni, Italo ; Vickery, Ross ; Kaufmann, Horacio

Abstract:

Purpose:

In neurogenic orthostatic hypotension, blood pressure falls when upright owing to impaired release of norepinephrine, leading to dizziness. Ampreloxetine, a selective norepinephrine reuptake inhibitor, increases circulating norepinephrine levels. This study explored the safety of ampreloxetine and its effect on blood pressure and symptoms in patients with neurogenic orthostatic hypotension.

Methods:

A multicenter ascending-dose trial (range 1–20 mg, Part A) was followed by a 1 day, double-blind, randomized, placebo-controlled study (median dose 15 mg, Part B). Eligible patients then enrolled in a 20-week, open-label, steady-state extension phase (median dose 10 mg, Part C) followed by a 4-week withdrawal. Assessments included the Orthostatic Hypotension Symptom Assessment Scale (item 1), supine/seated/standing blood pressure, and safety.

Results:

Thirty-four patients (age 66 ± 8 years, 22 men) were enrolled. Part A: The proportion of participants with a positive response (i.e., increase from baseline in seated systolic blood pressure of ≥ 10 mmHg) was greater with the 5 and 10 mg ampreloxetine doses than with placebo or other active ampreloxetine doses. Part B: Seated blood pressure increased 15.7 mmHg 4 h after ampreloxetine and decreased 14.2 mmHg after placebo [least squares mean difference (95% CI) 29.9 mmHg (7.6–52.3); P = 0.0112]. Part C: Symptoms of dizziness/lightheadedness improved 3.1 ± 3.0 points from baseline and standing systolic blood pressure increased 11 ± 12 mmHg. After 4 weeks of withdrawal, symptoms returned to pretreatment levels. The effect of ampreloxetine on supine blood pressure was minimal throughout treatment duration.

Conclusion:

Ampreloxetine was well tolerated and improved orthostatic symptoms and seated/standing blood pressure with little change in supine blood pressure.

Trial registration:

NCT02705755 (first posted March 10, 2016).

53

News (Medical) associated with Ampreloxetine hydrochloride

17 Dec 2024

·www.prnewswire.com

Theravance Biopharma to Conduct Investor Meetings During the J.P. Morgan 43rd Annual Healthcare Conference

DUBLIN, Dec. 17, 2024 /PRNewswire/ -- Theravance Biopharma, Inc. ("Theravance Biopharma" or the "Company") (NASDAQ: TBPH) today announced that members of its management team will hold investor meetings during the 43rd Annual J.P. Morgan Healthcare Conference, January 13-16, 2025, in San Francisco, CA. To request a one-on-one meeting with the Theravance Biopharma management team, please contact us at [email protected]. About Theravance Biopharma Theravance Biopharma, Inc.'s focus is to deliver Medicines that Make a Difference® in people's lives. In pursuit of its purpose, Theravance Biopharma leverages decades of expertise, which has led to the development of FDA-approved YUPELRI® (revefenacin) inhalation solution indicated for the maintenance treatment of patients with chronic obstructive pulmonary disease (COPD). Ampreloxetine, its late-stage investigational once-daily norepinephrine reuptake inhibitor in development for symptomatic neurogenic orthostatic hypotension (nOH) in patients with Multiple System Atrophy (MSA), has the potential to be a first in class therapy effective in treating a constellation of cardinal symptoms in MSA patients. The Company is committed to creating/driving shareholder value. For more information, please visit . THERAVANCE BIOPHARMA®, THERAVANCE® and the Cross/Star logo are registered trademarks of the Theravance Biopharma group of companies (in the U.S. and certain other countries). YUPELRI® is a registered trademark of Mylan Specialty L.P., a Viatris company. Trademarks, trade names or service marks of other companies appearing in this press release are the property of their respective owners. Contact: [email protected] 650-808-4045 SOURCE Theravance Biopharma, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Drug Approval

20 Nov 2024

·www.prnewswire.com

Theravance Biopharma to Participate in an Upcoming Investor Conference

DUBLIN, Nov. 20, 2024 /PRNewswire/ -- Theravance Biopharma, Inc. (NASDAQ: TBPH) will participate in a Fireside Chat at the 7th Annual Evercore HealthCONx Conference on Tuesday, December 3 at 11:15 am EST (8:15 am PST/4:15 pm GMT) and will be hosting in-person meetings with the investment community at the conference. Webcast of the event may be accessed by visiting Theravance.com, under the Investors section, Events and Presentations. Replay of the webcast will be archived on the Company's website for 30 days. About Theravance Biopharma Theravance Biopharma, Inc.'s focus is to deliver Medicines that Make a Difference® in people's lives. In pursuit of its purpose, Theravance Biopharma leverages decades of expertise, which has led to the development of FDA-approved YUPELRI® (revefenacin) inhalation solution indicated for the maintenance treatment of patients with chronic obstructive pulmonary disease (COPD). Ampreloxetine, its late-stage investigational once-daily norepinephrine reuptake inhibitor in development for symptomatic neurogenic orthostatic hypotension (nOH) in patients with Multiple System Atrophy (MSA), has the potential to be a first in class therapy effective in treating a constellation of cardinal symptoms in MSA patients. The Company is committed to creating/driving shareholder value. For more information, please visit . THERAVANCE BIOPHARMA®, THERAVANCE® and the Cross/Star logo are registered trademarks of the Theravance Biopharma group of companies (in the U.S. and certain other countries). YUPELRI® is a registered trademark of Mylan Specialty L.P., a Viatris company. Trademarks, trade names or service marks of other companies appearing in this press release are the property of their respective owners. Contact: [email protected] 650-808-4045 SOURCE Theravance Biopharma, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Drug Approval

24 Oct 2024

·www.prnewswire.com

Theravance Biopharma to Report Third Quarter 2024 Financial Results on November 12, 2024

DUBLIN, Oct. 24, 2024 /PRNewswire/ -- Theravance Biopharma, Inc. (NASDAQ: TBPH) will report its third quarter 2024 financial results and provide a business update after market close on Tuesday, November 12, 2024. An accompanying conference call and simultaneous webcast will be hosted at 5:00 pm EST (2:00 pm PST/10:00 pm GMT) that day. Conference Call Information To participate in the live call by telephone, please pre-register here. Those interested in listening to the conference call live via the internet may do so by visiting Theravance Biopharma's website at , under the Investors section, Events and Presentations. A replay of the webcast will be available on Theravance Biopharma's website for 30 days through December 12, 2024. About Theravance Biopharma Theravance Biopharma, Inc.'s focus is to deliver Medicines that Make a Difference® in people's lives. In pursuit of its purpose, Theravance Biopharma leverages decades of expertise, which has led to the development of FDA-approved YUPELRI® (revefenacin) inhalation solution indicated for the maintenance treatment of patients with chronic obstructive pulmonary disease (COPD). Ampreloxetine, its late-stage investigational once-daily norepinephrine reuptake inhibitor in development for symptomatic neurogenic orthostatic hypotension (nOH) in patients with Multiple System Atrophy (MSA), has the potential to be a first in class therapy effective in treating a constellation of cardinal symptoms in MSA patients. The Company is committed to creating/driving shareholder value. For more information, please visit . THERAVANCE BIOPHARMA®, THERAVANCE® and the Cross/Star logo are registered trademarks of the Theravance Biopharma group of companies (in the U.S. and certain other countries). YUPELRI® is a registered trademark of Mylan Specialty L.P., a Viatris company. Trademarks, trade names or service marks of other companies appearing in this press release are the property of their respective owners. Contact: [email protected] 650-808-4045 SOURCE Theravance Biopharma, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Drug ApprovalFinancial Statement

100 Deals associated with Ampreloxetine hydrochloride

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External Link

KEGG	Wiki	ATC	Drug Bank
D11688	-	-	DB15348

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Multiple System Atrophy	Phase 3	US	Theravance Biopharma, Inc.	22 Feb 2019
Multiple System Atrophy	Phase 3	AU	Theravance Biopharma, Inc.	22 Feb 2019
Multiple System Atrophy	Phase 3	AT	Theravance Biopharma, Inc.	22 Feb 2019
Multiple System Atrophy	Phase 3	BG	Theravance Biopharma, Inc.	22 Feb 2019
Multiple System Atrophy	Phase 3	CA	Theravance Biopharma, Inc.	22 Feb 2019
Multiple System Atrophy	Phase 3	DK	Theravance Biopharma, Inc.	22 Feb 2019
Multiple System Atrophy	Phase 3	EE	Theravance Biopharma, Inc.	22 Feb 2019
Multiple System Atrophy	Phase 3	FR	Theravance Biopharma, Inc.	22 Feb 2019
Multiple System Atrophy	Phase 3	DE	Theravance Biopharma, Inc.	22 Feb 2019
Multiple System Atrophy	Phase 3	HU	Theravance Biopharma, Inc.	22 Feb 2019

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


MDS2023	Phase 3	-	72	Ampreloxetine	mkmlkajvfp(qdvbjeblkd) = uymryzescd lbvjakctwu (xmvgsiafco )	Positive	27 Aug 2023
				Placebo	mkmlkajvfp(qdvbjeblkd) = ghzddbuipa lbvjakctwu (xmvgsiafco )
Phase 3 ampreloxetine program (MDS2023)	Phase 3	Multiple System Atrophy	68	Ampreloxetine	pnassajaun(mgljlzabcz) = xnrzizdqlp uvtwtblqwk (ensqonnglh )	Positive	27 Aug 2023
NCT03829657 (REDWOOD, CTgov)	Phase 3	Pure Autonomic Failure \| Multiple System Atrophy \| Neurogenic Orthostatic Hypotension ... View more	203	placebo (RW Treatment Period: Placebo)	axvscfnekq(gttaelcbet) = ijgcncnhnn eozyivkptd (yrfrvffxhf, ypqzwdcvfg - knrnzjurta) View more	-	20 Jan 2023
				Ampreloxetine (RW Treatment Period: Ampreloxetine)	axvscfnekq(gttaelcbet) = plzmwxzaaw eozyivkptd (yrfrvffxhf, tzzfjdears - zwuqotdsae) View more
NCT04095793 (OAK, CTgov)	Phase 3	Pure Autonomic Failure \| Neurogenic Orthostatic Hypotension \| Orthostatic hypertension	110	ampreloxetine	kwyzjhtezw(vevdfunbbx) = pgdbtvcggl tsbvuuiqcn (kqzsktfmjf, xbrllyphtf - goqvgaryfn) View more	-	30 Nov 2022
NCT03829657 (REDWOOD, Corporate Publications) Manual	Phase 3	Neurogenic Orthostatic Hypotension	-	Ampreloxetine	yjpamcocmw(uueyskywwv): difference = -1.6 (95% CI, -2.7 to -0.5) View more	Positive	02 Nov 2022
				Placebo
NCT03750552 (SEQUOIA, CTgov)	Phase 3	Pure Autonomic Failure \| Neurogenic Orthostatic Hypotension \| Orthostatic hypertension	195	ampreloxetine (Ampreloxetine)	pafirfvaab(xzmsamwncz) = ybnvvlalfq hnmeuevlac (hrtskywleh, hlctmatwfe - wmpigqzzlg) View more	-	14 Sep 2022
				Placebo (Placebo)	pafirfvaab(xzmsamwncz) = qgkvvjvfus hnmeuevlac (hrtskywleh, xrzyuyxwto - rlnjkfqlqj) View more
NCT01458340 (CTgov)	Phase 2	Attention Deficit Disorder With Hyperactivity	295	Placebo	xhekjforol(cxmcectqta) = cvvgpyvivm jwlqkzkmae (ylcsmbldtk, tfuxqoymuz - fcdszgzfon) View more	-	14 Mar 2022
NCT01693692 (CTgov)	Phase 2	Fibromyalgia	392	Placebo (Placebo)	vtcczndtgu(adkgosyump) = lsbkqsjvxb cqirhkstye (bevhfukpec, qcfnvqpggj - vatljdswpt) View more	-	04 Mar 2022
				TD-9855 Group 1 (TD-9855 Group 1)	vtcczndtgu(adkgosyump) = nhozitwgot cqirhkstye (bevhfukpec, dpihwiutyf - dcntwavmts) View more
NCT02705755 (Pubmed \| Clin Auton Res)	Phase 2	Neurogenic Orthostatic Hypotension	34	Ampreloxetine	dxxcitotsw(emlvntzkxa) = dqaiypdaxl kwwderjhzi (vkpejzfrzh )	-	17 Oct 2021
				Placebo	-
EAN2020	Not Applicable	-	-	Ampreloxetine 3-20mg	ljtslilxui(rfedurahkp) = qagwsiewdx sdubniuzmh (peqwufecuh )	-	22 May 2020