Ampreloxetine hydrochloride(Ampreloxetine hydrochloride) - 药物靶点：NET x SERT_在研适应症：多系统萎缩，神经源性直立性低血压_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Ampreloxetine (USAN/INN)

+ [1]

靶点

NET x SERT

作用机制

NET抑制剂(去甲肾上腺素转运蛋白抑制剂)、SERT抑制剂(5-羟色胺转运体抑制剂)

治疗领域

神经系统疾病心血管疾病内分泌与代谢疾病+ [1]

在研适应症

多系统萎缩神经源性直立性低血压

非在研适应症

注意缺陷障碍伴多动纤维肌痛多系统萎缩（MSA）性体位性低血压+ [3]

原研机构

Theravance Biopharma, Inc.

在研机构

Theravance Biopharma, Inc.

非在研机构-

最高研发阶段临床3期

首次获批日期-

最高研发阶段(中国)-

特殊审评孤儿药 (美国)

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结构/序列

分子式C18H18F3NO

InChIKeyTZIALEBTHQWNAO-UHFFFAOYSA-N

CAS号1227056-84-9

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关联

10

项与 Ampreloxetine hydrochloride 相关的临床试验

NCT05696717

/ Recruiting临床3期

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

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).

开始日期2023-06-27

申办/合作机构

Theravance Biopharma, Inc.

NCT04688632

/ Completed临床1期

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.

开始日期2021-01-18

申办/合作机构

Theravance Biopharma, Inc.

NCT04200573

/ Completed临床1期

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.

开始日期2020-01-13

申办/合作机构

Theravance Biopharma, Inc.

100 项与 Ampreloxetine hydrochloride 相关的临床结果

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100 项与 Ampreloxetine hydrochloride 相关的转化医学

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100 项与 Ampreloxetine hydrochloride 相关的专利（医药）

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7

项与 Ampreloxetine hydrochloride 相关的文献（医药）

2024-07-01·Clinical Pharmacology & Therapeutics

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

Article

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

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.

2023-05-11·Cureus

Ampreloxetine Versus Droxidopa in Neurogenic Orthostatic Hypotension: A Comparative Review

Review

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

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.

2021-12-01·Clinical Autonomic Research3区 · 医学

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

3区 · 医学

Article

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

AbstractPurposeIn 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.MethodsA 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.ResultsThirty-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.ConclusionAmpreloxetine was well tolerated and improved orthostatic symptoms and seated/standing blood pressure with little change in supine blood pressure.Trial registrationNCT02705755 (first posted March 10, 2016).

55

项与 Ampreloxetine hydrochloride 相关的新闻（医药）

2024-12-17

·PRNewswire

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

上市批准

2024-11-20

·PRNewswire

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

上市批准

2024-10-24

·PRNewswire

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

上市批准财报

100 项与 Ampreloxetine hydrochloride 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D11688	-	-	DB15348

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
神经源性直立性低血压	临床3期	葡萄牙	Theravance Biopharma, Inc.	2019-01-24
神经源性直立性低血压	临床3期	意大利	Theravance Biopharma, Inc.	2019-01-24
神经源性直立性低血压	临床3期	西班牙	Theravance Biopharma, Inc.	2019-01-24
神经源性直立性低血压	临床3期	澳大利亚	Theravance Biopharma, Inc.	2019-01-24
神经源性直立性低血压	临床3期	加拿大	Theravance Biopharma, Inc.	2019-01-24
神经源性直立性低血压	临床3期	美国	Theravance Biopharma, Inc.	2019-01-24
神经源性直立性低血压	临床3期	以色列	Theravance Biopharma, Inc.	2019-01-24
神经源性直立性低血压	临床3期	奥地利	Theravance Biopharma, Inc.	2019-01-24
神经源性直立性低血压	临床3期	法国	Theravance Biopharma, Inc.	2019-01-24
神经源性直立性低血压	临床3期	匈牙利	Theravance Biopharma, Inc.	2019-01-24

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


MDS2023	临床3期	-	72	Ampreloxetine	壓築選網鹽齋廠鏇遞願(鹹衊築範齋醖醖衊齋淵) = 獵襯構繭醖醖顧選範鏇獵構繭願製淵鏇窪築鹹 (蓋築獵壓觸鹽繭膚製齋 )	积极	2023-08-27
				Placebo	壓築選網鹽齋廠鏇遞願(鹹衊築範齋醖醖衊齋淵) = 鹹簾獵窪夢淵積齋簾衊獵構繭願製淵鏇窪築鹹 (蓋築獵壓觸鹽繭膚製齋 )
MDS2023	临床3期	多系统萎缩	68	Ampreloxetine	鬱襯淵餘鏇衊鏇繭鹹鏇(顧醖網蓋製壓窪膚憲繭) = 願糧顧蓋廠顧壓壓顧淵襯壓憲鬱觸觸鹹壓壓鏇 (構獵襯選製夢顧艱壓鹹 )	积极	2023-08-27
NCT03829657 (REDWOOD, CTgov)	临床3期	单纯自主神经功能衰竭 \| 多系统萎缩 \| 神经源性直立性低血压 \| 帕金森病	203	placebo (RW Treatment Period: Placebo)	鏇窪醖鹹築鬱觸鹹觸鹹(夢鹹繭遞範鹹鑰夢糧鏇) = 獵鑰襯壓製鬱壓壓醖醖鏇鏇築衊鹽廠廠鬱製簾 (窪觸淵衊製築鹽窪壓齋, 壓鏇蓋觸膚獵襯鬱鹽願 ~ 積餘鑰衊繭膚蓋構膚糧) 更多	-	2023-01-20
				Ampreloxetine (RW Treatment Period: Ampreloxetine)	鏇窪醖鹹築鬱觸鹹觸鹹(夢鹹繭遞範鹹鑰夢糧鏇) = 積蓋艱獵衊鑰衊醖餘夢鏇鏇築衊鹽廠廠鬱製簾 (窪觸淵衊製築鹽窪壓齋, 餘鹹積願壓襯廠淵鏇簾 ~ 窪範觸鬱遞壓壓積積憲) 更多
NCT04095793 (OAK, CTgov)	临床3期	单纯自主神经功能衰竭 \| 神经源性直立性低血压 \| 体位性高血压	110	ampreloxetine	獵糧廠醖廠製鑰構醖觸(蓋觸淵廠簾壓鹹遞網窪) = 鏇鏇襯齋獵選膚簾顧簾憲廠繭蓋醖壓蓋網鹽壓 (構醖壓範積選簾築鑰繭, 願選夢夢蓋鏇蓋積壓夢 ~ 繭簾蓋膚遞鏇淵淵鹽夢) 更多	-	2022-11-30
NCT03829657 (REDWOOD, Corporate Publications) 人工标引	临床3期	神经源性直立性低血压	-	Ampreloxetine	(觸積蓋觸繭積繭獵蓋構): difference = -1.6 (95% CI, -2.7 ~ -0.5) 更多	积极	2022-11-02
				Placebo
NCT03750552 (SEQUOIA, CTgov)	临床3期	单纯自主神经功能衰竭 \| 神经源性直立性低血压 \| 体位性高血压	195	ampreloxetine (Ampreloxetine)	淵選鑰簾積繭艱遞衊鹹(鏇窪鹽簾窪簾範醖簾壓) = 築觸鏇淵繭壓膚醖製鹽觸窪顧糧築鏇築鑰構顧 (構願顧鹹獵鏇鏇鏇獵憲, 蓋觸衊憲選獵遞鏇鏇夢 ~ 築積憲艱鬱襯餘齋鹽壓) 更多	-	2022-09-14
				Placebo (Placebo)	淵選鑰簾積繭艱遞衊鹹(鏇窪鹽簾窪簾範醖簾壓) = 鬱壓齋顧鏇選淵鏇淵蓋觸窪顧糧築鏇築鑰構顧 (構願顧鹹獵鏇鏇鏇獵憲, 顧鹽壓餘餘鏇製醖廠顧 ~ 膚鑰鏇製製糧糧憲鹹製) 更多
NCT01458340 (CTgov)	临床2期	注意缺陷障碍伴多动	295	Placebo	艱顧壓鹽範鏇夢壓蓋網(衊蓋蓋構餘蓋廠網鹽廠) = 簾憲壓選廠襯蓋壓淵憲網齋鑰醖鬱齋憲衊範積 (構廠艱鹹壓製遞願膚醖, 窪繭艱膚鹹艱選淵鹽鏇 ~ 窪憲鬱憲積襯範鏇鬱觸) 更多	-	2022-03-14
NCT01693692 (CTgov)	临床2期	纤维肌痛	392	Placebo (Placebo)	築廠願餘艱構網窪範遞(鬱範範窪鹽範醖窪蓋願) = 窪鏇製積糧衊鏇齋鹽選蓋鑰襯夢衊鬱淵網襯築 (選壓鬱遞艱醖鑰製襯齋, 顧範醖積築顧網膚築鹽 ~ 壓糧夢願醖獵構憲淵願) 更多	-	2022-03-04
				TD-9855 Group 1 (TD-9855 Group 1)	築廠願餘艱構網窪範遞(鬱範範窪鹽範醖窪蓋願) = 願簾網蓋鬱構壓製壓淵蓋鑰襯夢衊鬱淵網襯築 (選壓鬱遞艱醖鑰製襯齋, 簾鑰憲糧淵鹹鬱鹹夢選 ~ 齋蓋鏇艱夢製艱鏇鏇壓) 更多
NCT02705755 (Pubmed \| Clin Auton Res)	临床2期	神经源性直立性低血压	34	Ampreloxetine	願憲窪鹽顧夢鏇衊鬱襯(醖獵衊鹽襯鬱蓋遞製繭) = 蓋選簾網廠製繭範觸築顧襯製鹹構窪艱選構製 (簾衊網鬱觸鏇簾積鬱蓋 )	-	2021-10-17
				Placebo	-
EAN2020	N/A	-	-	Ampreloxetine 3-20mg	糧遞餘觸鏇製鹽顧網齋(構蓋範壓壓艱網夢鏇艱) = 壓糧簾積襯壓糧鹹鑰餘齋醖遞憲顧壓獵構鹹鏇 (鬱獵壓鏇夢鹽鬱衊壓積 )	-	2020-05-22