Two Part Study to Assess Comparative Bioavailability, Pharmacokinetics of a Single Dose of ACM-001.1, Two Single Doses of Pindolol (Part1) Followed by Evaluation of Steady State Pharmacokinetics, Pharmacodynamics of ACM-001.1 in HV (Part2)

The aim of this early phase two-part study was to compare the bioavailability (BA) pharmacokinetics (PK) and pharmacodynamics (PD) of racemic pindolol with the benzoate salt of the S-enantiomer of pindolol (ACM-001.1) and provide safety information. A total of 51 healthy male and female subjects were enrolled, and 48 healthy subjects completed the study.
Part 1 consisted of two Groups to compare BA and PK, Group 1 received two treatment sequences of a single dose of ACM-001.1 versus racemic pindolol; Group 2 ran in parallel with Group 1 and assessed the PK of a single dose of racemic pindolol in a single period.
Part 2 consisted of four groups, to evaluate the steady state PK and PD of ACM-001.1 with multiple ascending doses over 4 days.

开始日期2021-11-26

申办/合作机构

Actimed Therapeutics Ltd.初创企业

[+1]

CTRI/2011/05/001757 / Not yet recruiting临床2期

A multicentre, randomised, double-blind, placebo controlled,dose-finding phase II clinical study to evaluate the efficacy of two different doses of MT-102 administered over a sixteen week period in subjects with cachexia related to stage III and IV non-small cell lung cancer and colorectal cancer - Not applicable

开始日期2011-06-01

申办/合作机构

Veeda Clinical Research Ltd.

NCT01238107 / Completed临床2期

A Multicentre, Randomised, Double-blind, Placebo-controlled, Phase II Clinical Study to Evaluate Doses of MT-102 in Subjects With Cachexia Related to Stage III and IV Non-small Cell Lung Cancer and Colorectal Cancer

A phase II clinical study to evaluate MT-102 administered over a sixteen week period in subjects with cachexia related to non-small cell lung cancer and colorectal cancer

开始日期2011-04-01

申办/合作机构

Akamis Bio Ltd.

[+1]

100 项与 Espindolol 相关的临床结果

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100 项与 Espindolol 相关的转化医学

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100 项与 Espindolol 相关的专利（医药）

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项与 Espindolol 相关的文献（医药）

2024-09-01·Cancer Medicine

Efficacy and safety of pharmacotherapy for cancer cachexia: A systematic review and network meta‐analysis

Review

作者: Honda, Takeshi ; Kazahari, Hiroki ; Ichikawa, Yasuko ; Nagai, Hisashi ; Watanabe, Kiyotaka ; Chen, Hao ; Seki, Nobuhiko ; Ishihara, Masashi ; Tanzawa, Shigeru ; Ochiai, Ryusuke ; Horita, Nobuyuki

Abstract:

Background:

Cancer cachexia affects more than half of all cancer patients, reducing survival rates. Evidence‐based approaches are urgently needed to optimize treatment.

Methods:

A systematic review and network meta‐analysis were conducted to assess the effectiveness and safety of different pharmacotherapies for cancer cachexia. Three databases (PubMed, Cochrane Library, and Web of Science) were searched for the period from January 1, 2000, to March 20, 2024. The netmeta package in R software was used to calculate the pooled effect, employing a random effects model.

Results:

Seven placebo‐controlled randomized trials involving 1421 patients were analyzed. Pairwise analysis showed that body weight increases were 4.6 kg (95% confidence interval [CI] 0.83–8.37 kg) for olanzapine, 3.82 kg (95% CI 0.73–6.91 kg) for espindolol (20 mg), 2.36 kg (95% CI 1.84–2.89 kg) for anamorelin (100 mg), and 1.31 kg (95% CI 0.42–2.19 kg) for anamorelin (50 mg). In terms of safety profiles, olanzapine demonstrated the lowest odds ratio when compared to placebo, at 0.26 (95% CI 0.07–0.94), followed by anamorelin (50 mg) at 0.86 (95% CI 0.30–2.48), and anamorelin (100 mg) at 0.89 (95% CI 0.42–1.88). However, network meta‐analysis could not confirm the superiority of olanzapine over anamorelin in terms of efficacy and safety.

Conclusion:

Both olanzapine and anamorelin are useful in improving body weight in patients with cancer cachexia. Personalization may be helpful for different patients.

2023-05-01·European journal of heart failure

The small molecule ACM-001 improves cardiac function in a rat model of severe cancer cachexia.

Article

作者: Doehner, Wolfram ; von Haehling, Stephan ; Anker, Stefan D ; Van Linthout, Sophie ; Palus, Sandra ; Coats, Andrew J S ; Poetsch, Mareike S ; Springer, Jochen

AIMS:

Cachexia, a common manifestation of malignant cancer, is not only associated with weight loss, but also with severe cardiac atrophy and impaired cardiac function. Here, we investigated the effects of ACM-001 (0.3 or 3 mg/kg/day) in comparison to carvedilol (3 or 30 mg/kg/day), metropolol (50 or 100 mg/kg/day), nebivolol (1 or 10 mg/kg/day) and tertatolol (0.5 or 5 mg/kg/day) on cardiac mass and function in a rat cancer cachexia model.

METHODS AND RESULTS:

Young male Wistar Han rats were inoculated i.p. with 10⁸ Yoshida hepatoma AH-130 cells and treated once daily with verum or placebo by gavage. Cardiac function (echocardiography), body weight and body composition (nuclear magnetic resonance scans) were assessed. The hearts of animals were euthanized on day 11 (placebo and 3 mg/kg/day ACM-001) were used for signalling studies. Beta-blockers had no effect on tumour burden. ACM-001 reduced body weight loss (placebo: -34 ± 2.4 g vs. 3 mg/kg/day ACM-001: -14.8 ± 8.4 g, p = 0.033). Lean mass wasting was attenuated (placebo: -16.5 ± 2.34 g vs. 3 mg/kg/day ACM-001: -2.4 ± 6.7 g, p = 0.037), while fat loss was similar (p = 0.4) on day 11. Placebo animals lost left ventricular mass (-101 ± 14 mg), which was prevented only by 3 mg/kg/day ACM-001 (7 ± 25 mg, p < 0.01 vs. placebo). ACM-001 improved the ejection fraction (EF) (ΔEF: placebo: -24.3 ± 2.6 vs. 3 mg/kg/day ACM-001: 0.1 ± 2.9, p < 0.001). Cardiac output was 50% lower in the placebo group (-41 ± 4 ml/min) compared to baseline, while 3 mg/kg/day ACM-001 preserved cardiac output (-5 ± 8 ml/min, p < 0.01). The molecular mechanisms involved inhibition of protein degradation and activation of protein synthesis pathways.

CONCLUSION:

This study shows that 3 mg/kg/day ACM-001 restores the anabolic/catabolic balance in cardiac muscle leading to improved function. Moreover, not all beta-blockers have similar effects.

2023-02-01·Journal of cachexia, sarcopenia and muscle

The atypical β‐blocker S‐oxprenolol reduces cachexia and improves survival in a rat cancer cachexia model

Article

作者: Yuan, Luping ; Jové, Queralt ; Álvarez Ladrón, Natalia ; Palus, Sandra ; Oosterlee, Annemijn ; Anker, Markus S. ; Busquets, Silvia ; Argiles, Josep M. ; Coats, Andrew J.S. ; Szymczyk, Agata ; López‐Soriano, Francisco Javier ; Springer, Jochen ; Anker, Stefan D. ; Millman, Oliver ; Alves de Lima Junior, Edson ; von Haehling, Stephan

Abstract:

Background:

Beta‐blockers and selected stereoisomers of beta‐blockers, like bisoprolol and S‐pindolol (ACM‐001), have been shown to be effective in preclinical cancer cachexia models. Here, we tested the efficacy of stereoisomers of oxprenolol in two preclinical models of cancer cachexia—the Yoshida AH‐130 rat model and the Lewis lung carcinoma (LLC) mouse model.

Methods and Results:

In the Yoshida AH130 hepatoma rat cancer cachexia model and compared with placebo, 50 mg/kg/d S‐oxprenolol (HR: 0.49, 95% CI: 0.28–0.85, P = 0.012) was superior to 50 mg/kg/d R‐oxprenolol (HR: 0.83, 95% CI 0.38–1.45, P = 0.51) in reducing mortality (= reaching ethical endpoints). Combination of the three doses (12.5, 25 and 50 mg/kg/d) that had a significant effect on body weight loss in the S‐oxprenolol groups vs the same combination of the R‐oxprenolol groups lead to a significantly improved survival of S‐oxprenolol vs R‐oxprenolol (HR: 1.61, 95% CI: 1.08–2.39, P = 0.0185). Interestingly, there is a clear dose dependency in S‐oxprenolol‐treated (5, 12.5, 25 and 50 mg/kg/d) groups, which was not observed in groups treated with R‐oxprenolol. A dose‐dependent attenuation of weight and lean mass loss by S‐oxprenolol was seen in the Yoshida rat model, whereas R‐oxprenolol had only had a significant effect on fat mass. S‐oxprenolol also non‐significantly reduced weight loss in the LLC model and also improved muscle function (grip strength 428 ± 25 and 539 ± 37 g/100 g body weight for placebo and S‐oxprenolol, respectively). However, there was only a minor effect on quality of life indicators food intake and spontaneous activity in the Yoshida model (25 mg/kg/S‐oxprenolol: 11.9 ± 2.5 g vs placebo: 4.9 ± 0.8 g, P = 0.013 and also vs 25 mg/kg/d R‐oxprenolol: 7.5 ± 2.6 g, P = 0.025). Both enantiomers had no effects on cardiac dimensions and function at the doses used in this study. Western blotting of proteins involved in the anabolic/catabolic homoeostasis suggest that anabolic signalling is persevered (IGF‐1 receptor, Akt) and catabolic signalling is inhibited (FXBO‐10, TRAF‐6) by S‐pindolol, but not he R‐enantiomer. Expression of glucose transporters Glut1 and Glut 4 was similar in all groups, as was AMPK.

Conclusions:

S‐oxprenolol is superior to R‐oxprenolol in cancer cachexia animal models and shows promise for a human application in cancer cachexia.

项与 Espindolol 相关的新闻（医药）

2024-11-14

·GlobeNewswire-Health Care

Actimed Therapeutics Announces Professor David Ebsworth to Become Executive Chairman

Professor David Ebsworth to work closely alongside CEO Robin BhattacherjeeWill focus on fund raising efforts to support the planned IMPACT Phase 2b/3 trial for S-pindolol benzoate in cancer cachexiaProfessor Stefan Anker, Co-Founder of Actimed and Chair of the Scientific Advisory Board, also joins the Board of Directors London, UK – 14th November 2024. Actimed Therapeutics Ltd (“Actimed”), a UK based clinical stage specialty pharmaceutical company focused on bringing innovation to the treatment of cancer cachexia and other muscle wasting disorders, announces that Professor David Ebsworth will assume the role of Executive Chairman of Actimed. At the same time, Professor Stefan Anker, Founder and Chair of the Actimed Scientific Advisory Board, will join the Board of the Company as a Non-Executive Director. David has been Non-Executive Chairman of Actimed Therapeutics since April 2018. He has over 40 years of experience in the healthcare industry and is a past CEO of Galenica AG, Vifor Pharma AG and past global head of the Pharmaceutical Division of Bayer AG. David has chaired numerous private and public pharmaceutical companies and served on many Boards as either Chairman of the audit, remuneration or nominations and governance committees. David is Chair of the Supervisory Board at Synlab AG and Board member at Sartorius AG. David also currently serves as Chairman of Nasdaq listed Verona Pharma PLC, which he moved from AIM to Nasdaq in 2020. Verona recently gained approval for and has successfully launched Ohtuvayre (ensifentrine). David will work closely in partnership with CEO Robin Bhattacherjee to support the Company’s fund-raising activities to finance the planned Phase 2b/3 IMPACT clinical trial programme for Actimed’s lead asset, S-pindolol benzoate, in cancer cachexia. Actimed received FDA approval of its Investigational New Drug (IND) application for the IMPACT programme in August 2023. The Company plans to dose patients in 2025. Professor Stefan Anker, MD, PhD, co-founded Actimed Therapeutics in 2017, having previously founded Myotec (later renamed PsiOxus Therapeutics). Stefan has 30 years of academic research experience in cachexia and clinical trials development. He is founding Editor-in-Chief of the Journal of Cachexia, Sarcopenia and Muscle as well as the founding president of the International Society on Sarcopenia, Cachexia and Wasting Disorders. Stefan has been and is a member of more than 50 international clinical trial steering committees and is a named author on over 1,300 research papers. As Actimed advances the clinical development of S-pindolol benzoate, Stefan’s expertise and knowledge will provide important support to the Board and the Company. Robin Bhattacherjee, Chief Executive Officer of Actimed Therapeutics commented “I greatly look forward to David taking on the role of Executive Chairman and dedicating more time to advancing our efforts to bring S-pindolol benzoate to patients. David’s industry track record, contact network and Board expertise speak for themselves and will further strengthen our ability to finance and complete our planned clinical programme for this highly promising asset.” David Ebsworth, Executive Chair of Actimed added “I look forward to working more closely with Robin to achieve our objectives. I am deeply committed to ensuring success for Actimed in our mission to transform care for the many patients suffering from cancer cachexia and other muscle wasting disorders. Cancer cachexia remains a poorly treated condition with few recent advances in therapy. At Actimed, I believe we have an exciting opportunity to advance the standard of care when we successfully finance and complete the clinical development of S-pindolol benzoate and I am pleased to provide my full support to Robin and the Leadership Team in pursuit of this.” *** About Actimed Therapeutics Actimed Therapeutics is a clinical stage specialty pharmaceutical company focused on bringing innovation to the treatment of cachexia and other muscle wasting disorders, to transform the care of an underserved and vulnerable patient population. Cachexia is a wasting disease that is associated with cancer and other serious chronic illnesses and with significant morbidity and mortality. A significant number of cancer patients suffer from cachexia, and it is estimated that cachexia is responsible for up to 20% of all cancer deaths. Despite its prevalence and devastating clinical effects, there is no globally approved drug for the treatment or prevention of cancer-related cachexia. Actimed’s lead product, S-pindolol benzoate (ACM-001.1), targets multiple pathways that drive cachexia and has generated promising proof of concept Phase 2a clinical data in cachexia patients. Actimed is currently preparing for further clinical studies in cancer cachexia having received an Investigational New Drug (IND) approval from FDA for this programme in August 2023. Actimed also owns the global rights to its second asset, S-oxprenolol, which is being developed by the Company for the muscle wasting seen in amyotrophic lateral sclerosis (ALS) where loss of body mass and muscle wasting may impact survival. Actimed has licensed the global rights to develop and commercialise S-oxprenolol for cancer cachexia and any other indications outside of ALS to US company Faraday Pharmaceuticals. FOR MORE INFORMATIONActimed Therapeuticswww.actimedtherapeutics.com MEDiSTRAVA Frazer Hall, Erica HollingsworthTel: +44 (0)203 928 6900Email: actimed@medistrava.com ___________________________

临床2期高管变更上市批准

2024-09-04

·GlobeNewswire-Health Care

Actimed Therapeutics Announces US FDA Grant of Orphan Drug Designation to S-oxprenolol (ACM-002) for the Treatment of Amyotrophic Lateral Sclerosis (ALS)

London, UK – 4th September 2024. Actimed Therapeutics Ltd (“Actimed”), a UK based clinical stage specialty pharmaceutical company focused on bringing innovation to the treatment of cancer cachexia and other muscle wasting disorders, announces that the US Food and Drug Administration (FDA) has granted Orphan Drug Designation to S-oxprenolol (ACM-002) for the treatment of amyotrophic lateral sclerosis (ALS). ALS (also known as Lou Gehrig’s disease) is a progressive, fatal neuromuscular disease that affects nerve cells in the brain and spinal cord, eventually leading to a loss of muscle control and paralysis. ALS prevents motor neurons sending impulses from the brain and spinal cord to the muscles, causing muscle atrophy and weakness and has a mean survival of 3.5 years. Voluntary muscle action is progressively lost and in late-stage ALS patients may have difficulty communicating, swallowing, moving, and breathing. There is currently no cure for ALS. Cachexia, a complex wasting disease, may occur in the early stages of ALS and has a significant impact on quality of life, proving terminal in some patients. In pre-clinical ALS models, S-oxprenolol has demonstrated significant benefits including slowing disease progression, improvement in survival, attenuation of muscle loss, motor neuron protection, reduction in loss of body mass and improvements in lean body mass1. Robin Bhattacherjee, Chief Executive Officer of Actimed Therapeutics commented “We are pleased to receive Orphan Drug Designation for S-oxprenolol in ALS, where loss of body mass and muscle wasting can have a significant impact on survival. ALS is a devastating orphan disease of high, unmet medical need and the early non-clinical data we have generated for S-oxprenolol in this indication suggest that it could have a potential role in meeting some of the important needs of this under-served patient population”. FDA Orphan Drug Designation is granted to investigational therapies which are intended for the safe and effective treatment, diagnosis or prevention of rare diseases or conditions that affect fewer than 200,000 people in the United States. Orphan Drug Designation provides several benefits to drug developers, including certain development cost benefits in the US, increased FDA interaction and eligibility for seven-year market exclusivity following approval. *** About Actimed Therapeutics Actimed Therapeutics is a clinical stage specialty pharmaceutical company focused on bringing innovation to the treatment of muscle wasting disorders to transform the care of an underserved and vulnerable patient population. The lead area of focus for Actimed is specifically in cachexia. Cachexia is a wasting disease that is associated with cancer and other serious chronic illnesses and with significant morbidity and mortality. A significant number of cancer patients suffer from cachexia2 and it is estimated that cachexia is responsible for up to 20% of all cancer deaths3. A recent meta-analysis demonstrated that cachexia was associated with an 82% higher relative risk of mortality in patients with NSCLC versus no cachexia4. Despite its prevalence and devastating clinical effects, there is no globally approved drug for the treatment or prevention of cancer-related cachexia. The lead product of Actimed, S-pindolol benzoate (ACM-001.1) targets multiple pathways that drive cachexia and has generated promising proof of concept Phase 2a clinical data in cachexia patients. Actimed is currently preparing for further clinical studies in cancer cachexia having received an Investigational New Drug (IND) approval from FDA for this programme in August 2023. Actimed also owns the global rights to its second asset, S-oxprenolol, which is being developed by the Company for the muscle wasting seen in amyotrophic lateral sclerosis (ALS) where loss of body mass and muscle wasting may impact survival5. Actimed has licensed the global rights to develop and commercialise S-oxprenolol for cancer cachexia and any other indications outside of ALS to US company Faraday Pharmaceuticals. FOR MORE INFORMATIONActimed Therapeuticswww.actimedtherapeutics.com MEDiSTRAVA ConsultingFrazer Hall, Erica HollingsworthTel: +44 (0)203 928 6900Email: actimed@medistrava.com ___________________________ 1Suzuki et al, JCSM 2018; 9, 183-212. (Poster 5-17, page 200)2 Anker M et al., J. Cachexia, Sarcopenia and Muscle; 2019: 10: 22 – 243 Argilés JM et al, Nat Rev Cancer 2014; 14:754-624 Bonomi P. et al. The mortality burden of cachexia in patients with non-small-cell lung cancer: A meta-analysis; International Conference of Sarcopenia, Cachexia and Wasting Disorders, June 17 – 18 2023, Stockholm, abstract 2-18, page 1395Wolf J et al., PMID 28184974 DOI: 10.1007/s00115-117-0293

临床2期孤儿药

2024-09-04

·Pharmaceutical Technology

Actimed’s ALS candidate wins FDA orphan drug designation

ALS prevents motor neurons from sending impulses from the brain and spinal cord to the muscles, causing muscle atrophy and weakness. Image credit: Shutterstock / CC7. The US Food and Drug Administration (FDA) has granted an orphan drug designation to Actimed Therapeutics’ S-oxprenolol (ACM-002) for the treatment of amyotrophic lateral sclerosis (ALS). The UK-based pharma company will now be in line for tax credits for US-based clinical trials, and if the therapy is approved, the potential for seven years of market exclusivity in the designated indication, as per a 4 September press release. Actimed says S-oxprenolol shares “a similar pharmacology” to S-pindolol, which is an anabolic/catabolic transforming agent. S-pindolol benzoate, Actimed’s lead product, is being investigated for the treatment of the metabolic weight loss syndrome called cachexia. With S-oxprenolol, Actimed is targeting S-pindolol’s mechanistic approach in the wasting syndrome to address the loss of body mass and muscle wasting seen in ALS. ALS is the most common form of motor neuron disease. Muscle wasting is seen in patients as motor neuron degeneration means muscles no longer receive electrical signals. See Also: ESC 2024: Beta blocker treatment paradigm shifts for myocardial infarction Novavax wins FDA emergency approval for updated Covid-19 vaccine There are currently six FDA-approved therapies for ALS, though the agency has developed a five-year plan to accelerate the development of more treatments and improve medicine access. There have been a few recent setbacks in the space, including Amylyx Pharmaceutical’s Phase III failure and Ionis/Biogen’s decision to discontinue the development of their ALS candidate. In preclinical ALS models, S-oxprenolol has demonstrated an ability to attenuate muscle loss, improve lean body mass, and reduce the loss of overall body mass, amongst other benefits. Oxprenolol is a beta blocker usually used for the treatment of heart conditions such as angina and high blood pressure. While Actimed has not disclosed the mechanism of action in ALS, the related compound S-pindolol increases anabolism and muscle by partial beta-2 receptor agonism. Actimed is currently conducting trials for S-pindolol in cancer cachexia, a sub-type of the syndrome found in cancer patients. The compound has demonstrated positive proof of concept data in a Phase IIa study, with further clinical trials planned according to the company. Actimed has yet not unveiled details of a clinical programme for S-oxprenolol. Nonetheless, the company has already licensed the drug’s global rights for cancer cachexia and non-ALS indications to US company Faraday Pharmaceuticals. The deal, signed in 2021, included an upfront payment of $550,000 and $126.2m in milestone payments. Actimed’s CEO Robin Bhattacherjee said: “The early non-clinical data we have generated for S-oxprenolol in this indication suggest that it could have a potential role in meeting some of the important needs of this under-served patient population.”

上市批准临床2期孤儿药临床结果临床3期

100 项与 Espindolol 相关的药物交易

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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
结直肠癌	临床2期	德国	Akamis Bio Ltd.	2011-04-01
结直肠癌	临床2期	印度	Akamis Bio Ltd.	2011-04-01
结直肠癌	临床2期	马来西亚	Akamis Bio Ltd.	2011-04-01
转移性非小细胞肺癌	临床2期	德国	Akamis Bio Ltd.	2011-04-01
转移性非小细胞肺癌	临床2期	印度	Akamis Bio Ltd.	2011-04-01
转移性非小细胞肺癌	临床2期	马来西亚	Akamis Bio Ltd.	2011-04-01
恶病质	临床2期	德国	Akamis Bio Ltd.	2011-04-01
恶病质	临床2期	印度	Akamis Bio Ltd.	2011-04-01
恶病质	临床2期	马来西亚	Akamis Bio Ltd.	2011-04-01