Open label, Multicenter, Prospective Study to Characterize the Pharmacokinetics and Pharmacodynamics of Cufence (Trientine Dihydrochloride) and to Investigate the Efficacy and Safety in Wilson’s Disease Patients - TR-004 UNITED Study

Start Date08 Oct 2021

Sponsor / Collaborator-

CTR20211406 / Active, not recruitingPhase 2

一项在心力衰竭和射血分数降低患者中评价 INL1（Trientine）效果的随机化、双盲、安慰剂对照研究

[Translation] A randomized, double-blind, placebo-controlled study evaluating the effects of INL1 (Trientine) in patients with heart failure and reduced ejection fraction

目的：主要目的：评价12周时INL1（盐酸曲恩汀）与安慰剂相比在NYHA 心功能分级Ⅱ～Ⅲ级伴左心室射血分数降低（LVEF<40%）的心力衰竭患者中的疗效。次要目的：评价INL1（盐酸曲恩汀）与安慰剂相比在心力衰竭患者中的安全性和耐受性。描述12周治疗期间INL1（盐酸曲恩汀）的药代动力学（PK）特征

[Translation]

Objective: Primary objective: To evaluate the efficacy of INL1 (trientine hydrochloride) compared with placebo in patients with heart failure of NYHA class II-III with reduced left ventricular ejection fraction (LVEF<40%) at 12 weeks. Secondary objective: To evaluate the safety and tolerability of INL1 (trientine hydrochloride) compared with placebo in patients with heart failure. To describe the pharmacokinetic (PK) characteristics of INL1 (trientine hydrochloride) during 12 weeks of treatment

Start Date01 Jul 2021

Sponsor / Collaborator

Frontage Laboratories, Inc.

[+2]

NCT04706429 / Active, not recruitingPhase 2

A Randomised, Double-blind, Placebo-controlled, Phase 2 Evaluation of the Efficacy and Mechanism of Trientine in Patients With Hypertrophic Cardiomyopathy

This research study has been designed to test whether a drug called trientine dihydrochloride (also called Cufence) reduces heart muscle thickening, improves exercise capacity, improves heart function and reduces abnormal heart rhythms in patients with hypertrophic cardiomyopathy (HCM). The study is also assessing how trientine works in HCM. Participants will be prescribed either trientine or placebo, for a period of 12 months.

Start Date01 Dec 2020

Sponsor / Collaborator

Manchester University NHS Foundation Trust

[+5]

100 Clinical Results associated with Trientine Hydrochloride

100 Translational Medicine associated with Trientine Hydrochloride

100 Patents (Medical) associated with Trientine Hydrochloride

443

Literatures (Medical) associated with Trientine Hydrochloride

01 Jan 2024·Nuclear medicine and biology

64Cu production via the 68Zn(p,nα)64Cu nuclear reaction: An untapped, cost-effective and high energy production route

Article

Author: Andersson, Jan D ; Wilson, John ; Wuest, Frank ; Leier, Samantha ; Wuest, Melinda ; Nelson, Bryce J B ; Doupe, Jonathan

INTRODUCTION:

Copper-64 (⁶⁴Cu, t_1/2 = 12.7 h) is a positron emitter well suited for theranostic applications with beta-emitting ⁶⁷Cu for targeted molecular imaging and radionuclide therapy. The present work aims to evaluate the radionuclidic purity and radiochemistry of ⁶⁴Cu produced via the ⁶⁸Zn(p,nα)⁶⁴Cu nuclear reaction. Macrocyclic chelators DOTA, NOTA, TETA, and prostate-specific membrane antigen ligand PSMA I&T were radiolabeled with purified ⁶⁴Cu and tested for in vitro stability. [⁶⁴Cu]Cu-PSMA I&T was used to demonstrate in vivo PET imaging using ⁶⁴Cu synthesized via the ⁶⁸Zn(p,nα)⁶⁴Cu production route and its suitability as a theranostic imaging partner alongside ⁶⁷Cu therapy.

METHODS:

⁶⁴Cu was produced on a 24 MeV TR-24 cyclotron at a beam energy of 23.5 MeV and currents up to 70 μA using 200 mg ⁶⁸Zn encapsulated within an aluminum‑indium-graphite sealed solid target assembly. ⁶⁴Cu semi-automated purification was performed using a NEPTIS Mosaic-LC synthesis unit employing CU, TBP, and TK201 (TrisKem) resins. Radionuclidic purity was measured by HPGe gamma spectroscopy, while ICP-OES assessed elemental purity. Radiolabeling was performed with NOTA at room temperature and DOTA, TETA, and PSMA I&T at 95 °C. ⁶⁴Cu incorporation was studied by radio-TLC. ⁶⁴Cu in vitro stability of [⁶⁴Cu]Cu-NOTA, [⁶⁴Cu]Cu-DOTA, [⁶⁴Cu]Cu-TETA, and [⁶⁴Cu]Cu-PSMA I&T was assessed at 37 °C from 0 to 72 h in human blood serum. Preclinical PET imaging was performed at 1, 24, and 48 h post-injection with [⁶⁴Cu]Cu-PSMA I&T in LNCaP tumor-bearing mice and compared with [⁶⁸Ga]Ga-PSMA I&T.

RESULTS:

Maximum purified activity of 4.9 GBq [⁶⁴Cu]CuCl₂ was obtained in 5 mL of pH 2-3 solution, with 2.9 GBq ⁶⁴Cu concentrated in 0.5 mL. HPGe gamma spectroscopy of purified ⁶⁴Cu detected <0.3 % co-produced ⁶⁷Cu at EOB with no other radionuclidic impurities. ICP-OES elemental analysis determined <1 ppm Al, Zn, In, Fe, and Cu in the [⁶⁴Cu]CuCl₂ product. NOTA, DOTA, TETA, and PSMA I&T were radiolabeled with ⁶⁴Cu, resulting in maximum molar activities of 164 ± 6 GBq/μmol, 155 ± 31 GBq/μmol, 266 ± 34 GBq/μmol, and 117 ± 2 GBq/μmol, respectively. PET imaging in PSMA-expressing LNCaP xenografts resulted in high tumor uptake (SUV_mean = 1.65 ± 0.1) using [⁶⁴Cu]Cu-PSMA I&T, while [⁶⁸Ga]Ga-PSMA I&T yielded an SUV_mean of 0.76 ± 0.14 after 60 min post-injection.

CONCLUSIONS:

⁶⁴Cu was purified in a small volume amenable for radiolabeling, with yields suitable for preclinical and clinical application. The ⁶⁴Cu production and purification process and the favourable PET imaging properties confirm the ⁶⁸Zn(p,nα)⁶⁴Cu nuclear reaction as a viable ⁶⁴Cu production route for facilities with access to a higher energy proton cyclotron, compared to using expensive ⁶⁴Ni target material and the ⁶⁴Ni(p,n)⁶⁴Cu nuclear reaction.

ADVANCES IN KNOWLEDGE AND IMPLICATIONS FOR PATIENT CARE:

Our ⁶⁴Cu production technique provides an alternative production route with the potential to improve ⁶⁴Cu availability for preclinical and clinical studies alongside ⁶⁷Cu therapy.

01 Jan 2024·Nuclear medicine and biology

Chelation chemistry of manganese-52 for PET imaging applications

Article

Author: Lapi, Suzanne E ; Omweri, James M ; Wijeratne, Gayan B ; Decato, Daniel A ; Jayawardana, Samith B ; Tekin, Volkan ; Houson, Hailey A ; Saini, Shefali

INTRODUCTION:

Due to its decay and chemical properties, interest in manganese-52 has increased for development of long-lived PET radiopharmaceuticals. Its long half-life of 5.6 days, low average positron energy (242 keV), and sufficient positron decay branching ratio make it suitable for radiolabeling macromolecules for investigating slow biological processes. This work aims to establish suitable chelators for manganese-52 that can be radiolabeled at mild conditions through the evaluation of commercially available chelators.

METHODS:

Manganese-52 was produced through the nuclear reaction ^NatCr(p,n)⁵²Mn by irradiation of natural chromium targets on a TR24 cyclotron followed by purification through ion exchange chromatography. The radiolabeling efficiencies of chelators: DOTA, DiAmsar, TETA, DO3A, NOTA, 4'-Formylbenzo-15-crown-5, Oxo-DO3A, and DFO, were assessed by investigating the impact of pH, buffer type, and temperature. In vitro stability of [⁵²Mn]Mn(DO3A)^-, [⁵²Mn]Mn(Oxo-DO3A)^-, and [⁵²Mn]Mn(DOTA)^2- were evaluated in mouse serum. The radiocomplexes were also evaluated in vivo in mice. Crystals of [Mn(Oxo-DO3A)]^- were synthesized by reacting Oxo-DO3A with MnCl₂ and characterized by single crystal X-ray diffraction.

RESULTS:

Yields of 185 ± 19 MBq (5.0 ± 0.5 mCi) (n = 4) of manganese-52 were produced at the end of a 4 h, 15 μA, bombardment with 12.5 MeV protons. NOTA, DO3A, DOTA, and Oxo-DO3A chelators were readily radiolabeled with >96 % radiochemical purity at all conditions. Manganese radiocomplexes of Oxo-DO3A, DOTA, and DO3A remained stable in vitro up to 5 days and exhibited different biodistribution profiles compared to [⁵²Mn]MnCl₂. The solid-state structure of Mn-Oxo-DO3A complex was determined by single-crystal X-ray diffraction.

CONCLUSIONS:

DO3A and Oxo-DO3A are suitable chelators for manganese-52 which are readily radiolabeled at mild conditions with high molar activity, and demonstrate both in vitro and in vivo stability.

10 Oct 2023·Langmuir : the ACS journal of surfaces and colloids

Improvement in CO₂ Capture of Polyamine with Micro-Interfacial System.

Article

Author: Wu, Youting ; Meng, Weimin ; Zhang, Zhibing ; Chen, Meisi ; Li, Xinyao ; Zhang, Feng ; Li, Mengjia ; Liang, Yinchun

Polyamines have emerged as a promising class of CO₂ absorbents due to their remarkable sequestration capacity. However, their potential industrial application as aqueous absorbents is significantly hindered by a low regeneration efficiency and high energy consumption. To address these issues, this study investigates the use of triethylenetetramine (TETA) and ethylene glycol (EG) to develop a nonaqueous absorbent. The incorporation of EG enhances absorption performance and reduces the regeneration energy needed for TETA, whereas the high viscosity of the absorbent impedes absorption rate, amine efficiency, and regeneration efficiency. In order to enhance CO₂ capture, micron-sized reaction units (SiO₂@TETA-EG) were developed by encapsulating TETA solution with nanosilica. The SiO₂@TETA-EG composite exhibits a large specific surface area (99 m²/g), with a porous shell structure and improved fluidity, which effectively counteracts the negative effects caused by high viscosity. Notably, SiO₂@TETA-EG indicates a noticeably higher apparent rate constant of 4.29 min^-1 at 323.2 K compared to the TETA-EG solution. Furthermore, SiO₂@TETA-EG displays a 28.4% boost in regeneration efficiency while maintaining favorable stability in pore size and shape after regeneration.

News (Medical) associated with Trientine Hydrochloride

18 Jan 2024

·www.globenewswire.com

Orphalan announces China NMPA’s approval of its trientine tetrahydrochloride product for the treatment of Wilson disease

Orphalan announces China NMPA’s approval of its trientine tetrahydrochloride product for the treatment of Wilson disease Paris, France 18 January, 2024 - Orphalan SA (“Orphalan” or “the Company”), an international orphan drug development and commercialization company, today announces the approval of its trientine tetrahydrochloride product by China's National Medical Products Administration (NMPA). This product, already marketed as Cuprior® in the EU, the UK, Saudi Arabia, Switzerland, and Colombia, and as Cuvrior® in the US, represents the first trientine approved by the NMPA. It offers a new treatment option for Wilson disease in children aged five years and older and adults intolerant to penicillamine therapy. China is home to an estimated 80,000 individuals with Wilson disease, of whom approximately half have their diagnosis confirmed, and 25,000 are receiving regular treatment. The introduction of new treatment alternatives such as Orphalan’s trientine tetrahydrochloride, particularly for patients who are intolerant to currently available therapies, presents a significant opportunity to meet the needs of a broader segment of the Wilson disease population in China. Orphalan anticipates its product to be available in the country in the coming months. Dr Naseem Amin, Chief Executive Officer at Orphalan, said: “We are pleased with the marketing authorisation approval of our trientine tetrahydrochloride product in China, which offers a well-tolerated and effective treatment option for patients with Wilson disease. This approval is a crucial step towards providing a much-needed treatment option for the Wilson disease community in China and reaffirms our commitment to improving the experience for patients living with rare diseases worldwide.” Yan Qin, Director of Wuhan Tongxin (Wilson disease patient group in China) added: “We were thrilled when we heard that NMPA approved Orphalan's trientine tetrahydrochloride in China. It is a significant step for those of us living with Wilson disease, representing a much-needed alternative treatment option. This approval, a result of Orphalan's patient-focused approach, offers us a chance to better manage our condition with a new, effective treatment.” Wilson disease is a rare inherited disorder of copper transport primarily affecting the liver and brain. Early treatment with legacy agents such as D-penicillamine (DPA), trientine HCI, and zinc salts can effectively slow the progression of the disease, however these options may not be suitable for long-term care due to adverse events associated with DPA and the need for close monitoring during treatment with zinc salts and DPA. ENDS About Orphalan Orphalan is an international orphan drug development and commercialization company headquartered in Paris. Founded in 2011, the Company develops and deliver innovative therapies for people living with rare and debilitating diseases. Our trientine tetrahydrochloride product has been approved for the treatment of Wilson disease and is available in more than 20 countries, branded as Cuprior® in EU, the UK, Saudi Arabia, Switzerland and Columbia, and as Cuvrior® in the United States. For more information visit www.orphalan.com and follow us on LinkedIn. For more information, please contact: Orphalan: Géraldine van den Broek, Head of Corporate & BD Tel: +33 (0)1 42 49 82 64 info@orphalan.com ICR Consilium: Tracy Cheung, Sukaina Virji, Davide Salvi Tel: +44 (0) 203 709 5700 orphalan@consilium-comms.com

Drug ApprovalOrphan Drug

20 Apr 2023

·www.prnewswire.com

PANTHERx® Rare Announces Release of CUVRIOR™ (trientine tetrahydrochloride) to Treat Wilson Disease

PITTSBURGH, April 19, 2023 /PRNewswire/ -- PANTHERx® Rare, a leader in rare disease product patient access and support services in the United States, is pleased to announce the launch of CUVRIOR to treat stable Wilson Disease in adults who are de-coppered and able to take penicillamine. "We are pleased to add CUVRIOR to the list of PANTHERx® medications. The PANTHERx team works hard to make a positive difference in the lives of our patients who are dealing with devastating and debilitating diseases and CUVRIOR is yet another way we can make an impact," said Rob Snyder, president of PANTHERx® Rare. Wilson Disease is a rare genetic disorder caused by a mutation in the ATP7B gene, resulting in the accumulation of copper throughout the body. Copper deposits in the body lead to a wide array of symptoms including, but not limited to tremors, anxiety, jaundice due to liver injury, and Kayser-Fleischer rings (brown rings in the corneas of the eyes). Untreated, Wilson Disease can be fatal. Serious complications include problems with the liver, kidneys, neurological (e.g., tremors, clumsy gait, speech difficulties), psychological (e.g., depression, psychosis) and blood problems (anemia, jaundice). CUVRIOR is an innovative oral formulation of the active ingredient trientine created by Orphalan to treat adult patients with stable Wilson Disease who have already been de-coppered. CUVRIOR works by chelating copper in the body to decrease copper absorption and increase urinary copper excretion. In clinical trials, CUVRIOR was found to be well tolerated and non-inferior to penicillamine in reducing non-ceruloplasmin copper (NCC) levels in Wilson Disease patients. About PANTHERx Rare PANTHERx Rare is one of the largest and fastest growing rare pharmacies in the United States. PANTHERx transforms lives by delivering medicine breakthroughs, clinical excellence, and access solutions to people living with rare and devastating conditions. Although the overall incidence of rare diseases is as common as diabetes, less than 7% of the 7,000 known rare and devastating disorders have an FDA-approved therapy. Changes in federal policy and advances in science have led to a surge in FDA orphan drug approvals, providing tremendous hope to the rare disease community. PANTHERx was recently awarded Specialty Pharmacy of the Year by the National Association of Specialty Pharmacy (NASP) and earned the inaugural Accredited Distinction in Rare Diseases and Orphan Drugs from the Accreditation Commission for Health Care (ACHC). PANTHERx is now a five-time winner of the prestigious MMIT Patient Choice Award, including the 2022 honor. PANTHERx is headquartered in Pittsburgh, licensed in all 50 states, and holds accreditations from URAC, NABP, and ACHC. IMPORTANT SAFETY INFORMATION Do not use CUVRIOR if you are allergic to trientine or to any of the ingredients in CUVRIOR. Your Wilson's Disease symptoms could get worse when you start treatment. This could happen because too much copper is removed from the body in a short period of time. Your doctor may need to reduce your dose or stop CUVRIOR treatment. Copper deficiency may develop following treatment with CUVRIOR. Your doctor will do tests to monitor your urine and blood for copper. Iron deficiency may develop while taking CUVRIOR. If this happens, your doctor may tell you to take iron supplements for a limited time. Allergic reactions, such as a rash can occur. If a rash or other allergic reaction occurs, stop taking CUVRIOR and get emergency medical help. The most common side effects are pain in the abdomen, change in bowel habits, rash, hair loss (alopecia), and mood swings. Take CUVRIOR at least 1 hour apart from any other oral medicine. Tell your doctor about all the medicines you're taking, including over-the-counter medicines, vitamins, and herbal supplements. Avoid taking supplements when taking CUVRIOR. Taking CUVRIOR with mineral supplements (e.g., iron, zinc, calcium, magnesium) can reduce the effectiveness of CUVRIOR. If iron supplementation is necessary, take CUVRIOR at least 2 hours before or 2 hours after taking iron; for other mineral supplements (e.g., zinc, calcium, magnesium), take CUVRIOR at least 1 hour before or 2 hours after. Do not start or stop any medicines while taking CUVRIOR without talking to your doctor. These are not all the possible side effects of CUVRIOR. You are encouraged to report negative side effects of prescription drugs. Contact Orphalan at 1-800-961-8320 or FDA at 1-800-FDA-1088 or medwatch. Please see full Prescribing Information. 03/2023 US-ORPH-CUVR-023* - Orphalan reviewed and approved this material exclusively regarding CUVRIOR, Wilson disease and Orphalan related information and claims. SOURCE PANTHERx Rare Pharmacy

Orphan Drug

08 Nov 2022

·www.prnewswire.com

JelloX Debut Highlights Potential to Disrupt Cancer Pathology

SAN FRANCISCO, Nov. 8, 2022 /PRNewswire/ -- JelloX Biotech's debut at Intel® Innovation in September drew the attention of healthcare experts and pharmaceutical brands alike for the Taiwan-based startup's potential to shape the future of cancer pathology using 3D imaging technology. JelloX's products will help doctors diagnose and treat cancer tumors with greater speed and accuracy than ever before, all without added strain on budgets. Digital pathology, particularly using 3D imaging, is currently viewed by the healthcare industry as prohibitively expensive due to the need for costly graphics equipment, but JelloX plans to fill in this gap in the market with their innovative AI-powered software platform MetaLite® combined with an edge solution. The company is currently finalizing preparations to begin the FDA approval process for MetaLite® next year through the Software as a Medical Device path. Growing concerns about cancer JelloX's work is timely. A study released in The Harvard Gazette recently shows that cancer risks are rising with each new generation, and — while cancer mortality rates have been declining — the COVID-19 pandemic has caused delayed cancer screening, diagnosis, and treatment, exacerbating the problem and reversing this trend. JelloX prepares to solve these issues with MetaLite®. MetaLite® : the forefront of AI-driven 3D pathology MetaLite® is a cost-effective software platform that leverages AI to analyze 3D-rendered tissue samples rapidly across various parameters and then pinpoint and label tumors and biomarkers. "JelloX Biotech envisions a world where AI-driven 3D pathology empowers healthcare providers by making cancer diagnosis more precise, faster, and less costly," notes JelloX Biotech CEO Dr. Yen-Yin Lin. "MetaLite® plays a leading role in this future. Cancer diagnosis and treatment will be built around the platform's federated learning capabilities to grow a singular knowledge pool accessible to doctors around the world — a cancer pathology database that fully protects patient privacy." How MetaLite® facilitates cancer diagnosis and treatment MetaLite® elevates efficiency and effectiveness by addressing the extensive labor costs, painstaking processes, and myriad technical expenses associated with cancer pathology. Currently the common practice, manual diagnosis of physical biopsy samples is a complex process that takes many hours of exacting work by pathologists. MetaLite® expedites this by rapidly analyzing the many parameters of a sample, identifying cancerous tissue and biomarkers, and then labelling them. In fact, JelloX has developed a total solution prototype with MetaLite® software run on an Intel® device that can analyze every parameter in just a few minutes, compared with an hour on a standard computer and several hours manually. This solution also utilizes custom AI algorithms deployed through the Intel® Distribution of OpenVINO™ Toolkit to further accelerate the process. Besides being a lengthy process, studies have shown that when different doctors manually analyze the same sample, there is a 20% to 30% variation among the diagnoses[i], which has clear implications for treatment and the potential for misdiagnosis to occur. MetaLite® is not only capable of pinpointing tumors and biomarkers with high precision, but its AI enables it to continuously learn and optimize its capabilities — and these will grow exponentially with federated learning added to a future version. Furthermore, before 3D analysis can even begin, a physical tissue sample must be rendered into 3D format via a scanner. MetaLite® offers broad compatibility across scanner brands and formats. To learn more, visit . About JelloX Based in Hsinchu, Taiwan, JelloX Biotech Inc. is a startup founded by researchers from National Tsing Hua University that focuses on advancing cancer pathology through digital and 3D imaging and AI technology. SOURCE JelloX Biotech

100 Deals associated with Trientine Hydrochloride

External Link

KEGG	Wiki	ATC	Drug Bank
D00736	Trientine Hydrochloride	A16AX	DB06824

R&D Status

Approved

10 top approved records.

to view more data

Indication	Country/Location	Organization	Date
Hepatolenticular Degeneration	US	Bausch Health Americas, Inc.	08 Nov 1985

Developing

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Cardiomyopathy, Hypertrophic	Phase 2	GB	Univar Solutions, Inc.	01 Dec 2020
Heart Failure	Phase 2	US	Frontage Laboratories, Inc.	30 Dec 2019
Heart Failure	Phase 2	US	INNOLIFE CO., LTD.	30 Dec 2019
Heart Failure	Phase 2	US	CopMed，Inc.	30 Dec 2019
Myocardial Infarction	Phase 2	CN	INNOLIFE CO., LTD.	-
Myocardial Ischemia	Phase 2	CN	INNOLIFE CO., LTD.	-

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02426905 (EASL2019)	Phase 4	Hepatolenticular Degeneration	52	Trientine dihydrochloride	fynlxftbfn(hopduaezod) = 8 (15.4%) patients reported serious TEAEs piwgmnudfl (tgpcvbzpuv ) View more	-	12 Apr 2019
NCT01472874 (Pubmed \| Dig Dis Sci)	Not Applicable	Hepatolenticular Degeneration Maintenance	8	Trientine	zvhaxuqlfv(cmhxoochpk) = igmvabuqhk yiedpbxhyg (qnlljmngfg )	-	01 May 2015

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Leverages most recent intelligence information, enabling fullest potential.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis