COMT inhibitors(Catechol-O-methyl transferase inhibitors), DDC inhibitors(DOPA decarboxylase inhibitors), DRDs antagonists(Dopamine receptors antagonists)

Therapeutic Areas

Nervous System DiseasesEndocrinology and Metabolic Disease

Active Indication

Parkinson Disease

Inactive Indication-

Originator Organization

Orion Pharma Ltd.

Active Organization

Orion Pharma Ltd.

Orion Oyj

Inactive Organization-

Drug Highest PhaseApproved

First Approval Date

United States (11 Jun 2003),

Parkinson Disease

Regulation-

Structure/Sequence

Molecular FormulaC33H40N6O13

InChIKeyOTVUCEMFRGJEMR-FTXVUGNJSA-N

CAS Registry745835-09-0

Clinical Trials associated with Carbidopa/Entacapone/Levodopa

CTR20244480

/ CompletedNot Applicable

恩他卡朋双多巴片（Ⅱ）人体生物等效性研究

[Translation] Study on the bioequivalence of Entacapone Bidopa Tablets (Ⅱ) in human body

比较空腹给药条件下，山东京卫制药有限公司生产的恩他卡朋双多巴片（Ⅱ）（规格：左旋多巴100mg、卡比多巴25mg和恩他卡朋200mg）与Orion Corporation生产的恩他卡朋双多巴片（Ⅱ）（规格：左旋多巴100mg、卡比多巴25mg和恩他卡朋200mg，商品名：Stalevo ®/达灵复®）在中国健康成年参与者中吸收程度和吸收速度的差异，评价空腹状态下口服两种制剂的生物等效性，并评价山东京卫制药有限公司生产的恩他卡朋双多巴片（Ⅱ）（规格：左旋多巴100mg、卡比多巴25mg和恩他卡朋200mg）的安全性。

[Translation]

To compare the differences in absorption extent and rate of Entacapone Bidopa Tablets (II) (Specifications: 100 mg levodopa, 25 mg carbidopa, and 200 mg entacapone) produced by Shandong Jingwei Pharmaceutical Co., Ltd. and Entacapone Bidopa Tablets (II) (Specifications: 100 mg levodopa, 25 mg carbidopa, and 200 mg entacapone, trade name: Stalevo ®/Dalingfu ®) produced by Orion Corporation in healthy Chinese adult participants under fasting conditions, to evaluate the bioequivalence of the two oral preparations under fasting conditions, and to evaluate the safety of Entacapone Bidopa Tablets (II) (Specifications: 100 mg levodopa, 25 mg carbidopa, and 200 mg entacapone) produced by Shandong Jingwei Pharmaceutical Co., Ltd.

Start Date26 Dec 2024

Sponsor / Collaborator

Jewim Pharmaceutical (Shandong) Co., Ltd

CTR20241719

/ CompletedNot Applicable

受试制剂恩他卡朋双多巴片（Ⅱ）与参比制剂达灵复@在中国健康成年参与者空腹和餐后状态下的生物等效性试验

[Translation] Bioequivalence study of the test preparation Entacapone Bidopa Tablets (II) and the reference preparation Dalingfu@ in healthy adult participants in China under fasting and fed conditions

研究空腹和餐后状态下单次口服受试制剂恩他卡朋双多巴片（Ⅱ）与参比制剂达灵复®在健康参与者体内的药代动力学特征，计算主要药动学参数，比较制剂间药动学参数AUC和Cmax的差异，评价受试制剂与参比制剂是否具有生物等效性。研究受试制剂恩他卡朋双多巴片（Ⅱ）与参比制剂达灵复®在中国健康参与者中的安全性。

[Translation]

To study the pharmacokinetic characteristics of the test preparation Entacapone Bidopa Tablets (II) and the reference preparation Dalingfu® in healthy participants after a single oral administration in the fasting and postprandial state, calculate the main pharmacokinetic parameters, compare the differences in pharmacokinetic parameters AUC and Cmax between the preparations, and evaluate whether the test preparation and the reference preparation are bioequivalent. To study the safety of the test preparation Entacapone Bidopa Tablets (II) and the reference preparation Dalingfu® in healthy Chinese participants.

Start Date29 May 2024

Sponsor / Collaborator

Zhejiang Jingxin Pharmaceutical Co., Ltd.

CTR20241436

/ CompletedNot Applicable

恩他卡朋双多巴片（II）在中国健康受试者中空腹和餐后给药条件下随机、开放、单剂量、两序列、四周期、完全重复交叉生物等效性试验

[Translation] A randomized, open-label, single-dose, two-sequence, four-period, fully repeated crossover bioequivalence study of entacapone bidopa tablets (II) in Chinese healthy subjects under fasting and fed conditions

主要研究目的：按有关生物等效性试验的规定，选择Orion Corporation为持证商的恩他卡朋双多巴片（II）（商品名：达灵复，规格：左旋多巴100mg、卡比多巴25mg、恩他卡朋200mg）为参比制剂，对四川科伦药业股份有限公司提供的受试制剂恩他卡朋双多巴片（II）（规格：左旋多巴100mg、卡比多巴25mg、恩他卡朋200mg）进行空腹和餐后给药人体生物等效性试验，比较受试制剂中药物的吸收速度和吸收程度与参比制剂的差异是否在可接受的范围内，评估两种制剂在空腹和餐后给药条件下的生物等效性。次要研究目的：观察健康志愿受试者口服受试制剂恩他卡朋双多巴片（II）（规格：左旋多巴100mg、卡比多巴25mg、恩他卡朋200mg）和参比制剂恩他卡朋双多巴片（II）（商品名：达灵复，规格：左旋多巴100mg、卡比多巴25mg、恩他卡朋200mg）的安全性。

[Translation]

Main research purpose: According to the relevant provisions of bioequivalence test, Orion Corporation is selected as the licensee of Entacapone Bidopa Tablets (II) (trade name: Dalingfu, specifications: levodopa 100mg, carbidopa 25mg, entacapone 200mg) as the reference preparation, and the test preparation Entacapone Bidopa Tablets (II) (specifications: levodopa 100mg, carbidopa 25mg, entacapone 200mg) provided by Sichuan Kelun Pharmaceutical Co., Ltd. is conducted on the human bioequivalence test of fasting and postprandial administration, to compare whether the absorption rate and degree of the drug in the test preparation are within the acceptable range with the reference preparation, and to evaluate the bioequivalence of the two preparations under fasting and postprandial administration conditions. Secondary study objective: To observe the safety of oral administration of the test preparation Entacapone Bidopa Tablets (II) (Specifications: levodopa 100 mg, carbidopa 25 mg, entacapone 200 mg) and the reference preparation Entacapone Bidopa Tablets (II) (trade name: Dalingfu, specifications: levodopa 100 mg, carbidopa 25 mg, entacapone 200 mg) to healthy volunteers.

Start Date20 May 2024

Sponsor / Collaborator

Sichuan Kelun Pharmaceutical Co., Ltd.

100 Clinical Results associated with Carbidopa/Entacapone/Levodopa

100 Translational Medicine associated with Carbidopa/Entacapone/Levodopa

100 Patents (Medical) associated with Carbidopa/Entacapone/Levodopa

Literatures (Medical) associated with Carbidopa/Entacapone/Levodopa

01 Aug 2024·Neurology and Therapy

The Catechol O-Methyltransferase Inhibitor Entacapone in the Treatment of Parkinson’s Disease: Personal Reflections on a First-in-Class Drug Development Programme 40 Years On

Review

Author: Pollesello, Piero ; Männistö, Pekka T ; Hanttu, Anna ; Keränen, Tapani ; Reinikainen, Kari J

In the 1980s, Orion Pharma, then a mid-ranking Nordic area pharmaceutical company, established a drug development programme on the inhibition of catechol O-methyltransferase (COMT). This enzyme, which plays an important role in the inactivation of catecholamine neurotransmitters and drugs with a catechol structure, thus came under consideration as a target in the innovative translational and clinical programme we describe in this historical review. The starting point was the conjecture that a peripherally acting COMT inhibitor might improve entry of levodopa into the brain. This had potentially significant implications for the medical treatment of Parkinson's disease (PD). The rationale was that more efficient delivery of levodopa to the brain might allow the high therapeutic doses of levodopa to be reduced and the dose interval to be extended. Elucidation of structure-activity relations paved the way for the discovery and development of entacapone, a 5-nitrocatechol that was a potent and highly specific inhibitor of COMT. Experience in phase III clinical trials established that entacapone, used as an adjunct to regular or controlled-release levodopa preparations (also including a peripherally acting dopa-decarboxylase inhibitor), increased ON-time and reduced OFF-time and improved clinical condition in patients with PD experiencing wearing-off, often with a reduced daily levodopa dose. Several of these studies also identified that entacapone improved patients' quality of life and was cost-effective. Subsequently, entacapone has been amalgamated into a triple-combination preparation (Stalevo®) with levodopa and carbidopa to create a flexible and convenient drug therapy for patients with PD who have end-of-dose motor fluctuations not stabilised on levodopa/dopa-decarboxylase inhibitor treatment. This review offers a historical perspective on a successful programme of drug development by researchers who played central roles in the progress from exploratory hypothesis to registered pharmaceutical product.

01 Nov 2023·European journal of neurology

Real-world considerations regarding the use of the combination of levodopa, carbidopa, and entacapone (Stalevo^® ) in Parkinson's disease.

Review

Author: Reichmann, Heinz

An important aim in long-term levodopa therapy is to prolong the duration of symptomatic efficacy of each dose without increasing peak plasma concentrations above the threshold for the emergence of dyskinesias. One strategy is to enhance levodopa delivery to the brain by co-administering it with inhibitors of peripheral dopa-decarboxylase and catechol-O-methyltransferase (COMT). Levodopa, carbidopa and entacapone (LCE), available in a range of fixed-dose combinations as the branded formulation Stalevo^® (Orion Pharma), has been developed to address this requirement and has been in general use for 20 years, having first been evaluated in randomized controlled trials. Experience with LCE has established that improved levodopa pharmacokinetics achieved with dual-enzyme inhibition are translated into improved clinical efficacy, including the possibility of reducing total levodopa dosage with no loss of therapeutic effect. The ease and tolerability of switching to LCE has been affirmed in the SIMCOM trial and by personal experience detailed in this review. Some 300,000 patient-years of safety data are available for LCE, including trial data for up to 5 years. Most adverse effects associated with LCE are attributable to the levodopa component rather than the enzyme inhibitors. The hepatotoxicity observed with the class comparator tolcapone has not been observed with entacapone, the COMT inhibitor in LCE, and there is no formal requirement to monitor liver function during LCE therapy. Other common side effects include diarrhoea, which is one of the more prominent non-dopaminergic adverse events, and urine discolouration, which is harmless but about which patients may require reassurance.

01 Nov 2023·European journal of neurology

The 20th anniversary of the first clinical use of Stalevo^®.

Author: Reichmann, Heinz ; Poewe, Werner ; Jenner, Peter

News (Medical) associated with Carbidopa/Entacapone/Levodopa

28 Aug 2024

·www.fiercepharma.com

Stada reports rosy earnings as CEO tempers expectations around possible sale, IPO

“Together with our 11,500 employees, my focus is on keeping Stada on a record-breaking trajectory in the second half of the year and growing faster than our competitors,” Stada Arzneimittel’s CEO, Peter Goldschmidt, said in a statement Wednesday. As Stada Arzneimittel’s private equity owners continue to weigh their options around a potential sale or public offering, the German drugmaker gave a good indication Wednesday of exactly what it can bring to the table.Over the first six months of the year, Stada generated sales of 2.02 billion euros ($2.2 billion), growing revenues 9% compared with the same period in 2023, the company said in a release. For the same period that ended June 30, Stada grew earnings before interest, taxes, depreciation, and amortization by 11% to 465.3 million euros ($515 million).All three of Stada’s business segments—consumer healthcare, generics and specialty pharma—contributed to the revenue growth, with specialty pharma delivering the biggest year-over-year change. The company also said it enjoyed a boon from its “rapidly growing” biosimilar offerings and from the launches of differentiated neurology and nephrology products.Notably, the question of whether Stada will eventually be sold—a prospect that’s been making headlines since last August— “will be decided exclusively by our owners,” the company’s CEO, Peter Goldschmidt, said in an emailed statement.He added that there is “no update” on Stada’s sales plans at this time and explained that the drugmaker’s owners, Cinven and Bain Capital, are “examining various options, including an IPO.”“Together with our 11,500 employees, my focus is on keeping Stada on a record-breaking trajectory in the second half of the year and growing faster than our competitors,” Goldschmidt added. Taking a closer look at the numbers, Stada’s specialty pharma arm grew sales 14% to 417.3 million euros ($464 million) during the first half of 2024. Stada credited the specialty pharma growth to its swelling biosimilar portfolio plus brands like the Parkinson’s disease therapy Lecigon and the orphan medicine Kinpeygo in a rare kidney disease.Elsewhere, generics sales jumped 12% to 838.2 million euros ($932 million), driven in part by the launch of the complex copycats for deep vein thrombosis, rivaroxaban and dabigatran, across multiple European countries, Stada said. Rivaroxaban is the generic of Johnson & Johnson’s Xarelto, while dabigatran is sold by Boehringer Ingelheim under the brand name Pradaxa.In its release, Stada called its generics business a “consistent and sustainable growth driver” for the company, noting that it expects to benefit from a generics launch pipeline that already covers some “80% of original medicines that will lose exclusivity over the next few years.”As for the last pillar of Stada’s business, the company’s consumer healthcare segment saw revenues climb 3% to 768.3 million euros ($854 million).Last August, Bloomberg reported that Stada’s owners, Cinven and Bain, were weighing options for the company, including a possible sale. At the time, sources close to the talks told the news service that the sale could value Stada at 10 billion euros or more. Goldschmidt last year told the German Press Agency that Cinven and Bain were conducting “initial exploratory talks” around the potential fate of the company, though he stressed that the investors were under “no pressure to sell.”More recently, Stada in April kicked off talks with potential buyers in a sale that could value the company at around 8 billion euros, Bloomberg reported at the time, citing people with knowledge of the discussions. The news outlet’s sources added that Stada’s private equity owners were also weighing a potential initial public offering.Bain and Cinven agreed to buy Stada for 5.3 billion euros in 2017. The deal gave the private equity firms control of what was one of the last independent generic drug makers in Europe.

AcquisitionBiosimilarIPO

09 Apr 2024

·www.prnewswire.com

Intrance Medical Systems Inc signs LOI purchase commitment for clinical trials with Parkinson's diseases patients

STOCKHOLM, April 9, 2024 /PRNewswire/ -- Tridentify are delighted to announce that Intrance Medical Systems Inc. now have signed a LOI purchase commitment of $ 300 000. Their Tridentify safeguarding solution will be used for the 'logistic journey' of the drug component for clinical trials in at least Europe and the US for patients with Parkinson diseases in advanced stage. The clinical development program for US registration has recently been initiated, with a larger more extensive study planned for late 2024. "Intrance Medical Systems is focused on the development and commercialization of its lead clinical product for the treatment of advanced Parkinson's disease. The product, Lecigon, is successfully marketed and available across Europe (by Britannia Pharmaceuticals). Intrance Medical plans to bring this innovative system to the US, Canada, Japan, Taiwan and LATAM. The US clinical development program includes key studies where accurate data to the FDA is paramount. Since Lecigon requires an unbroken cold supply chain and whose properties can change if improperly handled, we have found that Tridentify has a unique solution with monitoring and continuous calculation of remaining shelf life. We're excited about our collaboration and anticipate extending our partnership in the future," says Patrick Shea, CEO at Intrance Medical Systems Inc. " Tridentify is excited about the next steps with Intrance Medical Inc. Together with Intrance we want to ensure high quality standards in their important development of a new Parkinson treatment. We are proud to be able to safeguard the shipments for the clinical trials in Europe and in the US, as well as to support the important safety for patients with severe diseases," says Ann-Christine Jungmar, CEO at Tridentify. For further information, kindly contact: Ann-Christine Jungmar, CEO Tridentify +46 708 71 46 76 [email protected] This information was brought to you by Cision The following files are available for download:

Drug ApprovalClinical Study

16 May 2023

·www.businesswire.com

Intrance Medical Systems Appoints Ashley Prange as Vice President of Business Development

NEW YORK--( BUSINESS WIRE )--Intrance Medical Systems, Inc., a biopharmaceutical company focused on the development and commercialization of its lead clinical product for the treatment of advanced Parkinson’s disease, today announced the appointment of Ashley Prange to the position of Vice President of Business Development. “ We are pleased to welcome Ashley to Intrance at an important time when we are making continued progress with our lead asset for advanced Parkinson’s disease, preparing to initiate our pivotal clinical trial, and successfully implementing other key strategic initiatives,” said Patrick Shea, Chief Executive Officer of Intrance Medical Systems. “ Ashley is a wonderful addition to our team. Her experience leading commercial and business development activities within the pharmaceutical industry will be tremendously valuable as we strengthen our focus on strategic partnerships in the U.S. and other select countries to ensure our innovative drug-device therapy reaches as many patients with advanced Parkinson’s disease as possible.” In her role at Intrance Medical Systems, Ms. Prange will be responsible for building and implementing the company’s strategic partnering initiatives for the U.S., Japan, Taiwan, Canada, and South America. Specifically, she will be instrumental in helping Intrance initiate ex-U.S. out-licensing activities as well as explore commercial collaborations in the U.S. for its lead clinical product, known as Lecigon® in Europe, to ensure optimal geographic coverage. Intrance Medical Systems formally established its U.S. operations in April 2021 with the goal to bring its novel treatment approach for late-stage Parkinson’s disease to markets where the company owns and controls all intellectual property and commercial rights. These markets include the U.S., Canada, Mexico, South America, Japan and Taiwan. In the U.S., Intrance has submitted an Initial New Drug (IND) application to the U.S. Food and Drug Administration (FDA) under the 505(b)(2) pathway. “ As we continue to see impressive physician and patient adoption of Lecigon across approximately 20 countries in Europe by the work of STADA/Britannia, we are steadfast in our mission to bring our novel drug-device system to the U.S. and other key markets to help improve patient quality of life and treatment outcomes,” added Ulf Rosén, Co-founder and Chairman of the Board of Intrance Medical Systems. Ms. Prange has strong commercial and business development experience across multiple therapeutic areas, including neurology and Central Nervous System (CNS) diseases. She formerly served as Director of Business Development at Azurity Pharmaceuticals, where she led the licensing and product acquisition team responsible for identifying strategic business opportunities. Prior to Azurity, she was Director of Business Development at Arbor Pharmaceuticals (acquired by Azurity in 2021) working closely with the board and management team to spearhead high-priority strategic corporate transactions. Ms. Prange earned her bachelor’s degree in Journalism specializing in Advertising and Sports Marketing from the University of North Carolina Chapel Hill. About Intrance Medical Systems Intrance Medical Systems, Inc., is a private biopharmaceutical company focused on the development and commercialization of its lead clinical product for the treatment of advanced Parkinson’s disease in the U.S., Canada, South America, Japan and Taiwan. Intrance’s lead product, known as Lecigon® in the European market, is a fixed-dose combination treatment of levodopa, carbidopa and entacapone for enteral infusion in advanced Parkinson’s disease patients. The company is planning to advance its U.S. clinical development program in this target indication and has filed an Investigational New Drug (IND) application with the U.S. Food and Drug Administration (FDA) under the 505(b)(2) pathway. For more information, visit intrancemedical.com .

Executive Change

100 Deals associated with Carbidopa/Entacapone/Levodopa

External Link

KEGG	Wiki	ATC	Drug Bank
-	Carbidopa/Entacapone/Levodopa	N04BA03	-

R&D Status

10 top approved records.

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Indication	Country/Location	Organization	Date
Parkinson Disease	United States	Orion Pharma Ltd.	11 Jun 2003

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


MDS2023	Not Applicable	Parkinson Disease	9	Levodopa-entacapone-carbidopa intestinal gel (LECIG)	mrrewhbjkv(ixfnnfcppt) = in 4/9 patients (44.4%) qrasfatgoe (mkemulrfvs ) View more	-	27 Aug 2023
ParkReg (MDS2023)	Not Applicable	Parkinson Disease plasma levels of homocysteine (p-Hcy)	150	Levodopa-entacapone-carbidopa intestinal gel (LECIG)	vdcwlgeldz(fqtsrssfoy) = lcluzlyekd zwdakldyav (kaalkaohxp ) View more	Positive	27 Aug 2023
MDS2023	Not Applicable	Parkinson Disease	16	Levodopa-entacapone-carbidopa intestinal gel	mmqgntvmfi(ncyfjwrqri) = mqsozewmhy pbqqnkbkzo (wwwgjfjprh ) View more	-	27 Aug 2023
Phase IV study (Pubmed \| J Neural Transm (Vienna))	Phase 4	-	-	Levodopa/carbidopa/entacapone (LCE)	jmpxyouflh(qmrymhmpwu) = agtgejkprw nkbuegfitw (oplcjyqtqd )	Positive	01 Apr 2014
S23.005 (AAN2013)	Phase 2	Parkinson Disease	117	ODM-101/65mg	fazyjhbron(idajglpegy) = Dyskinesias reported as spontaneous adverse events were more commonly reported for ODM-101/105 mg vs other treatments. gybpvqzfcm (ghorkboseg )	-	12 Feb 2013
S23.005 (AAN2013)	Phase 2	Parkinson Disease	117	ODM-101/105mg		-	12 Feb 2013
NCT00391898 (CTgov)	Phase 4	Parkinson Disease	95	Levodopa/carbidopa/entacapone (Levodopa/Carbidopa/Entacapone)	viuezaeksb(myhqqctwpy) = aqlbdpenfe elxkvylbav (wtyzuwojin, 2.8) View more	-	15 Mar 2011
NCT00391898 (CTgov)	Phase 4	Parkinson Disease	95	Levodopa/carbidopa (Levodopa/Carbidopa)	viuezaeksb(myhqqctwpy) = brpteqvhtv elxkvylbav (wtyzuwojin, 3.0) View more	-	15 Mar 2011
NCT00219284 (CTgov)	Phase 4	Parkinson Disease	359	Carbidopa/levodopa/entacapone (Immediate Switch)	qcvcagvpoc(sjeqsvhdym) = wezmlcnyzl ddmvqdzevg (avajqqnbjk, 0.66) View more	-	15 Mar 2011
NCT00219284 (CTgov)	Phase 4	Parkinson Disease	359	Carbidopa/levodopa/entacapone (Delayed Switch)	qcvcagvpoc(sjeqsvhdym) = vazgmhcufd ddmvqdzevg (avajqqnbjk, 0.58) View more	-	15 Mar 2011
NCT00099268 (STRIDE-PD, CTgov)	Phase 3	Parkinson Disease	747	Carbidopa/levodopa/entacapone	vdzzxsfaht = nydunlqrvp fkqkewvhop (dkiqudlatx, amrfafdsck - rkhdedpaqt) View more	-	08 Mar 2011
NCT00642356 (CTgov)	Phase 4	Parkinson Disease	14	Carbidopa/levodopa/entacapone (Carbidopa/Levodopa/Entacapone)	huuqrplyai(ihleozxnmf) = anjjaoqkib eszjdosice (iccyvvjfoq, 0.90) View more	-	11 Jan 2011
NCT00642356 (CTgov)	Phase 4	Parkinson Disease	14	Immediate release carbidopa/levodopa (Immediate Release Carbidopa/Levodopa)	huuqrplyai(ihleozxnmf) = wcjegxyxcq eszjdosice (iccyvvjfoq, 2.49) View more	-	11 Jan 2011

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