A Phase I, Open-Label, Randomized 3-Period Crossover Study in Healthy Male Subjects to Evaluate the Pharmacodynamic Interactions Between YM150 on Naproxen at Steady-State

The primary objective of this study is to evaluate whether naproxen and darexaban which have different effects on blood coagulation influence each other in their effects. Also it will be investigated whether the blood levels of either drug are influenced by the presence of the other drug. In addition, the safety and tolerability of each drug and the combination of the drugs will be investigated.

Start Date01 Jan 2010

Sponsor / Collaborator

Astellas Pharma, Inc.

100 Clinical Results associated with Darexaban Maleate

100 Translational Medicine associated with Darexaban Maleate

100 Patents (Medical) associated with Darexaban Maleate

Literatures (Medical) associated with Darexaban Maleate

13 Jan 2023·Medicine

Efficacy of 11 anticoagulants for the prevention of venous thromboembolism after total hip or knee arthroplasty: A systematic review and network meta-analysis

Review

Author: Zou, Miao ; Xu, Xinru ; Zhao, Pengfei ; Huang, Zhihao ; Xu, Dan

Background::

To systematically review the efficacy of 11 anticoagulants in the treatment of venous thromboembolism (VTE) after total hip or knee arthroplasty.

Methods::

PubMed, Cochrane Library, Embase, Web of Science, China National Knowledge Infrastructure, Wanfang Data, VIP, and China Biology Medicine databases were electronically searched for studies assessing the efficacy of different anticoagulants for the prevention of VTE after total hip or knee arthroplasty from January 1, 2010, to January 27, 2022. Two reviewers independently screened the literature, extracted data, and graded the evidence using Confidence in Network Meta-Analysis. The network meta-analysis was then performed using Stata 16.0 software and R 4.1.0 software.

Results::

A total of 61 articles were included. The results of network meta-analysis showed that apixaban, edoxaban, fondaparinux, rivaroxaban, and darexaban were the most effective anticoagulants for the prevention of deep vein thrombosis in patients undergoing total hip or knee arthroplasty (P < .05), while there was no difference in the efficacy among the anticoagulants for the prevention of pulmonary embolism (P > .05).

Conclusion::

Apixaban, edoxaban, fondaparinux, rivaroxaban, and darexaban have the best efficacy for the prevention of VTE after total hip or knee arthroplasty.

01 Nov 2021·Drugs

Direct Oral Anticoagulants Combined with Antiplatelet Therapy in the Treatment of Coronary Heart Disease: An Updated Meta-analysis

Review

Author: Lei, Hao ; Liu, Leiling ; Xu, Danyan ; Tang, Ying ; Hu, Jiahui

BACKGROUND:

Direct oral anticoagulants (DOACs) combined with antiplatelet therapy for acute coronary syndrome (ACS) may reduce ischemic events, but there is no consensus on bleeding risk. Moreover, the effect of DOACs on stable coronary artery disease (CAD) needs to be elucidated. We conducted a meta-analysis to summarize the efficacy and safety of DOACs combined with antiplatelet therapy in the treatment of stable CAD and ACS.

METHODS:

We searched PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials, then performed a systematic review of all 17 randomized controlled trials.

RESULTS:

For patients with stable CAD, DOACs combined with antiplatelet therapy significantly reduced the rate of major adverse cardiovascular events (MACE) (risk ratio; 95% confidence interval: 0.88; 0.81-0.95) and ischemic stroke (0.62; 0.50-0.77), with a relatively low risk of major bleeding (1.72; 1.42-2.07). For patients with ACS, the combination of DOACs reduced the risk of MACE (0.91; 0.85-0.97), myocardial infarction (MI) (0.90; 0.83-0.98), and ischemic stroke (0.75; 0.58-0.97), accompanied by increased non-fatal bleeding events and intracranial hemorrhage (3.42; 1.76-6.65). Results were similar when restricting the analysis to phase III studies except for the rate of stroke in patients with ACS.

CONCLUSIONS:

Combination therapy reduced the incidence of MI in ACS patients, but the risk of bleeding from intracranial hemorrhaging outweighs the benefit of MACE driven by MI. That is due to combination therapy having no positive impact on mortality; thus, the benefit-risk balance may be more favorable in patients with stable CAD.

01 Apr 2021·Pharmacological researchQ2 · MEDICINE

Ranking the efficacy of anticoagulants for the prevention of venous thromboembolism after total hip or knee arthroplasty: A systematic review and a network meta-analysis

Q2 · MEDICINE

Review

Author: Feng, Weili ; Huang, Daoqiang ; Wang, Xiaoping ; Lu, Anqi

BACKGROUND:

Anticoagulants are essential in the prevention of venous thromboembolism. However, the effectiveness and safety of different anticoagulants have always been controversial. Therefore, we aimed to expand the sample of anticoagulant results and rank the efficacy and safety of 19 anticoagulants in the prevention of venous thromboembolism when total knee or total hip arthroplasty procedure is performed.

METHODS:

A systematic review and network meta-analysis of randomized trials of adult patients undergoing total hip or knee arthroplasty were conducted. The trials were identified from PubMed, Web of Science, Cochrane Library, and Embase databases, in which anticoagulants were used as interventions randomized controlled trial. The incidence of venous embolism and bleeding are the key outcomes of assessing the efficacy of intervention drugs. We used the Physical Therapy Evidence Database (PEDro) to assess risk bias and used pairwise comparison and network meta-analysis with random effects to estimate the summary relative risk. The study has been registered with PROSPERO, number CRD42020200747.

RESULTS:

From the 4083 identified manuscripts, 45,067 participants from 53 randomized trials were included in the analysis and randomly assigned to 19 anticoagulants. With Enoxaparin as a control, Rivaroxaban (risk difference 0.07, 95 % credible interval 0.06 to 0.08), Edoxaban (RD 0.09, 95 % CrI 0.08 to 0.11), and Apixaban (RD 0.05, 95 % CrI 0.04 to 0.06) had the best effect in preventing VTE. However, in terms of comprehensive bleeding rate, Apixaban, Edoxaban, and Darexaban were the most effective and stable. Although effective in preventing VTE, bleeding remains relatively high in Rivaroxaban. Enoxaparin is low-molecular-weight heparin that is widely used in clinics, and although its overall efficacy is not the best, its efficacy and safety are very stable.

CONCLUSION:

According to the available data, Apixaban, Edoxaban, and Darexaban are better than any anticoagulants in the prevention of VTE and bleeding during total knee or total hip arthroplasty. In our study, Fondaparinux, Eribaxaban, Dalteparin, Betrixaban, Bemiparin, Reviparin, Acenocoumarol, and Tinzaparin were scarce in the included studies, therefore, more evidence is needed to prove their efficacy and safety.

News (Medical) associated with Darexaban Maleate

15 Feb 2011

·www.astellas.com

Astellas Pharma Inc.: Withdraws Application for Marketing Approval of Darexaban (YM150), an Oral Direct Factor Xa Inhibitor, in Japan

Tokyo, February 15, 2011 - Astellas Pharma Inc. (“Astellas”; headquarters: Tokyo; President and CEO: Masafumi Nogimori) announced that it withdrew a market authorization application for darexaban maleate (“darexaban”; generic name; development code name: YM150), an oral Factor Xa direct inhibitor, which was submitted to the Ministry of Health, Labour and Welfare (“MHLW”) in Japan. The application is for the indication of the prevention of venous thromboembolism (“VTE”) in patients at risk, such as those undertaking orthopedic surgical procedures in the lower limbs. On September 29, 2010, Astellas submitted the application to MHLW. Subsequently, Pharmaceuticals and Medical Devices Agency (“PMDA”) provided their view that Astellas should conduct additional clinical studies to supplement the current application package in order to achieve approval. Following that discussion with PMDA, Astellas decided to withdraw the application today. Astellas is considering the appointment of a partner for the development and commercialization of darexaban for the indications of the prevention of VTE in the U.S. and Europe, and stroke prevention in atrial fibrillation globally. Astellas expects to decide future plan, including the indication of VTE in Japan, based on the outcome of the partnership discussion above. The impact of the application withdrawal on Astellas’ current fiscal year (from April 1, 2010 to March 31, 2011) financial forecast will be immaterial. * VTE is a condition consisting of both Pulmonary Embolism (“PE”) and Deep-Vein Thrombosis (“DVT”) causing PE. DVT is the disease condition caused by the formation of blood clot in the deep vein. PE is the disease condition caused by a blockage of the pulmonary artery by a blood clot which is formed mainly in the deep vein and reaches the lungs through the blood stream, resulting in the disturbance in the pulmonary circulation. It is extremely important to prevent DVT, which frequently occurs after orthopedic surgical procedures in the lower limbs and the abdominal area, because the mortality of PE is high. ###

Drug Approval

29 Sep 2010

·www.astellas.com

Astellas Pharma Inc.: Submits Application for Marketing Approval of Darexaban (YM150), an Oral Direct Factor Xa Inhibitor, in Japan

Tokyo, September 29, 2010 - Astellas Pharma Inc. (“Astellas”; headquarters: Tokyo; President and CEO: Masafumi Nogimori) announced that it submitted a market authorization application for darexaban maleate (“darexaban”; generic name; development code name: YM150) to the Ministry of Health, Labour and Welfare today in Japan. Astellas is seeking an approval for the indication of the prevention of venous thromboembolism (“VTE”) in patients at risk, such as those undertaking orthopedic surgical procedures in the lower limbs. Darexaban is an oral Factor Xa inhibitor discovered and developed by Astellas. Darexaban directly and selectively inhibits activated Factor X in the cascade of blood coagulation and, thus, is expected to prevent VTE by suppressing the thrombin production. The two Phase-II/III studies, which enrolled patients after having elective total knee or hip replacement surgeries in Japan and other Asian countries proved superior efficacy of darexaban over placebo in VTE prevention. The development program also supported safety of darexaban. Currently YM150 is under global development for indications of prevention of VTE , stroke prevention in atrial fibrillation (“AF”) patients and the prevention of ischemic vascular events in subjects with recent acute coronary syndromes (“ACS”). The North American Phase-II study for VTE prevention in patients after elective primary knee arthroplasty demonstrated dose dependent efficacy of darexaban in VTE prevention. The international Phase-IIa study, which was conducted in Japan and other Asian countries, etc., identified optimal dose range for further development of darexaban for stroke prevention in AF patients. Astellas expects to provide an additional therapeutic option, and further contribute to VTE prevention by introducing darexaban, an oral anticoagulant with a new mechanism of action, into the Japanese market. * VTE is a condition consisting of both Pulmonary Embolism (“PE”) and Deep-Vein Thrombosis (“DVT”) causing PE. DVT is the disease condition caused by the formation of blood clot in the deep vein. PE is the disease condition caused by a blockage of the pulmonary artery by a blood clot which is formed mainly in the deep vein and reaches the lungs through the blood stream, resulting in the disturbance in the pulmonary circulation. It is extremely important to prevent DVT, which frequently occurs after orthopedic surgical procedures in the lower limbs and the abdominal area, because the mortality of PE is high. ###

Drug ApprovalClinical Result

100 Deals associated with Darexaban Maleate

External Link

KEGG	Wiki	ATC	Drug Bank
D09817	Darexaban Maleate	-	DB12289

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Coronary Thrombosis	Phase 3	Denmark	Astellas Pharma Europe BV	26 Aug 2009
Acute Coronary Syndrome	Phase 3	Germany	Astellas Pharma Europe BV	12 Aug 2009
Stroke	Phase 3	Germany	Astellas Pharma Europe BV	12 Aug 2009
Venous Thromboembolism	Phase 3	United States	Astellas Pharma Europe Ltd.	01 Apr 2009
Venous Thromboembolism	Phase 3	Australia	Astellas Pharma Europe Ltd.	01 Apr 2009
Venous Thromboembolism	Phase 3	Austria	Astellas Pharma Europe Ltd.	01 Apr 2009
Venous Thromboembolism	Phase 3	Bosnia and Herzegovina	Astellas Pharma Europe Ltd.	01 Apr 2009
Venous Thromboembolism	Phase 3	Brazil	Astellas Pharma Europe Ltd.	01 Apr 2009
Venous Thromboembolism	Phase 3	Canada	Astellas Pharma Europe Ltd.	01 Apr 2009
Venous Thromboembolism	Phase 3	Colombia	Astellas Pharma Europe Ltd.	01 Apr 2009

Clinical Result

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00942435 (Pubmed \| Thromb Res)	Phase 3	-	-	Darexaban 15 mg bid	hkqqinhfye(bptmkwzman) = othwidotbi cmndkjfnef (whifowjyxj ) View more	-	01 Sep 2012
				Darexaban (YM150) (Mechanical prophylaxis)	hkqqinhfye(bptmkwzman) = gvwbzxltip cmndkjfnef (whifowjyxj ) View more
NCT00353678 (ONYX-2, Pubmed \| J Thromb Haemost)	Not Applicable	Venous Thromboembolism	1,017	YM150 5 mg	wvautvvsew(vmgeeezgaj) = hpqcvznuas mvjmhuppvd (goojjoikdd )	-	01 Apr 2010
				YM150 10 mg	wvautvvsew(vmgeeezgaj) = cllqeoobpm mvjmhuppvd (goojjoikdd )

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