| 2014年8月19日，美国食品与药物管理局(FDA)批准了钠葡萄糖共同转运蛋白2(SGLT2)抑制剂坎格列净(canagliflozin)与二甲双胍的固定复方制剂用于治疗成人2型糖尿病。该药商标名为Invokamet，包括50或150 mg 坎格列净或500或1000mg 二甲双胍的片剂，推荐剂量为每日两次，是美国市场上的首个坎格列净与二甲双胍的固定复方制剂。 此次FDA对Invokamet的批准基于杨森公司发布的III期临床试验数据。该III期临床试验共有4732人参与，数据表明，相较二甲双胍和其他单药治疗，INVOKAMET能大幅度降低患者体内的HbA1c水平，INVOKAMET与相应剂量坎格列净+二甲双胍联合治疗方案具有等效性。 FDA批准Invokamet作为一种辅助药物，结合运动和饮食，用于改善2型糖尿病成人患者的血糖控制，主要用于: （1）服用坎格列净或二甲双胍单药不能充分控制血糖水平的患者； （2）已经在接受坎格列净+二甲双胍两种药物联合治疗的患者。 Invokamet不适用于1型糖尿病和糖尿病酮症酸中毒的治疗。 在美国，Invokamet是首个SGLT2抑制剂和二甲双胍固定剂量复方产品。此前，Invokamet已于2014年4月获欧盟批准上市。 Invokamet同时还附带黑框警告，即二甲双胍累积有可能会出现乳酸酸中毒，可致死。患者如果有严重肾功能或属于血液透析治疗阶段，也禁止服用该药物。 Invokamet(Canagliflozin and Metformin Hydrochloride) Tablets New Drugs Online Report for canagliflozin + metformin IR Information Generic Name: canagliflozin + metformin IR Trade Name: Vokanamet (EU), Invokamet (US) Entry Type: New formulation Developmental Status UK: Launched EU: Launched US: Approved (Licensed) UK launch Plans: Available only to registered users Actual UK launch date: October 2014 Comments Nov 14: Price 60 x 50/850mg tabs and 60 x 50/1000mg; both £39.20 [12]. 03/11/2014 16:15:02 Oct 14: Vokanamet 50 mg/1000 mg film-coated tablets launched in the UK [11]. 16/10/2014 11:48:56 Aug 14: Approved in the US [10] 11/08/2014 22:09:57 Apr 14: The European Commission has approved VOKANAMET® (a fixed-dose therapy combining canagliflozin and immediate release metformin hydrochloride) in the EU, for the treatment of adults with type 2 diabetes mellitus to improve glycaemic control [8]. 19/06/2014 14:51:02 Feb 14: Johnson & Johnson submit a response to the FDA [9]. 19/06/2014 14:50:50 Feb 14: Positive opinion granted in the EU for the treatment type 2 diabetes mellitus [7] 22/02/2014 18:15:48 Dec 13: The FDA has issued a complete response letter for a fixed-dose combination of canagliflozin and immediate-release metformin to treat adults with T2DM. The letter asks for additional information to support the comparability of the twice-daily dosing regimen of canagliflozin as part of the canagliflozin and metformin combination and the once-daily dosing of canagliflozin as a single agent. Janssen believes it can supply this information based on available clinical data [6]. 13/12/2013 13:41:35 Mar 13: Filed in EU Mar 13 [5] 26/03/2013 14:44:39 Dec 12: New Drug Application submitted to US FDA [4] 13/12/2012 12:05:23 PIII in EU & US [1]. 06/12/2011 16:02:22 Trial or other data Apr 12: No further update. 19/04/2012 14:18:16 Four PI studies in healthy volunteers started in 4Q 11: NCT01454622 is evaluating the bioequivalence of canagliflozin/metformin immediate-release vs. the individual components in 64 US subjects from the US; NCT01459094 is an open-label crossover study comparing the bioavailability of canagliflozin/metformin IR when given with or without food in 24 US volunteers; NCT01463774 is comparing fixed-dose canagliflozin/metformin to separate canagliflozin & metformin in 64 US subjects; NCT01463228 is assessing the bioequivalence of the fixed-dose combination vs. individual components in 64 US individuals [2]. 07/12/2011 10:30:27 Evidence Based Evaluations EPAR http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/002656/WC500166672.pdf References Available only to registered users Category BNF Category: Other antidiabetics (06.01.02.03) Pharmacology: Selective sodium glucose co-transporter type 2 (SGLT2) inhibitor plus biguanide, metformin Epidemiology: Over 5% of men & 4% of women in England have diagnosed diabetes, & it has been estimated that 3.1% of men & 1.5% of women aged 35 and over have undiagnosed diabetes (85% type 2) [3]. Indication: Type 2 diabetes mellitus Method(s) of Administration Oral Company Information Name: Janssen-Cilag US Name: Scios NICE Information In timetable: - PBR Likely Healthcare Resource Group included. Implications Available only to registered users |