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新型2型糖尿病药ertugliflozin具有强大的降血糖疗效

2016-06-20 05:52:34 作者：新特药房来源：互联网浏览次数：0 文字大小：【大】【中】【小】

简介： 2016年6月13日美国两大制药巨头默沙东（Merck & Co）和辉瑞（Pfizer）在美国新奥尔良举行的2016年第76届美国糖尿病协会（ADA）科学会议（2016年06月10日-14日）上公布了糖尿病新药ertugliflozin 2项关键I ...

关键字：ertugliflozin 新型2型糖尿病口服药强大的降血糖

2016年6月13日美国两大制药巨头默沙东（Merck & Co）和辉瑞（Pfizer）在美国新奥尔良举行的2016年第76届美国糖尿病协会（ADA）科学会议（2016年06月10日-14日）上公布了糖尿病新药ertugliflozin 2项关键III期临床研究的积极数据。ertugliflozin是一种实验性、口服、SGLT-2抑制剂，开发用于2型糖尿病患者的治疗。来自这2个研究的数据显示，2种口服剂量ertugliflozin（5mg和15mg，每天口服一次）均使糖化血红蛋白（A1C）实现了统计学意义的显著降低，均达到了研究的主要终点。此次公布的数据，也是ertugliflozin临床开发项目VERTIS的首批数据。
VERTIS Mono是一项为期26周的调查性研究，评估了ertugliflozin作为一种单药疗法用于2型糖尿病的治疗。数据显示，与安慰剂组相比，2种口服剂量ertugliflozin（5mg和15mg，每日口服一次）治疗组糖化血红蛋白（A1C）显著降低0.99%和1.16%，数据具有统计学显著差异（均为P＜0.001）。此外，与安慰剂组相比，2种口服ertugliflozin（5mg和15mg，每日口服一次）治疗组有显著更高比例的患者实现A1C＜7%的治疗目标（5mg组28.3%，15mg组35.8%，安慰剂组13.1%，P值均小于0.001），达到了研究的次要终点。
VERTIS Factorial也是一项为期26周的调查性研究，评估了ertugliflozin联合默沙东DPP-IV抑制剂捷诺维（Januvia，通用名：西他列汀，sitagliptin）用药的疗效和安全性。数据显示，与ertugliflozin单药组和sitagliptin单药组相比，ertugliflozin+sitagliptin联合治疗组糖化血红蛋白（A1C）实现更大幅度的下降，达到了研究的主要终点。2种剂量联合治疗组（ertugliflozin+sitagliptin，5mg+100mg，15mg+100mg）A1C均下降1.5%，5mg剂量ertugliflozin单药组A1C下降1.0%，15mg剂量ertugliflozin单药组A1C下降1.1%，100mg剂量sitagliptin单药组A1C下降1.1%（联合治疗组 vs 单药组，P值均＜0.001）。
此外，ertugliflozin+sitagliptin联合治疗组有更高比例的患者实现A1C＜7.0%的治疗目标。具体而言，ertugliflozin+sitagliptin（5mg+100mg）联合治疗组有52.3%的患者实现A1C＜7.0%治疗目标，ertugliflozin+sitagliptin（15mg+100mg）联合治疗组为49.2%，ertugliflozin（5mg）单药组为26.4%，ertugliflozin（15mg）单药组为31.9%，sitagliptin（100mg）单药组为32.8%（联合治疗组 vs 但药物，P值均＜0.001）。
目前，双方正在推进的有关ertugliflozin的心血管（CV）预后研究VERTIS CV已扩展至调查ertugliflozin降低2型糖尿病群体CV风险的优越性，该研究目前的目标是招募大约8000例患有心血管疾病的2型糖尿病患者。
默沙东和辉瑞已计划于2016年底向美国食品和药物管理局（FDA）提交2种固定剂量组合片剂（ertugliflozin+Januvia，ertugliflozin+二甲双胍）的新药申请（NDA）。VERTIS临床项目共包括9个III期临床研究，涉及约1.26万例2型糖尿病患者。
New Drugs Online Report for ertugliflozin
Information
Generic Name: ertugliflozin
Trade Name:
Synonym: PF-04971729, MK-8835
Entry Type: New molecular entity
Development and Regulatory status
UK: Phase III Clinical Trials
EU: Phase III Clinical Trials
US: Phase III Clinical Trials
UK launch Plans: Available only to registered users
Actual UK launch date:
Comments
Oct 15: PIII development continues [7].
17/12/2015 12:27:00
Apr 13: Ertugliflozin is PIII ready, with trials expected to begin later in 2013 [1].
30/04/2013 13:14:53
Trial or other data
Jun 16: Merck and Pfizer are doubling their ertugliflozin cardiovascular outcomes study (NCT01986881), now looking to enroll 8,000 patients with Type 2 diabetes and established vascular disease, and they added two secondary endpoints, cardiovascular death and a composite endpoint covering CV death and hospitalization for heart failure. The primary endpoint in Merck and Pfizer´s outcomes trial is still a non-inferiority test of ertugliflozin against placebo on a common composite CV endpoint comprising CV death, heart attack and stroke. News of the expanded outcomes trial came along with data from two pivotal studies, in which ertugliflozin hit its blood-sugar goals. EMPA-REG and LEADER will be presented in the next few days at ADA. In the first, a 5-mg ertugliflozin dose cut A1C by 0.99% compared with placebo, and a 15-mg dose beat placebo with a 1.16% reduction. More patients on ertugliflozin also hit an A1C goal of 7%, at 28.2% and 35.8%, compared with 13.1% for placebo. In the other study, ertugliflozin combined with Januvia beat Merck’s blockbuster DPP-4 drug alone. Adding the SGLT2 drug to Januvia achieved an A1C reduction of 1.5% at both the 5-mg and 15-mg ertugliflozin doses, compared with 1% for that drug alone and 1.1% for a 100-mg dose of Januvia alone [10].
14/06/2016 09:07:00
Jan 16: NCT02226003 has closed to recruitment but the study is ongoing with a primary completion date of Jan 16 [9].
08/01/2016 14:57:27
Sep 14: PIII trial (NCT02226003) initiated to evaluate the safety and efficacy of ertugliflozin, in combination with sitagliptin in patients with T2DM with inadequate glycemic control on diet and exercise. The trial will enrol ~300 patients in the US, UK and other countries [8].
08/01/2016 14:56:04
Apr 14: NCT02099110 is a PIII, randomized, double-blind, multicenter study of the combination of ertugliflozin + sitagliptin vs ertugliflozin and sitagliptin alone, in the treatment of 1250 subjects with T2DM with inadequate glycaemic control on metformin monotherapy. The primary outcomes are: change from baseline in HbA1C to week 26, and number who experience an adverse event (AE) and the number who discontinue because of an AE over 1 year. The study starts in Apr 14 and is due to complete May 16. [6]
10/04/2014 09:00:53
Jan 14: NCT02033889 is a PIII randomized, double-blind, placebo-controlled, 26-week multicenter study with a 78-week extension of ertugliflozin in 600 subjects with type 2 diabetes mellitus and inadequate glycemic control on metformin monotherapy. The primary outcomes are change from baseline in HbA1C at Week 26, number of participants experiencing an adverse event up to week 106 and number of participants discontinuing study treatment. The study starts Jan 14 and is due to complete Sep 17 (primary completion date Dec 15) [5].
15/01/2014 21:04:37
Jan 14: NCT02036515 is a PIII, multicentre, randomized, double-blind, placebo-controlled trial of ertugliflozin in the treatment of 405 subjects with type 2 diabetes mellitus who have inadequate glycaemic control on metformin and sitaglIptin. The primary outcomes are change from baseline in HbA1C at Week 26, number of participants experiencing an adverse event up to week 54 and number of participants discontinuing study treatment. The study starts Mar 14 and is due to complete Apr 16 (primary completion date Sep 15) [5].
15/01/2014 21:04:23
Dec 13: NCT01999218 is a PIII, multicentre, randomized, double-blind, active-comparator-controlled study of the addition of ertugliflozin (5 or 15mg/daily) vs glimepiride (up to 8mg daily) in 1230 subjects with T2DM who have inadequate glycaemic control on metformin. Open label sitagliptin will be allowed as rescue medication. The primary outcomes are: change from baseline in HbA1C at week 52; and number of participants experiencing an adverse event and discontinuing study treatment because of an AE up to week 106. The study starts Dec 13 and is due to complete Mar 17 [4].
05/12/2013 08:54:35
Nov 13: NCT01986881 is a randomized, double-blind, placebo-controlled, study to assess cardiovascular outcomes following treatment with ertugliflozin in 3900 subjects with T2DM and established vascular disease. The primary outcome is time to first occurrence of any component of the composite endpoint of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke. The study starts Dec 13 and is due to complete Apr 20 [3].
21/11/2013 15:50:44
Nov 13: NCT01986855 this study will evaluate efficacy and safety of ertugliflozin (5mg and 15mg) vs placebo in 468 participants with T2DM with Stage 3 Chronic Kidney Disease (CKD) who have inadequate glycemic control on background antihyperglycemic therapy. The 67 week study will comprise a 1-week Screening Period, a 10-week wash-off period from metformin, if needed, and a 2-week placebo run-in period, a 52-week double-blind treatment period, and a 14-day post-treatment follow-up period. The primary outcome is change from baseline in A1C at Week 26. The study starts Dec 13 and is due to complete Aug 16 [3].
21/11/2013 15:50:30
Oct 13: NCT01958671 is a PIII, randomized, double-blind, placebo-controlled, 26-week multicentre study with a 26-week extension to evaluate the efficacy and safety of ertugliflozin monotherapy in the treatment of 450 subjects with T2DM and Inadequate glycaemic control despite diet and exercise. The primary outcome is change from baseline in HbA1c and the number of AEs and discontinuations. The study starts Oct 13 and is due to complete Mar 16 [2].
11/10/2013 14:35:40
Apr 13: Merck (MSD) and Pfizer have entered into a worldwide (except Japan) collaboration agreement for the development and commercialization of Pfizer’s ertugliflozin.including ertugliflozin-containing fixed-dose combinations with metformin and sitagliptin tablets [1]
30/04/2013 13:15:13
References
Available only to registered users
Category
BNF Category: Other antidiabetics (06.01.02.03)
Pharmacology: Sodium glucose cotransporter (SGLT2) inhibitor
Epidemiology: Estimated UK prevalence of diagnosed diabetes was 2.9 million people in 2011; 85% have T2DM and about 72% are receiving medication. It is thought a further 850,000 are undiagnosed.
Indication: Type 2 diabetes mellitus
Additional Details: dual, triple therapy
Method(s) of Administration
Oral
Company Information
Name: Merck Sharp & Dohme (MSD)
US Name: Pfizer
Further Information
Anticipated commissioning route (England) CCG
High cost drug list? Awaiting Update
Implications Available only to registered users