[Translation] A randomized, open-label, single-dose, two-period, double-crossover bioequivalence study of amlodipine besylate tablets in healthy Chinese adult participants under fasting and fed conditions

主要目的：以山西汾河制药有限公司生产的苯磺酸氨氯地平片（10 mg）为受试制剂，按生物等效性试验的有关规定，与辉瑞制药有限公司持有的苯磺酸氨氯地平片（商品名：络活喜/Norvasc，规格：10 mg）为参比制剂，进行生物等效性试验，比较两种制剂在空腹和餐后条件下单次给药的生物等效性。次要目的：评估单剂口服受试制剂（苯磺酸氨氯地平片，T）和参比制剂（苯磺酸氨氯地平片（商品名：络活喜/Norvasc），R）在中国健康成年参与者中的安全性。

[Translation]

Primary objective: To conduct a bioequivalence study using amlodipine besylate tablets (10 mg) produced by Shanxi Fenhe Pharmaceutical Co., Ltd. as the test preparation and amlodipine besylate tablets (trade name: Norvasc, specification: 10 mg) held by Pfizer Pharmaceuticals Co., Ltd. as the reference preparation according to the relevant provisions of the bioequivalence study, and to compare the bioequivalence of the two preparations under fasting and postprandial conditions after a single dose. Secondary objective: To evaluate the safety of a single oral dose of the test preparation (amlodipine besylate tablets, T) and the reference preparation (amlodipine besylate tablets (trade name: Norvasc, R) in healthy adult participants in China.

Start Date03 Jan 2025

Sponsor / Collaborator

Shanxi Fenhe Pharmaceutical Factory

CTR20244587

/ RecruitingPhase 3

在S086单药治疗不能有效控制血压的原发性高血压患者中，评价S086联合氨氯地平治疗的有效性和安全性的多中心、随机、双盲、平行对照的Ⅲ期临床研究

[Translation] A multicenter, randomized, double-blind, parallel-controlled phase III clinical study to evaluate the efficacy and safety of S086 combined with amlodipine in patients with essential hypertension whose blood pressure cannot be effectively controlled by S086 alone

主要目的：S086联合氨氯地平治疗原发性高血压的有效性；次要目的：S086联合氨氯地平治疗原发性高血压的安全性；

[Translation]

Primary purpose: The effectiveness of S086 combined with amlodipine in the treatment of essential hypertension; Secondary purpose: The safety of S086 combined with amlodipine in the treatment of essential hypertension;

Start Date26 Dec 2024

Sponsor / Collaborator

Shenzhen Salubris Pharmaceuticals Co., Ltd.

NCT06523465

/ RecruitingPhase 4IIT

A Prospective, Multi-center, Randomized Trial to Compare Statin Combined with CCB to MRA Combined with CCB in Primary Aldosteronism Treatment

The drug treatment for primary aldosteronism (PA) is limited and difficult to improve long-term cardiovascular outcomes. This study plans to enroll patients with primary aldosteronism and randomly divide into 3 groups: scheme 1: Statin combined with amlodipine besylate, scheme 2: Statin combined with Spironolactone and Amlodipine besylate. scheme 3: Amlodipine besylate combined with Spironolactone , to observe the changes in plasma aldosterone level, 24-hour urinary aldosterone, blood pressure, and long-term cardiovascular risk.

Start Date10 Sep 2024

Sponsor / Collaborator

Third Military Medical University

100 Clinical Results associated with Amlodipine Besylate

100 Translational Medicine associated with Amlodipine Besylate

100 Patents (Medical) associated with Amlodipine Besylate

8,946

Literatures (Medical) associated with Amlodipine Besylate

01 Apr 2025·MARINE POLLUTION BULLETIN

Passive sampling of contaminants of emerging concern in a Caribbean urban estuary of Puerto Rico

Article

Author: Bauzá-Ortega, Jorge F ; Mansilla-Rivera, Imar ; Rodríguez-Sierra, Carlos J

Contaminants of emerging concern (CECs) have not been extensively studied in Caribbean estuaries, particularly in Puerto Rico. Polar organic chemical integrative samplers were deployed in surface waters at five sampling sites in the San Juan Bay Estuary to investigate the occurrence and distribution of 137 CECs, resulting in the detection of 64 chemicals (51 pharmaceuticals and personal care products "PPCPs", 12 hormones plus sucralose) at least in one sampling site, and with 35 chemicals obtaining a 100 % detection frequency. Wastewater intrusion was implicated in the presence of CECs based on the detection of sucralose and other wastewater tracers. Condado Lagoon was the most polluted site impacted by untreated wastewater, showing the highest levels of 30 of the 64 detected CECs, and the largest proportion of detected CECs, particularly PPCPs. Levels of estrone and 17β-estradiol represent a high potential risk for adverse effects on aquatic organisms in this Caribbean urban estuary.

01 Apr 2025·NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY

A single-dose, randomized, crossover bioequivalence study of levamlodipine besilate tablets in healthy subjects

Article

Author: Su, Zhengjie ; Yang, Debin ; Liu, Zhengzhi ; Deng, Qiaohuan ; Yang, Haimiao ; Cheng, Yang ; Zhou, Yannan ; Wang, Yanli

Levamlodipine, the levorotatory form of amlodipine racemate, has a blood pressure-lowering effect that is twice that of the racemate. The study aims to establish a foundation for the clinical application of the test drug by conducting a phase I clinical bioequivalence trial, comparing its bioequivalence and safety with the reference drug in healthy Chinese subjects. Recruiting 26 healthy subjects for separate bioequivalence trials in both fasting and fed conditions. The subjects will orally administer 2.5-mg test drug and 5-mg reference drug. A chiral method was used for bioanalytics and liquid chromatography-tandem mass spectrometry was employed to quantify the (S)-amlodipine concentrations at various time points after administration. In fasting condition, the geometric mean ratios (GMRs) for the primary pharmacokinetic parameters C_max, AUC_0-t, and AUC_0-∞ are 100.24%, 103.63%, and 103.24%, respectively. The 90% confidence intervals (CIs) fall within the range of 80-125%, satisfying the established bioequivalence criteria. Similarly, upon oral administration of the drugs in the fed condition, the GMRs for C_max, AUC_0-t, and AUC_0-∞ are 96.48%, 99.90%, and 99.62%, respectively. The corresponding 90% CIs are within the limits of 80-125%, meeting the predefined bioequivalence standards. Furthermore, both drugs exhibited favorable safety profiles. The results show that the two drugs are bioequivalent in healthy Chinese subjects under both fasting and fed conditions. The two drugs both had similar PK parameters and good safety.

01 Apr 2025·SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY

Spectrophotometric method based on Continuous wavelet transform and ratio substraction methods for the rapid simultaneous quantification of Valsartan, Amlodipine, and hydrochlorothiazide in cardiovascular tablet formulation

Article

Author: Sohrabi, Mahmoud Reza ; Hajilo, Saeedeh

The present study quantified simultaneous determination of the active components included in Valzomix HCT tablets are hydrochlorothiazide (HCT), valsartan (VAL), and amlodipine (AML). Two chemometric methods-continuous wavelet transform (CWT) and ratio subtraction (RS)-along with a rapid and effective spectrophotometric approach-which does not require preparatory separation-were used to do the analysis. The CWT approach applied the zero-crossing method to analyze several wavelet families and selected the Daubechies 2, Symlet 2, and Biorthogonal 1.3 wavelets. At wavelengths of 215, 224, and 233 nm, respectively, each wavelet was selected based on its unique scale characteristics for the purpose of measuring the medicines. The quantification and detection limits for AML and VAL varied between 0.0406 and 0.3906 μg/mL, with recovery rates sometimes above 97 % and root mean square errors below 2. The RS technique identified satisfactory values between 0.1594 and 0.1663 μg/mL. The recovery rates varied from 99.52 % to 102.70 %, with quantification limits of 0.3064 to 0.7669 μg/mL. Both approaches demonstrated relative standard deviations below 1 % and average recovery rates over 94 % in the sample analysis. A one-way ANOVA with a 95 % confidence interval demonstrated no major variances in the methods.

News (Medical) associated with Amlodipine Besylate

13 Jan 2025

·www.globenewswire.com

George Medicines signs exclusive licensing agreement with Bausch Health to commercialize GMRx2 in Canada, Mexico, Columbia and Central America

George Medicines signs exclusive licensing agreement with Bausch Health to commercialize GMRx2 in Canada, Mexico, Columbia and Central America Bausch Health gains exclusive rights to single-pill triple combination therapy for hypertensionGeorge Medicines receives upfront milestone payment and is eligible for regulatory and commercial milestones, and a stepped royalty rate in licensed territoriesGMRx2 has potential to be the only triple combination approved for the treatment of hypertension including initial treatment London, UK, 13 January 2025 – George Medicines, a late-stage biopharmaceutical company focused on addressing significant unmet needs in cardiometabolic disease, has entered into an exclusive licensing and supply agreement with Bausch Health Companies Inc. (NYSE/TSX: BHC) (‘Bausch Health’), a global, diversified pharmaceutical company enriching lives through a relentless drive to deliver better health outcomes, granting Bausch Health exclusive rights to seek regulatory approval of, and to commercialize, GMRx2 in Canada, Mexico, Columbia and Central America. GMRx2, George Medicines’ lead pipeline candidate for the treatment of hypertension including initial treatment, is a proprietary single-pill combination of three best-in-class medicines: telmisartan, amlodipine and indapamide. Developed in ultra-low dose, low-dose, and standard-dose options, it has the potential to be the only triple combination approved for the initial treatment of hypertension. The innovative formulation is designed for optimal efficacy, safety and adherence. With a multi-mechanism approach and at lower dosing than today’s therapies, GMRx2 is designed to deliver the synergistic efficacy benefits of a triple therapy while maintaining tolerability. Under the terms of the licensing agreement, George Medicines receives an upfront milestone payment and is eligible for regulatory and commercial milestone payments, as well as a future recurring revenue stream through a stepped royalty rate on sales of GMRx2 in the licensed territories. In return, Bausch Health is granted a license to exclusively commercialize GMRx2, supplied by George Medicines, in Canada, Mexico, Columbia and Central America. Bausch Health is responsible for seeking regulatory approval of GMRx2, with support from George Medicines. Mark Mallon, Chief Executive Officer of George Medicines, said: “This announcement marks a significant milestone for George Medicines, and in Bausch Health we have secured a strong commercial partner who shares our belief in the potential of GMRx2 to enable more patients to achieve better blood pressure control and improve on current hypertension treatment approaches.” Cees Heiman, Senior Vice President, Europe and Canada, Bausch Health, said: “In Canada, seven and a half million people, about 1 in 4 adults, live with hypertension1, and too many do not have their condition under control. The clinically-proven efficacy of GMRx2 compared to dual combinations, coupled with its good tolerability, have the potential to address key challenges in current hypertension treatment approaches. This partnership with George Medicines underscores our commitment to deliver better health outcomes for patients.” Fernando Zarate, Vice President, Latin America, Bausch Health, said: “GMRx2 is a critical innovation that we believe can meaningfully advance cardiovascular care in Mexico, Colombia and Central America. While prevalence of hypertension remains high in the region, its treatment and control is low2. In GMRx2 we have an opportunity to change that.” Globally, many diagnosed hypertension patients are not currently achieving sufficient blood pressure (BP) control because they are on inadequate therapy, are not receiving the right combination of medicines at the right doses or are not taking their treatment as prescribed. With the latest professional guidelines from the European Society of Cardiology3 recommending lower target BP levels and early use of combination therapy, an effective, low-dose, single-pill triple combination with good tolerability provides an opportunity to significantly advance the management of hypertension. GMRx2 is backed by a comprehensive clinical development program, including two pivotal Phase III studies, published in 2024 in the Journal of the American College of Cardiology4 and The Lancet5, demonstrating GMRx2 significantly reduced BP and improved BP control rates, when compared against dual therapy and against placebo. The triple combination was also investigated in the Nigerian VERONICA trial6, which compared GMRx2 with existing, standard of care and reported better BP lowering and control among those receiving GMRx2. In all trials, tolerability was good, with no increase in withdrawal from treatment due to adverse events. A global trial investigating the potential of GMRx2 for the prevention of stroke in people who have had intracerebral hemorrhage (the most severe type of stroke) is ongoing7. GMRx2 has not received regulatory approval for commercial use in any country. A New Drug Application (NDA) to the US Food and Drug Administration (FDA) seeking US approval of GMRx2 for the treatment for hypertension, including initiation of treatment, is ongoing with a Prescription Drug User Fee Act (PDUFA) goal date of 5 June 2025. Regulatory submissions in other territories are anticipated in 2025. George Medicines is an independent spin-out company from The George Institute for Global Health, one of the world’s leading medical research institutes with a focus on addressing global health inequity. The Company is backed by George Health, the commercial arm of The George Institute, and Brandon Capital, Australia’s leading life sciences venture capital firm. Ends References: Hypertension Canada Annual Report https://hypertension.ca/wp-content/uploads/2024/10/HC-2024-Annual-Report-Final.pdf)Prevalence, Awareness, Treatment, and Control of Hypertension in the Southern Cone of Latin America; Am J Hypertens; doi: 10.1093/ajh/hpw092 https://academic.oup.com/ajh/article/29/12/1343/27082962024 ESC Guidelines for the management of elevated blood pressure and hypertension; European Heart Journal, Volume 45, Issue 38, 7 October 2024, Pages 3912–4018, https://doi.org/10.1093/eurheartj/ehae178Rodgers A, Salam A, Schutte AE, . . .Whelton P. Efficacy and Safety of a Novel Low-Dose Triple Single-Pill Combination Compared With Placebo for Initial Treatment of Hypertension. Journal of the American College of Cardiology. 2024;0(0). doi:10.1016/j.jacc.2024.08.025Efficacy and safety of a novel low-dose triple single-pill combination, compared with dual combinations for treatment of hypertension; The Lancet; doi: 10.1016/S0140-6736(24)01744-6Ojji DB, Salam A, Sani MU, . . .Rodgers A. Low-dose triple-pill vs standard-care protocols for hypertension treatment in Nigeria: a randomized clinical trial. doi:10.1001/jama.2024.18080. JAMA. 2024.10.1001/jama.2024.18080TRIDENT: Triple therapy prevention of Recurrent Intracerebral Disease EveNts Trial https://www.tridentstudy.org/ About George Medicines George Medicines is a late-stage biopharmaceutical company addressing significant unmet need in the treatment of cardiometabolic diseases with innovative combinations of best-in-class existing treatments, designed for optimal efficacy and safety. Combining best-in-class molecules from existing medicines in novel low-dose formulations, George Medicines is developing innovative and proprietary treatments to be more efficacious, safer and accessible than currently available treatment options. These multi-mechanism, single-pill combinations offer the potential to bring significant improvements in clinical outcomes and therapy adherence in patients with cardiometabolic disorders, including hypertension and diabetes, each of which remain the leading causes of premature death and disability worldwide. For more information, please visit www.george-medicines.com. Media contacts ICR Healthcare David Daley, Lindsey Neville, Tom Daniel georgemedicines@icrhealthcare.com; Tel: +44 (0) 203 709 5700

Phase 3License out/inClinical Result

08 Jan 2025

·www.echemi.com

80 batches of drugs recalled urgently! A major decision by the National Medical Products Administration

Recently, the National Medical Products Administration announced an important decision to stop the production, sale, and use of Hyoscine Butylbromide Tablets, and to revoke its drug registration certificate. According to the announcement issued by the National Medical Products Administration on January 3, titled “Announcement on the Revocation of the Drug Registration Certificate for Hyoscine Butylbromide Tablets (2025 No. 2)”, Hyoscine Butylbromide Tablets, an antibacterial drug also known as Loperamide, will no longer circulate in the market of our country. This decision is effective immediately, and the products already on the market will be recalled by the marketing authorization holder and supervised by provincial drug regulatory authorities for destruction or other harmless disposal measures. A total of 80 batches of Hyoscine Butylbromide Tablets are involved. In addition, in another announcement issued by the National Medical Products Administration on December 2, 2024, it was also announced that 58 drug registration certificates, including 11 batches of Hyoscine Butylbromide Tablets, have been revoked. Based on Article 83 of the Drug Administration Law of the People's Republic of China and other relevant regulations, these drugs have been required to stop production and sale due to unclear efficacy, serious adverse reactions, or other hazards to human health. Hyoscine Butylbromide Tablets are a compound preparation, with the main active ingredients including Hyoscine Tincture, Sulfamethoxazole, and Trimethoprim, primarily used to treat dysentery caused by Shigella and other sensitive pathogenic bacteria causing enteritis. However, with the withdrawal of this drug from the market, other drugs such as Montmorillonite Powder will take on the responsibility for treating diarrhea. According to data from Miiine, the incidence of gastrointestinal diseases is on the rise and is becoming more prevalent among younger populations. In the first three quarters of 2022, the sales of anti-diarrheal drugs and intestinal anti-inflammatory/infection drugs in public hospitals in key provinces and cities in China exceeded 1.2 billion yuan, a year-on-year increase of 6.30%. The sales scale of Montmorillonite Powder in the three major terminal markets in China has exceeded 1 billion yuan, with the outpatient market being the main sales channel, rising by 60%, making it the Top 2 product in anti-diarrheal and intestinal anti-inflammatory/infection drugs. Statistics from Cyborg Blue show that 145 drug registration certificates were revoked in 2024. In the announcement on December 2, 2024, in addition to Hyoscine Butylbromide Tablets, it also included 3 batches of Losartan Potassium Tablets, 2 batches of Phenazone Tablets, 2 batches of Amlodipine Besylate Tablets, 2 batches of Entecavir Tablets, 2 batches of Compound Snake Gall and Chuan Bei Powder, and 2 batches of Rifampicin Capsules. Phenazone, as a pyrazolone analgesic and antipyretic, was launched early in our country, but its injection and nasal drops have severe adverse reactions, with risks outweighing benefits, and alternative medications are available, leading to its registration certificate being revoked in 2020. Although oral preparations like Phenazone Tablets still have certain clinical value, the National Medical Products Administration has implemented risk control measures by revising the instructions to add safety warnings, restricting applicable populations and indications. In the domestic market for antipyretic and analgesic drugs, Phenazone has a low market share and is declining. Data from Cyborg Blue shows that there are 861 approvals for "Phenazone Tablets," involving many companies and intense market competition. As related drug approvals are revoked, this market will face further fragmentation. Finally, according to the relevant provisions of the Regulations on the Implementation of the Drug Administration Law of the People's Republic of China and the Drug Registration Management Measures, the National Medical Products Administration decided on April 11, 2024, to revoke the registration certificates for 87 drugs, including Pancreatin Injection. Cyborg Blue’s analysis found that drugs such as 7 batches of Iohexol Injection, 6 batches of Insulin Glargine Injection, 4 batches of Detemir Insulin Injection, 4 batches of Vardenafil Hydrochloride Tablets, and 3 batches of Brain Protein Hydrolysate Injection were also revoked. Please note that the number of drugs counted in the text has not been deduplicated. No. Marketing Authorization Holder Approval Number 1 Shijiazhuang Lesheng Pharmaceutical Co., Ltd. SFDA H13023949 2 Jiangzhong Pharmaceutical Co., Ltd. SFDA H36022316 3 Shijiazhuang Fourth Pharmaceutical Co., Ltd. SFDA H13023932 4 Shijiazhuang Grey Pharmaceutical Co., Ltd. SFDA H13023934 5 Handan Bailin Pharmaceutical Co., Ltd. SFDA H13023945 6 Hebei Yongfeng Pharmaceutical Co., Ltd. SFDA H13023943 7 China National Pharmaceutical Group Wuhan Zhonglian Fourth Pharmaceutical Co., Ltd. SFDA H42022497 8 Jiangsu Enhua Pharmaceutical Co., Ltd. SFDA H32025932 9 Jiangxi Hongshuo Pharmaceutical Co., Ltd. SFDA H36022013 10 Jiangxi Hongshuo Pharmaceutical Co., Ltd. SFDA H36022244 11 Jiangsu Chenpai Pharmaceutical Group Co., Ltd. SFDA H32025935 12 North China Pharmaceutical Hebei Huanuo Co., Ltd. SFDA H13024102 13 North China Pharmaceutical Hebei Huanuo Co., Ltd. SFDA H13024073 14 Hebei Hengli Group Pharmaceutical Co., Ltd. SFDA H13024253 15 Hebei Tianzhi Pharmaceutical Co., Ltd. SFDA H13024245 16 Hebei Dongfeng Pharmaceutical Co., Ltd. SFDA H13024170 17 Hebei Jinzhuan Pharmaceutical Co., Ltd. SFDA H13024269 18 Tianjin Baihai Pharmaceutical Co., Ltd. SFDA H12021099 19 Henan Daxin Pharmaceutical Co., Ltd. SFDA H41024876 20 Henan Daxin Pharmaceutical Co., Ltd. SFDA H41025013 21 Shanxi Xinxing Pharmaceutical Co., Ltd. SFDA H14023068 22 Jiangxi Jiminke Pharmaceutical Co., Ltd. SFDA H36022305 23 Suzhou Hongsun Pharmaceutical Co., Ltd. SFDA H32025897 24 Jiangsu Puhua Kesheng Pharmaceutical Co., Ltd. SFDA H32026256 25 Guangxi Tiantianle Pharmaceutical Co., Ltd. SFDA H45021319 26 Tianjin Central Pharmaceutical Co., Ltd. SFDA H12021120 27 Tianjin Central Pharmaceutical Co., Ltd. SFDA H12021117 28 Shanghai Modern Harsen (Shangqiu) Pharmaceutical Co., Ltd. SFDA H41024989 29 Tianjin Pacific Pharmaceutical Co., Ltd. SFDA H12021100 30 Hebei Guojin Pharmaceutical Co., Ltd. SFDA H13023940 31 Hebei Kaiwei Pharmaceutical Co., Ltd. SFDA H13023920 32 Hebei Sanshi Pharmaceutical Co., Ltd. SFDA H13023928 33 Yuanda Pharmaceutical (China) Co., Ltd. SFDA H42022649 34 Shanxi Tongda Pharmaceutical Co., Ltd. SFDA H14023309 35 Shanxi Guorun Pharmaceutical Co., Ltd. SFDA H14023402 36 Shanxi Fenhe Pharmaceutical Co., Ltd. SFDA H14023200 37 Shanxi Wanhui Pharmaceutical Co., Ltd. SFDA H14023333 38 Jilin Wantong Pharmaceutical Co., Ltd. SFDA H22025288 39 Changchun Overseas Pharmaceutical Group Co., Ltd. SFDA H22026726 40 Shijiazhuang Xiehe Pharmaceutical Co., Ltd. SFDA H13024084 41 Shandong Xinyi Pharmaceutical Co., Ltd. SFDA H37023541 42 Kuihua Pharmaceutical Group (Hengshui) Defier Co., Ltd. SFDA H13023979 43 Shijiazhuang Kanghewai Pharmaceutical Co., Ltd. SFDA H13024261 44 Shandong Xinhua Pharmaceutical Co., Ltd. SFDA H37023523 45 Hebei Yuzhilin Pharmaceutical Co., Ltd. SFDA H13024426 46 Xinhai Yansheng Pharmaceutical Co., Ltd. SFDA H41024907 47 Fu'an Pharmaceutical Group Yantai Zhichu Pharmaceutical Co., Ltd. SFDA H37023543 48 Dingfukang Pharmaceutical Co., Ltd. SFDA H41025139 49 Dingfukang Pharmaceutical Co., Ltd. SFDA H41025174 50 Changchun Changqing Pharmaceutical Group Co., Ltd. SFDA H22025234 51 Henan Baiquan Pharmaceutical Co., Ltd. SFDA H41024840 52 Changzhou Kangpu Pharmaceutical Co., Ltd. SFDA H32025910 53 Henan Baiquan Pharmaceutical Co., Ltd. SFDA H41025575 54 Lepu Hengjiuyuan Pharmaceutical Co., Ltd. SFDA H41024862 55 Hebei Ruicen Pharmaceutical Co., Ltd. SFDA H13023953 56 Hainan Xiansheng Pharmaceutical Co., Ltd. SFDA H46020588 57 Hainan Xiansheng Pharmaceutical Co., Ltd. SFDA H46020604 58 Yaodu Pharmaceutical Group Co., Ltd. SFDA H13023951 59 Shandong Xinyi Pharmaceutical Co., Ltd. SFDA H37023939 60 Shijiazhuang Pharmaceutical Group Ouyi Pharmaceutical Co., Ltd. SFDA H13023952 61 Tianfang Pharmaceutical Co., Ltd. SFDA H41024887 62 Lepu Hengjiuyuan Pharmaceutical Co., Ltd. SFDA H41025576 63 Zhejiang Huisong Pharmaceutical Co., Ltd. SFDA H33022412 64 Zhejiang Huisong Pharmaceutical Co., Ltd. SFDA H33022411 65 Shanghai Kaibao Xinyi (Xinxiang) Pharmaceutical Co., Ltd. SFDA H41024834 66 Henan Xueyinghua Pharmaceutical Co., Ltd. SFDA H41024896 67 Henan Xueyinghua Pharmaceutical Co., Ltd. SFDA H41025009 68 Shijiazhuang Pharmaceutical Group Zhongnuo Pharmaceutical (Shijiazhuang) Co., Ltd. SFDA H13023994 69 Handan Furong Pharmaceutical Co., Ltd. SFDA H13024077 70 Hebei Tiancheng Pharmaceutical Co., Ltd. SFDA H13024056 71 Hebei Kangtai Pharmaceutical Co., Ltd. SFDA H13024041 72 Guangdong Bidi Pharmaceutical Co., Ltd. SFDA H44025328 73 Guangdong Bidi Pharmaceutical Co., Ltd. SFDA H44024963 74 Zhengzhou Furuitang Pharmaceutical Co., Ltd. SFDA H41025579 75 Chongqing Kerui Pharmaceutical (Group) Co., Ltd. SFDA H50021730 76 Baiyun Mountain Dongtai Shangqiu Pharmaceutical Co., Ltd. SFDA H41024872 77 Xinxiang Changle Pharmaceutical Co., Ltd. SFDA H41024895 78 Xinxiang Changle Pharmaceutical Co., Ltd. SFDA H41025012 79 Baiyun Mountain Dongtai Shangqiu Pharmaceutical Co., Ltd. SFDA H41025008 80 Tianfang Pharmaceutical Co., Ltd. SFDA H41025010

Drug ApprovalNDA

18 Oct 2024

·www.globenewswire.com

Phase III trial results of novel triple combination pill for hypertension published in The Lancet

Phase III trial results of novel triple combination pill for hypertension published in The Lancet Novel combination pill significantly reduced blood pressure and improved control rates vs dual therapy, with good tolerability and no increase in adverse event related withdrawalsTriple combination approach aligns with latest European Society of Cardiology hypertension guidelines recommending increased use of combination therapies Subject to regulatory review, following New Drug Application (NDA) filed with FDA in August, GMRx2 would be the first triple combination approved for initial treatment of hypertension London, UK, 18 October 2024 – George Medicines, a late-stage biopharmaceutical company focused on addressing significant unmet needs in cardiometabolic disease treatment, today announced that The Lancet has published results from its pivotal Phase III clinical trial of GMRx2. A proprietary combination of three best-in-class medicines, telmisartan, amlodipine and indapamide, developed in an ultra-low dose (triple quarter-dose), low-dose (triple half-dose), and triple standard-dose options, GMRx2 was compared with dual combinations, for the treatment of hypertension (high blood pressure), including initiation of treatment. The triple combination’s multi-mechanism approach is designed to deliver optimal efficacy and safety while promoting patient adherence. The research, “Efficacy and safety of a novel low-dose triple single-pill combination of telmisartan, amlodipine and indapamide, compared with dual combinations for treatment of hypertension: a randomised, double-blind, active-controlled, international clinical trial”, is published in the 19 October issue of The Lancet. The international trial, conducted in seven countries, met all primary efficacy and safety endpoints: GMRx2 was more effective than each dual therapy, significantly reducing both home- and clinic-measured blood pressure (BP) and improving BP control rates, with both standard- and half-dose forms.GMRx2 half-dose achieved 63% clinic BP control <140/90 mmHg, which rose to 74% at the end of follow-up on GMRx2 standard-dose – superior to all three dual combinations at standard-dose (53-61%).Assessed against more stringent BP control rates of <130/80 mmHg, GMRx2 standard dose achieved 56% control rates, again clinically and statistically superior to all three dual combinations (33-44%).Tolerability was good, with no increase in withdrawal from treatment due to adverse events. This treatment approach aligns with recently updated European Society of Cardiology (ESC) guidelines for hypertension management1, which recommend lower blood pressure levels to begin treatment among those at raised risk and greater use of combination therapy, starting off with dual low-dose followed by a triple low -dose therapy. Chair of the trial’s steering committee, Dr. Paul Whelton, Show Chwan Chair of Global Public Health at Tulane University, New Orleans, Louisiana, and President of the World Hypertension League, commented: “This trial, conducted across seven countries and diverse populations, demonstrates that GMRx2 provides significantly better blood pressure control compared to dual combinations, while maintaining an excellent safety profile. The findings are particularly noteworthy as they show efficacy at lower blood pressure levels, aligning with the latest guideline recommendations. This new single-pill combination has the potential to address the critical need for more effective and tolerable treatment options to achieve and maintain blood pressure control in the many patients who remain uncontrolled on current therapies.” Dr. Anthony Rodgers, Chief Medical Officer of George Medicines, and Professorial Fellow at The George Institute for Global Health, said: “These findings, now published in The Lancet, provide robust evidence for the potential of GMRx2 to transform hypertension management. The superior efficacy of this triple combination therapy compared to dual combinations, coupled with its good tolerability, addresses key challenges in current hypertension treatment approaches and directly supports recent guideline recommendations. Subject to regulatory approval, we believe GMRx2 could play a crucial role in addressing the global burden of hypertension and improving patient outcomes.” These results, along with data from other recent trials, including the VERONICA trial in Nigeria, funded by the National Health and Medical Research Council (NHMRC) of Australia, supported by The George Institute for Global Health and recently published in JAMA, and a placebo-controlled Phase III study recently published in the Journal of the American College of Cardiology, provide a comprehensive body of evidence supporting the efficacy and safety of GMRx2 across various patient populations and dosing regimens. In August 2024 George Medicines announced its submission to the US Food and Drug Administration (FDA) of a New Drug Application (NDA) for GMRx2. Data from GMRx2’s clinical development program will support additional global regulatory filings. George Medicines is an independent spin-out company from The George Institute for Global Health, one of the world’s leading medical research institutes with a focus on addressing global health inequity. The Company is backed by George Health, the commercial arm of The George Institute, and Brandon Capital, Australia’s leading life sciences venture capital firm. The Company’s GMRx2 development program built on earlier research by The George Institute, including the 700-patient TRIUMPH trial undertaken in Sri Lanka in 2016/17, which found that among patients with mild to moderate hypertension, treatment with a low-dose triple combination pill led to an increased proportion of patients achieving their target blood pressure goal versus usual care. Ends About the clinical trialA Phase III trial among 1,385 patients in Australia, Czech Republic, New Zealand, Poland, Sri Lanka, UK and the US, standard- and half-dose forms of GMRx2 were tested against dual combinations of its component drugs. The trial’s primary efficacy outcome was the difference between GMRx2 and its comparators in home blood pressure change from randomization to week 12. The head-to-head trial provides the first large scale comparison of a low- and standard-dose triple combination pill and its dual combinations at the same doses. It assessed the safety and efficacy of the triple combination among patients with starting blood pressure levels that were considerably lower than those in previous trials. About hypertension (high blood pressure)Globally, more than one billion adults have hypertension2. Many diagnosed patients aren’t achieving sufficient blood pressure control because they are on inadequate therapy, aren’t receiving the right combination of medicines at the right doses or aren’t taking their treatment as prescribed or continuing their treatment in the long term. The major, globally recognized treatment guidelines3 recommend the use of fixed dose combination therapy for most patients with hypertension, including for first-line treatment and yet, in practice, newly diagnosed patients will often still be prescribed monotherapy treatment. This is despite a broad evidence base indicating that, individually, blood pressure medicines are only modestly effective at reducing blood pressure, even at high doses, and most patients will require two or more medicines to achieve control. As dosage of hypertension drugs is increased, so too are side effects, which can preclude the use of high doses for many patients. These side effect challenges, alongside the management of multiple hypertension medicines being taken together with treatments for other conditions, can significantly impact treatment compliance and adherence, including failure to take medications as prescribed and to persist on long-term therapy. About George Medicines George Medicines is a late-stage biopharmaceutical company addressing significant unmet need in the treatment of cardiometabolic diseases with innovative combinations of best-in-class existing treatments, designed for optimal efficacy and safety. Combining best-in-class molecules from existing medicines in novel low-dose formulations, George Medicines is developing innovative and proprietary treatments to be more efficacious, safer and accessible than currently available treatment options. These multi-mechanism, single-pill combinations offer the potential to bring significant improvements in clinical outcomes and therapy adherence in patients with cardiometabolic disorders, including hypertension and diabetes, each of which remain the leading causes of premature death and disability worldwide. The Company’s lead candidate, GMRx2, has completed a Phase III development program for the treatment of hypertension, including first-line therapy, and a global trial focused on the prevention of recurrent intracerebral hemorrhage (the most severe type of stroke) is underway. George Medicines is an independent spin-out company from The George Institute for Global Health, one of the world’s leading medical research institutes with a focus on addressing global health inequity. The Company is backed by George Health, the commercial arm of The George Institute, and Brandon Capital, Australia’s leading life sciences venture capital firm. For more information, please visit www.george-medicines.com. References 2024 ESC Guidelines for the management of elevated blood pressure and hypertension https://www.escardio.org/Guidelines/Clinical-Practice-Guidelines/Elevated-Blood-Pressure-and-HypertensionWorld Health Organization Hypertension factsheet https://www.who.int/news-room/fact-sheets/detail/hypertension2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines https://www.ahajournals.org/doi/10.1161/HYP.0000000000000065; WHO Guideline for the pharmacological treatment of hypertension in adults https://iris.who.int/bitstream/handle/10665/344424/9789240033986-eng.pdf; 2024 ESC Guidelines for the management of elevated blood pressure and hypertension https://www.escardio.org/Guidelines/Clinical-Practice-Guidelines/Elevated-Blood-Pressure-and-Hypertension Media contacts ICR Consilium David Daley, Lindsey Neville, Isabelle Abdou georgemedicines@consilium-comms.com; Tel: +44 (0) 203 709 5700

Phase 3Clinical ResultNDA

100 Deals associated with Amlodipine Besylate

External Link

KEGG	Wiki	ATC	Drug Bank
D00615	Amlodipine Besylate	C08CA01	DBSALT001054

R&D Status

Approved

10 top approved records.

to view more data

Indication	Country/Location	Organization	Date
Deglutition Disorders	Canada	Pendopharm, Inc.	11 Jan 2019
Angina Pectoris	United Kingdom	Pfizer Inc.	01 Jan 1990
Angina Pectoris, Variant	United Kingdom	Pfizer Inc.	01 Jan 1990
Angina, Stable	United Kingdom	Pfizer Inc.	01 Jan 1990
Coronary Artery Disease	United Kingdom	Pfizer Inc.	01 Jan 1990
Hypertension	United Kingdom	Pfizer Inc.	01 Mar 1989

Developing

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Resistant hypertension	Phase 3	Belgium	Boehringer Ingelheim GmbH	01 Oct 2007
Resistant hypertension	Phase 3	Canada	Boehringer Ingelheim GmbH	01 Oct 2007
Resistant hypertension	Phase 3	Denmark	Boehringer Ingelheim GmbH	01 Oct 2007
Resistant hypertension	Phase 3	Finland	Boehringer Ingelheim GmbH	01 Oct 2007
Resistant hypertension	Phase 3	France	Boehringer Ingelheim GmbH	01 Oct 2007
Resistant hypertension	Phase 3	Netherlands	Boehringer Ingelheim GmbH	01 Oct 2007
Resistant hypertension	Phase 3	Norway	Boehringer Ingelheim GmbH	01 Oct 2007
Resistant hypertension	Phase 3	Philippines	Boehringer Ingelheim GmbH	01 Oct 2007
Resistant hypertension	Phase 3	South Africa	Boehringer Ingelheim GmbH	01 Oct 2007
Resistant hypertension	Phase 3	South Korea	Boehringer Ingelheim GmbH	01 Oct 2007

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


COMBINE study (ESH2024)	Not Applicable	-	213	Indapamide/Amlodipine 1.5/5 mg SPC	tzhoqztiho(npfsmwnjfo) = observed in 4 patients (2.16%) kjqactdrib (qjsmvmuast ) View more	Positive	01 May 2024
ESH2024	Not Applicable	Hypertension	-	Amlodipine	tikfupikvu(thzeeltiel) = mmsoldimys upzbzncbih (otuuyyoukc )	Positive	01 May 2024
ESH2024	Not Applicable	Hypertension	-	Lercanidipine	tikfupikvu(thzeeltiel) = hsdpmazjly upzbzncbih (otuuyyoukc )	Positive	01 May 2024
NCT01956786 (Pubmed \| J Clin Hypertens (Greenwich))	Not Applicable	Hyperhomocysteinemia \| Hypertension	351	Amlodipine-FA tablet (amlodipine 5 mg/FA 0.4 mg)	-	Positive	11 Jul 2023
NCT01956786 (Pubmed \| J Clin Hypertens (Greenwich))	Not Applicable	Hyperhomocysteinemia \| Hypertension	351	Amlodipine 5 mg/FA 0.8 mg tablet	-	Positive	11 Jul 2023
ESH2022	Not Applicable	Hypertension	729	Telmisartan/Amlodipine Single-Pill Combination Therapy	sqlaxbieoh(wmrhfttmdz) = xikmdnswau dwrujbnswy (ilbwlxwyeu ) View more	Positive	01 Jun 2022
ESH2022	Not Applicable	Obesity, Abdominal	60	Olmesartan/Amlodipine combination therapy	npshvcssei(zqxxdrdxvu) = aatglzfmfp mqzprpobse (zvyodxmeyd, 82–105) View more	Positive	01 Jun 2022
ESH2022	Phase 3	Essential Hypertension	150	Amlodipine 5 mg + Bisoprolol 5 mg + Perindopril 5 mg (Single Pill Combination)	jucecqedud(oaxolzkomn) = Less treatment-related adverse events were reported in group A (1.3%) versus in group B (6.9%) aucqwjsfsa (iitbydsblg )	Positive	01 Jun 2022
ESH2022	Phase 3	Essential Hypertension	150	Amlodipine 5 mg + Bisoprolol 5 mg + Perindopril 5 mg (Free Combination)		Positive	01 Jun 2022
Interim Analysis of a Pilot Randomized Controlled Study (ENDO2021)	Not Applicable	Pheochromocytoma	20	Prazosin	vfxiqgfgmd(gnqmkhzfik) = krlpcfktew iduyzjarez (dehkyoccuw, 14 [14–42])	Positive	03 May 2021
AVANGARD STUDY (ESH2021)	Not Applicable	-	658	Perindopril arginine/amlodipine single-pill combination (SPC)	kptysriwrj(ygmivldwlj) = 0.21% syzdtnzeaf (levdewmptl ) View more	Positive	01 Apr 2021
ESH2021	Not Applicable	Dyslipidemias \| Hypertension	-	Amlodipine Besilate/Atorvastatin Calcium Hydrate (Caduet Combination Tablets)	cmtoeqbtjp(ekauxlhkmd) = swpofwmnsv lmeoihrllm (buwivewbph )	Positive	01 Apr 2021
FIXE (ESH2019)	Not Applicable	Diabetes Mellitus \| Hypertension	28	Perindopril/Indapamide/Amlodipine 10/2.5/10 mg	vzfiwhvwca(aifrjtwaol) = eqhkvomicb auxqbrvxja (cibahqutcl ) View more	Positive	01 Jul 2019

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

Chat with Hiro

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. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis