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Around 70% of patients diagnosed with hypertension exhibit increased levels of renin. SPH3127, an inventive renin inhibitor, has shown favorable tolerability and sustained pharmacodynamic inhibitory impact on plasma renin activity (PRA) during previous phase I trials. This phase II study was conducted to investigate the efficacy and safety of SPH3127 in patients with essential hypertension. This study was conducted in patients with mild to moderate essential hypertension, utilizing a randomized, double-blind, placebo-controlled design. The patients were administered either tablet of SPH3127 at doses of 50 mg, 100 mg, or 200 mg, or a placebo. A total of 122 patients were included in the study, with 121 patients included in the full analysis set. Among these patients, there were 30 individuals in each subgroup receiving different dosage regimens of SPH3127, and 31 patients in the placebo group. The reductions in mean sitting diastolic blood pressure (msDBP) after 8 weeks compared to baseline were 5.7 ± 9.5, 8.6 ± 8.8, and 3.8 ± 10.6 mmHg in the SPH3127 50-, 100-, and 200 mg groups, respectively. In the placebo group, the reduction was 3.1 ± 8.4 mmHg. The corresponding reductions in mean sitting systolic blood pressure (msSBP) were 11.8 ± 13.0, 13.8 ± 11.2, 11.1 ± 13.1, and 7.7 ± 9.7 mmHg in each respective group. SPH3127 is a promising drug for the treatment of patients with essential hypertension. The recommended dosage is 100 mg daily.Clinical trial registration: This study was registered in ClinicalTrials.gov (NCT03756103).

Titel:	A randomized, double-blind, placebo-controlled, phase IIa, clinical study on investigating the efficacy and safety of SPH3127 tablet in patients with essential hypertension.
Autor/in / Beteiligte Person:	Wang, F ; Liu, L ; Ruan, H ; Chen, X ; Zhang, Y ; Yu, Z ; Li, Y ; Guan, Y ; Wang, J ; Huang, K ; Yu, S ; Cao, Y ; Ding, C ; Chang, L ; Huang, Y ; Lv, Q ; Ma, C
Zeitschrift:	Hypertension research : official journal of the Japanese Society of Hypertension, 2024-04-17
Veröffentlichung:	Ahead of Print, 2024
Medientyp:	academicJournal
ISSN:	1348-4214 (electronic)
DOI:	10.1038/s41440-024-01657-z
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article Language: English [Hypertens Res] 2024 Apr 17. <i>Date of Electronic Publication: </i>2024 Apr 17. References: Harrison DG, Coffman TM, Wilcox CS. Pathophysiology of Hypertension: The Mosaic Theory and Beyond. Circ Res. 2021;128:847–63. (PMID: 10.1161/CIRCRESAHA.121.318082337933288023760) ; Te Riet L, Van Esch JH, Roks AJ, van den Meiracker AH, Danser AH. Hypertension: renin-angiotensin-aldosterone system alterations. Circ Res. 2015;116:960–75. (PMID: 10.1161/CIRCRESAHA.116.303587) ; Pool JL. Direct renin inhibition: focus on aliskiren. J Manag Care Pharm. 2007;13:21–33. (PMID: 17970614) ; Wu CH, Mohammadmoradi S, Chen JZ, Sawada H, Daugherty A, Lu HS. Renin-Angiotensin System and Cardiovascular Functions. Arterioscler Thromb Vasc Biol. 2018;38:e108–e116. (PMID: 10.1161/ATVBAHA.118.311282299503866039412) ; Wood JM, Maibaum J, Rahuel J, Grütter MG, Cohen NC, Rasetti V, et al. Structure-based design of aliskiren, a novel orally effective renin inhibitor. Biochem Biophys Res Commun. 2003;308:698–705. (PMID: 10.1016/S0006-291X(03)01451-712927775) ; Andersen K, Weinberger MH, Egan B, Constance CM, Wright M, Lukashevich V, et al. Comparative efficacy of aliskiren monotherapy and ramipril monotherapy in patients with stage 2 systolic hypertension: subgroup analysis of a double-blind, active comparator trial. Cardiovasc Ther. 2010;28:344–9. (PMID: 10.1111/j.1755-5922.2010.00148.x20406241) ; Duprez DA, Munger MA, Botha J, Keefe DL, Charney AN. Aliskiren for geriatric lowering of systolic hypertension: a randomized controlled trial. J Hum Hypertens. 2010;24:600–8. (PMID: 10.1038/jhh.2009.10720033075) ; Harel Z, Gilbert C, Wald R, Bell C, Perl J, Juurlink D, et al. The effect of combination treatment with aliskiren and blockers of the renin-angiotensin system on hyperkalaemia and acute kidney injury: systematic review and meta-analysis. BMJ. 2012;344:e42. (PMID: 10.1136/bmj.e42222325393253766) ; Iijima D, Sugama H, Takahashi Y, Hirai M, Togashi Y, Xie J, et al. Discovery of SPH3127: A Novel, Highly Potent, and Orally Active Direct Renin Inhibitor. J Med Chem. 2022;65:10882–97. (PMID: 10.1021/acs.jmedchem.2c0083435939295) ; Jing S, Xu R, Yang K, Liu W, Zhang L, Ke Y, et al. Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of SPH3127: A Phase I, Randomized, Double-Blind, Placebo-Controlled Trial. Clin Ther. 2021;43:735 e731–735.e714. (PMID: 10.1016/j.clinthera.2021.01.025) ; Musini VM, Fortin PM, Bassett K, Wright JM. Blood pressure lowering efficacy of renin inhibitors for primary hypertension: a Cochrane systematic review. J Hum Hypertens. 2009;23:495–502. (PMID: 10.1038/jhh.2008.16219158826) ; Zhu JR, Sun NL, Yang K, Hu J, Xu G, Hong H, et al. Efficacy and safety of aliskiren, a direct renin inhibitor, compared with ramipril in Asian patients with mild to moderate hypertension. Hypertens Res. 2012;35:28–33. (PMID: 10.1038/hr.2011.15021900941) ; Oh BH, Mitchell J, Herron JR, Chung J, Khan M, Keefe DL. Aliskiren, an oral renin inhibitor, provides dose-dependent efficacy and sustained 24-hour blood pressure control in patients with hypertension. J Am Coll Cardiol. 2007;49:1157–63. (PMID: 10.1016/j.jacc.2006.11.03217367658) ; Sen S, Sabırlı S, Ozyiğit T, Uresin Y. Aliskiren: review of efficacy and safety data with focus on past and recent clinical trials. Ther Adv Chronic Dis. 2013;4:232–41. (PMID: 10.1177/2040622313495288239979273752183) ; White WB, Bresalier R, Kaplan AP, Palmer BF, Riddell RH, Lesogor A, et al. Safety and tolerability of the direct renin inhibitor aliskiren: a pooled analysis of clinical experience in more than 12,000 patients with hypertension. J Clin Hypertens. 2010;12:765–75. (PMID: 10.1111/j.1751-7176.2010.00352.x) ; Gradman AH, Schmieder RE, Lins RL, Nussberger J, Chiang Y, Bedigian MP. Aliskiren, a novel orally effective renin inhibitor, provides dose-dependent antihypertensive efficacy and placebo-like tolerability in hypertensive patients. Circulation. 2005;111:1012–8. (PMID: 10.1161/01.CIR.0000156466.02908.ED15723979) Contributed Indexing: Keywords: Cardiovascular; Efficacy; Essential hypertension; SPH3127; Safety Molecular Sequence: ClinicalTrials.gov NCT03756103 Entry Date(s): Date Created: 20240417 Latest Revision: 20240417 Update Code: 20240418

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A randomized, double-blind, placebo-controlled, phase IIa, clinical study on investigating the efficacy and safety of SPH3127 tablet in patients with essential hypertension.