A Phase I/IIa, Randomized, Double-blind, Placebo Controlled Study to Evaluate the Safety, and Pharmacokinetics of Single and Multiple Ascending Dose of RP3128 in HV and Effect on LAR to Allergen Challenge in Mild Asthmatics

RP3128 is a calcium release activated calcium (CRAC) channel modulator. The purpose of this study is to evaluate the safety, tolerability and pharmacokinetics of single and multiple ascending dose(s) of RP3128 in healthy volunteers and to evaluate the effect on late phase asthmatic response to allergen challenge in patients with mild asthma.

开始日期2016-11-03

申办/合作机构

Rhizen Pharmaceuticals AG

100 项与 RP-3128 相关的临床结果

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100 项与 RP-3128 相关的转化医学

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项与 RP-3128 相关的文献（医药）

2021-06-01·Journal of Clinical Pharmacy and Therapeutics4区 · 医学

A first‐in‐human study to evaluate the safety, tolerability and pharmacokinetics of RP3128, an oral calcium release‐activated calcium (CRAC) channel modulator in healthy volunteers

4区 · 医学

Article

作者: Vakkalanka, Swaroop V. ; Barde, Prajak J. ; Nair, Ajit ; Viswanadha, Srikant ; Veeraraghavan, Sridhar

WHAT IS KNOWN AND OBJECTIVERP3128, a novel, orally available modulator of calcium released activated calcium (CRAC) channel, is being developed for the potential treatment of autoimmune and inflammatory diseases. RP3128 showed nano-molar potency and activity in a range of in vitro and in vivo models of inflammation. We report a first-in-human study investigating the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of RP3128 in healthy subjects.METHODSA randomized, double-blind, placebo-controlled trial of single (25, 50, 100, 200 and 400 mg) and multiple (7 days: 25, 100 and 400 mg once daily) doses of RP3128 were performed. Thirty-two and 24 subjects were randomized in the single ascending dose (SAD) and multiple ascending dose (MAD) parts, respectively.RESULTS AND DISCUSSIONRP3128 was well tolerated, with no dose-limiting toxicity at single and multiple doses. Incidence of treatment emergent adverse events (TEAEs) did not increase with ascending RP3128 doses. No changes were seen in cognitive function and ECG parameters. RP3128 was rapidly absorbed. Elimination was slow with a half-life of more than 80 h. Exposures increased with increasing doses. Accumulation was seen on repeated dosing. PD response, as evidenced by lower plasma levels of tumour necrosis factor-alfa (TNFα) and interleukin-4 (IL-4), was seen when compared to pre-dose values or placebo.WHAT IS NEW AND CONCLUSIONThe safety, tolerability and PK/PD profile of RP3128 demonstrates its potential to be developed in inflammatory disorders and support further clinical development (ClinicalTrials.gov number: NCT02958982).

2016-02-01·European Journal of Pharmacology3区 · 医学

Pharmacodynamic evaluation of RP3128, a novel and potent CRAC channel inhibitor in guinea pig models of allergic asthma

3区 · 医学

Article

作者: Kocmalova, Michaela ; Viswanadha, Srikant ; Sutovska, Martina ; Franova, Sona ; Vakkalanka, Swaroop

The increase in intracellular Ca(2+) levels through the activation of Ca(2+) release-activated Ca(2+) (CRAC) channels is essential for mediating a wide scale of immune cell responses. Emerging evidence indicates an involvement of abnormal CRAC channel activity in human diseases such as certain types of immunodeficiency, autoimmunity and allergic disorders. This objective of this study was to evaluate the therapeutic potency of a novel CRAC channel inhibitor, RP3128, in experimental models of allergic asthma using guinea pigs. Ovalbumin-induced allergic airway inflammation was determined upon acute and long-term (14 days) oral administration of RP3128. In vivo changes in specific airways resistance (sRaw) and amplitude of isometric contraction (mN) of ASM (in vitro) were estimated to evaluate bronchodilatory effect upon acute and long-term administration of RP3128 or salbutamol. Exhaled nitric oxide (eNO), immunohistochemical and histological analysis of cellular infiltration in airways tissue, and levels of cytokines in plasma as well as bronchoalveolar lavage fluid (BALF), were determined using Bio-Plex® 200 System (BIO-RAD, USA). Ciliary beat frequency (CBF, in Hz) was estimated using a high-speed video camera and LabVIEW™ Software. Additionally, the impact of RP3128 and budesonide on mucociliary clearance was determined. Acute and long-term administration of RP3128 resulted in significant bronchodilation. Long-term administration of RP3128 exceeded the bronchodilatory effect of salbutamol and significantly decreased eNO and cytokine levels in plasma and BALF, which together with histological and immunohistochemical analysis validated its anti-inflammatory effect compared to budesonide. Data demonstrate the therapeutic potential of RP3128 in respiratory diseases causally associated with allergic inflammation.

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适应症	最高研发状态	国家/地区	公司	日期
哮喘	临床3期	加拿大	Rhizen Pharmaceuticals AG	2016-11-03
过敏性哮喘	临床前	印度	Incozen Therapeutics Pvt Ltd.	2016-02-01
过敏性哮喘	临床前	瑞士	Rhizen Pharmaceuticals AG	2016-02-01

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


ERS2018	N/A	慢性阻塞性肺疾病 \| 哮喘	-	RP3128	願醖鹹範淵窪廠夢觸鹽(窪網窪鑰壓製鹽簾觸範) = 廠淵顧願築觸廠簾網網網艱餘淵選淵顧選廠憲 (積鬱構廠膚淵獵夢艱鏇 ) 更多	积极	2018-09-15
				RP3128 + Fluticasone	選鹹齋獵觸蓋鹽壓繭鏇(觸積願齋廠觸築鬱糧簾) = 鏇廠選網築鑰糧襯築獵製鏇願顧獵觸鑰遞蓋鹽 (積鏇艱構淵築鹹憲網築 )