[Translation] A multicenter, randomized, double-blind, positive-controlled, parallel-group Phase II clinical study on the efficacy and safety of OR12000 compound tablets in the treatment of patients with moderate to severe essential hypertension

1. 比较QR12000复方片与其单方QR01019钾盐在中、重度原发性高血压患者中的降压效果。 2. 比较QR12000复方片与缬沙坦在中、重度原发性高血压患者中的降压效果。 3. 比较QR12000复方片与诺欣妥在中、重度原发性高血压患者中的降压效果。 4. 评估QR12000复方片在中、重度原发性高血压患者的安全性。 5. 评估QR12000复方片在中、重度原发性高血压患者中生物标志物的特征。 6. 评估QR12000复方片中主要活性成分在中重度原发性高血压患者中的药代动力学（PK）特征及PK-PD关系。

[Translation]

1. To compare the antihypertensive effects of QR12000 compound tablets and its single QR01019 potassium salt in patients with moderate and severe essential hypertension. 2. To compare the antihypertensive effects of QR12000 compound tablets and valsartan in patients with moderate and severe essential hypertension. 3. To compare the antihypertensive effects of QR12000 compound tablets and Entresto in patients with moderate and severe essential hypertension. 4. To evaluate the safety of QR12000 compound tablets in patients with moderate and severe essential hypertension. 5. To evaluate the characteristics of biomarkers of QR12000 compound tablets in patients with moderate and severe essential hypertension. 6. To evaluate the pharmacokinetic (PK) characteristics and PK-PD relationship of the main active ingredients in QR12000 compound tablets in patients with moderate and severe essential hypertension.

Start Date29 Dec 2022

Sponsor / Collaborator

Wuhan Createrna Science and Technology Co.,Ltd.

CTR20211564 / CompletedPhase 1

一项在中国健康成年受试者中评估进食对QR12000复方片生物利用度影响的单次给药、随机、两周期交叉研究

[Translation] A single-dose, randomized, two-period crossover study to evaluate the effect of food intake on the bioavailability of QR12000 compound tablets in healthy Chinese adult subjects

主要目的：评估高脂饮食对健康成年受试者单次口服QR12000复方片的药代动力学（PK）特征的影响。次要目的：1) 观察健康成年受试者单次口服QR12000复方片的安全性；2)评估高脂饮食对健康成年受试者单次口服QR12000复方片安全性的影响。

[Translation]

Primary objective: To evaluate the effect of a high-fat diet on the pharmacokinetic (PK) characteristics of a single oral administration of QR12000 compound tablets in healthy adult subjects. Secondary objectives: 1) To observe the safety of a single oral administration of QR12000 compound tablets in healthy adult subjects; 2) To evaluate the effect of a high-fat diet on the safety of a single oral administration of QR12000 compound tablets in healthy adult subjects.

Start Date24 Jul 2021

Sponsor / Collaborator

Wuhan Createrna Science and Technology Co.,Ltd.

100 Clinical Results associated with CD10 x AT2R

100 Translational Medicine associated with CD10 x AT2R

0 Patents (Medical) associated with CD10 x AT2R

Literatures (Medical) associated with CD10 x AT2R

01 Mar 2022·Asian Journal of AndrologyQ2 · MEDICINE

Local renin angiotensin system and sperm DNA fragmentation

Q2 · MEDICINE

ArticleOA

Author: Hervás Barbara, Gotzone ; Franco Iriarte, Yosu ; Rodríguez Gallego, María Victoria ; Aparicio Prieto, María Victoria ; Echevarría Orella, Enrique ; Casis Saenz, Luis ; Valdivia Palacín, Asier

The renin angiotensin system (RAS) appears to influence male fertility at multiple levels. In this work, we analyzed the relationship between the RAS and DNA integrity. Fifty male volunteers were divided into two groups (25 each): control (DNA fragmentation ≤20%) and pathological (DNA fragmentation >20%) cases. Activities of five peptidases controlling RAS were measured fluorometrically: prolyl endopeptidase (which converts angiotensin [A] I and A II to A 1–7), neutral endopeptidase (NEP/CD10: A I to A 1–7), aminopeptidase N (APN/CD13: A III to A IV), aminopeptidase A (A II to A III) and aminopeptidase B (A III to A IV). Angiotensin-converting enzyme (A I to A II), APN/CD13 and NEP/CD10 were also assessed by semiquantitative cytometry and quantitative flow cytometry assays, as were the receptors of all RAS components: A II receptor type 1 (AT1R), A II receptor type 2 (AT2R), A IV receptor (AT4R or insulin-regulated aminopeptidase [IRAP]), (pro)renin receptor (PRR) and A 1–7 receptor or Mas receptor (MasR) None of the enzymes that regulate levels of RAS components, except for APN/CD13 (decrease in fragmented cells), showed significant differences between both groups. Micrographs of RAS receptors revealed no significant differences in immunolabeling patterns between normozoospermic and fragmented cells. Labeling of AT1R (94.3% normozoospermic vs 84.1% fragmented), AT4R (96.2% vs 95.3%) and MasR (97.4% vs 87.2%) was similar between the groups. AT2R (87.4% normozoospermic vs 63.1% fragmented) and PRR (96.4% vs 48.2%) were higher in non-fragmented spermatozoa. These findings suggest that fragmented DNA spermatozoa have a lower capacity to respond to bioactive RAS peptides.

01 Mar 2021·British Journal of Clinical PharmacologyQ2 · MEDICINE

Increased concentrations of bioactive adrenomedullin subsequently to angiotensin‐receptor/neprilysin‐inhibitor treatment in chronic systolic heart failure

Q2 · MEDICINE

Article

Author: Bartko, Philipp E. ; Cho, Anna ; Arfsten, Henrike ; Haslacher, Helmuth ; Strunk, Guido ; Spinka, Georg ; Prausmüller, Suriya ; Hülsmann, Martin ; Struck, Joachim ; Novak, Johannes ; Pavo, Noemi ; Goliasch, Georg

AimsThe clinically investigated rationale for neprilysin (NEP)‐inhibition by angiotensinreceptor‐NEPinhibitor (ARNi) therapy is to induce elevations in endogenous natriuretic peptides. NEP, however, cleaves a broad spectrum of substrates, which partially hold significant implications in heart failure with reduced ejection fraction (HFrEF). The effect of NEP inhibition on these peptides has not been investigated thoroughly. This study explored the response of adrenomedullin (ADM) regulation to the initiation of ARNi.MethodsSeventy‐four patients with stable HFrEF and initiation of ARNi were prospectively enrolled, 67 patients on continuous angiotensin‐converting‐enzyme inhibitor(ACEi)/angiotensin‐receptor blocker (ARB) therapy served as control. Plasma bioactive‐ADM (bio‐ADM), mid‐regional‐pro‐ADM (MR‐proADM), B‐typenatriuretic peptide (BNP) and N‐terminal‐pro‐BNP (NT‐proBNP) were determined at baseline, short‐term, 1‐year and 2‐year follow up.ResultsFollowing ARNi initiation both bio‐ADM and MR‐proADM concentrations were significantly increased at early and long‐term follow up (bio‐ADM [pg/mL]: 26.0 [interquartile range {IQR}: 17.7–37.5] vs. 50.8 [IQR: 36.5–78.1] vs. 54.6 [IQR: 42.0–97.1] vs. 57.4 [IQR: 48.5–161.6]; MR‐proADM [nmol/L]: 0.87 [IQR: 0.64–1.12] vs. 1.25 [IQR: 0.93–1.79] vs. 1.42 [IQR: 0.95–1.90] vs. 1.60 [IQR: 1.12–2.46], P < .0001 for all). The ratios bio‐ADM/MR‐proADM and BNP/NT‐proBNP increased during ARNi‐therapy proving improved availability of bioactive peptides. The proportional increase of bio‐ADM markedly exceeded BNP increase. Patients converted to ARNi showed similar biomarker patterns irrespective of baseline renin–angiotensin system blocker therapy, i.e. ACEi or ARB (P > .05 for all), indicating that activation of the ADM‐axis arises particularly from NEPinhibition.ConclusionThe significant increase of MR‐proADM and bio‐ADM together with an elevated bioADM/MR‐proADM ratio suggest both enhanced formation and reduced breakdown of bioactive ADM following the initiation of ARNi. Activation of the ADM‐axis represents a so far unrecognized effect of ARNi.

16 Jul 2017·Lung Cancer International

Alterations in Gene Expression of Components of the Renin-Angiotensin System and Its Related Enzymes in Lung Cancer

Article

Author: Goldstein, Benjamin ; Speth, Robert C. ; Trivedi, Malav

Objectives. The study assessed the existence and significance of associations between the expression of fifteen renin-angiotensin system component genes and lung adenocarcinoma. Materials and Methods. NCBI’s built-in statistical tool, GEO2R, was used to calculate Student’s t-tests for the associations found in a DNA expression study of adenocarcinoma and matched healthy lung tissue samples. The raw data was processed with GeneSpring™ and then used to generate figures with and without Sidak’s multiple comparison correction. Results. Ten genes were found to be significantly associated with adenocarcinoma. Seven of these associations remained statistically significant after correction for multiple comparisons. Notably, AGTR2, which encodes the AT2 angiotensin II receptor subtype, was significantly underexpressed in adenocarcinoma tissue (p<0.01). AGTR1, ACE, ENPEP, MME, and PRCP, which encode the AT1 angiotensin II receptor, angiotensin-converting enzyme, aminopeptidase N, neprilysin, and prolylcarboxypeptidase, respectively, were also underexpressed. AGT, which encodes angiotensinogen, the angiotensin peptide precursor, was overexpressed in adenocarcinoma tissue. Conclusion. The results suggest an association between the expression of the genes for renin-angiotensin system-related proteins and adenocarcinoma. While further research is necessary to conclusively demonstrate a link between the renin-angiotensin system and lung cancers, the results suggest that the renin-angiotensin system plays a role in the pathology of adenocarcinoma.

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