Effect of Repeated Dosing of Clarithromycin on PK of Linaprazan Glurate/Linaprazan, Effect of Single Dose of Linaprazan Glurate on PK of Clarithromycin, Single/Repeated Dosing of Linaprazan Glurate on PK of Midazolam to Healthy Subjects

This is a phase I, open-label, fixed sequence design, drug-drug-interaction (DDI) study divided in 2 parts. Part I is designed to evaluate whether concomitant treatment with linaprazan glurate and clarithromycin, a strong inhibitor of cytochrome P450 3A4 (CYP3A4) and P-glycoprotein P (PgP), leads to an effect on the systemic exposure to linaprazan glurate and linaprazan and whether there is an effect on the pharmacokinetics of clarithromycin after a single dose of linaprazan glurate. Part II is designed to evaluate the effect of repeated doses of linaprazan glurate on the pharmacokinetics (PK) of a sensitive substrate of CYP3A (midazolam).

Start Date27 Nov 2022

Sponsor / Collaborator

Cinclus Pharma Holding AB

NCT05627518

/ CompletedPhase 1

A Randomized, Single Dose, Crossover Study in Healthy Volunteers to Investigate the Relative Bioavailability of Linaprazan for a New Oral Tablet Formulation of Linaprazan Glurate, and to Assess the Effect of Food on the Pharmacokinetics of Linaprazan

This is a single-center, open-label, randomized, single dose, 3-way crossover study in healthy volunteers designed to evaluate the relative bioavailability of a new oral tablet formulation of linaprazan glurate in comparison to a previously studied oral tablet formulation under fasting conditions, and to assess the effect of a high fat, high calorie meal on the pharmacokinetics (PK) of linaprazan glurate and the active substance linaprazan after the administration of the new oral tablet formulation.

Start Date15 Nov 2022

Sponsor / Collaborator

Cinclus Pharma AGStartup

NCT05469854

/ RecruitingPhase 1

A Phase I Study to Investigate the Pharmacokinetics and ECG Effects of Two Single Ascending Doses of Linaprazan Glurate Given as Oral Tablets to Healthy Subjects

This is a Phase I, single-center, double blind, placebo-controlled, parallel-group, randomized study designed to evaluate the PK, cardiodynamic ECG effects, safety, and tolerability of 2 single ascending oral doses of linaprazan glurate. The study will explore the PK properties of linaprazan glurate and linaprazan as well as the cardiodynamic ECG effects, safety, and tolerability after the administration of single doses (300 mg, 600 mg, 200 mg and a final dose level of maximum 400 mg) of linaprazan glurate, using 25 mg base formulation (300 mg and 600 mg doses) and 25 mg and 100 mg HCl formulation (200 mg and final dose level of maximum 400 mg) oral tablets.

Start Date13 Jul 2022

Sponsor / Collaborator

Cinclus Pharma AGStartup

100 Clinical Results associated with Linaprazan

100 Translational Medicine associated with Linaprazan

100 Patents (Medical) associated with Linaprazan

Literatures (Medical) associated with Linaprazan

01 May 2024·Journal of Pharmaceutical and Biomedical Analysis

Absorption, distribution, metabolism and excretion of linaprazan glurate in rats

Article

Author: Liu, Donghui ; Xiu, Jin ; Diao, Xingxing ; Yang, Chen ; Zhang, Xinyue ; Lu, Ming ; Zheng, Yuandong ; Yuan, Yali ; Hu, Pingsheng ; Yang, Ying

Linaprazan (AZD0865, TX07) is one of potassium-competitive acid blockers. However, linaprazan is rapidly excreted from the body, shortening its acid inhibition property. Linaprazan glurate (X842) is a prodrug of linaprazan with a prolonged inhibitory effect on gastric acid secretion. Linaprazan glurate has entered clinical trials, but few studies have reported its metabolism in non-clinical and clinical settings. In this study, we studied the pharmacokinetics, tissue distribution, mass balance, and metabolism of linaprazan glurate in rats after a single oral dose of 2.4 mg/kg (100 µCi/kg) [¹⁴C]linaprazan glurate. The results demonstrated that linaprazan glurate was mainly excreted via feces in rats with 70.48% of the dose over 168 h. The plasma AUC₀_-_∞ of linaprazan glurate in female rats was 2 times higher than that in male rats. Drug-related substances were mainly concentrated in the stomach, eyes, liver, small intestine, and large intestine after administration. In blood, drug-related substances were mostly distributed into plasma instead of hemocytes. In total, 13 metabolites were detected in rat plasma, urine, feces, and bile. M150 (2,6-dimethylbenzoic acid) was the predominant metabolite in plasma, accounting for 80.65% and 67.65% of AUC_0-24_h in male and female rats, respectively. Based on the structures, linaprazan glurate was mainly hydrolyzed into linaprazan, followed by a series of oxidation, dehydrogenation, and glucuronidation in rats. Besides, CES2 is the main metabolic enzyme involved in the hydrolysis of linaprazan glurate to linaprazan.

01 Jun 2020·Saudi Journal of Biological SciencesQ3 · BIOLOGY

Curcumin-loaded cockle shell-derived calcium carbonate nanoparticles: A novel strategy for the treatment of lead-induced hepato-renal toxicity in rats

Q3 · BIOLOGY

ArticleOA

Author: Danmaigoro, Abubakar ; Rahim, Ezamin Bin Abdul ; Mohd Moklas, Mohamad Aris ; Mailafiya, Maryam Muhammad ; Abubakar, Kabeer ; Zakaria, Zuki Abu Bakar ; Chiroma, Samaila Musa

Lead (Pb) toxicity affects the hepatic and renal systems resulting to homeostasis imbalance. Curcumin is a strong antioxidant but has restrained clinical applications due to its poor bioavailability. Nanomedicine showed promising potentials in drug delivery and has brought forth the use of cockle shell-derived aragonite calcium carbonate nanoparticles (CSCaCO₃NP) to enhance the effectiveness and targeted delivery of curcumin (Cur). Thus, this study aimed at evaluating the therapeutic effect of curcumin-loaded CSCaCO₃NP (Cur- CSCaCO₃NP) on lead-induced hepato-renal toxicity in rats. Thirty-six male adults Sprague-Dawley rats were randomly assigned into five groups. All groups contained six rats each except for group A, which contained 12 rats. All rats apart from the rats in group A (control) were orally administered a flat dose of 50 mg/kg of lead for four weeks. Six rats from group A and B were euthanized after four weeks of lead induction. Oral administration of curcumin (100 mg/kg) for group C and Cur-CSCaCO₃NP (50 and 100 mg/kg) for groups D and E respectively, commenced immediately after 4 weeks of lead induction which lasted for 4 weeks. All rats were euthanized at the 8th week of the experiment. Further, biochemical, histological and hematological analysis were performed. The findings revealed a biochemical, hematological and histological changes in lead-induced rats. However, treatments with the Cur-CSCaCO₃NP and free curcumin reversed the aforementioned changes. Although, Cur-CSCaCO₃NP presented better therapeutic effects on lead-induced toxicity in rats when compared to free curcumin as there was significant improvements in hematological, biochemical and histological changes which is parallel with attenuation of oxidative stress. The findings of the current study hold great prospects for Cur-CSCaCO₃NP as a novel approach for effective oral treatment of lead-induced hepato-renal impairments.

01 Sep 2014·Alimentary Pharmacology & TherapeuticsQ1 · MEDICINE

Predictors of either rapid healing or refractory reflux oesophagitis during treatment with potent acid suppression

Q1 · MEDICINE

Article

Author: Hughes, N. ; Persson, T. ; Wernersson, B. ; Kahrilas, P. J. ; Denison, H. ; Howden, C. W.

SummaryBackgroundLittle is known regarding patient characteristics that influence the speed of reflux oesophagitis (RO) healing.AimTo investigate patient characteristics that may influence RO healing rates.MethodsA post hoc analysis of clinical trial data for potent acid suppression treatment of RO (esomeprazole or AZD0865) was conducted. Group A underwent endoscopy at baseline, week 2 and 4, and group B at baseline, week 4 and 8. Group A patients were sub‐grouped as ‘rapid’ (healed at 2 weeks) or unhealed at 2 weeks. Group B patients were sub‐grouped as ‘slow’ (healed at 8 weeks, not at 4 weeks) or ‘refractory’ (not healed at 8 weeks). Logistic regression analysis was performed only for comparisons within group A.ResultsAt 2, 4 and 8 weeks, RO had healed in 68%, 65% and 61% of patients unhealed at previous endoscopy, respectively. Low‐grade [vs. high‐grade (C or D)] RO was the only independent predictor of rapid healing in group A after logistic regression analysis. Significantly more rapid healers had low grade RO (A or B) at baseline than patients with refractory RO (84% vs. 49%; P < 0.001), and significantly more refractory patients had frequent regurgitation at baseline than slow healers (80% vs. 63%; P = 0.039).ConclusionsLow‐ (vs. high‐) grade RO determines the most rapid benefit from acid suppression. Roughly two‐thirds of patients healed with each time increment of potent acid suppression therapy. This suggests that some unhealed patients may still heal with continued therapy and that truly refractory RO is rare. (ClinicalTrials.gov: NCT00206245).

News (Medical) associated with Linaprazan

04 Dec 2024

·cincluspharma.com

Linaprazan glurate receives marketing approval in China

Cinclus Pharma, a clinical-stage pharmaceutical company developing molecules for the treatment of gastric acid-related diseases, today announced that its leading drug candidate, linaprazan glurate, has received its first marketing approval for the treatment of gastroesophageal reflux disease (GERD). The approval by the National Medical Products Administration (NMPA) paves the way for commercialization in the People’s Republic of China in 2025. The approved product was developed together with Cinclus Pharma’s partner Jiangsu Sinorda Biomedicine Co., Ltd, (“Sinorda”) in preclinical studies and independently developed in clinical phases in China by Sinorda. The approval of linaprazan glurate in China follows local clinical trials that demonstrated the drug's safety, efficacy, and ability to address a significant unmet need in GERD. Following the approval, pricing and reimbursement discussions will be initiated laying the foundation for expected product launch in China in 2025. “We are thrilled to announce this highly significant marketing approval for linaprazan glurate in China, a market that represents an immense opportunity for expanding access to this innovative treatment. This achievement clearly reflects the strength of our partner Sinorda, our science, and takes us one important step closer to delivering a therapy meeting an unmet need in a global patient population,” said Christer Ahlberg, CEO of Cinclus Pharma. Cinclus Pharma has a license agreement with Sinorda for the development and commercialization of linaprazan glurate in China and other selected regions of Asia. Sinorda sub-licensed the manufacturing and industrial sales rights for linaprazan glurate in China, Hong Kong, Macau and Taiwan to SPH Sine Pharmaceutical Laboratories Co., Ltd, a company within the Shanghai Pharmaceuticals group, one of China’s leading public pharmaceutical and healthcare companies. For additional information, please contact: Christer Ahlberg, CEO Phone: +46 70 675 33 30 e-mail: christer.ahlberg@cincluspharma.com Charlotte Stjerngren, IR Phone: +46 70 876 87 87 e-mail: charlotte.stjerngren@cincluspharma.com About Cinclus Pharma Cinclus Pharma Holding AB (publ) is a late-stage clinical pharmaceutical company developing drugs for the treatment of acid-related diseases and disorders of the upper gastrointestinal tract. The company's leading drug candidate is linaprazan glurate, a prodrug of P-CAB linaprazan, which was originally developed by AstraZeneca. Linaprazan glurate has the potential to heal erosions in the esophageal mucosa and relieve symptoms of gastroesophageal reflux disease (GERD) more effectively than current treatments like proton pump inhibitors (PPI). The safety and efficacy of linaprazan and linaprazan glurate have been documented in over 30 phase I and two phase II studies involving more than 3,000 participants. Planning for phase III studies is currently underway, with an expected start in 2025. GERD affects approximately 133 million adults in the US and EU, and there is a significant need for new drugs to treat the most severe cases: around 10 million patients. Linaprazan glurate is developed to meet these needs. For more information, visit www.cincluspharma.com. This information is information that Cinclus Pharma Holding AB (publ) is obliged to make public pursuant to the EU Market Abuse Regulation. The information was submitted for publication, through the agency of the contact persons set out above, at 2024-12-04 15:40 CET. Attachments Linaprazan glurate receives marketing approval in China

License out/inDrug ApprovalPhase 2Phase 3

22 Nov 2024

·cincluspharma.com

Cinclus Pharma agrees on pediatric study plan with FDA

Cinclus Pharma, a clinical-stage pharmaceutical company developing molecules for the treatment of acid-related diseases, today announces that it has reached an agreement with the US Food and Drug Administration (FDA) on the company’s initial Pediatric Study Plan (iPSP). The regulatory agreement on a pediatric study plan is a prerequisite for market approval of a new medicine for adult patients, such as linaprazan glurate. It also provides an opportunity for an expanded approval for use in children. "The agreement on our pediatric study plan with the FDA is a prerequisite for market approval in the US, so it’s really a milestone. Now that we have agreed with both the EMA and the FDA, we have taken an important step towards making linaprazan glurate available to patients, thereby fulfilling a large unmet need. Furthermore, an approved pediatric indication would significantly increase the target population for linaprazan glurate,” said Christer Ahlberg, CEO of Cinclus Pharma. The company’s agreed iPSP mainly includes a clinical efficacy and safety trial where approximately 100 pediatric patients will be treated with linaprazan glurate on the same treatment schedule as in the company’s phase III trials in adult eGERD patients. The study plan is essentially the same as Cinclus Pharma recently agreed with the European Medicines Agency (EMAs) Pediatric Committee (PDCO). A regulatory agreement of a pediatric study plan must be obtained before a sponsor may submit a Marketing Authorization Application for approval to commercialize a new medicine for adult patients. Cinclus Pharma submitted its proposed iPSP to FDA in December 2023 and has been going through the regulatory review processes since then. The company’s agreed iPSP includes a deferral under which the pediatric efficacy and safety trial is anticipated to be undertaken after a Marketing Authorization Application has been submitted. For additional information, please contact: Christer Ahlberg, CEO Phone: +46 70 675 33 30 e-mail: christer.ahlberg@cincluspharma.com Charlotte Stjerngren, IR Phone: +46 70 876 87 87 e-mail: charlotte.stjerngren@cincluspharma.com About Cinclus Pharma Cinclus Pharma Holding AB (publ) is a late-stage clinical pharmaceutical company developing drugs for the treatment of acid-related diseases and disorders of the upper gastrointestinal tract. The company's leading drug candidate is linaprazan glurate, a prodrug of P-CAB linaprazan, which was originally developed by AstraZeneca. Linaprazan glurate has the potential to heal erosions in the esophageal mucosa and relieve symptoms of gastroesophageal reflux disease (GERD) more effectively than current treatments like proton pump inhibitors (PPI). The safety and efficacy of linaprazan and linaprazan glurate have been documented in over 30 phase I and two phase II studies involving more than 3,000 participants. Planning for phase III studies is currently underway, with an expected start in 2025. GERD affects approximately 133 million adults in the US and EU, and there is a significant need for new drugs to treat the most severe cases: around 10 million patients. Linaprazan glurate is developed to meet these needs. For more information, visit www.cincluspharma.com. Attachments Cinclus Pharma agrees on pediatric study plan with FDA

Phase 2Phase 3

29 Oct 2024

·cincluspharma.com

Cinclus Pharma agrees on Pediatric Investigation Plan (PIP) with EMA

Cinclus Pharma, a clinical-stage pharmaceutical company developing molecules for the treatment of acid-related diseases, today announces that it has reached an agreement with the European Medicines Agency’s (EMA) Paediatric Commmittee (PDCO) on the company’s Pediatric Investigation Plan (PIP). The regulatory agreement on a pediatric study plan is a pre-requisite for marketing approval of a new medicine for adult patients, such as linaprazan glurate. It also provides an opportunity for an expanded approval for use in children. "It is incredibly satisfying that our pediatric study plan has been agreed. It is a prerequisite for market approval in the EU, so it’s really a milestone. In addition, an approved pediatric indication would of course also significantly increase our target population,” said Christer Ahlberg, CEO of Cinclus Pharma. The company’s agreed PIP mainly includes a clinical efficacy and safety trial where approximately 100 pediatric patients will be treated with linaprazan glurate on the same treatment schedule as in the company’s phase III trials in adult eGERD patients. When a new medicine is developed for adult patients, that medicine must also be tested for potential application to pediatric patients. The sponsor must develop an overall plan to select the specific form or stage of the disease to be treated, to adapt the dosing and administration of the medicine for pediatric physiology, and to evaluate the safety and efficacy of the medicine in pediatric patients. A regulatory agreement of a pediatric study plan must be obtained before a sponsor may submit a Marketing Authorization Application for approval to commercialize a new medicine for adult patients. Cinclus Pharma submitted its proposed PIP to EMA in December 2023 and has been going through the regulatory review processes since then. The company’s agreed PIP includes a deferral under which the pediatric efficacy and safety trial is anticipated to be undertaken after a Marketing Authorization Application has been submitted. For additional information, please contact: Christer Ahlberg, CEO Phone: +46 70 675 33 30 e-mail: christer.ahlberg@cincluspharma.com Charlotte Stjerngren, IR Phone: +46 70 876 87 87 e-mail: charlotte.stjerngren@cincluspharma.com About Cinclus Pharma Cinclus Pharma Holding AB (publ) is a late-stage clinical pharmaceutical company developing drugs for the treatment of acid-related diseases and disorders of the upper gastrointestinal tract. The company's leading drug candidate is linaprazan glurate, a prodrug of P-CAB linaprazan, which was originally developed by AstraZeneca. Linaprazan glurate has the potential to heal erosions in the esophageal mucosa and relieve symptoms of gastroesophageal reflux disease (GERD) more effectively than current treatments like proton pump inhibitors (PPI). The safety and efficacy of linaprazan and linaprazan glurate have been documented in over 30 phase I and two phase II studies involving more than 3,000 participants. Planning for phase III studies is currently underway, with an expected start in 2025. GERD affects approximately 133 million adults in the US and EU, and there is a significant need for new drugs to treat the most severe cases: around 10 million patients. Linaprazan glurate is developed to meet these needs. For more information, visit www.cincluspharma.com. Attachments Cinclus Pharma agrees on Pediatric Investigation Plan (PIP) with EMA

Phase 3Phase 2

100 Deals associated with Linaprazan

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Gastroesophageal Reflux	Phase 1	GB	AstraZeneca PLC	01 May 2004
Gastroesophageal Reflux	Phase 1	DE	AstraZeneca PLC	01 May 2004
Gastroesophageal Reflux	Phase 1	NO	AstraZeneca PLC	01 May 2004
Gastroesophageal Reflux	Phase 1	FR	AstraZeneca PLC	01 May 2004
Gastroesophageal Reflux	Phase 1	CA	AstraZeneca PLC	01 May 2004
Gastroesophageal Reflux	Phase 1	FI	AstraZeneca PLC	01 May 2004
Gastroesophageal Reflux	Phase 1	IT	AstraZeneca PLC	01 May 2004
Gastroesophageal Reflux	Phase 1	US	AstraZeneca PLC	01 May 2004
Gastroesophageal Reflux	Phase 1	DK	AstraZeneca PLC	01 May 2004
Gastroesophageal Reflux	Phase 1	SE	AstraZeneca PLC	01 May 2004

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05633147 (CTgov)	Phase 1	Medication interactions	35	Linaprazan glurate+Clarithromycin (Part I)	svobzyxfig(xzerjneaau) = nwfvnwxudy rbpmiiwszl (lsiaofrmyk, vtfnbjaoxo - ffpolgzzzp) View more	-	03 Jan 2025
				Linaprazan glurate hydrochloride (HCl)+Midazolam (Part II)	smupqytkik(qluwqobdpl) = ytovpjkbbo pfmwfltygo (gknhejtxay, jvxldiqorn - bzmafvlqgx) View more

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