linaprazan glurate (X842) / Cinclus Pharma, Jiangsu Sinorda Biomedicine - LARVOL DELTA

OPTIMISED BIOPHARMACEUTICAL AND PHARMACOKINETIC PROPERTIES OF A LINAPRAZAN GLURATE TABLET FORMULATION TO BE USED IN PHASE 3 STUDIES (DDW 2025) - "An optimized linaprazan glurate HCl tablet formulation has been developed for Phase 3, with a later t max and an approximately 2-fold higher bioavailability than the initial tablet and only a minor impact of food intake on linaprazan AUC inf . In addition, the linaprazan glurate HCl tablet provided dose-proportional increase in linaprazan plasma exposure as reflected by AUC and C max . Reference: Flezar M et al."

P3 data • PK/PD data

PHARMACOKINETICS AND PHARMACODYNAMICS OF LINAPRAZAN GLURATE AFTER MULTIPLE ORAL DOSES UP TO 14 DAYS IN HEALTHY SUBJECTS (DDW 2025) - "The PK and PD properties of LG indicate a strong clinical efficacy potential in patients with acid related disease to be confirmed in a phase 3 program. A rapid onset of effect was observed in all dosing groups, with sustained maintenance of pH>4 in all subjects and a pH>5 HTR exceeding 80% at steady state in the two highest dosing groups. Repeated oral doses of LG at 25, 50, and 75 mg QD and BID over 14 days were safe and well-tolerated."

Clinical • PK/PD data

Investigate Linaprazan Glurate/Linaprazan in Healthy Subjects (clinicaltrials.gov) - P1 | N=75 | Completed | Sponsor: Cinclus Pharma Holding AB | Active, not recruiting ➔ Completed

Trial completion • Gastroesophageal Reflux Disease

Clinical Trial: Dose-Finding Study of Linaprazan Glurate, A Novel Potassium-Competitive Acid Blocker, Versus Lansoprazole for the Treatment of Erosive Oesophagitis. (PubMed, Aliment Pharmacol Ther) - P2 | "Linaprazan glurate demonstrated high 4-week healing rates compared to lansoprazole, with a good safety profile, supporting its further development."

Journal • Gastroesophageal Reflux Disease • Gastrointestinal Disorder

A Randomized, Comparative Trial of a Potassium-Competitive Acid Blocker (X842) and Lansoprazole for the Treatment of Patients with Erosive Esophagitis. (PubMed, Clin Transl Gastroenterol) - "Our findings confirmed that X842 had efficacy and a favourable safety profile similar to those of lansoprazole. Therefore, X842, a novel P-CAB, is expected to become a promising therapeutic agent for EE."

Journal • Gastrointestinal Disorder

PHARMACOKINETICS AND PHARMACODYNAMICS OF LINAPRAZAN GLURATE AFTER MULTIPLE ORAL DOSES UP TO 14 DAYS IN HEALTHY SUBJECTS (UEGW 2024) - "A rapid onset of pH>4 HTR was seen with LG with a clear dose response. The two highest dosing groups achieved above 90% pH>4 HTR excluding the initial 90 min after the first dose.Repeated oral doses of LG 25, 50 and 75 mg QD and BID for 14 days were safe and well tolerated."

Clinical • PK/PD data • Gastroenterology • Pain

Potassium-competitive Acid Blockers: Current Clinical Use and Future Developments. (PubMed, Curr Gastroenterol Rep) - "Four different P-CABs (vonoprazan, tegoprazan, fexuprazan and keverprazan) are currently available...The available data show that-in the above two clinical indications-P-CABs provide similar or better efficacy in comparison with PPIs. Their safety in the short-term overlaps that of PPIs, but data from long-term treatment are needed."

Journal • Review • Gastroenterology • Gastroesophageal Reflux Disease • Infectious Disease • Peptic Ulcer

COMPARATIVE EFFICACY OF VONOPRAZAN WITH PROTON PUMP INHIBITORS AND OTHER POTASSIUM-COMPETITIVE ACID BLOCKERS FOR REFLUX ESOPHAGITIS: A NETWORK META-ANALYSIS (DDW 2024) - "Randomized controlled trials of (1) endoscopy-confirmed RE patients ≥18 years ( ) receiving at least of these intervention arms: vonoprazan tegoprazan kenoprazan fexuprazan linaprazan glurate and/or any oral PPIs (3) reporting at least 1 clinical outcomes of healing rate at 4 weeks for vonoprazan and 8 weeks for PPIs and other P-CABs and (4) those including > 0 patients per group were considered...1) esomeprazole 40mg:1...4) ilaprazole 10mg:...8) lansoprazole 30mg:1...4) omeprazole 40mg:1...1) pantoprazole 40mg:1...8) and rabeprazole 0mg:1...ConclusionThis is the first study showing similar efficacy of 4-week vonoprazan course to 8-week PPI course and other P-CABs in healing RE. These results may be helpful to inform clinical practice."

Retrospective data • Gastroesophageal Reflux Disease • Gastrointestinal Disorder

A Study to Investigate the Pharmacokinetics and ECG Effects of Linaprazan Glurate (clinicaltrials.gov) - P1 | N=113 | Recruiting | Sponsor: Cinclus Pharma AG | Trial completion date: Dec 2023 ➔ Dec 2024 | Trial primary completion date: Dec 2023 ➔ Dec 2024

Trial completion date • Trial primary completion date • Gastroesophageal Reflux Disease

Absorption, distribution, metabolism and excretion of linaprazan glurate in rats. (PubMed, J Pharm Biomed Anal) - "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."

Journal • Preclinical

Investigate Linaprazan Glurate/Linaprazan in Healthy Subjects (clinicaltrials.gov) - P1 | N=72 | Active, not recruiting | Sponsor: Cinclus Pharma Holding AB | Trial completion date: Sep 2023 ➔ Mar 2024

Trial completion date • Gastroesophageal Reflux Disease

LINAPRAZAN GLURATE IS HIGHLY EFFECTIVE IN TREATING MODERATE TO SEVERE EROSIVE ESOPHAGITIS: A DOUBLE-BLIND, RANDOMIZED, DOSE FINDING STUDY (UEGW 2023) - "Aims & This is a randomized, double-blind, active comparator-controlled, 5-arm parallel group, dose-finding study of LG, with lansoprazole (LAN) as the active comparator, on the 4-week healing of EE, with safety and tolerability as secondary endpoints. High EE healing rates were seen after 4 weeks of LG treatment in the overall LA grade C/D cohort, with the highest healing rate seen for 75 mg BID. In combination with good safety and tolerability results, these findings support further development of LG for the treatment of erosive esophagitis due to GERD."

Clinical • Gastroesophageal Reflux Disease • Gastrointestinal Disorder

LINAPRAZAN GLURATE IS WELL TOLERATED IN THE TREATMENT OF PATIENTS WITH EROSIVE ESOPHAGITIS: A DOUBLE-BLIND, RANDOMIZED, DOSE FINDING STUDY (UEGW 2023) - "This Phase 2 study aimed to investigate safety, tolerability, and healing rates after 4 weeks of treatment with LG or lansoprazole (LAN). LG was well-tolerated with no dose-related increase in AEs, and the safety profile was comparable to that of LAN. In combination with promising efficacy results, these findings support further development of LG for the treatment of erosive esophagitis due to GERD."

Clinical • Constipation • Fatigue • Gastroesophageal Reflux Disease • Gastrointestinal Disorder • Hepatology • Infectious Disease • Novel Coronavirus Disease • Pain

A Study to Investigate the Pharmacokinetics and ECG Effects of Linaprazan Glurate (clinicaltrials.gov) - P1 | N=113 | Recruiting | Sponsor: Cinclus Pharma AG | N=63 ➔ 113 | Trial completion date: Apr 2023 ➔ Dec 2023 | Trial primary completion date: Apr 2023 ➔ Dec 2023

Enrollment change • Trial completion date • Trial primary completion date • Gastroesophageal Reflux Disease

Effect of Clarithromycin on PK of Linaprazan, Linaprazan on PK of Clarithromycin and Linaprazan on PK of Midazolam (clinicaltrials.gov) - P1 | N=35 | Completed | Sponsor: Cinclus Pharma Holding AB | Recruiting ➔ Completed

Trial completion

LINAPRAZAN GLURATE IS HIGHLY EFFECTIVE IN TREATING MODERATE TO SEVERE EROSIVE ESOPHAGITIS: A DOUBLE-BLIND, RANDOMIZED, DOSE FINDING STUDY (DDW 2023) - "Methods This was a randomized, double-blind, active comparator-controlled, 5-arm parallel group, dose-finding study of LG, with lansoprazole (LAN) for comparison of safety outcome, on 4-week endoscopic healing of erosive esophagitis, with safety and tolerability as secondary endpoints. LG was generally well-tolerated, and the safety profile was comparable to that of LAN. These results support further development of LG for the treatment of erosive esophagitis."

Clinical • Gastrointestinal Disorder • Infectious Disease

Effect of Clarithromycin on PK of Linaprazan, Linaprazan on PK of Clarithromycin and Linaprazan on PK of Midazolam (clinicaltrials.gov) - P1 | N=36 | Recruiting | Sponsor: Cinclus Pharma Holding AB | Trial completion date: Feb 2023 ➔ May 2023 | Trial primary completion date: Jan 2023 ➔ May 2023

Trial completion date • Trial primary completion date

Investigate Linaprazan Glurate/Linaprazan in Healthy Subjects (clinicaltrials.gov) - P1 | N=72 | Active, not recruiting | Sponsor: Cinclus Pharma Holding AB | Recruiting ➔ Active, not recruiting | Trial completion date: Mar 2023 ➔ Aug 2023

Enrollment closed • Trial completion date • Gastroesophageal Reflux Disease

Investigate Linaprazan Glurate/Linaprazan in Healthy Subjects (clinicaltrials.gov) - P1 | N=72 | Recruiting | Sponsor: Cinclus Pharma Holding AB

New P1 trial • Gastroesophageal Reflux Disease

A Study to Investigate the Pharmacokinetics and ECG Effects of Linaprazan Glurate (clinicaltrials.gov) - P1 | N=63 | Recruiting | Sponsor: Cinclus Pharma AG | Trial completion date: Sep 2022 ➔ Apr 2023 | Trial primary completion date: Sep 2022 ➔ Apr 2023

Trial completion date • Trial primary completion date • Gastroesophageal Reflux Disease

BA: Relative Bioavailability of Linaprazan for the Test Formulation vs. Reference Formulation (clinicaltrials.gov) - P1 | N=54 | Completed | Sponsor: Cinclus Pharma AG | Recruiting ➔ Completed

Trial completion

Effect of Clarithromycin on PK of Linaprazan, Linaprazan on PK of Clarithromycin and Linaprazan on PK of Midazolam (clinicaltrials.gov) - P1 | N=36 | Recruiting | Sponsor: Cinclus Pharma Holding AB | Not yet recruiting ➔ Recruiting

Enrollment open

BIOAVAILABILITY STUDY OF LINAPRAZAN GLURATE 100 MG FORMULATIONS IN HEALTHY VOLUNTEERS UNDER FED AND FASTING CONDITIONS RAZISKAVA BIOLOŠKE UPORABNOSTI ENEGA POSAMIČNEGA ODMERKA FORMULACIJ LINAPRAZAN GLURATA 100 MG, PRI ZDRAVIH PROSTOVOLJCIH PO OBROKU IN V POGOJIH NA TEŠČE (clinicaltrialsregister.eu) - P1/2 | N=52 | Ongoing | Sponsor: Cinclus Pharma Holding AB

New P1/2 trial

Effect of Clarithromycin on PK of Linaprazan, Linaprazan on PK of Clarithromycin and Linaprazan on PK of Midazolam (clinicaltrials.gov) - P1 | N=36 | Not yet recruiting | Sponsor: Cinclus Pharma Holding AB

New P1 trial

BA: Relative Bioavailability of Linaprazan for the Test Formulation vs. Reference Formulation (clinicaltrials.gov) - P1 | N=54 | Recruiting | Sponsor: Cinclus Pharma AG

New P1 trial