A Phase 1, Open Label, Randomized, Parallel-group, Single Center Study to Investigate Pharmacokinetics and Pharmacodynamics (Intragastric pH) of Linaprazan Glurate/Linaprazan After Single and 14 Days'Repeated Oral Administration of Linaprazan Glurate to Healthy Subjects

This is a Phase I, single-center, open label parallel-group, randomized study designed to evaluate the pharmacokinetics (PK), pharmacodynamics (PD, by continuous intragastric pH measurment), safety and tolerability of single and repeated oral doses of linaprazan glurate in 3 different dose levels given once- (QD) or twice daily (BID), for 14 days, with an additional single dose after 2, 4 or 6 days of drug holiday. The population will include healthy male and female subjects.
The subjects will be followed up to 28 days post IMP dosing.

Start Date26 Jan 2023

Sponsor / Collaborator

Cinclus Pharma Holding AB

NCT05633147

/ CompletedPhase 1

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 Holding AB

100 Clinical Results associated with Linaprazan glurate

100 Translational Medicine associated with Linaprazan glurate

100 Patents (Medical) associated with Linaprazan glurate

Literatures (Medical) associated with Linaprazan glurate

01 May 2025·ALIMENTARY PHARMACOLOGY & THERAPEUTICS

Clinical Trial: Dose‐Finding Study of Linaprazan Glurate, A Novel Potassium‐Competitive Acid Blocker, Versus Lansoprazole for the Treatment of Erosive Oesophagitis

Article

Author: Unge, Peter ; Andersson, Kjell ; Popadiyn, Ivan ; Yektaei, Elham ; Rosenholm, Maria ; Vaezi, Michael ; Sharma, Prateek ; Larsson, Kajsa ; Armstrong, David ; Rosztóczy, Andras

ABSTRACT:

Background:

Linaprazan glurate, a potassium‐competitive acid blocker, is in development for the treatment of erosive oesophagitis and other acid‐related diseases.

Aim:

To evaluate the 4‐week healing rate and safety of four linaprazan glurate dosing regimens in patients with erosive oesophagitis.

Methods:

This double‐blind, dose‐finding study compared linaprazan glurate to lansoprazole. We included patients with endoscopically confirmed erosive oesophagitis (validated by a central review board) if they had Los Angeles (LA) grade C/D or LA grade A/B with partial response to at least 8 weeks of proton pump inhibitor therapy. Patients were randomised to 4 weeks of linaprazan glurate (25, 50, 75 or 100 mg twice daily) or lansoprazole (30 mg once daily), followed by 4 weeks of open‐label lansoprazole.

Results:

Of 248 patients randomised, central review confirmed erosive oesophagitis in 182 at screening endoscopy. Across all doses, linaprazan glurate achieved a 4‐week healing rate of 71.1% in intention‐to‐treat (ITT) analysis and 80.9% in per protocol (PP) analysis. In comparison, lansoprazole achieved healing rates of 60.6% (ITT) and 59.1% (PPS). The best performing linaprazan glurate dosing group outperformed lansoprazole by 28% in patients with LA grade A/B with partial PPI response and by more than 50% in patients with LA grade C/D.

Conclusions:

Linaprazan glurate demonstrated high 4‐week healing rates compared to lansoprazole, with a good safety profile, supporting its further development.

Trial Registration:

ClinicalTrials.gov: NCT05055128; EudraCT: 2020‐003319‐91

01 Nov 2024·Current gastroenterology reports

Potassium-competitive Acid Blockers: Current Clinical Use and Future Developments

Review

Author: Scarpignato, Carmelo ; Hunt, Richard H

Abstract:

Purpose of the Review:

Acid suppression with proton pump inhibitors (PPIs) represents the standard of care in the treatment of acid-related diseases. However, despite their effectiveness, PPIs display some intrinsic limitations, which underlie the unmet clinical needs that have been identified over the past decades. The aims of this review are to summarize the current status and future development of the new class of antisecretory drugs (potassium-competitive acid blockers, P-CABs) that have recently been introduced into medical practice.

Recent Findings:

Over the past decades, clinical needs unmet by the current acid suppressants have been recognized, especially in the management of patients with GERD, Helicobacter pylori infection and NSAID-related peptic ulcer. The failure to address these needs is mainly due to their inability to achieve a consistent acid suppression in all patients and, particularly, to control nighttime acidity. It was then realized that an extended duration of acid suppression would exert additional benefits. The available data with P-CABs show that they are able to address these unmet clinical needs.

Summary:

Four different P-CABs (vonoprazan, tegoprazan, fexuprazan and keverprazan) are currently available. However, only two of them are approved outside Asia. Vonoprazan is available in North, Central and South America while tegoprazan is marketed only in Latin American countries. Two other compounds (namely linazapran glurate and zestaprazan) are presently under clinical development. While clinical trials on GERD have been performed with all P-CABs, only vonoprazan and tegoprazan have been investigated as components of Helicobacter pylori eradication regimens. 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.

01 May 2024·Journal of pharmaceutical and biomedical analysis

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

Article

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

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.

News (Medical) associated with Linaprazan glurate

22 May 2025

·www.fiercepharma.com

Zentiva inks €220M deal to commercialize AstraZeneca GI cast-off in Europe

Cinclus Pharma was founded in 2014 by a group of former AstraZeneca employees who wanted to take linaprazan further. Former Sanofi subsidiary Zentiva has signed off on up to 220 million euros for the rights to commercialize and manufacture an ex-AstraZeneca asset for gastric-acid-related diseases in Europe.Under the terms of the deal, Zentiva is paying Cinclus Pharma 13 million euros upfront, with a near-term milestone payment of 5 million euros to follow next year, according to a May 22 release. The total possible value of the agreement, at 220 million euros, includes the upfront payment and all commercial and regulatory milestones. In return, Zentiva has secured the rights to commercialize and manufacture linaprazan glurate in Europe. Cinclus can also receive tiered double-digit royalties on net sales in Europe. The partnership applies to the U.K., Switzerland and all the countries in the European Economic Area.“This alliance establishes a fully integrated set of capabilities covering everything necessary to bring linaprazan glurate to the market across Europe,” Cinclus CEO Christer Ahlberg said in the release. “This collaboration not only de-risks our path to European approval but also positions us to capture significant global value, particularly in the U.S. market where we retain full commercial rights and see a substantial commercial opportunity.”Linaprazan glurate is a potassium-competitive acid blocker that Cinclus is developing for severe erosive gastroesophageal reflux disease (eGERD). Cinclus, which is based in Sweden, plans to test the asset in a phase 3 trial starting in the third quarter of this year.Linaprazan glurate was approved by Chinese regulators as a GERD treatment in December 2024, and Cinclus has previously set out plans to launch the drug itself in China this year. eGERD occurs when stomach acid backs up into the esophagus, damaging the gastric tube’s lining. The condition can cause heartburn, trouble swallowing and chest pain, among other symptoms.Linaprazan was initially developed by AstraZeneca and tested in phase 1 and 2 trials between 2001 and 2005, according to Cinclus’ website. Cinclus was founded in 2014 by a group of former AstraZeneca employees who wanted to take the molecule further after the Big Pharma lost interest in the drug.Cinclus unveiled data from a phase 2 dose-selection study of linaprazan in November 2022. The study compared linaprazan with over-the-counter competitor lansoprazole but was not statistically powered to test whether there was a significant difference between the two, Cinclus said at the time. A post hoc analysis of the data found that eGERD patients treated with linaprazan glurate had higher rates of healing, as assessed by an endoscopic evaluation, than those given lansoprazole, Cinclus said.Zentiva also has a history with Big Pharma; the Czech drugmaker was a subsidiary of Sanofi from 2008 to 2018, with a focus on generics. Zentiva was acquired by private equity firm Advent International in 2018 and is now taking a turn into brand-name products.“This partnership marks a key milestone for Zentiva as we continue expanding our portfolio beyond generics into high-value specialty medicines,” Zentiva Chief Scientific Officer Martin Albert said in the release. “Linaprazan glurate is a complementary asset that perfectly fits our strategy to leverage our excellence in generics and deliver game-changing treatments to patients across Europe.”

Drug ApprovalPhase 1License out/inPhase 2Acquisition

22 May 2025

·cincluspharma.com

Cinclus Pharma Partners with Zentiva to Commercialize Linaprazan Glurate in Europe

Cinclus Pharma establishes a strategic alliance and licensing agreement with Zentiva, a leading European pharmaceutical company, for the commercialization and manufacturing of its lead asset, linaprazan glurate, in Europe. The agreement covers all member states in EEA, UK and Switzerland. The total deal value, including upfront and regulatory and commercialization milestone payments is EUR 220 million, which includes an upfront payment of EUR 13 million and a near-term milestone of EUR 5 million in 2026. Cinclus Pharma is also entitled to tiered double-digit royalties on net sales in Europe, starting in the high-teens and exceeding 20% at the highest tier levels. Cinclus Pharma Holding AB (publ) (STO: CINPHA), a clinical-stage biopharmaceutical company focused on developing novel therapies for the treatment of gastric acid-related diseases, today announced an agreement with Zentiva k.s., a leading European pharmaceutical company, for the commercialization and manufacturing of its lead asset, linaprazan glurate, in Europe. The product is a next-generation potassium-competitive acid blocker (PCAB) designed for the treatment of severe erosive gastroesophageal reflux disease (eGERD). The addressable market is estimated at 19 million patients globally, including approx. 10 million across Europe and the US. Cinclus Pharma expects to initiate its first Phase III study with linaprazan glurate in Q3 2025. The total deal value, including an upfront payment and all regulatory and commercial milestones is EUR 220 million (approximately SEK 2,4 billion). As part of the transaction, Zentiva will make an upfront payment of EUR 13 million (approximately SEK 143 million) and Cinclus Pharma is eligible for a near-term milestone payment of EUR 5 million (approximately SEK 55 million) in 2026. Cinclus Pharma is also eligible to receive tiered double-digit royalties on net sales in Europe, starting in the high teens and exceeding 20% at the highest tiers. “The alliance with Zentiva marks a significant inflection point for Cinclus Pharma,” said Christer Ahlberg, CEO of Cinclus Pharma. “We are particularly excited given Zentiva’s commercial reach and operational strength across Europe. This alliance establishes a fully integrated set of capabilities covering everything necessary to bring linaprazan glurate to the market across Europe. The alliance benefits from world-leading expertise in gastroenterology-focused development, regulatory affairs, manufacturing and commercialization. This collaboration not only de-risks our path to European approval but also positions us to capture significant global value, particularly in the US market where we retain full commercial rights and see a substantial commercial opportunity” “This partnership marks a key milestone for Zentiva as we continue expanding our portfolio beyond generics into high-value specialty medicines. Linaprazan glurate is a complementary asset that perfectly fits our strategy to leverage our excellence in generics and deliver game-changing treatments to patients across Europe. With our strong pan-European commercial platform, we are proud to be the trusted partner to bring this innovative therapy to those suffering from severe erosive GERD” said Martin Albert, CSO, Zentiva. About Zentiva Zentiva provides health and wellbeing for all generations. It is a European company developing, producing, and delivering high-quality, affordable medicines to more than 100 million people in over 30 countries across Europe and beyond. Zentiva has four wholly owned manufacturing sites and a broad network of external manufacturing partners to ensure supply security. The company is private equity-owned, delivering sustainable growth, with an ambitious plan for the years to come. Invitation to webcast 09.00 CEST The company will host a webcast today at 09:00 am CEST with a presentation and a Q&A session. If you wish to participate via webcast please use the link below. Via the webcast you are able to ask written questions. https://live.events.inderes.com/press-conference-may-22 If you wish to participate via teleconference please register on the link below. After registration you will be provided phone numbers and a conference ID to access the conference. You can ask questions verbally via the teleconference. https://events.inderes.com/live/press-conference-may-22/dial-in For additional information, please contact: Christer Ahlberg, CEO Phone: +46 70 675 33 30 e-mail: christer.ahlberg@cincluspharma.com Henrik Vikström, IR Phone: +46 70 952 80 06 e-mail: henrik.vikström@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 2025-05-22 07:30 CEST. Attachments Cinclus Pharma Partners with Zentiva to Commercialize Linaprazan Glurate in Europe

License out/inPhase 2Phase 3

07 Apr 2025

·cincluspharma.com

New scientific article highlights good healing results for Cinclus Pharma's drug candidate linaprazan glurate for the treatment of eGERD

Cinclus Pharma AB (publ), a developer of drugs for the treatment of gastric acid-related diseases, announced today that a scientific article has been published with data from a phase II study showing high healing rates for patients with severe forms of erosive gastroesophageal reflux disease, eGERD. The results support the continued development of linaprazan glurate as a next-generation drug for gastric acid-related diseases. The article, titled Randomised Controlled Trial: A Dose-Finding Study of Linaprazan glurate, A Novel Potassium Competitive Acid Blocker, vs. Lansoprazole for the Treatment of Erosive Esophagitis, has been published online in the scientific journal Alimentary Pharmacology & Therapeutics and is written by Prateek Sharma, Michael Vaezi, Peter Unge, Kjell Andersson, Kajsa Larsson, Ivan Popadiyn, Maria Rosenholm, Andras Rosztóczy, Elham Yektaei and David Armstrong. The published article presents data from a phase II clinical trial in which the treatment with linaprazan glurate (the next generation of PCAB) showed a high healing rate among patients suffering from eGERD. For patients who were not healed after eight weeks of treatment with proton pump inhibitor, the best-performing dose of linaprazan glurate achieved a 100 percent healing rate after four weeks, a higher rate of 28 percentage points compared to the treatment with the proton pump inhibitor lansoprazole. The healing rate for patients with moderate to severe eGERD was 93 percent, which was 50 percentage points higher than the treatment with lansoprazole. The results support the continued development of linaprazan glurate as a next-generation drug for gastric acid-related diseases. "The study shows very good healing rates, both for patients previously treated with PPI without being healed and for patients with severe eGERD, which highlights the potential of our drug candidate. We look forward to initiating the phase III program of linaprazan glurate during 2025”, says Kajsa Larsson, Chief Medical Officer at Cinclus Pharma. "The results show how effective treatment with linaprazan glurate is compared to today's standard treatment, and in extension also the first generation of PCAB. Cinclus Pharma's drug meets the medical need of the patients who suffer the most with the severe forms of eGERD, which constitutes a large market with blockbuster potential," said Christer Ahlberg, CEO of Cinclus Pharma. To access the article, please click the following link: http://doi.org.libproxy1.nus.edu.sg/10.1111/apt.70109 For additional information, please contact: Christer Ahlberg, CEO Phone: +46 70 675 33 30 e-mail: christer.ahlberg@cincluspharma.com Henrik Vikström, IR Phone: +46 70 952 80 06 e-mail: henrik.vikström@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 New scientific article highlights good healing results for Cinclus Pharma's drug candidate linaprazan glurate for the treatment of eGERD

Phase 2Clinical ResultPhase 3

100 Deals associated with Linaprazan glurate

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Esophagitis, Peptic	China	Shanghai Sinorda Pharmaceutical Technology Co., Ltd.	01 Dec 2024

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Erosive esophagitis	Phase 2	United States	Cinclus Pharma AG	11 Aug 2021
Erosive esophagitis	Phase 2	Bulgaria	Cinclus Pharma AG	11 Aug 2021
Erosive esophagitis	Phase 2	Czechia	Cinclus Pharma AG	11 Aug 2021
Erosive esophagitis	Phase 2	Georgia	Cinclus Pharma AG	11 Aug 2021
Erosive esophagitis	Phase 2	Hungary	Cinclus Pharma AG	11 Aug 2021
Erosive esophagitis	Phase 2	Poland	Cinclus Pharma AG	11 Aug 2021
Erosive esophagitis	Phase 2	Serbia	Cinclus Pharma AG	11 Aug 2021
Erosive esophagitis	Phase 2	Ukraine	Cinclus Pharma AG	11 Aug 2021
Gastroesophageal Reflux	Phase 2	European Union	Cinclus Pharma AG	22 Jan 2020
Duodenal Ulcer	Phase 2	China	Sinorda Biomedicine Co., Ltd.	-

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05742984 (CTgov)	Phase 1	Gastroesophageal Reflux	75	Linaprazan Glurate (25 mg Linaprazan Glurate QD)	hyvgcyleey(anagrkuvyq) = zfgdrwolms pwsuqdmtqe (quqohqalch, 1650.6) View more	-	07 May 2025
				Linaprazan Glurate (50 mg Linaprazan Glurate QD)	hyvgcyleey(anagrkuvyq) = meeowclaft pwsuqdmtqe (quqohqalch, 2281.0) View more
NCT05055128 (Pubmed \| Aliment Pharmacol Ther) Manual	Phase 2	Erosive esophagitis	248	Linaprazan Glurate	wzabqfctif(acwiphcilc) = cxwwgglrbs smctptdoke (boxaxiomym ) View more	Positive	04 Apr 2025
				Lansoprazole	wzabqfctif(acwiphcilc) = rvpkqdtdia smctptdoke (boxaxiomym ) View more
NCT04531475 (Phase 2 study, Pubmed \| Clin Transl Gastroenterol)	Phase 2	Erosive esophagitis	90	X842 50 mg	qpctoxljcy(bpeuflenil) = The incidence of drug-related treatment-emergent adverse events did not differ among groups drerlenuns (dqogephszh ) View more	Positive	01 Apr 2025
				X842 100 mg
NCT05633147 (CTgov)	Phase 1	Medication interactions	35	Linaprazan glurate+Clarithromycin (Part I)	nmewsiaalj(osvzlujukd) = wxjmgzeqpq upzpzftdid (ilahavicsp, 5649) View more	-	03 Jan 2025
				Midazolam+Linaprazan glurate hydrochloride (HCl) (Part II)	nzeopgbukp(yxrxrgngrv) = yevwndzgtv fhcudpybuf (qjmskwyhsb, 13.98) View more
UEGW2024	Not Applicable	-	-	25 mg LG QD	ptxiortnas(sfljoetjqk) = headache yfjoyfgcwn (sojqwyoufy ) View more	-	13 Oct 2024
				50 mg LG QD
DDW2024	Not Applicable	-	-	Vonoprazan-based triple therapy	syihcbtzjj(sipejngefq): RR = 1.17 (95% CI, 1.11 - 1.22)	-	18 May 2024
				Conventional PPI-based triple therapy
NCT05055128 (CTgov)	Phase 2	Erosive esophagitis \| Gastroesophageal Reflux	248	Lansoprazole+X842 Dummy (X842 25 mg BID)	tfabqhyrlx = dydjhdvjjn ithgvqnkqh (uybsucpitv, wbpcazflhx - dlktxxmvoy) View more	-	01 Nov 2023
				Lansoprazole+X842 Dummy (X842 50 mg BID)	tfabqhyrlx = pmjkighste ithgvqnkqh (uybsucpitv, wlhgyzmzat - likihrybbt) View more

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