A Single Dose, Fasting state, Crossover Replicate Bioequivalence Study of Naproxen 500 mg/Esomeprazole 20 mg, modified-release tablets (Antibiotice S.A.) vs. Vimovo® 500 mg/20 mg film-coated tablets (Grunenthal Gmbh)

Start Date31 Oct 2024

Sponsor / Collaborator-

CTIS2023-508621-27-00

/ CompletedPhase 1

A Single Dose, Fed state, Crossover Replicate, Bioequivalence Study of Naproxen 500 mg/ Esomeprazole 20 mg modified-release tablets (Antibiotice S.A.) versus Vimovo® 500 mg/20 mg film coated tablets (Grunenthal GmbH)

Start Date05 Mar 2024

Sponsor / Collaborator-

NCT03092193

/ CompletedPhase 4IIT

Clinical Pharmacokinetics of Cytochrome P450: Influence on the Pharmacokinetics of Naproxen (CYP2C8 and CYP2C9) and Associated Naproxen-esomeprazole (CYP2C19)

The family of cytochrome P450 (CYP) is the most important drug metabolizing enzymes which contributes to the metabolism of a large proportion of drugs in humans. Some CYP450 enzymes reduce or alter the pharmacodynamic activity of many drugs and are involved in oxidative metabolism and elimination of many drugs commonly used by the population. Polymorphisms in CYP2C8 and CYP2C9 are common in different populations around the world and genetic variations in these alleles can cause decreased enzyme activity to nonsteroidal anti-inflammatory drugs (NSAIDs) such as celecoxib, diclofenac, ibuprofen, indomethacin, lornoxicam, meloxicam, valdecoxib, piroxicam, tenoxicam and naproxen. This compromise the bioavailability of the drug can alter the pharmacokinetics of these drugs and patients with mutations in these genes can exhibit increased plasma concentrations of values and areas under the curve (AUC), in addition to decreased clearance of drugs. Associations between NSAIDs and gastric protectors or proton pump inhibitors (PPIs) have become common nowadays, especially in patients who make chronic use of these drugs. Naproxen associated to esomeprazole, a proton pump inhibitor (PPI), was launched in the market recently and its application in acute pain is not yet elucidated. Esomeprazole suffers strong influence of CYP2C19 (hepatic drug-metabolizing enzyme that degrades PPIs). In patients with high enzyme activity of the CYP2C19, the drug can suffer high enzymatic degradation, and its diminished effect. Moreover, in patients with low enzyme CYP2C19 activity, the effect of acid inhibition by PPIs can be very strong.

Start Date01 Mar 2017

Sponsor / Collaborator

University of Sao Paulo

[+1]

100 Clinical Results associated with Esomeprazole Magnesium/Naproxen

100 Translational Medicine associated with Esomeprazole Magnesium/Naproxen

100 Patents (Medical) associated with Esomeprazole Magnesium/Naproxen

Literatures (Medical) associated with Esomeprazole Magnesium/Naproxen

01 Dec 2018·Pediatric rheumatology online journalQ3 · MEDICINE

A 6-month, multicenter, open-label study of fixed dose naproxen/esomeprazole in adolescent patients with juvenile idiopathic arthritis

Q3 · MEDICINE

ArticleOA

Author: Lovell, Daniel J ; Jerath, Rita ; Von Scheven, Emily ; Francis-Sedlak, Megan ; Naddaf, Henry ; Alpan, Oral ; Reinhardt, Adam ; Dare, Jason A ; Zeft, Andrew ; Jung, Lawrence ; LaMoreaux, Brian D ; Gottlieb, Beth ; Goldsmith, Donald ; Holt, Robert J ; Ball, Julie ; Gupta, Ramesh

BACKGROUND:

Juvenile idiopathic arthritis (JIA) is an inflammatory arthritis of unknown etiology, which lasts for greater than 6 weeks with onset before 16 years of age. JIA is the most common chronic rheumatic disease in children. NSAIDs have been the mainstay of initial management with naproxen (NAP) being commonly used, but they may cause serious side effects such as gastric ulcers which can be reduced by concomitant administration of proton pump inhibitors, such as esomeprazole (ESO).

METHODS:

Primary objective was to evaluate the safety and tolerability of 3 fixed doses of NAP/ESO in JIA patients aged 12 to 16 years. Forty-six children and adolescents with JIA by International League of Associations for Rheumatology criteria, mean age of 13.6 years, from 18 US sites were prospectively enrolled over 2 years and followed for up to 6 months. Doses of the NAP/ESO fixed combination were based on baseline weight. The exploratory efficacy outcome was assessed with the ACR Pediatric-30, - 50, - 70, - 90 Response and the Childhood Health Assessment Questionnaire (CHAQ) discomfort and functional scores at months 1, 3, and 6 as change from baseline. Occurrence and causality were assessed for treatment emergent AEs (TEAEs) and discontinuations were monitored monthly.

RESULTS:

Forty-six patients received at least 1 dose of naproxen/esomeprazole and 36 completed the trial. Thirty-seven (80.4%) had at least 1 treatment emergent adverse event (TEAE) and, with the exception of 2 events in one patient, all of the TEAEs were mild or moderate. Frequent TEAEs (≥5% of patients) were upper respiratory tract and gastrointestinal related. Eleven (23.9%) had at least 1 TEAE considered to be related to study drug. Four patients (8.7%) discontinued due to a TEAE with one of these being the only serious AE reported, acute hepatitis. Mean number of active joints at baseline was 3.1. Improvement in JIA signs and symptoms occurred at most assessments and by month 6, the percentage of patients with an ACR Pediatric-30, - 50, - 70, and - 90 Response was 47.1, 38.2, 32.4, and 17.6%, respectively. The percent of patients achieving ACR Pediatric response increased over time. CHAQ discomfort improved at each assessment and functional scores improved at all assessments for 'Arising, Walking, and Activities' with several improved for 'Dressing and Grooming, Eating, Hygiene, and Grip'. There was no indication of a dose-related efficacy effect.

CONCLUSION:

NAP/ESO was well tolerated in JIA patients aged 12 to 16 years with high levels of response to ACR criteria. No new safety signals were identified for the well-characterized components of this fixed dosed JIA treatment, which was developed to reduce the risk of gastric ulcers.

TRIAL REGISTRATION:

Clinicaltrials.gov, NCT01544114 . Registered February 21, 2012.

01 Sep 2016·Drug development and industrial pharmacyQ4 · MEDICINE

Novel naproxen/esomeprazole magnesium compound pellets based on acid-independent mechanism:in vitroandin vivoevaluation

Q4 · MEDICINE

Article

Author: Kan, Shuling ; Lu, Jing ; Liu, Jianping ; Zhao, Yi ; Zhang, Wenli

The purpose of this study was to develop the novel naproxen/esomeprazole magnesium compound pellets (novel-NAP/EMZ) depending on EMZ acid-independent mechanism which has been proved to be predominate in the mechanism of co-therapy with nonsteroidal anti-inflammatory drug. The novel-NAP/EMZ compound pellets, composed of NAP colon-specific pellets (NAP-CSPs) and EMZ modified-release pellets (EMZ-MRPs), were prepared by fluid-bed coating technology with desired in vitro release profiles. The resulting pellets were filled into hard gelatin capsules for in vivo evaluation in rats and compared with the reference compound pellets, consisted of NAP enteric-coated pellets (NAP-ECPs) and EMZ immediate-release pellets (EMZ-IRPs). The reference compound pellets were prepared simulating the drug delivery system of VIMOVO(®). In vivo pharmacokinetics, EMZ-MRPs had significantly larger AUC0-t (p < 0.01), 1.67 times more than that of EMZ-IRPs, and prolonged mean residence time (7.55 ± 0.12 h) than that of IRPs (1.46 ± 0.39 h). NAP-CSPs and NAP-ECPs showed similar AUC0-t. Compared to the reference compound pellets, the novel-NAP/EMZ compound pellets did not show distinct differences in histological mucosal morphology. However, biochemical tests exhibited enhanced total antioxidant capacity, increased nitric oxide content and reduced malondialdehyde level for novel-NAP/EMZ compound pellets, indicating that the acid-independent action took effect. The gastric pH values of novel-NAP/EMZ compound pellets were at a low and stable level, which could ensure normal physiological range of human gastric pH. As a result, the novel-NAP/EMZ compound pellets may be a more suitable formulation with potential advantages by improving bioavailability of drug and further reducing undesirable gastrointestinal damages.

01 Apr 2014·ChiralityQ4 · CHEMISTRY

Single Enantiomer Versus Racemate: Chiral Distinction in the Proton Pump Inhibitors Omeprazole and Esomeprazole

Q4 · CHEMISTRY

Article

Author: Pogodin, Sergey ; Agranat, Israel ; Marom, Hili

ABSTRACT:

Chiral distinction in the proton pump inhibitor drugs omeprazole and in its chiral‐switch esomeprazole magnesium was studied employing the Density Functional Theory (DFT) method. At B3LYP/6‐311G(d,p), the 6‐methoxy∙∙∙6‐methoxy and 5‐methoxy∙∙∙5‐methoxy homochiral and heterochiral dimers were calculated. The chiral distinction free energies (ΔΔG298,(RS‐SS)) between the cyclicC2‐(S,S)‐ andCi‐(R,S)‐dimers with two intermolecular hydrogen bonds are 3.8, 1.9 (with BSSE counterpoise correction), and –6.9 (with D3 dispersion and BSSE counterpoise corrections) kJ/mol. Adding water as an implicit solvent (polarized continuum model [PCM] model) resulted in a chiral distinction energy of –3.3 kJ/mol, indicating a reversal of the order of the relative stabilities ofC2‐(S,S)‐ andCi‐(R,S)‐dimers. The chiral distinction free energies between the corresponding (less stable)C1‐dimers with one intermolecular hydrogen bond are –9.3, –5.8 (with BSSE CC), 17.6 (D3 + BSSE CC), and –3.2 (H2O) kJ/mol. The results highlight the contention that omeprazole is not just a superposition of its enantiomer constituents. They are consistent with the pharmacological evidence of enantiomer–enantiomer interactions in omeprazole versus esomeprazole and the differences between the drugs omeprazole and esomeprazole magnesium and support the lodged application for regulatory supplementary protection certificate (SPC) exclusivity for the esomeprazole‐related combination drug Vimovo.Chirality 26:214–227, 2014.© 2014 Wiley Periodicals, Inc.

News (Medical) associated with Esomeprazole Magnesium/Naproxen

02 Jun 2025

·www.prnewswire.com

Grünenthal announces acquisition of the rights to Cialis® from Lilly in Mexico, Brazil & Colombia

Grünenthal announces that it agreed to acquire the commercial rights to Cialis® from Eli Lilly and Company in Mexico, Brazil and Colombia, further strengthening Grünenthal's footprint in Latin America. As part of the acquisition, Grünenthal will transfer the manufacturing of Cialis® to its production site in Chile. Since 2017, Grünenthal has invested more than €2 billion in successful M&A transactions, significantly strengthening its profitability. AACHEN, Germany, June 2, 2025 /PRNewswire/ -- Grünenthal today announced the acquisition of the commercial rights to Cialis® (tadalafil) in Mexico, Brazil and Colombia from Eli Lilly and Company. Over the next few years, Grünenthal and Lilly will work together to transfer the manufacturing to Grünenthal's production site in Santiago, Chile, that will supply Cialis® for Mexico, Brazil and Colombia moving forward. The transaction is expected to close in the third quarter of 2025, subject to the satisfaction of customary closing conditions. Grünenthal will finance the transaction using available liquidity. The financial terms of the transaction are not disclosed. Cialis® is indicated for the oral treatment of erectile dysfunction and signs and symptoms of benign prostatic hyperplasia in adult men[1]. The acquisition will expand Grünenthal's Latin American Men's Health product portfolio. "Executing on our strategy of targeted acquisitions, Cialis® will expand our existing portfolio in the region and strengthen Grünenthal's Latin American business", says Gabriel Baertschi, CEO, Grünenthal. "In 2022, we acquired Nebido®, a long-acting treatment for testosterone deficiency, and with Cialis® we can continue to serve our existing customer base and foster our growth in key Latin American markets." Through the acquisition of Cialis®, Grünenthal continues executing its strategy of acquiring established medicines to expand its portfolio and increase its profitability. Since 2017, Grünenthal has invested over €2 billion in the acquisition of established medicines, including Nebido®, the European rights to Crestor® and Nexium®, as well as the global rights to Vimovo® (excluding the U.S. and Japan), Qutenza® and Zomig® (excluding Japan). In 2023, Grünenthal established Grünenthal Meds, a joint venture with Kyowa Kirin International, which manages a portfolio of 13 brands primarily focused on pain management and, in 2024, acquired the US company Valinor Pharma and the product Movantik®. About Grünenthal Grünenthal is a global leader in pain management and related diseases. As a science-based, fully integrated pharmaceutical company, we have a long track record of bringing innovative treatments and state-of-the-art technologies to patients worldwide. Our purpose is to change lives for the better – and innovation is our passion. We focus all our activities and efforts on working towards our vision of a World Free of Pain. Grünenthal is headquartered in Aachen, Germany, and has affiliates in 28 countries across Europe, Latin America, and the U.S. Our products are available in approx. 100 countries. In 2024, Grünenthal employed around 4,300 people and achieved revenues of €1.8 billion. More information: Follow us on: LinkedIn: Grunenthal Group Instagram: grunenthal For further information, please contact: Maren Thurow Head Global Communication Grünenthal GmbH 52099 Aachen E-Mail: [email protected] Phone: +44 7917 196855 [1] In Mexico Cialis® is indicated for the oral treatment of erectile dysfunction and symptoms of benign prostatic hyperplasia in adult men. SOURCE Grünenthal Group WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

AcquisitionDrug Approval

23 Jul 2024

·www.pharmaceutical-technology.com

Grünenthal gains Valinor Pharma and constipation drug Movantik

The acquisition aligns with Grünenthal’s strategy to expand its product portfolio. Credit: fizkes / Shutterstock. Grünenthal has announced the acquisition of US-based Valinor Pharma, along with its opioid-induced constipation (OIC) therapy Movantik, in a $250m deal which includes complete royalty obligations. The transaction will be financed using Grünenthal’s available liquidity. Movantik, known as Moventig outside the US, is an oral treatment for OIC in adults with chronic non-cancer pain. The acquisition broadens Grünenthal’s portfolio of established treatments and strengthens its growing presence in the US market. In 2023 Movantik generated gross sales exceeding $200m in the US. See Also: Merck secures FDA authorisation for Ebola vaccine Ervebo US proposes rules for drug importation from Canada Grünenthal previously acquired the therapy in Europe as part of a joint venture (JV) with Kyowa-Kirin. With the purchase of Valinor, Grünenthal now owns the worldwide rights to the product, excluding Canada. Grünenthal US president Marv Kelly stated: “We are excited to welcome Valinor and expand our portfolio offering to pain specialists with Movantik.” Since 2017, the company has added several products to its lineup, including Nebido, the European rights to Crestor and Nexium, and the worldwide rights to Vimovo, Qutenza and Zomig, with Japan as an exception for the latter two. In 2023, Grünenthal also established a JV, Grünenthal Meds, with Kyowa Kirin International. This JV manages a pain-management-focused portfolio of 13 brands. Grünenthal has invested more than €2bn in successful mergers and acquisitions. Its CEO Gabriel Baertschi stated: “As a pain specialist, Movantik is a perfect fit for Grünenthal with our existing customer base and complementary product portfolio. “The acquisition of Valinor Pharma strengthens our footprint in the United States, the most important growth market for Grünenthal.”

AcquisitionDrug Approval

22 Jul 2024

·www.pharmaindustrial-india.com

Grunenthal Announces Acquisition of Valinor Pharma

Grünenthal has acquired Valinor Pharma and its product Movantik (naloxegol), with a total deal value of approx. USD 250 million, inclusive of all royalty obligations. Grünenthal will finance the transaction using available liquidity. Movantik is indicated for the oral treatment of opioid-induced constipation (OIC) in adult patients with chronic non-cancer pain. The transaction further expands Grünenthal's portfolio of established medicines and adds to the company's growing US business. Gross sales from Movantik in the United States reached over USD 200 million in 2023. "As a pain specialist, Movantik is a perfect fit for Grünenthal with our existing customer base and complementary product portfolio,” said Gabriel Baertschi, CEO, Grünenthal. "The acquisition of Valinor Pharma strengthens our footprint in the United States, the most important growth market for Grünenthal," Baertschi added. Marv Kelly, President of Grünenthal US, commented, "We are excited to welcome Valinor and expand our portfolio offering to pain specialists with Movantik.” Grünenthal acquired the product in Europe (branded Moventig outside of the US) in 2023 as part of a joint venture with Kyowa-Kirin. The acquisition of Valinor makes Grünenthal the worldwide owner of the brand (ex-Canada). With Movantik, Grünenthal continues to execute its strategy of acquiring established medicines to expand its portfolio and increase the company's profitability. Since 2017, Grünenthal has acquired several established medicines, including Nebido, the European rights to Crestor and Nexium, as well as the global rights to Vimovo (excluding the US and Japan), Qutenza and Zomig (excluding Japan). In 2023, Grünenthal established Grünenthal Meds, a joint venture with Kyowa Kirin International, which manages a portfolio of 13 brands primarily focused on pain management. Grünenthal has invested more than EUR 2 billion in successful M&A transactions.

Acquisition

100 Deals associated with Esomeprazole Magnesium/Naproxen

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Indication	Country/Location	Organization	Date
Ankylosing Spondylitis	United States	Horizon Medicines LLC	30 Apr 2010
Osteoarthritis	United States	Horizon Medicines LLC	30 Apr 2010
Rheumatoid Arthritis	United States	Horizon Medicines LLC	30 Apr 2010

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Indication	Highest Phase	Country/Location	Organization	Date
Osteoarthritis, Knee	Phase 3	United States	POZEN, Inc.	01 Apr 2008
Stomach Ulcer	Phase 3	United States	POZEN, Inc.	01 Mar 2007

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01544114 (Pubmed \| Pediatr Rheumatol Online J) Manual	Phase 4	Juvenile Idiopathic Arthritis	46	naproxen/esomeprazole	igkuodewvq(sqkhzfpust) = ghldimpqov cbdmodzyne (niuofsthgr ) View more	Positive	26 Jun 2018
EULAR2018	Not Applicable	Juvenile Idiopathic Arthritis	-	250 mg/20 mg nap/eso	ipxuvlpryi(rkglygbqxu) = xoofxosuvn olmtmflrwc (luvwvqjbso ) View more	-	13 Jun 2018
				375 mg/20 mg nap/eso	ipxuvlpryi(rkglygbqxu) = ftkexxtsvb olmtmflrwc (luvwvqjbso )
NCT01544114 (CTgov)	Phase 4	Juvenile Idiopathic Arthritis	46	VIMOVO (VIMOVO 250 mg/20 mg)	nfuotzajbi = lcbrdbxepa cyicvxxvax (acuizweyfu, xcyheohgdt - pzcmjkfmog) View more	-	04 Oct 2017
				VIMOVO (VIMOVO 375 mg/20 mg)	nfuotzajbi = bcrvunxqnn cyicvxxvax (acuizweyfu, hacrdqvkjr - hmgtcsngyn) View more
NCT00664560 (CTgov)	Phase 3	Osteoarthritis, Knee	614	VIMOVO+PN ((PN 400 (VIMOVO) Twice Daily))	kqstmbjvzl(cliiyrihlj) = lzoetvbijp dzbyekfgsz (zczdpsxxbc, 26.8) View more	-	27 Feb 2012
				Celebrex ((Celebrex 200 mg Once Daily))	kqstmbjvzl(cliiyrihlj) = ncarfzupqc dzbyekfgsz (zczdpsxxbc, 26.2) View more
NCT00665431 (CTgov)	Phase 3	Osteoarthritis, Knee	610	VIMOVO+PN ((PN 400 (VIMOVO) Twice Daily))	avfwqoxfyu(ecjfyanvbv) = rzzjregktd dbrmoxafso (mdtkcgjhku, 27.5) View more	-	06 Dec 2011
				Celebrex ((Celebrex 200 mg Once Daily))	avfwqoxfyu(ecjfyanvbv) = profazsakf dbrmoxafso (mdtkcgjhku, 25.2) View more
NCT00527787 (CTgov)	Phase 3	Stomach Ulcer	434	Naproxen	ibgbgaorwn = izzcoemoxx tibouxcskp (yhtfmhzksg, okmrotqngi - iqfszopemx) View more	-	28 Dec 2010
NCT01129011 (CTgov)	Phase 3	Stomach Ulcer	420	Naproxen	ulkszqnkly = yxugpjcmfw eryrvfeuak (icsijfmprd, mrtwtfxpst - gtwgoivlmg) View more	-	28 Dec 2010
NCT00594854 (CTgov)	Phase 3	Stomach Ulcer	20	PN+naproxen+esomeprazole (PN400 (VIMOVO))	fcjlygnaod = riwguygutr czxrdeauce (pmaxqxpbns, wgxpamamqg - ksxtcnalsu) View more	-	22 Sep 2010
				misoprostol+diclofenac (Arthrotec)	fcjlygnaod = dkxngofexz czxrdeauce (pmaxqxpbns, iwgoqgugrf - akzdwqdvan) View more
NCT00527904 (CTgov)	Phase 3	Stomach Ulcer	239	PN+naproxen+esomeprazole	phiciulhir = eoghrvktky mgbqzorvai (pahspqvpwu, gprexotzuw - divjnwbndb) View more	-	20 Aug 2010

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