Delving into the Latest Updates on Laropiprant/Nicotinic Acid with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Cordaptive, ER niacin/laropiprant, ERN/LRPT

+ [13]

Target

HCAR3 x NIACR1 x PGD2 receptor

Action

agonists, antagonists

Mechanism

HCAR3 agonists(HM74 nicotinic acid GPCR agonists), NIACR1 agonists(Hydroxycarboxylic acid receptor 2 agonists), PGD2 receptor antagonists(Prostaglandin D2 receptor antagonists)

Therapeutic Areas

Endocrinology and Metabolic DiseaseCardiovascular DiseasesCongenital Disorders+ [1]

Active Indication-

Inactive Indication

AtherosclerosisCardiovascular DiseasesCombined hyperlipidemia+ [11]

Originator Organization

Merck Sharp & Dohme Corp.

Active Organization-

Inactive Organization

Merck Sharp & Dohme Corp.Merck Sharp & Dohme Ireland Ltd.Merck GmbH

Drug Highest PhaseWithdrawn

First Approval Date

European Union (03 Jul 2008),

DyslipidemiasPrimary hypercholesterolemia

Regulation-

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Structure/Sequence

Molecular FormulaC6H5NO2

InChIKeyPVNIIMVLHYAWGP-UHFFFAOYSA-N

CAS Registry59-67-6

View All Structures (2)

A randomized, multicenter, open-label, two-arm, parallel, phase III study to evaluate the efficacy and safety of nicotinic acid administered in combination with simvastatin for 6 months in comparison to simvastatin therapy alone in inhibiting the progression of atherosclerosis in patients with carotid arteries stenosis and dyslipidemia.

Start Date02 Mar 2015

Sponsor / Collaborator-

NCT01683656

/ TerminatedPhase 4IIT

ER Niacin/Laropiprant Impact on Cardiovascular Markers and Atheroprogression in HIV-infected Individuals on cART

HIV-infected patients are at increased risk for cardiovascular disease. Large investigations support an inverse correlation between HDL-C levels and coronary heart disease. Therefore a treatment lowering HDL-C such as niacin could reduce the risk of atheroprogression not only through its benefit in terms of lipid profile, but also by reducing atherosclerotic inflammation.
The study aims at showing that a therapy targeting HDL-C increase in HIV-infected patients on suppressive cART has the potential for reducing subclinical atherosclerotic inflammation associated with HIV itself in HIV-individuals on cART.
NILACH is a randomised, multicenter, double blind, placebo controlled, 48 weeks trial to test the effect of the newly marketed niacin/laropiprant on carotid intima-media thickness (IMT) in 90 subjects.
Regimen 1: ER niacin/laropiprant 1g/20 mg for the first 4 weeks and 2g/40mg from week 5 to the end of the study (the titration aims to reduce adverse reactions)
Regimen 2: ER niacin/laropiprant placebo p.m.
The primary end point is the change in mean common carotid intima-media thickness from baseline and 48 weeks, compared between the niacin/laropiprant group and the placebo group.
The proposed in vivo experiments should provide insights on the potential benefits of niacin treatment of cardiovascular disease in HIV patients. In addition, we will be able to further clarify the role of systemic inflammatory mediators in the development of early atherosclerosis of HIV-infected patients on antiretroviral therapy. Detection and treatment of non-infectious co-morbidities such as cardiovascular diseases have become essential for HIV-infected individuals exposed to lifelong antiretroviral therapy and go beyond mere management of opportunistic infections or virologic suppression.

Start Date01 Aug 2012

Sponsor / Collaborator

Les Hôpitaux Universitaires de Genève

[+3]

NCT01583647

/ TerminatedPhase 1

A Single Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of ER Niacin/Laropiprant in Adolescents With Heterozygous Familial Hypercholesterolemia

The purpose of this study is to determine the pharmacokinetics of laropiprant following administration of a single dose of 1 (Panel A) and 2 (Panel B) combination tablets of MK-0524A in adolescents with heterozygous familial hypercholesterolemia.

Start Date01 Jun 2012

Sponsor / Collaborator

Merck Sharp & Dohme Corp.

100 Clinical Results associated with Laropiprant/Nicotinic Acid

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100 Translational Medicine associated with Laropiprant/Nicotinic Acid

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100 Patents (Medical) associated with Laropiprant/Nicotinic Acid

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443

Literatures (Medical) associated with Laropiprant/Nicotinic Acid

01 Mar 2025·Food Chemistry

Collaborative stabilizing effect of trehalose and myofibrillar protein on high internal phase emulsions: Improved freeze-thaw stability and 3D printability

Article

Author: Huang, Qilin ; Kong, Yaqiu ; Chen, Jieling ; Hong, Zehan ; Guo, Ruotong

This study investigated the improvement of adding trehalose (Tre) on freeze-thaw (F-T) stability and 3D printability of myofibrillar protein (MP)-based high internal phase emulsions (HIPEs), also the underlying mechanism. Appropriate Tre addition formed thicker shell-like structure around MP by hydrogen bonds, and induced protein unfolding to ameliorate amphiphilicity. Additionally, Tre promoted the MP diffusion to interface to reduce interfacial tension. After interface saturation, Tre inducing MP rearrangement contributed more to form compact interface layer. Larger interface coverage increased hydrophobic interactions between droplets, constructing stronger MP-Tre-HIPEs gel network, inhibiting more free water to form ice crystals, confirmed by reduced destabilization index and freezing point. Such gel network enhanced their own viscoelasticity and thixotropic recovery, exhibiting superior printing accuracy. Conversely, excessive Tre aggregates (15 %-20 %) competed with MP for interfacial adsorption and filled between interfacial layer of adjacent droplets, weakening gel network. These findings expanded MP-HIPEs high-value application in frozen-foods and 3D printing.

01 Mar 2025·Plant Physiology and Biochemistry

CmTGA8-CmAPX1/CmGSTU25 regulatory model involved in trehalose induced cold tolerance in oriental melon seedlings

Article

Author: Liang, Adan ; Dong, Lin ; Zhang, Yujie ; Shao, Li ; Han, Yuqing ; Liu, Tao ; Khan, Abid ; Xu, Dongdong ; Qi, Hongyan

Plants have developed complex regulatory networks to adapt to various stresses, including cold stress. Trehalose (Tre), known as the "sugar of life," plays a crucial role in enhancing cold tolerance by triggering antioxidation. However, the underlying regulatory mechanisms remain unclear. This study examines the transcription factor gene CmTGA8, which is induced by Tre under normal and cold conditions in melon seedlings (Cucumis melo L.), through transcriptome analysis and RT-qPCR. Reverse genetic analyses showed that silencing CmTGA8 reduced ascorbate peroxidase (APX) and glutathione S-transferase (GST) activities, suppressed CmAPX1 and CmGSTU25 expression, and increased cold susceptibility in melon seedlings. Our previous reports illustrated that Tre treatment significantly induced the expression of respiratory burst oxidase homologues (CmRBOHD) gene, encoding NADPH oxidases responsible for generating apoplastic H₂O₂. Silencing CmRBOHD markedly inhibited CmTGA8, CmAPX1, and CmGSTU25 expression and reduced cold tolerance. Moreover, H₂O₂ treatment upregulated CmTGA8 expression, while the NADPH oxidase inhibitor diphenyleneiodonium (DPI) treatment downregulated it. Additionally, CmTGA8 physically interacted with CmAPX1 and CmGSTU25 to promote their expression. Silencing CmGSTU25 decreased GST activity and ferric reducing ability of plasma (FRAP), further increasing cold sensitivity. These findings identify a novel regulatory hierarchy of the H₂O₂-CmTGA8-CmAPX1/CmGSTU25 cascade in the Tre-mediated cold response pathway in melon seedlings.

01 Feb 2025·Diabetes, Obesity and Metabolism

Intermittent fasting for weight management and metabolic health: An updated comprehensive umbrella review of health outcomes

Article

Author: Guo, Heng ; Yang, Siyu ; Li, Zhe ; Sun, Yiqi ; Zheng, Yingming ; Yang, Hongge ; Li, Jiqian ; Cheng, Sheng ; Li, Xingang ; Hua, Zixin ; Song, Siyang ; Li, Dandan ; Liao, Yin ; Li, Ze

AbstractAimsTo provide an updated comprehensive evaluation of the quality and evidence association of existing studies on health outcomes related to intermittent fasting (IF).Materials and MethodsWe conducted a systematic search of PubMed, Web of Science, Cochrane Library, and Embase databases, covering literature up to June 2024. Meta‐analyses and systematic reviews that include adult populations and quantitatively analyse health outcomes related to IF interventional studies are included. For evidence with complete data, we reanalyzed health evidence effect sizes and 95% confidence intervals using random‐effects models. Article quality and the certainty of the evidence were graded using A Measurement Tool to Assess Systematic Reviews (AMSTAR‐2), Grading of Recommendations Assessment, Development and Evaluation (GRADE) system, and a standardized credibility grading system.ResultsTwelve meta‐analysis studies and 122 health outcome associations with IF were identified. High‐quality evidence indicated significant associations between time‐restricted eating (TRE) and weight loss, fat mass reduction, decreased fasting insulin and glycosylated haemoglobin levels in overweight or obese adults, as well as between the 5:2 diet and reduced low‐density lipoprotein cholesterol levels. Moderate‐to‐low‐quality evidence suggested associations between modified alternate‐day fasting and improvements in body weight, lipid profile and blood pressure. Additionally, high‐to‐low‐quality evidence showed that IF regimens effectively improved liver health in non‐alcoholic fatty liver disease.ConclusionsThis umbrella review highlights IF, especially TRE, as a promising intervention for weight and metabolic health, particularly beneficial for overweight or obese adults. We also highlight the need for further extensive research to understand the long‐term effects, individualized IF plans and potential adverse effects of IF in different populations.

1

News (Medical) associated with Laropiprant/Nicotinic Acid

01 May 2008

·www.pharmatimes.com

FDA sends warning letter to Merck & Co over vaccines plant

Merck & Co’s week of woe has continued with the news that US regulators have told the firm to correct what are described as “numerous manufacturing deficiencies” at its main vaccines plant. The US Food and Drug Administration has issued a warning letter to Merck having conducted an inspection of the firm’s West Point, Pennsylvania facility between November 26, 2007 and January 17 this year. The agency’s investigators say they documented “significant deviations from current good manufacturing practice” at the plant in the manufacture of vaccine products, bulk drug substances and drug components. The products manufactured at the West Point site include Merck & Co’s cervical cancer vaccine Gardasil and ProQuad, its combination jab against measles, mumps, rubella and chicken pox. Also produced at the facility are the Haemophilus influenzae type B vaccine PedvaxHIB and ComVax for haemophilius b and hepatitis B and 1.2 million doses of these two jabs were voluntarily recalled in December because Merck said it could not assure sterility of those specific vaccine lots. The warning letter, which is posted on the FDA’s website in a heavily edited form, has been issued because Merck's response to the FDA’s initial inspection report was "inadequate to address the serious deviations noted”. Most of the myriad complaints appear to deal with procedural errors but the agency stresses it "does not believe that the issues identified will affect the safety of the vaccines" made at the facility. Merck says that it is committed to working with the FDA to address these issues, adding that it does not distribute contaminated products and is confident in their “quality, effectiveness and safety”. The letter comes in a week when Merck’s stock has taken a bashing after the FDA rejected applications firstly for a proposed fixed combination of Singulair (montelukast) and S-P’s Claritin (loratadine) as a treatment for allergic rhinitis and secondly for its new cholesterol compound MK-0524A (extended-release niacin/laropiprant).

Vaccine

100 Deals associated with Laropiprant/Nicotinic Acid

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External Link

KEGG	Wiki	ATC	Drug Bank
-	Laropiprant/Nicotinic Acid	C10AD52	DB11629

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Dyslipidemias	Preclinical	Iceland	Merck Sharp & Dohme Ireland Ltd.	03 Jul 2008
Dyslipidemias	Preclinical	Liechtenstein	Merck Sharp & Dohme Ireland Ltd.	03 Jul 2008
Dyslipidemias	Preclinical	European Union	Merck Sharp & Dohme Ireland Ltd.	03 Jul 2008
Dyslipidemias	Preclinical	Norway	Merck Sharp & Dohme Ireland Ltd.	03 Jul 2008
Primary hypercholesterolemia	Preclinical	Norway	Merck Sharp & Dohme Ireland Ltd.	03 Jul 2008

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00461630 (HPS2-THRIVE, Pubmed \| Clin Ther)	Phase 3	-	25,673	Niacin-laropiprant	(xuxcqacgfq): HR = 1.38 (95% CI, 1.17 - 1.63) View more	-	01 Sep 2019
				Placebo
ERS2016	Not Applicable	-	24	TRE 54 µg	arrdaausjd(rdvgwmuwbf) = lnmmoejxfn idsbijitra (kogiaiqhgi ) View more	-	01 Sep 2016
				C16TR 85 µg	arrdaausjd(rdvgwmuwbf) = apuklplceq idsbijitra (kogiaiqhgi ) View more
ISC2016	Not Applicable	Cerebral Hemorrhage	-	Laropiprant (DP1-/- mice)	dukwgsbqfq(foropyigqk) = cbwscjxusf kffxazqqce (gwzoizhpqq )	-	01 Feb 2016
				Laropiprant (Wildtype (WT) mice)	dukwgsbqfq(foropyigqk) = dlghnhqetv kffxazqqce (gwzoizhpqq )
NCT00289900 (MK-0524B-024 \| 0524B-024, CTgov)	Phase 3	Hyperlipidemia, Familial Combined	2,340	Simvastatin+MK-0524A (MK-0524B 2g/20 mg)	dovuyhikga(brkfljwjym) = eydaxidkme jpsunommia (ozvekketul, lsnfarootz - fcxxczxcan) View more	-	26 Jan 2016
				Simvastatin+MK-0524A (MK-0524B 2g/40mg)	dovuyhikga(brkfljwjym) = iaeggnkxxk jpsunommia (ozvekketul, ikpmglpzil - fcpurpwkhu) View more
ISC2015	Not Applicable	Cerebral Hemorrhage PGD2 \| DP1	-	Laropiprant (Wildtype (WT) mice)	coodkavfxy(bogvswauzw) = hjwofdthuw eyzvfqsxlz (uswecpbrhc ) View more	-	01 Feb 2015
				Laropiprant (DP1-/- C57Bl/6 mice)	coodkavfxy(bogvswauzw) = blrpaykjnw eyzvfqsxlz (uswecpbrhc ) View more
NCT00461630 (HPS2-THRIVE, Pubmed \| N Engl J Med)	Phase 3	-	25,673	Extended-release niacin-laropiprant	wgkwuybgpo(swunzupnxu) = plttzrvtcm xzuzjfwgjj (wwaoiorgto ) View more	Negative	17 Jul 2014
				Placebo	hhtbgkdlii(eharaklfkt) = wdrrdfapzk imrfgfmmda (qqktmiqamk )
NCT01118598 (Pubmed \| Diabetes Obes Metab)	Phase 4	Polycystic Ovary Syndrome	25	Niacin/laropiprant	(idhfnkaynm) = dkhukhhfsa zjjnbrkzej (laacomkvnl ) View more	-	01 Jun 2014
				Placebo	(idhfnkaynm) = nwieoziaqn zjjnbrkzej (laacomkvnl ) View more
NCT01239992 (CTgov)	Phase 4	Hyperlipoproteinemias \| Metabolic Syndrome	12	Niacin/ Laropiprant	hwlevoikmo(zhdwxdrjjv) = ingrzfheuc duinsldylk (nymovkxjgw, rmwfivwxbb - hhmurazexp) View more	-	10 Apr 2014
NCT01274559 (0524A-133, CTgov)	Phase 3	Primary hypercholesterolemia	1,173	Extended-release niacin/laropiprant (ERN/LRPT) (Extended-release Niacin/Laropiprant)	cobxfkswnr(xwmxuoqqqs) = jbsslmcidm chmkuhdkoo (lodgqtkeob, mburljntjy - nohevewggu) View more	-	14 Mar 2014
				Placebo (Placebo)	cobxfkswnr(xwmxuoqqqs) = retdzbivty chmkuhdkoo (lodgqtkeob, pvxczeofwx - zzqcbburom) View more
NCT01414166 (0524A-108, CTgov)	Phase 3	Cardiovascular Diseases \| Dyslipidemias	244	LPRT+laropiprant+Extended-release niacin (ERN/LPRT)	tnbgijahip(frwniendzi) = xpfizzcjha clrjgbocrd (gixtcgukcs, rsolgveure - oipydorzuv) View more	-	14 Mar 2014
				placebo (Placebo)	tnbgijahip(frwniendzi) = nfojcadgyv clrjgbocrd (gixtcgukcs, lnwkmeivdz - gyexqxyqeg) View more