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

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

AtherosclerosisCombined hyperlipidemiaDiabetes Mellitus, Type 2+ [7]

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

EU (03 Jul 2008),

DyslipidemiasPrimary hypercholesterolemia

Regulation-

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Structure

Molecular FormulaC21H19ClFNO4S

InChIKeyNXFFJDQHYLNEJK-CYBMUJFWSA-N

CAS Registry571170-77-9

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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308

Literatures (Medical) associated with Laropiprant/Nicotinic Acid

01 Feb 2025·FOOD AND CHEMICAL TOXICOLOGY

Protective effect of trehalose on sperm chromatin condensation failure and semen quality decline in BDE-209-exposed mice

Article

Author: Wang, Yi ; Chen, Siju ; Zheng, Qi ; Zhang, Shengquan ; Zhang, Sumei ; He, Huan ; Zhai, Jinxia ; Zhang, Taifa ; Wang, Bo ; Huang, Dake ; Wei, Yu ; Gao, Xin

BDE-209 exposure induced male reproductive toxicity with sperm quality decline. However, the role of autophagy in this was unclear. The purpose was to evaluate the protective effect and its potential mechanism of trehalose (Tre, autophagy inducer) on reproductive damage during spermiogenesis induced by BDE-209. We used 2% w/v Tre and 75 mg/kg/d BDE-209 cotreated mice for 42 days. GC-2 spd cells were cotreated with Tre, chloroquine (CQ, inhibition of autophagic flux), compound C (CC, AMPK inhibitor), and BDE-209. Tre intake significantly recovered decrease in sexual organ ratio and poor sperm quality in BDE-209-exposed mice. Supplementation with Tre rescued sperm head malformation by improving aberrant histone-protamine exchange in BDE-209-exposed mice. However, Tre intake couldn't restore the acrosome biogenesis. In addition, Tre supplementation improved testicular damage induced by BDE-209. BDE-209 blocked autophagic flux with increased P62 and LC3BⅡ/Ⅰ levels. Mechanistically, CQ treatment aggravated elevation of P62 and LC3BⅡ/Ⅰ levels induced by BDE-209, otherwise, CC and Tre treatments inhibited the rise in p-AMPK, p-ULK1, P62 and LC3BⅡ/Ⅰ levels induced by BDE-209. Tre supplementation improved reproductive injury in BDE-209-exposed mice by regulating autophagic flow via AMPK-ULK1 signaling pathways, which providing a new theoretical basis and possible therapeutic targets for male reproductive toxicity.

01 Jan 2025·AMERICAN HEART JOURNAL

Effects of fortified eggs and time-restricted eating on cardiometabolic health: The prosperity trial

Article

Author: Holdsworth, Dave ; Misialek, Kurt ; Slaugh, Bartel T. ; Yancy, William S. ; Yancy, William S ; Green, Cynthia L. ; Green, Cynthia L ; Harrington, Josephine ; Voss, Kathleen ; Mentz, Robert J ; Aberle, Laura H. ; Pagidipati, Neha ; Slaugh, Bartel T ; Nouhravesh, Nina ; Mentz, Robert J. ; Wieand, Mandee ; Aberle, Laura H

BACKGROUND:

Given the increasing interest in dietary interventions to improve cardiovascular health, this trial assessed the impact of fortified eggs (FE) versus nonegg supplemented diet and time-restricted eating (TRE) versus usual care diet on cardiovascular biomarkers.

METHODS:

The study was a unblinded, 2-by-2 factorial design, which randomized patients, with either a prior cardiovascular event or 2 cardiovascular risk factors, to FE or a nonegg supplemented diet and TRE or usual care diet. Patients randomized to FE were instructed to consume at least 12 FE/week (with eggs provided); those on a nonegg supplemented diet restricted egg consumption to <2 eggs/week. TRE participants were instructed to consume all calories within an 8-hour window daily and fasted for the remaining 16 hours. Patients randomized to usual diet were advised to maintain current dietary habits. Follow-up was performed in-person at 1 and 4 months, and telephone calls at 2 and 3 months. Co-primary endpoints were 4-month LDL- and HDL-cholesterol. Secondary endpoints included additional lipids, cardiometabolic- and inflammatory biomarkers and micronutrient levels at 4-months.

RESULTS:

Overall, 140 patients were randomized with median (25th, 75th percentiles) age 66 (58, 73) years; 72 (51%) women, 38 (27%) Black, and 33 (24%) with diabetes mellitus. The difference in least squares (LS) means from baseline to 4-months for HDL and LDL levels revealed no significant clinical difference between FE vs nonegg supplemented diet (HDL: -0.64 mg/dL [95% CI: -3.86, 2.58]; LDL: -3.14 mg/dL [-10.81, 4.52]) and TRE vs usual care diet (HDL: 1.51 mg/dL [-1.65, 4.68]; LDL 1.17 mg/dL [-6.36, 8.70]). Prespecified subgroups revealed a nonsignificant HDL increase and LDL decrease with FE in patients ≥65 years.

CONCLUSIONS:

These data did not demonstrate clinically relevant differences in changes in LDL and HDL levels over 4 months with FE and TRE compared with nonegg supplemented diet and usual care diet, respectively, providing evidence that adverse short-term lipid and biomarker changes did not occur with FE consumption.

TRIAL REGISTRATION:

ClinicalTrials.gov Identifier: NCT04673721.

01 Jan 2025·APPETITE

“It just made sense to me!” A Qualitative Exploration of Individual Motivation for Time-Restricted Eating

Article

Author: Thompson, Sandra C ; Katzenellenbogen, Judith M ; Rathomi, Hilmi S ; Rathomi, Hilmi S. ; Katzenellenbogen, Judith M. ; Mavaddat, Nahal ; Thompson, Sandra C.

Time-Restricted Eating (TRE), a form of intermittent fasting, has gained popularity for weight control and metabolic health. It is not incorporated into dietary and clinical guidelines, and hence is generally not being recommended to the public. This qualitative study explores how individuals have discovered TRE as a form of dietary practice and their motivations for practising it. Using purposive and snowball sampling, we recruited 21 participants who had engaged in TRE for at least 3 months (range 3 months to over 5 years). In-depth interviews were conducted with an interview guide developed based on the Health Belief Model. We utilised an inductive coding process and thematic analysis to identify the factors motivating TRE adoption. Seven main themes emerged: (1) dissatisfaction and resistance to prior or traditional approaches, (2) perceived broader health benefits, (3) principles of TRE deemed logical, (4) low to no cost of adoption, (5) manageable psychosocial barriers, (6) being non-restrictive and easy to use, and (7) compatibility with personal lifestyle. This study provided insights into early phase of TRE adoption among individuals in real world settings. Future research should explore health practitioners' perspectives on TRE to better understand the acceptability and potential use of TRE as a weight management approach.

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

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Dyslipidemias	EU	Merck Sharp & Dohme Ireland Ltd.	03 Jul 2008
Dyslipidemias	IS	Merck Sharp & Dohme Ireland Ltd.	03 Jul 2008
Dyslipidemias	LI	Merck Sharp & Dohme Ireland Ltd.	03 Jul 2008
Dyslipidemias	NO	Merck Sharp & Dohme Ireland Ltd.	03 Jul 2008
Primary hypercholesterolemia	EU	Merck Sharp & Dohme Ireland Ltd.	03 Jul 2008
Primary hypercholesterolemia	IS	Merck Sharp & Dohme Ireland Ltd.	03 Jul 2008
Primary hypercholesterolemia	LI	Merck Sharp & Dohme Ireland Ltd.	03 Jul 2008
Primary hypercholesterolemia	NO	Merck Sharp & Dohme Ireland Ltd.	03 Jul 2008

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Diabetes Mellitus, Type 2	Phase 3	-	Merck Sharp & Dohme Corp.	01 Jul 2007
Flushing	Phase 3	-	Merck Sharp & Dohme Corp.	01 Apr 2007
Heterozygous familial hypercholesterolemia	Phase 3	-	Merck Sharp & Dohme Corp.	01 Sep 2006
Hyperlipoproteinemia Type II	Phase 3	-	Merck Sharp & Dohme Corp.	01 Sep 2006
Hypercholesterolemia	Phase 3	-	Merck Sharp & Dohme Corp.	01 Jul 2006
Combined hyperlipidemia	Phase 3	-	Merck Sharp & Dohme Corp.	01 Dec 2005
Hyperlipidemia, Familial Combined	Phase 3	-	Merck Sharp & Dohme Corp.	01 Dec 2005
Atherosclerosis	Phase 3	US	Merck GmbH	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00286234 (CTgov)	Phase 4	Hypertriglyceridemia \| Metabolic Syndrome	68	placebo+omacor+niaspan (Dual Placebo)	vmzikplflu(kumidxidrl) = udhnxdtxwo bbtqxambjf (agtfbafble, wttvsdkeda - srxhqjktsf) View more	-	26 Oct 2021
				niacin (Niaspan)	vmzikplflu(kumidxidrl) = qdxjpcsohl bbtqxambjf (agtfbafble, qsoatmlefi - feagwjtnye) View more
NCT00461630 (HPS2-THRIVE, Pubmed \| Clin Ther)	Phase 3	-	25,673	Niacin-laropiprant	bnhgliztdn(svjfbymyqf): HR = 1.38 (95% CI, 1.17 - 1.63) View more	-	01 Sep 2019
				Placebo
NCT00796887 (ISC2018)	Phase 2	Stroke	27	Extended-release niacin 500 mg	rshgcvvfcu(ppgnicosqb) = omrrezrblc nsajcrndfh (bjnouztkhn )	Negative	22 Jan 2018
				Placebo	rshgcvvfcu(ppgnicosqb) = ncedjerssv nsajcrndfh (bjnouztkhn )
NCT00461630 (HPS2-THRIVE, Pubmed \| Circ Cardiovasc Qual Outcomes)	Phase 3	Diabetes Mellitus \| Coronary Disease \| Peripheral Arterial Disease	25,673	Extended-release niacin with laropiprant	etqjnebmuv(srdrazuxwc) = UK £101 [SE £37]; US $145 [SE $53] tczpulimff (rhgvyyhwfd ) View more	-	01 Jul 2016
NCT00728910 (CENTAUR, CTgov)	Phase 2	Dyslipidemias	25	atorvastatin	loawgshcrp(zkyfxhpupq) = fhepwdzvbq stofwijmxj (htmkenuztt, fuhfnupqkx - zdqdndikaq) View more	-	29 Feb 2016
ISC2016	Not Applicable	Cerebral Hemorrhage	-	Laropiprant (DP1-/- mice)	qpkdihfjam(grdbqaibhf) = vsknktnziw vsdsakuqky (npdcopvqxz )	-	01 Feb 2016
				Laropiprant (Wildtype (WT) mice)	qpkdihfjam(grdbqaibhf) = oattqxgpjx vsdsakuqky (npdcopvqxz )
NCT00289900 (MK-0524B-024 \| 0524B-024, CTgov)	Phase 3	Hyperlipidemia, Familial Combined	2,340	Simvastatin+MK-0524A (MK-0524B 2g/20 mg)	ohgxhjpqid(coewyubcnr) = vtxjgalsfe zqezctkgga (mcxvdwzmop, ezyqupczzn - bqefkdgqrn) View more	-	26 Jan 2016
				Simvastatin+MK-0524A (MK-0524B 2g/40mg)	ohgxhjpqid(coewyubcnr) = jixdidkbgv zqezctkgga (mcxvdwzmop, odzihttthc - poeebxocpl) View more
ISC2015	Not Applicable	Cerebral Hemorrhage	-	Laropiprant (Wildtype (WT) mice)	kefxurnvlm(adnhewrfne) = jcyfkcjbrr pvqwwhtrtp (bksuhdrxre ) View more	-	01 Feb 2015
				Laropiprant (DP1-/- C57Bl/6 mice)	kefxurnvlm(adnhewrfne) = hdvsbvqnrj pvqwwhtrtp (bksuhdrxre ) View more
NCT01239992 (CTgov)	Phase 4	Hyperlipoproteinemias \| Metabolic Syndrome	12	Niacin/ Laropiprant	znodbqbegz(goepdftxbu) = kmwojpjbqg uczoqlhhst (riojnydflu, txwfnlnpwn - ajnpuhstyl) View more	-	10 Apr 2014
NCT01414166 (0524A-108, CTgov)	Phase 3	Cardiovascular Diseases \| Dyslipidemias	244	LPRT+laropiprant+Extended-release niacin (ERN/LPRT)	mnklafiufm(fgcaenvzou) = aqjgsxaayu tjmhfvncvn (iakaypfhfi, jegffufqnx - usndeuewjl) View more	-	14 Mar 2014
				placebo (Placebo)	mnklafiufm(fgcaenvzou) = abokpxghyp tjmhfvncvn (iakaypfhfi, dmrqcyvomu - ekomeuaqwk) View more