Delving into the Latest Updates on Aleglitazar with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Aleglitazar (USAN)

+ [1]

Target

PPARα x PPARγ

Mechanism

PPARα agonists(Peroxisome proliferator-activated receptor α agonists), PPARγ agonists(Peroxisome proliferator-activated receptor γ agonists)

Therapeutic Areas

Cardiovascular DiseasesCongenital DisordersEndocrinology and Metabolic Disease+ [1]

Active Indication-

Inactive Indication

Acute Coronary SyndromeCardiovascular AbnormalitiesCardiovascular Diseases+ [7]

Originator Organization

F. Hoffmann-La Roche Ltd.

Active Organization-

Inactive Organization

Hoffmann-La Roche, Inc.F. Hoffmann-La Roche Ltd.

Shanghai Roche Pharmaceuticals Ltd.

Drug Highest PhaseSuspendedPhase 3

First Approval Date-

RegulationSpecial Review Project (CN)

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Structure

Molecular FormulaC24H23NO5S

InChIKeyDAYKLWSKQJBGCS-NRFANRHFSA-N

CAS Registry475479-34-6

This randomized, double-blind, placebo-controlled study will evaluate the potential of aleglitazar to reduce the risk of end stage renal disease and cardiovascular mortality in patients with type 2 diabetes mellitus and chronic kidney disease. Patients will be randomized to receive oral daily doses of aleglitazar or matching placebo. The anticipated time on study treatment is approximately 3 years.

Start Date01 Dec 2013

Sponsor / Collaborator

Hoffmann-La Roche, Inc.

CTR20130320 / SuspendedPhase 3

评价ALEGLITAZAR单药治疗与安慰剂相比较，对未经降糖药物治疗的2型糖尿病患者的疗效、安全性和耐受性

[Translation] To evaluate the efficacy, safety, and tolerability of ALEGLITAZAR monotherapy compared with placebo in patients with type 2 diabetes who are not receiving glucose-lowering medications

通过治疗26周后HbA1c的变化，评价Aleglitazar与安慰剂相比较，对未经降糖药物治疗的2型糖尿病患者血糖控制的疗效、安全性和耐受性

[Translation]

To evaluate the efficacy, safety, and tolerability of aleglitazar compared with placebo in patients with type 2 diabetes who were not treated with glucose-lowering drugs, as measured by changes in HbA1c after 26 weeks of treatment

Start Date17 Jun 2013

Sponsor / Collaborator

F. Hoffmann-La Roche Ltd.

[+1]

NCT01871428 / CompletedPhase 3

A Multicenter, Randomized, Doubleblind, Placebo-Controlled, Phase III Study to Assess the Efficacy, Safety and Tolerability of Aleglitazar Monotherapy Compared With Placebo in Patients With Type 2 Diabetes Mellitus (T2D) Who Are Drug-Naïve to Antihyperglycemic Therapy

This multicenter, randomized, double-blind, placebo-controlled study will evaluate the efficacy, safety and tolerability of aleglitazar monotherapy in patients with Type 2 diabetes mellitus who are drug-naïve to anti-hyperglycemic therapy. Patients will be randomized to receive either aleglitazar 150 mcg orally daily or placebo for 26 weeks.

Start Date01 Jun 2013

Sponsor / Collaborator

Hoffmann-La Roche, Inc.

100 Clinical Results associated with Aleglitazar

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100 Translational Medicine associated with Aleglitazar

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100 Patents (Medical) associated with Aleglitazar

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51

Literatures (Medical) associated with Aleglitazar

01 Oct 2024·The American Journal of Pathology

Chronic Peroxisome Proliferator-Activated Receptor α/γ and Cannabinoid Receptor 2 Agonist Treatments Attenuated Visceral Adipose Tissue (VAT)–Derived Extracellular Vesicle–Related VAT and Intestinal Abnormalities in Nonalcoholic Steatohepatitis Mice

Article

Author: Su, Chien-Wei ; Yang, Ying-Ying ; Huang, Chia-Chang ; Wang, Ching-Hsiang ; Yang, Ching-Wen ; Hou, Ming-Chih ; Li, Tzu-Hao ; Lin, Han-Chieh ; Yeh, Hsiao-Yun ; Tsai, Hung-Cheng

This study explores the mechanisms and combined effects of chronic peroxisome proliferator-activated receptor (PPAR)α/γ and cannabinoid receptor 2 (CB₂R) agonists on visceral adipose tissue (VAT)-derived extracellular vesicle (EV) release and associated systemic/VAT inflammation, decreased VAT capillary density/fibrosis, and intestinal inflammation/hyperpermeability in nonalcoholic steatohepatitis (NASH) mice. NASH mice received 1 month of PPARα/γ agonist aleglitazar (10 mg/kg per day) or CB₂R agonist JWH015 (3 mg/kg per day) alone or combined. High EV release from VAT of NASH mice was associated with severe systemic/VAT/intestinal inflammation, reduced capillary network of VAT, and intestinal hyperpermeability. Combined JWH015 with aleglitazar treatment significantly suppressed high-fat diet-induced obesity/adiposity, inhibited VAT expansion, reduced VAT inflammation/fibrosis, normalized VAT capillary network, and attenuated intestinal mucosal injury, inflammation, and hyperpermeability in NASH + aleglitazar + JWH015 mice. The inhibition of AT-derived EV release and hypoxia-inducible factor (HIF)1α levels in AT-derived EV, normalization of CB₂R, PPARα, PPARγ, PPARγ1, PPARγ2, tight junction proteins, vascular endothelial growth factor/CD31 expression, and down-regulation of HIF1α, monocyte chemoattractant protein-1, and transforming growth factor-β1 were observed in the VAT and intestine of the NASH + aleglitazar + jwh015 group. In vitro experiments revealed that PPARα/γ and CB₂R activation attenuated NASH AT-derived EV-induced pathogenic changes in the J774/SVEC4-10/Caco2/3T3-L1 cell system. This study suggested that VAT-derived EVs contribute to the pathogenesis of nonalcoholic fatty liver disease and that combined PPARα/γ and CB₂R agonist treatment reduces VAT-released EV release and HIF1/monocyte chemoattractant protein-1 signals to ameliorate hepatic steatosis and VAT/intestine abnormalities of NASH mice.

01 Feb 2024·Diabetes Research and Clinical Practice

Impact of age on the predictive value of NT-proBNP in patients with diabetes mellitus stabilised after an acute coronary syndrome

Article

Author: Angeli, Fabio ; Grobbee, Diederick E ; Stähli, Barbara E ; Tardif, Jean-Claude ; Schwartz, Gregory G ; Heerspink, Hiddo J L ; Cavallini, Claudio ; Pancani, Silvia ; Savonitto, Stefano ; Perrone Filardi, Pasquale ; Lincoff, A Michael ; Mannini, Andrea ; Morici, Nuccia ; Nozza, Anna ; Cosentino, Francesco

AIMSTo assess the impact of age on the prognostic value of NT-proBNP concentration in patients with type-2 diabetes mellitus (T2DM) stabilised after an Acute Coronary Syndrome (ACS).METHODSThe AleCardio study compared aleglitazar with placebo in 7226 patients with T2DM and recent ACS. Patients with heart failure were excluded. Median follow-up was 104 weeks. Baseline NT-proBNP plasma concentration was measured centrally. Multivariable Cox regression was used to determine the mortality predictive information provided by NT-proBNP across age groups.RESULTSMedian age was 61y (IQR 54, 67). NT-proBNP concentration increased by quartile (Q) of age (median 264, 318, 391, and 588 pg/ml). Compared to Q1, patients in Q4 of NT-proBNP had higher (p < 0.001) adjusted HR for all-cause (aHR 6.9; 95 % CI 4.0-12) and cardiovascular (11; 5.4-23) death. Within each age Q, baseline NT-proBNP in patients who died was 3 times higher than in survivors (all p < 0.001). When age and NT-proBNP levels were modeled as continuous variables, their interaction term was nonsignificant. The relative prognostic information provided by NT-proBNP (percent of total X²) increased from 38 % in age Q1 to 75 % in age Q4 for mortality, and from 50 % to 88 % for CV death.CONCLUSIONSAmong patients with T2DM stabilised after an ACS, NT-proBNP level predicts death irrespective of age.

01 Jan 2020·Diabetes, Obesity and MetabolismQ2 · MEDICINE

Exposure and response analysis of aleglitazar on cardiovascular risk markers and safety outcomes: An analysis of the AleCardio trial

Q2 · MEDICINE

Article

Author: Schwartz, Gregory G. ; Stevens, Jasper ; Svensson, Anders ; Weichert, Arlette ; Wedel, Hans ; Grobbee, Diederick E. ; Schrieks, Ilse C. ; Heerspink, Hiddo J. L. ; Nicholls, Stephen J. ; Koomen, Jeroen V. ; Lincoff, A. Michael

AbstractAimsThe AleCardio trial aimed to characterize the efficacy and safety of peroxisome proliferator‐activated receptor‐αγ agonist aleglitazar in patients with type 2 diabetes mellitus and acute coronary syndrome. The trial terminated early because of futility and safety signals. We evaluated whether the safety signals could be attributed to increased exposure to aleglitazar.Materials and MethodsThe AleCardio trial enrolled 7226 patients to receive aleglitazar 150 μg or matching placebo on top of standard care. A population pharmacokinetic analysis was conducted in a pharmacokinetic substudy to identify covariates that explained interindividual variability in exposure. Subsequently, the effect of these covariates on surrogate and clinical outcomes was assessed in the full patient population.ResultsConcomitant administration of clopidogrel was identified as a covariate that influenced the apparent clearance of aleglitazar. Patients using clopidogrel had a mean predicted area under the plasma‐concentration‐time curve (AUC0–24) of 174.7 ng h/mL (SD: ±112.9 ng h/mL) versus 142.2 ng h/mL (SD: ±92.6 ng h/mL) in patients without clopidogrel. The effect of aleglitazar compared with placebo on HbA1c, haemoglobin, serum creatinine and adiponectin was modified by concomitant clopidogrel use (P for interaction 0.007, 0.002, <0.001 and < 0.001, respectively).ConclusionsConcomitant use of clopidogrel was identified as a covariate that explained interindividual variability in exposure to aleglitazar. Patients using clopidogrel showed an additional lowering of HbA1c, at the expense of an additional decrease in haemoglobin, and an increase in serum creatinine and adiponectin. Clopidogrel is a moderate inhibitor of CYP2C8. Because aleglitazar is metabolized by CYP2C8, a pharmacokinetic interaction could explain differences in exposure and response to aleglitazar.

100 Deals associated with Aleglitazar

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External Link

KEGG	Wiki	ATC	Drug Bank
D08845	Aleglitazar	-	DB08915

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Diabetes Mellitus, Type 2	Phase 3	IN	F. Hoffmann-La Roche Ltd.	05 Jan 2010
Diabetes Mellitus, Type 2	Phase 3	TH	Shanghai Roche Pharmaceuticals Ltd.	05 Jan 2010
Diabetes Mellitus, Type 2	Phase 3	KR	F. Hoffmann-La Roche Ltd.	05 Jan 2010
Diabetes Mellitus, Type 2	Phase 3	KR	F. Hoffmann-La Roche Ltd.	05 Jan 2010
Diabetes Mellitus, Type 2	Phase 3	SE	Shanghai Roche Pharmaceuticals Ltd.	05 Jan 2010
Diabetes Mellitus, Type 2	Phase 3	IN	F. Hoffmann-La Roche Ltd.	05 Jan 2010
Diabetes Mellitus, Type 2	Phase 3	KR	F. Hoffmann-La Roche Ltd.	05 Jan 2010
Diabetes Mellitus, Type 2	Phase 3	IN	F. Hoffmann-La Roche Ltd.	05 Jan 2010
Diabetes Mellitus, Type 2	Phase 3	SE	Shanghai Roche Pharmaceuticals Ltd.	05 Jan 2010
Diabetes Mellitus, Type 2	Phase 3	SE	Shanghai Roche Pharmaceuticals Ltd.	05 Jan 2010

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01197911 (CTgov)	Phase 1	-	38	aleglitazar (Normal Hepatic Function)	wwlfpzmqyz(cxfszwrljy) = bfiocrbxnh vgdujhxxjg (giwffprdch, rjqaxpmbrr - nautdznosm) View more	-	24 Dec 2015
				aleglitazar (Mild Hepatic Impairment)	wwlfpzmqyz(cxfszwrljy) = agifymiixz vgdujhxxjg (giwffprdch, hjdbvcybpb - jchrlfnhrv) View more
NCT01715818 (ALEPREVENT, Pubmed \| Am Heart J) Manual	Phase 3	Diabetes Mellitus, Type 2 \| Prediabetic State	1,996	aleglitazar	(wujdroonec) = Despite the brief duration of treatment, aleglitazar induced favorable changes in glycosylated hemoglobin and blood lipids, similar for participants with T2D or prediabetes. ernxofozdq (uutffjbrok ) View more	Negative	01 Jul 2015
				Placebo
NCT01691846 \| NCT01691989 \| NCT01691755 (Pubmed \| Diabetes Obes Metab) Manual	Phase 3	Diabetes Mellitus, Type 2	591	aleglitazar	(ouxfbfsitp) = Reductions in HbA1c concentration from baseline to week 26 were statistically significantly greater with aleglitazar than with placebo. qeiqqacrgn (jucajdcdwh )	Positive	01 Jun 2015
				Placebo
NCT01043029 (AleNephro, Pubmed \| BMC Nephrol)	Phase 2	Diabetes Mellitus, Type 2 \| Chronic Kidney Diseases	302	Aleglitazar 150 μg/day	mtuxvjrujo(sgnqnyekdb) = Superior improvements in high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and triglycerides, with similar effects on glycosylated hemoglobin were observed with aleglitazar versus pioglitazone powlmtazec (kjrxamqneu )	-	18 Nov 2014
				Pioglitazone 45 mg/day
NCT01042769 (AleCardio, Pubmed \| J Coll Physicians Surg Pak)	Phase 3	Diabetes Mellitus, Type 2 \| Acute Coronary Syndrome	7,226	Aleglitazar 150 µg	(finykqtgfk) = dcixgqtxsj lqpejaufhu (qlrmazqagf )	Negative	16 Apr 2014
				Placebo	(finykqtgfk) = hfafucjqee lqpejaufhu (qlrmazqagf )
NCT00388518 (SYNCHRONY, Pubmed \| Lancet)	Phase 2	Diabetes Mellitus, Type 2	332	Aleglitazar 50 mug	qhnzyymbep(ncstiqyagv) = zdsnkmfikz pqaegjodvb (dxytqdsaaj, 0.00 to -0.70)	-	11 Jul 2009
				Aleglitazar 150 mug	qhnzyymbep(ncstiqyagv) = hlyuncwmmt pqaegjodvb (dxytqdsaaj, -0.99 to -1.70) View more