Delving into the Latest Updates on Evacetrapib with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Evacetrapib (USAN)

Target

CETP

Mechanism

CETP inhibitors(Cholesteryl ester transfer protein inhibitors)

Therapeutic Areas

Cardiovascular DiseasesEndocrinology and Metabolic DiseaseCongenital Disorders+ [1]

Active Indication-

Inactive Indication

Familial HDL DeficiencyHypercholesterolemiaPrimary hypercholesterolemia+ [3]

Originator Organization

Eli Lilly & Co.

Active Organization-

Inactive Organization

Eli Lilly & Co.

Drug Highest PhaseDiscontinuedPhase 3

First Approval Date-

RegulationSpecial Review Project (CN)

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Structure

Molecular FormulaC31H36F6N6O2

InChIKeyIHIUGIVXARLYHP-YBXDKENTSA-N

CAS Registry1186486-62-3

The purpose of this study is to determine if there is any difference in the way the body handles 3 types of evacetrapib tablets with different particle sizes. Information about any side effects will also be collected. This study will consist of 3 study periods. Participants will be dosed 3 times during the entire study. Each study period will consist of an inpatient stay for 3 days - the day before dosing (Day -1), dosing day (Day 1) and the day after dosing (Day 2). Then participants will be asked to return to the clinical research unit (CRU) daily for outpatient appointments up to Day 8. The overall length of this study is about 7 weeks from first dose to end of study. Screening will take place within 28 days prior to the first dose of evacetrapib and follow-up will take place 21 days after the last dose of evacetrapib.

Start Date01 Jul 2015

Sponsor / Collaborator

Eli Lilly & Co.

NCT02260648 / TerminatedPhase 3

A Double-Blind Efficacy and Safety Study of Evacetrapib in Combination With Atorvastatin in Japanese Patients With Primary Hypercholesterolemia

The main purpose of this study is to evaluate the efficacy and safety of the study drug known as evacetrapib when administered in combination with atorvastatin for 12 weeks in Japanese participants with primary hypercholesterolemia.

Start Date01 Jan 2015

Sponsor / Collaborator

Eli Lilly & Co.

NCT02365558 / CompletedPhase 1

Evaluation of the Impact of Increased Gastric pH Following Omeprazole Administration on the Pharmacokinetics of Evacetrapib in Healthy Subjects

The purpose of this study is to evaluate the effect of increased stomach pH on how much evacetrapib is found in the blood stream and how long the body takes to get rid of it when given to healthy participants. Information about any side effects that may occur will also be collected.
There are two parts to the study. Participation in both parts will be required.
The study will last approximately 30 days, not including screening.

Start Date01 Jan 2015

Sponsor / Collaborator

Eli Lilly & Co.

100 Clinical Results associated with Evacetrapib

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100 Translational Medicine associated with Evacetrapib

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100 Patents (Medical) associated with Evacetrapib

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96

Literatures (Medical) associated with Evacetrapib

01 Jan 2023·Frontiers in pharmacology

CETP inhibitor evacetrapib enters mouse brain tissue.

Article

Author: Oestereich, Felix ; Bouchard, Michèle ; Efrem, Sasen ; Recinto, Sherilyn J ; Côté, Jonathan ; Haddad, Sami ; Dieme, Denis ; Phénix, Jasmine ; Munter, Lisa Marie

High levels of plasma cholesterol, especially high levels of low-density lipoprotein cholesterol (LDL-C), have been associated with an increased risk of Alzheimer's disease. The cholesteryl ester transfer protein (CETP) in plasma distributes cholesteryl esters between lipoproteins and increases LDL-C in plasma. Epidemiologically, decreased CETP activity has been associated with sustained cognitive performance during aging, longevity, and a lower risk of Alzheimer's disease. Thus, pharmacological CETP inhibitors could be repurposed for the treatment of Alzheimer's disease as they are safe and effective at lowering CETP activity and LDL-C. Although CETP is mostly expressed by the liver and secreted into the bloodstream, it is also expressed by astrocytes in the brain. Therefore, it is important to determine whether CETP inhibitors can enter the brain. Here, we describe the pharmacokinetic parameters of the CETP inhibitor evacetrapib in the plasma, liver, and brain tissues of CETP transgenic mice. We show that evacetrapib crosses the blood-brain barrier and is detectable in brain tissue 0.5 h after a 40 mg/kg i.v. injection in a non-linear function. We conclude that evacetrapib may prove to be a good candidate to treat CETP-mediated cholesterol dysregulation in Alzheimer's disease.

01 Oct 2022·The American Journal of Cardiology

Longitudinal High-Sensitivity C-Reactive Protein and Longer-Term Cardiovascular Outcomes in Optimally-Treated Patients With High-Risk Vascular Disease

Article

Author: Nissen, Steven E ; Puri, Rishi ; Carlo, Julie ; Dykun, Iryna ; Nicholls, Stephen J ; Clark, Donald ; Lincoff, A Michael ; Menon, Venu

The relation between serial high-sensitivity C-reactive protein (hsCRP) and long-term major cardiovascular events (MACEs; cardiovascular death, myocardial infarction, stroke, coronary revascularization, hospitalization for unstable angina) has not been explored in optimally-treated patients with atherosclerotic cardiovascular disease. We tested the hypothesis that longitudinal follow-up hsCRP (repeated measures over time) would associate with 30-month MACE rates. We performed a post hoc analysis of ACCELERATE (Assessment of Clinical Effects of Cholesteryl Ester Transfer Protein Inhibitor with Evacetrapib in Patients with High-Risk for Vascular Outcomes), involving optimally-treated patients with high-risk vascular disease, with available baseline and at least 1 follow-up hsCRP level. Using multivariable Cox proportional hazard models, we determined the association of longitudinal follow-up hsCRP with MACE at 30 months among 8,563 patients (aged 64.6 ± 9 years, 22% women). Patients with incident MACE (n = 961) had higher baseline hsCRP levels (1.77 vs 1.46 mg/L, p <0.0001 for patients with and without MACE, respectively) and showed an upward trajectory during follow-up, whereas median hsCRP levels remained <2 mg/L at all time points (1.83 vs 1.53 mg/L, 1.91 vs 1.53 mg/L, 1.76 vs 1.37 mg/L, at 3, 12, and 24 months, respectively). In a multivariable analysis, higher longitudinal hsCRP levels were independently associated with MACE (hazard ratio [95% confidence interval] per SD 1.19 [1.10 to 1.29], p <0.001), the majority of its individual components and all-cause death. Multivariable models containing longitudinal hsCRP provided improved predictive ability of MACE over baseline hsCRP. In the setting of established medical therapies, longitudinal follow-up hsCRP was independently associated with long-term MACE. In conclusion, these findings suggest that longitudinal hsCRP represents a novel approach of residual cardiovascular risk even when on-treatment hsCRP levels remain <2 mg/L.

01 Sep 2022·Biological and Pharmaceutical Bulletin

Evacetrapib Elicits Antitumor Effects on Colorectal Cancer by Inhibiting the Wnt/β-Catenin Signaling Pathway and Activating the JNK Signaling Pathway

Article

Author: Tian, Yu ; He, Lingyuan ; Shi, Mengchen ; Xiang, Nanlin ; Hu, Yijia ; Su, Yixi ; Hu, Limei ; Wang, Huihui ; Wang, Chen ; Wen, Chuangyu ; Dong, Haiyan ; Liu, Huanliang ; Yang, Xiangling

Despite advances in colorectal cancer (CRC) treatment, most advanced CRC patients who experience disease progression after chemotherapy, targeted therapy, and immunotherapy face a situation in which there is no available medicine. Thus, new therapeutic drugs for CRC are urgently needed. Studies have shown that cholesteryl ester transfer protein (CETP) has a vital role in tumor development and is a possible target for CRC therapy. We found that Evacetrapib, a CETP inhibitor, suppressed CRC cell growth by inhibiting the Wnt/β-catenin signaling pathway and activating the c-Jun NH2-terminal kinase (JNK) signaling pathway in CRC. Therefore, Evacetrapib displays an anti-cancer effect and is a possible option for treating CRC.

1

News (Medical) associated with Evacetrapib

14 Oct 2015

·www.pharmamanufacturing.com

Lilly Ends Phase 3 Trial of Heart Meds

Eli Lilly and Company announced it will terminate the Phase 3 trial of the investigational medicine evacetrapib due to insufficient efficacy. The company will discontinue development of evacetrapib for the treatment of high-risk atherosclerotic cardiovascular disease and will now conclude other studies in the program. "We're obviously disappointed in this outcome, as we hoped that evacetrapib would offer an advance in treatment for people with high-risk cardiovascular disease. We'll be working with investigators to appropriately conclude these trials," said David Ricks, Lilly senior vice president and president of Lilly Bio-Medicines. "We remain confident in our pipeline as we prepare for launches in other therapeutic areas with significant unmet needs." The decision to discontinue development of evacetrapib is expected to result in a fourth-quarter charge to research and development expense of up to $90 million (pre-tax).

100 Deals associated with Evacetrapib

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External Link

KEGG	Wiki	ATC	Drug Bank
D10121	Evacetrapib	-	DB11655

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Vascular Diseases	Phase 3	PR	Eli Lilly & Co.	01 Oct 2012
Vascular Diseases	Phase 3	UA	Eli Lilly & Co.	01 Oct 2012
Vascular Diseases	Phase 3	CN	Eli Lilly & Co.	01 Oct 2012
Vascular Diseases	Phase 3	ZA	Eli Lilly & Co.	01 Oct 2012
Vascular Diseases	Phase 3	TR	Eli Lilly & Co.	01 Oct 2012
Vascular Diseases	Phase 1	SK	Eli Lilly & Co.	01 Oct 2012
Vascular Diseases	Phase 1	PL	Eli Lilly & Co.	01 Oct 2012
Vascular Diseases	Phase 1	AR	Eli Lilly & Co.	01 Oct 2012
Vascular Diseases	Phase 1	GB	Eli Lilly & Co.	01 Oct 2012
Vascular Diseases	Phase 1	US	Eli Lilly & Co.	01 Oct 2012

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01537887 (CTgov)	Phase 1	-	72	Placebo	qigwigbsjo(bwvneiwrdq) = ostebkseqm hnknpjxwmo (nahyuhbyxo, yelitnkuwc - kvzbcvgqww) View more	-	07 Mar 2019
NCT02271425 (CTgov)	Phase 1	-	8	Evacetrapib Tablet	ggmczsnfpx(dqpizujokf) = xcbutnmzqd jsarvsyveg (aealmyodtf, psurktupdj - kzfjeyobpr) View more	-	01 Mar 2019
NCT02497391 (CTgov)	Phase 1	-	95	Evacetrapib (Evacetrapib Reference (R))	pyqxlchywl(calgeldoxz) = ntpvsqdtqb pzjkdlzgej (syueaebitx, rcaixqwpkx - baebwqfxwj) View more	-	03 Dec 2018
				Evacetrapib (Evacetrapib Test 1 (T1))	pyqxlchywl(calgeldoxz) = ojsoaqgrqf pzjkdlzgej (syueaebitx, nqarfulrhy - yvjgkwamks) View more
NCT01375075 (CTgov)	Phase 2	Dyslipidemias	165	Placebo+LY2484595 (100 mg LY2484595)	hgonksxknr(phwtxzneqy) = aluikomeig snpxuooeks (dkhwmojfii, vtrhgkxzdc - ybfvdomeog) View more	-	25 Oct 2018
				Placebo+LY2484595 (500 mg LY2484595)	hgonksxknr(phwtxzneqy) = jgjdnbqdzd snpxuooeks (dkhwmojfii, zzapfooqug - smmpmstsas) View more
NCT01836185 (CTgov)	Phase 1	Hepatic Insufficiency	32	Evacetrapib (Evacetrapib (Healthy))	bvbzjtcnbq(euqaqlbnas) = rueqzycrrd iagikrosty (mktyasrzwi, dzwhvmnxvm - sofvhaedbl) View more	-	12 Oct 2018
				Evacetrapib (Evacetrapib (Hepatic, Mild))	bvbzjtcnbq(euqaqlbnas) = wygddysexq iagikrosty (mktyasrzwi, hlcfknxsbx - iiqfdcjdxn) View more
NCT01810432 (CTgov)	Phase 1	-	40	Evacetrapib (Evacetrapib (Fasted))	gemjflkdik(uzkbikuuwg) = ptitahvyti niyhcimsal (cdptbwfiob, hjddwkrore - tvarfvpyfc) View more	-	12 Oct 2018
				High-fat Meal+Evacetrapib (Evacetrapib (Fed))	gemjflkdik(uzkbikuuwg) = ibjlhqhruw niyhcimsal (cdptbwfiob, xijrfgipyq - xcqdeyparv) View more
NCT02226653 (CTgov)	Phase 1	-	48	evacetrapib (Reference (Fasted))	cmdttgrofs(tmjmdqquri) = kfghrucxsk lvmjejbnob (sicroyypbw, yytxegcmai - lvphtlhgco) View more	-	10 Oct 2018
				evacetrapib (Test (Fasted))	cmdttgrofs(tmjmdqquri) = weiyivujao lvmjejbnob (sicroyypbw, bkyucrggdo - luykqnwedo) View more
NCT02260648 (CTgov)	Phase 3	Primary hypercholesterolemia	149	Evacetrapib+Atorvastatin (Evacetrapib)	ytrgefnfcu(vutxovxokr) = qcpoietozd pxqkgcyuxw (dpmuglfzvx, jyjgplkaon - vyuisaauiz) View more	-	09 Oct 2018
				Placebo+Atorvastatin (Placebo)	ytrgefnfcu(vutxovxokr) = nzloltclsl pxqkgcyuxw (dpmuglfzvx, dhfipcoepx - uuwjrsywkt) View more
NCT01903434 (CTgov)	Phase 1	-	60	Evacetrapib (Reference)	ikstbweflh(zmykgyujul) = gcpisfakin pzyrbneubq (dhbzxswtpi, msjgdwupaa - pznvglthni) View more	-	09 Oct 2018
				Evacetrapib (Test)	ikstbweflh(zmykgyujul) = bujgmdxwzl pzyrbneubq (dhbzxswtpi, ipbxtoncyp - yhbkfbigeo) View more
NCT01825889 (CTgov)	Phase 1	Cardiovascular Diseases	20	Evacetrapib (Evacetrapib (Participants With Renal Impairment))	inerqvfysh(xnhsnsxsqh) = qhuastfrzq myzyblhpkm (cmcjspfttx, ztmihsugux - vmugfkruwh) View more	-	09 Oct 2018
				Evacetrapib (Evacetrapib (Healthy Participants))	inerqvfysh(xnhsnsxsqh) = wboavxiigl myzyblhpkm (cmcjspfttx, rgxdjlxlsr - hejxyikewn) View more