Delving into the Latest Updates on LY-2623091 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

MR

Mechanism

MR antagonists(Mineralocorticoid receptor antagonists)

Therapeutic Areas

Cardiovascular DiseasesUrogenital Diseases

Active Indication-

Inactive Indication

Chronic Kidney DiseasesEssential Hypertension

Originator Organization

Eli Lilly & Co.

Active Organization-

Inactive Organization

Eli Lilly & Co.

Drug Highest PhasePendingPhase 2

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC30H30FN5O3

InChIKeyYPCLDHGBEKZGEB-RUDKWAFVSA-N

CAS Registry1162264-07-4

The first purpose of this study is to evaluate the effect of itraconazole (and possibly diltiazem) on the amount of LY2623091 in the blood stream and how long the body takes to get rid of it.
The second purpose of the study is to evaluate the effect of LY2623091 on the amount of simvastatin (and possibly tadalafil) in the blood stream and how long the body takes to get rid of it.
The safety and tolerability of LY2623091 when given with itraconazole, simvastatin and diltiazem or tadalafil will be evaluated.
There will be three groups of participants in this study. Results from Groups 1 and 2 will be analyzed during the study to determine whether to enroll participants in Group 3 or 4. The study is expected to last up to 40 days from the first dose to follow-up (inclusive). Screening may occur up to 28 days prior to enrollment.

Start Date01 Nov 2014

Sponsor / Collaborator

Eli Lilly & Co.

NCT02242981

/ CompletedPhase 1

Disposition of [14C]-LY2623091 Following Oral Administration in Healthy Subjects

This type of study is called a radiolabeled study. For this study, LY2623091 (study drug) has been specially prepared to contain radiolabeled carbon [^14C]. [^14C] is a naturally occurring radioactive form of the element, carbon. This study will increase understanding about how the drug appears in the blood, urine, and stool after it is administered to healthy participants. Information about any side effects that may occur will also be collected. This study will last up to 22 days for each participant, not including screening. Screening is required within 28 days prior to enrollment

Start Date01 Sep 2014

Sponsor / Collaborator

Eli Lilly & Co.

NCT02194465

/ CompletedPhase 2

A Randomized, Placebo-Controlled, Double-Blinded, Parallel, Phase 2a Study to Evaluate the Safety and Efficacy of LY2623091 in Patients With Primary Hypertension

The main purpose of this study is to evaluate the safety and effectiveness of the study drug known as LY2623091 in participants with high blood pressure.

Start Date01 Aug 2014

Sponsor / Collaborator

Eli Lilly & Co.

100 Clinical Results associated with LY-2623091

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100 Translational Medicine associated with LY-2623091

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100 Patents (Medical) associated with LY-2623091

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3

Literatures (Medical) associated with LY-2623091

01 May 2021·Drug Development ResearchQ3 · MEDICINE

Role of mineralocorticoid receptor antagonists in kidney diseases

Q3 · MEDICINE

Review

Author: Joharapurkar, Amit ; Jain, Mukul ; Patel, Vishal

AbstractMineralocorticoid receptor (MR) antagonists, for example, spironolactone and eplerenone, are in clinical use to treat hypertension. Increasing evidence suggests that mineralocorticoid receptor activation causes the pathogenesis and progression of chronic kidney disease. Aldosterone‐induced MR activation increases inflammation, fibrosis, and oxidative stress in the kidney. MR antagonists (MRAs) have demonstrated therapeutic actions in chronic kidney disease (CKD), diabetic nephropathy (DN), renal fibrosis, and drug‐induced renal injury in preclinical and clinical studies. We have summarized and discussed these studies in this review. The nonsteroidal MRA, esaxerenone, recently received approval for the treatment of hypertension. It has also shown a positive therapeutic effect in phase 3 clinical trials in patients with DN. Other nonsteroidal MRA such as apararenone, finerenone, AZD9977, and LY2623091 are in different clinical trials in patients with hypertension suffering from renal or hepatic fibrotic diseases. Hyperkalemia associated with MRA therapy has frequently led to the discontinuation of the treatment. The new generation nonsteroidal MRAs like esaxerenone are less likely to cause hyperkalemia at therapeutic doses. It appears that the nonsteroidal MRAs can provide optimum therapeutic benefit for patients suffering from kidney diseases.

01 Jun 2017·The Journal of Clinical PharmacologyQ3 · MEDICINE

Journal of Clinical Pharmacology

Q3 · MEDICINE

Article

Author: Wang, Evan B. ; Dickinson, Gemma L. ; Chaudhary, Archana ; Waterhouse, Timothy H.

LY2623091 is a selective, orally active, nonsteroidal, competitive mineralocorticoid receptor antagonist that blocks the actions of aldosterone and other mineralocorticoid receptor ligands at the receptor level. The aim of this work was to explore and establish a population pharmacokinetic model, quantify the degree of interindividual variability, and identify significant disease-, patient-, and study-specific covariates that alter the disposition of LY2623091. The data included concentrations from 294 healthy subjects and patients with hypertension and/or chronic kidney disease (CKD), sampled in 5 phase 1 and 2 studies. The pharmacokinetics of LY2623091 was well described by a 2-compartment model with first-order absorption and elimination. Formulation (on oral bioavailability) as well as weight and age (both on apparent central volume of distribution) were found to be significant covariates. The relative bioavailability of the capsule formulation was 68.4% compared to that of the solution. Hypertension and CKD status were not significant covariates. The pharmacokinetic model suggests that given the same dose, patients with hypertension and/or CKD would receive a similar exposure compared to subjects without these disease conditions.

01 Sep 2015·Current Opinion in Nephrology and HypertensionQ3 · MEDICINE

Nonsteroidal antagonists of the mineralocorticoid receptor

Q3 · MEDICINE

Review

Author: Eitner, Frank ; Nowack, Christina ; Kolkhof, Peter

PURPOSE OF REVIEWThe broad clinical use of steroidal mineralocorticoid receptor antagonists (MRAs) is limited by the potential risk of inducing hyperkalemia when given on top of renin-angiotensin system blockade. Drug discovery campaigns have been launched aiming for the identification of nonsteroidal MRAs with an improved safety profile. This review analyses the evidence for the potential of improved safety profiles of nonsteroidal MRAs and the current landscape of clinical trials with nonsteroidal MRAs.RECENT FINDINGSAt least three novel nonsteroidal MRAs have reportedly demonstrated an improved therapeutic index (i.e. less risk for hyperkalemia) in comparison to steroidal antagonists in preclinical models. Five pharmaceutical companies have nonsteroidal MRAs in clinical development with a clear focus on the treatment of chronic kidney diseases. No clinical data have been published so far for MT-3995 (Mitsubishi), SC-3150 (Daiichi-Sankyo), LY2623091 (Eli Lilly) and PF-03882845 (Pfizer). In contrast, data from two clinical phase II trials are available for finerenone (Bayer) which demonstrated safety and efficacy in patients with heart failure and additional chronic kidney diseases, and significantly reduced albuminuria in patients with diabetic nephropathy. Neither hyperkalemia nor reductions in kidney function were limiting factors to its use.SUMMARYNovel, nonsteroidal MRAs are currently tested in clinical trials. Based on preclinical and first clinical data, these nonsteroidal MRAs might overcome the limitations of today's steroidal antagonists.

100 Deals associated with LY-2623091

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB15367

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Essential Hypertension	Phase 2	US	Eli Lilly & Co.	01 Aug 2014
Essential Hypertension	Phase 2	PR	Eli Lilly & Co.	01 Aug 2014
Essential Hypertension	Phase 2	CA	Eli Lilly & Co.	01 Aug 2014
Chronic Kidney Diseases	Phase 2	ZA	Eli Lilly & Co.	01 Sep 2011
Chronic Kidney Diseases	Phase 2	BG	Eli Lilly & Co.	01 Sep 2011

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02242981 (CTgov)	Phase 1	-	6	LY2623091	szntgdttui(xikcmklrpj) = ezxpvtvync ocdjudljww (wcvvhvihbi, bnibzlzuoi - gauztygcte) View more	-	26 Jun 2020
NCT02194465 (CTgov)	Phase 2	Essential Hypertension	304	Placebo (Placebo)	ojwjoglafk(uljoiuseba) = kaowchuyim fyhyoadhiw (bgotbumagy, fcnoodqqfy - mqrgijomfx) View more	-	26 Jun 2020
				Placebo+LY2623091 (13 mg LY2623091)	ojwjoglafk(uljoiuseba) = nzzqjbiskr fyhyoadhiw (bgotbumagy, rnhgnkdxvb - ozettsupub) View more
NCT02300259 (CTgov)	Phase 1	-	48	LY2623091 (LY2623091 (Group 1))	wedglwdkha(lzouuwopzb) = mcmkalmgtf cfzbidgqlz (bxbhfpllxv, ifaxauscgn - ujpfhttmbx) View more	-	26 Jun 2020
				Itraconazole+LY2623091 (Itraconazole + LY2623091 (Group 1))	wedglwdkha(lzouuwopzb) = nhsslgvoou cfzbidgqlz (bxbhfpllxv, mdxcmxobpa - vmttrdpkwm) View more