A Phase 2, Double-Blind, Randomized, Placebo-Controlled, Parallel-Group Study to Evaluate Efficacy, Safety and Pharmacokinetics After 2-weeks Administration of CPL207280 (GPR40 Agonist) in Subjects With Type 2 Diabetes (T2D)

The planned study is to evaluate the efficacy, safety and pharmacokinetic (PK) properties of CPL207280 after multiple (14 days) administration in patients with type 2 diabetes.

Start Date21 Jan 2022

Sponsor / Collaborator

Celon Pharma SA

[+1]

EUCTR2021-002947-32-PL / Unknown statusPhase 2

A Phase 2, Double-Blind, Randomized, Placebo-Controlled, Parallel-Group Study to Evaluate Efficacy, Safety and Pharmacokinetics after 2-weeks Administration of CPL207280 (GPR40 agonist) in Subjects With Type 2 Diabetes (T2D)

Start Date28 Oct 2021

Sponsor / Collaborator

Celon Pharma SA

NCT04622111 / CompletedPhase 1

One Centre, Single Ascending Dose and Double Blind Multiple Ascending Dose, Safety and Pharmacokinetics Phase I Study of CPL207280 Compound in Healthy Volunteers.

The planned study is to determine the safety and pharmacokinetic properties of CPL207280 compound after single and multiple (two weeks) administration in healthy volunteers.

Start Date27 May 2020

Sponsor / Collaborator

Celon Pharma SA

[+1]

100 Clinical Results associated with CPL-207-280

100 Translational Medicine associated with CPL-207-280

100 Patents (Medical) associated with CPL-207-280

Literatures (Medical) associated with CPL-207-280

01 Dec 2021·European journal of medicinal chemistryQ1 · MEDICINE

Discovery and development of CPL207280 as new GPR40/FFA1 agonist

Q1 · MEDICINE

Article

Author: Pieczykolan, Jerzy ; Wąsińska-Kałwa, Małgorzata ; Dawid, Urszula ; Smuga, Damian ; Wiśniewski, Krzysztof ; Gurba-Bryśkiewicz, Lidia ; Gałązka, Kinga ; Buda, Paweł ; Hołowińska, Dagmara ; Dzida, Radosław ; Mach, Mateusz ; Matłoka, Mikołaj ; Bazydło-Guzenda, Katarzyna ; Dubiel, Krzysztof ; Wieczorek, Maciej ; Stelmach, Filip

Due to a unique mechanism that limits the possibility of hypoglycemia, the free fatty acid receptor (FFA1) is an attractive target for the treatment of type 2 diabetes. So far, however, none of the promising agonists have been able to enter the market. The most advanced clinical candidate, TAK-875, was withdrawn from phase III clinical trials due to liver safety issues. In this article, we describe the key aspects leading to the discovery of CPL207280 (13), the design of which focused on long-term safety. The introduction of small, nature-inspired acyclic structural fragments resulted in compounds with retained high potency and a satisfactory pharmacokinetic profile. Optimized synthesis and upscaling provided a stable, solid form of CPL207280-51 (45) with the properties required for the toxicology studies and ongoing clinical trials.

01 Oct 2021·Molecular pharmacology

CPL207280, a Novel G Protein–Coupled Receptor 40/Free Fatty Acid Receptor 1–Specific Agonist, Shows a Favorable Safety Profile and Exerts Antidiabetic Effects in Type 2 Diabetic Animals

Article

Author: Vialichka, Varvara ; Pieczykolan, Jerzy ; Matloka, Mikolaj ; Kaminska, Bozena ; Teska-Kaminska, Malgorzata ; Dzida, Radoslaw ; Bazydlo-Guzenda, Katarzyna ; Smuga, Damian ; Hucz-Kalitowska, Joanna ; Buda, Pawel ; Mach, Mateusz ; Stelmach, Filip ; Dubiel, Krzysztof ; Wieczorek, Maciej

G protein-coupled receptor (GPR) 40 is a free fatty acid receptor mainly expressed in pancreatic β-cells activated by medium- and long-chain fatty acids and regulating insulin secretion via an increase in cytosolic free calcium ([Ca²⁺]_i). Activation of GPR40 in pancreatic β-cells may improve glycemic control in type 2 diabetes through enhancement of glucose-stimulated insulin secretion. However, the most clinically advanced GPR40 agonist-TAK-875 (fasiglifam)-was withdrawn from phase III because of its hepatotoxicity resulting from the inhibition of pivotal bile acid transporters. Here, we present a new, potent CPL207280 agonist and compare it with fasiglifam in numerous in vitro and in vivo studies. CPL207280 showed greater potency than fasiglifam in a Ca²⁺ influx assay with a human GPR40 protein (EC₅₀ = 80 vs. 270 nM, respectively). At the 10 µM concentration, it showed 3.9 times greater enhancement of glucose-stimulated insulin secretion in mouse MIN6 pancreatic β-cells. In Wistar Han rats and C57BL6 mice challenged with glucose, CPL207280 stimulated 2.5 times greater insulin secretion without causing hypoglycemia at 10 mg/kg compared with fasiglifam. In three diabetic rat models, CPL207280 improved glucose tolerance and increased insulin area under the curve by 212%, 142%, and 347%, respectively. Evaluation of potential off-target activity (Safety47) and selectivity of CPL207280 (at 10 μM) did not show any significant off-target activity. We conclude that CPL207280 is a potent enhancer of glucose-stimulated insulin secretion in animal disease models with no risk of hypoglycemia at therapeutic doses. Therefore, we propose the CPL207280 compound as a compelling candidate for type 2 diabetes treatment. SIGNIFICANCE STATEMENT: GPR40 is a well-known and promising target for diabetes. This study is the first to show the safety and effects of CPL207280, a novel GPR40/free fatty acid receptor 1 agonist, on glucose homeostasis both in vitro and in vivo in different diabetic animal models. Therefore, we propose the CPL207280 compound as a novel, glucose-lowering agent, overcoming the unmet medical needs of patients with type 2 diabetes.

01 Apr 2024·Diabetes, obesity & metabolism

First‐in‐human study of CPL207280, a novel G‐protein‐coupled receptor 40/free fatty acid receptor 1 agonist, in healthy volunteers after single and multiple administration

Article

Author: Wieczorek, Maciej ; Jarus-Dziedzic, Katarzyna ; Tratkiewicz, Ewa ; Gierczak-Pachulska, Agnieszka ; Bazydło-Guzenda, Katarzyna ; Rabczenko, Daniel ; Juszczyk, Ewelina ; Buda, Paweł ; Rudzki, Piotr J ; Buś-Kwaśnik, Katarzyna ; Segiet-Święcicka, Agnieszka

Abstract:

Aim:

To assess the safety, tolerability and pharmacokinetic (PK) profile of single and multiple doses of CPL207280, a new G‐protein‐coupled receptor 40 agonist developed to treat type 2 diabetes (T2D).

Methods:

The phase 1 study in healthy volunteers (White, age 18–55 years, body mass index 18.5–29.9 kg/m2) was performed after single (24 subjects, 5–480 mg) and multiple (32 subjects, 60–480 mg) once‐daily administration of CPL207280. The effect of food intake and interaction with metformin were evaluated in additional cohort (12 subjects, 120 mg). The primary objective was the safety and tolerability of CPL207280. Secondary objectives included PK and pharmacodynamic (PD) characteristics (glucose, insulin, C‐peptide, proinsulin, glucagon levels) observed during the 14‐day treatment period.

Results:

No deaths or serious adverse events (AEs) were reported. All reported AEs were classified as unrelated to the study product. No clinically significant differences in safety parameters were observed between cohorts and no food or metformin effect on safety parameters was identified. The ascending dose of CPL207280 caused an increase in the PK parameters maximum observed plasma concentration (Cmax) or area under the plasma concentration–time curve up to 24 h. However, dose‐normalized Cmax decreased with ascending dose. There was no relationship between the CPL207280 dose or prandial state and terminal elimination half‐life and terminal elimination rate constant. No clear relationship between CPL207280 dose and PD area under the effect curve values was observed.

Conclusions:

CPL207280 was found to be safe and well tolerated by healthy volunteers (with a low risk of hepatotoxicity) for up to 14 days of administration. The PK profile of CPL207280 supports single‐daily administration and justifies further development of this therapy for patients with T2D.

News (Medical) associated with CPL-207-280

22 Jun 2021

·www.globenewswire.com

Celon Pharma Files for Approval of Phase II Trial of CPL’280, a Second Generation GPR40 Agonist, in Type 2 Diabetes

KIELPIN, Poland, June 22, 2021 (GLOBE NEWSWIRE) -- Celon Pharma today announced filing for approval to start a Phase II clinical study of CPL’280, its second generation GPR40 agonist in type 2 diabetes. This double-blind, randomized, placebo-controlled, multiple dose Phase II study will evaluate the ability of orally administered CPL’280 to control blood glucose in patients with diagnosed type 2 diabetes. Both naive and metformin-inadequate responders will be administered once-daily CPL’280 for two weeks. Safety and pharmacokinetics will be secondary endpoints. The trial plans to include 80 patients. Celon Pharma expects to dose the first patient in Q4 2021 and top-line results are anticipated in 1H 2022. CPL’280 was designed to improve on the drawbacks of the first generation GPR40 agonists. The molecule, which is structurally different from the first generation agonists, is free from known risk factors associated with liver injury, i.e. bile acid transporter inhibition and the formation of reactive metabolites. The molecule showed strong evidence of safety both in preclinical and Phase I clinical studies including liver safety. Liver injury was a known risk factor identified for fasiglifam, which was the most advanced first generation GPR40 agonist which was terminated in late-stage clinical development. Maciej Wieczorek, PhD, Celon Pharma CEO, commented: “We are looking forward to advancing this Phase 2 trial with CPL’280, which has shown significant potential to improve the current standard of care in diabetes. Our molecule has completed a preclinical program showing robust efficacy in multiple diabetic animal models and has also demonstrated efficacy beyond better glycemic control in diabetic neuropathy animal models. Diabetic neuropathy, which is one of the most common long-term complications of type 2 diabetes, is planned to be the second indication in the clinical development of CPL’280.” About Celon Pharma Celon Pharma is an integrated biopharmaceutical company which designs, develops, manufactures and distributes pharmaceutical products. It was founded in 2002 by Maciej Wieczorek, PHD. The company currently has approx. 500 employees. It employs approx. 160 scientists responsible for research and development, half of whom either have a PhD or are in the process of acquiring their PhD. The Company's pipeline includes more than a dozen projects for the development of innovative drugs with therapeutic groups such as oncology, neuro-psychiatry, autoimmunity and metabolism. The company has its own research and development laboratories, which allow it to develop its own pharmaceutical technologies by using extensive laboratory equipment resources, as well as the experience and expertise of its staff. It also has a modern manufacturing facility where dry pharmaceutical forms are manufactured. Over the last few years, the Company has introduced products into the market in the following therapeutic areas: oncology, central nervous system diseases, cardiology, HIV treatment, respiratory diseases. The Company has been developing the technology for manufacturing inhalation drugs and several projects of innovative drugs since 2007. It has been listed on the Warsaw Stock Exchange since 2016. More information can be obtained by contacting:Małgorzata Siewierskamedia@celonpharma.com

CollaborateInnovative Drug

01 Apr 2021

·www.biospace.com

Celon Pharma Announces CPL’280, Second Generation Oral GPR40 Agonist, Meets Primary Endpoint in Phase 1 Trial

KIELPIN, Poland, April 01, 2021 (GLOBE NEWSWIRE) -- Celon Pharma S.A. today announced the successful completion of a Phase 1 trial of its second generation GPR40 agonist, CPL’280. This agent is in development for the treatment of Diabetes and Diabetic Neuropathy and met its primary endpoint, with no adverse safety signals detected. “We are very pleased with the results from this Phase 1 trial, demonstrating that CPL’280 is safe and well tolerated,” said Maciej Wieczorek, PhD, Celon Pharma's Chief Executive Officer and Head of Research & Development. “CPL’280 is part of a deep innovative pipeline of proprietary programs that strive to improve upon limitations identified in first-generation molecules. Based on these data, Celon Pharma plans to initiate Phase 2 proof-of-concept studies with CPL’280 in Type 2 Diabetes and Diabetic Neuropathy in the coming months and has submitted data on CPL’280 for publication.” In the trial, CPL’280 was administered orally in single and multiple ascending doses in healthy volunteers to assess safety and pharmacokinetic parameters (PK). Pharmacokinetic interactions with metformin and food were also tested. No adverse events associated with administration of CPL’280 were observed, the primary endpoint of the trial. No alanine aminotransferase (ALT), aspartate transaminase (AST) or any other liver toxicity measures were elevated in the study which is particularly critical as first generation GPR40 agonists were previously terminated in late-stage development due to liver toxicity risks. Pharmacokinetics were linear and no interactions with food or metformin were noted. CPL’280 is structurally different from first generation molecules and is designed to improve on the liver toxicity signal identified in earlier programs. The molecule showed robust efficacy in animal diabetic models. It is also the first GPR40 agonist which demonstrated efficacy in diabetic neuropathy animal models after oral administration. ABOUT CELON PHARMA Celon Pharma is an integrated biopharmaceutical company which designs, develops, manufactures and distributes pharmaceutical products. It was founded in 2002 by Maciej Wieczorek, PhD. The Company currently has approx. 450 employees. It employs approx. 160 scientists responsible for research and development, half of whom either have a PhD or are in the process of acquiring their PhD. The Company's pipeline includes more than a dozen projects for the development of innovative drugs with therapeutic groups such as oncology, neuro-psychiatry, autoimmunity and metabolism. The Company has its own research and development laboratories, which allow it to develop its own pharmaceutical technologies by using extensive laboratory equipment resources, as well as the experience and expertise of its staff. It also has a modern manufacturing facility where dry pharmaceutical forms are manufactured. Over the last few years, the Company has introduced products into the market in the following therapeutic areas: oncology, central nervous system diseases, cardiology, HIV treatment, respiratory diseases. The Company has been developing the technology for manufacturing inhalation drugs and several projects of innovative drugs since 2007. It has been listed on the Warsaw Stock Exchange since 2016. Disclaimer This press release (“Press release”) has been prepared by Celon Pharma S.A. (the “Company”). By reading the Press release, you agree to be bound by the following limitations. This Press release is strictly confidential to the recipient. Neither this Press release or any part hereof nor the information contained herein may be reproduced or redistributed, passed on, or the contents otherwise divulged, directly or indirectly, to any other person or published, in whole or in part. If you gain access to this Press release by mistake, or you are not an addressee of this Press release or a person authorized to use this Press release, please bear in mind the confidential nature of this Press release and immediately contact the Company in order to return it to the Company. The Press release does not constitute an offer to sell or subscribe for or a solicitation of an offer to purchase or subscribe for securities. This Press release is provided for informational purposes only. This Press release does not constitute or form part of and should not be construed as an offer, solicitation or invitation to sell or issue, or an offer, solicitation or invitation to, subscribe for, underwrite, buy or otherwise acquire, securities of the Company or any of its subsidiaries in any jurisdiction, or an inducement/recommendation to enter into investment activity in any jurisdiction. Neither this Press release nor any part hereof, nor the fact of its distribution or issuance, shall form the basis of, or be relied on in connection with, any contract, commitment or investment decision whatsoever. The information contained herein is only preliminary and indicative and does not purport to contain the information that would be required to evaluate the Company, its financial position and/or any investment decision. This Press release is not intended to provide, and should not be relied upon for, accounting, legal or tax advice nor does it constitute an investment recommendation. This Press release is given in conjunction with an oral press release and should not be taken out of context. No information included in this Press release may be considered as investment advice or investment recommendation. The information contained in the Press release has not been independently verified. No repress release, warranty or undertaking, expressed or implied, is made as to, and no reliance should be placed on, the fairness, accuracy, completeness or correctness of the information or the opinions contained herein. Matters discussed in this Press release may constitute forward-looking statements. Forward-looking statements constitute statements that are other than statements of historical fact. Statements which include the words “expects”, “intends”, “plans”, “believes”, “projects”, “anticipates”, “will”, “targets”, “aims”, “may”, “would”, “could”, “continue” and similar statements of a future or forward-looking nature identify such forward-looking statements. Forward-looking statements include in particular statements regarding the financial performance, business strategy, plans and objectives of the Company for future operations (including growth potential). All forward-looking statements included in this Press release address matters that involve known and unknown risks, uncertainties and other factors which could cause the Company’s actual results, performance or achievements to differ materially from those indicated in such forward-looking statements and from past results, performance or achievements of the Company. Such forward-looking statements are based upon various assumptions and estimates regarding future events, including numerous assumptions regarding the Company’s present and future business strategies and future operating environment. Although the Company believes that these estimates and assumptions are reasonable, they may prove to be incorrect. The information, opinions and forward-looking statements contained in this Press release speak only as at the date of this Press release and are subject to change without notice. The Company, its directors, agents, employees and advisors do not intend to, and expressly disclaim any duty, undertaking or obligation to, make or disseminate any supplement, amendment, update or revision to any of the information, opinions or forward-looking statements contained in this Press release to reflect any change in events, conditions or circumstances. To the extent permitted under the applicable provisions of law, neither the Company nor any of their affiliates, advisers or representatives shall have any liability whatsoever (in negligence or otherwise) for any loss however arising from any use of this Press release or its contents or otherwise arising in connection with this Press release. This Press release is not for distribution or use by any person or entity in any jurisdiction where such distribution or use would be contrary to local law or regulation or which would subject the Company or any of its affiliates to authorization, notification, licensing or other registration requirements under applicable laws. Any failure to comply with this restriction may constitute a violation of United States securities laws. Persons into whose possession this Press release comes should observe all such restrictions. Obtain more information by contacting: Małgorzata Siewierska media@celonpharma.com

CollaborateInnovative Drug

100 Deals associated with CPL-207-280

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Diabetes Mellitus, Type 2	Phase 2	PL	Celon Pharma SA	21 Jan 2022
Diabetic Neuropathies	Phase 2	-	Celon Pharma SA	-

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04622111 (Phase 1, EASD2021)	Phase 1	-	32	CPL207280 60 mg	drxftcnmdn(uyceaibfkw) = The administration of CPL207280 was generally safe and well-tolerated with no serious AEs. All adverse events were classified as not related to the study product. No increase in the tested hepatic parameters (ALT, AST, ALP, bilirubin, creatinine) was observed. There were no hypoglycaemia episodes during the study. bbrhcmptos (jwgifzuqpv )	Positive	01 Oct 2021
				CPL207280 480 mg
NCT04622111 (CPL207280, Pubmed)	Phase 1	-	68	CPL207280	atxretoffl(iewhkieiya) = mxpxyerbjd eqefcqkxaa (dhahkdnvcz ) View more	-	04 Aug 2021
EASD2018	Not Applicable	Ca 2+	-	CPL207-280CA	kivknbglrj(wmzkyhsprq) = tplywkdymz nrtcfsdjib (gpyjbjyafb )	Positive	03 Oct 2018
				Fasiglifam	kivknbglrj(wmzkyhsprq) = deymicofwc nrtcfsdjib (gpyjbjyafb )

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