PMID- 38204407
OWN - NLM
STAT- MEDLINE
DCOM- 20240305
LR  - 20240305
IS  - 1463-1326 (Electronic)
IS  - 1462-8902 (Linking)
VI  - 26
IP  - 4
DP  - 2024 Apr
TI  - 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.
PG  - 1376-1385
LID - 10.1111/dom.15439 [doi]
AB  - 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/m(2) ) 
      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 (C(max) ) or area under the plasma 
      concentration-time curve up to 24 h. However, dose-normalized C(max) 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.
CI  - (c) 2024 Celon Pharma. Diabetes, Obesity and Metabolism published by John Wiley & 
      Sons Ltd.
FAU - Bazydlo-Guzenda, Katarzyna
AU  - Bazydlo-Guzenda K
AUID- ORCID: 0000-0002-7970-3926
AD  - R&D Center, Celon Pharma S.A., Kazun Nowy, Poland.
FAU - Jarus-Dziedzic, Katarzyna
AU  - Jarus-Dziedzic K
AD  - BioResearch Group, Clinical Site, Kajetany, Poland.
FAU - Gierczak-Pachulska, Agnieszka
AU  - Gierczak-Pachulska A
AUID- ORCID: 0009-0005-6508-5759
AD  - R&D Center, Celon Pharma S.A., Kazun Nowy, Poland.
FAU - Buda, Pawel
AU  - Buda P
AUID- ORCID: 0000-0002-1304-6871
AD  - R&D Center, Celon Pharma S.A., Kazun Nowy, Poland.
FAU - Rudzki, Piotr J
AU  - Rudzki PJ
AUID- ORCID: 0000-0002-4622-4849
AD  - R&D Center, Celon Pharma S.A., Kazun Nowy, Poland.
FAU - Bus-Kwasnik, Katarzyna
AU  - Bus-Kwasnik K
AUID- ORCID: 0000-0003-4484-7142
AD  - Lukasiewicz Research Network, Industrial Chemistry Institute, Warsaw, Poland.
FAU - Juszczyk, Ewelina
AU  - Juszczyk E
AUID- ORCID: 0000-0001-5629-5635
AD  - R&D Center, Celon Pharma S.A., Kazun Nowy, Poland.
FAU - Tratkiewicz, Ewa
AU  - Tratkiewicz E
AD  - R&D Center, Celon Pharma S.A., Kazun Nowy, Poland.
FAU - Rabczenko, Daniel
AU  - Rabczenko D
AUID- ORCID: 0000-0002-9746-2003
AD  - CleanDataLabs, Warsaw, Poland.
FAU - Segiet-Swiecicka, Agnieszka
AU  - Segiet-Swiecicka A
AUID- ORCID: 0000-0001-7978-3893
AD  - CleanDataLabs, Warsaw, Poland.
FAU - Wieczorek, Maciej
AU  - Wieczorek M
AD  - R&D Center, Celon Pharma S.A., Kazun Nowy, Poland.
LA  - eng
GR  - POIR.01.01.01-00-0334/17-00/Narodowe Centrum Badan i Rozwoju/
PT  - Journal Article
DEP - 20240111
PL  - England
TA  - Diabetes Obes Metab
JT  - Diabetes, obesity & metabolism
JID - 100883645
RN  - 0 (Fatty Acids, Nonesterified)
RN  - 0 (CPL207280)
RN  - 9100L32L2N (Metformin)
RN  - 0 (Caproates)
SB  - IM
MH  - Humans
MH  - Adolescent
MH  - Young Adult
MH  - Adult
MH  - Middle Aged
MH  - Fatty Acids, Nonesterified
MH  - *Diabetes Mellitus, Type 2/drug therapy
MH  - Healthy Volunteers
MH  - Area Under Curve
MH  - *Metformin/adverse effects
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - *Caproates
OTO - NOTNLM
OT  - GPR40/FFAR1
OT  - drug development
OT  - pharmacodynamics
OT  - pharmacokinetics
OT  - phase I-II study
OT  - type 2 diabetes
EDAT- 2024/01/11 07:42
MHDA- 2024/03/05 06:47
CRDT- 2024/01/11 03:51
PHST- 2023/12/11 00:00 [revised]
PHST- 2023/09/13 00:00 [received]
PHST- 2023/12/18 00:00 [accepted]
PHST- 2024/03/05 06:47 [medline]
PHST- 2024/01/11 07:42 [pubmed]
PHST- 2024/01/11 03:51 [entrez]
AID - 10.1111/dom.15439 [doi]
PST - ppublish
SO  - Diabetes Obes Metab. 2024 Apr;26(4):1376-1385. doi: 10.1111/dom.15439. Epub 2024 
      Jan 11.