PMID- 30809967 OWN - NLM STAT- MEDLINE DCOM- 20200804 LR - 20200804 IS - 2160-7648 (Electronic) IS - 2160-763X (Linking) VI - 8 IP - 7 DP - 2019 Oct TI - Study on Drug-Drug Interactions Between Chiglitazar, a Novel PPAR Pan-Agonist, and Metformin Hydrochloride in Healthy Subjects. PG - 934-941 LID - 10.1002/cpdd.668 [doi] AB - Chiglitazar (CHI) is a potent and selective peroxisome proliferator-activated receptor potentially for the treatment of patients with type 2 diabetes mellitus (T2DM). An open-label, randomized, 3-period crossover and self-controlled study was conducted to investigate drug-drug interaction potential between CHI and metformin hydrochloride (MET). Eligible subjects received a single oral dose of CHI (48 mg), MET (1000 mg), or a combination in each period, followed by serial blood sampling collected for up to 48 hours postdose, and safety was assessed throughout the trial. The area under the plasma concentration-time curves from time 0 to 48 hours (AUC(0-48 h) ) of CHI was similar following administration alone or with MET (AUC(0-48h) , 12 540 ng.h/mL [9811-15 269 ng.h/mL] vs 12 130 ng.h/mL [9304-14 956 ng.h/mL]; 90% confidence interval [CI] of its geometric mean ratio [GMR], 89.7%-103.8%), whereas the maximum concentration (C(max) ) of CHI was reduced during coadministration, as its 90%CI of the GMR was slightly outside the acceptance range for bioequivalence (C(max) , 1620 ng/mL [1418-1822 ng/mL] vs 1420 ng/mL [1049-1791 ng/mL], 90%CI GMR, 77.%-94.1%). However, it was not considered clinically meaningful. The MET exposures remained consistent in the absence or presence of CHI (AUC(0-48 h) , 12 570 ng.h/mL [10681-14 459 ng.h/mL] vs 13 190 [10973-15 407 ng.h/mL); 90%CI of GMR: 99.1%-110.5%; C(max) , 1790 ng/mL [1448-2132 ng/mL] vs 1820 ng/mL [1510-2130 ng/mL]; 90%CI of GMR, 94.2%-110.9%). No moderate to severe adverse events were reported. Our study indicated no clinically significant pharmacokinetic drug-drug interaction between CHI and MET and demonstrated good tolerance in subjects. These results support future application of CHI in combination with MET for treatment of T2DM. CI - (c) 2019, The American College of Clinical Pharmacology. FAU - Yi, Ling AU - Yi L AD - Drug Clinical Trials Institution, The First Affiliated Hospital of Soochow University, Suzhou City, Jiangsu Province, P.R.China. AD - Laboratory of Phase I Clinical Study, The First Affiliated Hospital of Soochow University, Suzhou City, Jiangsu Province, P.R.China. FAU - Zhang, Hua AU - Zhang H AD - Drug Clinical Trials Institution, The First Affiliated Hospital of Soochow University, Suzhou City, Jiangsu Province, P.R.China. AD - Laboratory of Phase I Clinical Study, The First Affiliated Hospital of Soochow University, Suzhou City, Jiangsu Province, P.R.China. FAU - Zhang, Jin-Wen AU - Zhang JW AD - Exploratory Research Department, Shenzhen Chipscreen Biosciences Ltd., BIO-Incubator, Shenzhen Hi-Tech Industrial Park, Guangdong, Shenzhen, China. FAU - You, Xiao-Ming AU - You XM AD - Drug Clinical Trials Institution, The First Affiliated Hospital of Soochow University, Suzhou City, Jiangsu Province, P.R.China. AD - Laboratory of Phase I Clinical Study, The First Affiliated Hospital of Soochow University, Suzhou City, Jiangsu Province, P.R.China. FAU - Ning, Zhi-Qiang AU - Ning ZQ AD - Exploratory Research Department, Shenzhen Chipscreen Biosciences Ltd., BIO-Incubator, Shenzhen Hi-Tech Industrial Park, Guangdong, Shenzhen, China. FAU - Yu, Jia AU - Yu J AD - Exploratory Research Department, Shenzhen Chipscreen Biosciences Ltd., BIO-Incubator, Shenzhen Hi-Tech Industrial Park, Guangdong, Shenzhen, China. FAU - Qian, Li-Fang AU - Qian LF AD - Drug Clinical Trials Institution, The First Affiliated Hospital of Soochow University, Suzhou City, Jiangsu Province, P.R.China. AD - Laboratory of Phase I Clinical Study, The First Affiliated Hospital of Soochow University, Suzhou City, Jiangsu Province, P.R.China. FAU - Miao, Li-Yan AU - Miao LY AD - Drug Clinical Trials Institution, The First Affiliated Hospital of Soochow University, Suzhou City, Jiangsu Province, P.R.China. AD - Laboratory of Phase I Clinical Study, The First Affiliated Hospital of Soochow University, Suzhou City, Jiangsu Province, P.R.China. LA - eng PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20190227 PL - United States TA - Clin Pharmacol Drug Dev JT - Clinical pharmacology in drug development JID - 101572899 RN - 0 (Carbazoles) RN - 0 (Drug Combinations) RN - 0 (Propionates) RN - 0 (chiglitazar) RN - 9100L32L2N (Metformin) SB - IM MH - Administration, Oral MH - Area Under Curve MH - Carbazoles/*administration & dosage/*pharmacokinetics MH - China MH - Cross-Over Studies MH - Drug Combinations MH - Drug Interactions MH - Female MH - Healthy Volunteers MH - Humans MH - Male MH - Metformin/*administration & dosage/*pharmacokinetics MH - Propionates/*administration & dosage/*pharmacokinetics MH - Therapeutic Equivalency OTO - NOTNLM OT - chiglitazar OT - drug-drug interaction OT - healthy subjects OT - peroxisome proliferator-activated receptor (PPAR) OT - type 2 diabetes mellitus (T2DM) EDAT- 2019/02/28 06:00 MHDA- 2020/08/05 06:00 CRDT- 2019/02/28 06:00 PHST- 2018/09/15 00:00 [received] PHST- 2019/01/28 00:00 [accepted] PHST- 2019/02/28 06:00 [pubmed] PHST- 2020/08/05 06:00 [medline] PHST- 2019/02/28 06:00 [entrez] AID - 10.1002/cpdd.668 [doi] PST - ppublish SO - Clin Pharmacol Drug Dev. 2019 Oct;8(7):934-941. doi: 10.1002/cpdd.668. Epub 2019 Feb 27.