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Study on Drug‐Drug Interactions Between Chiglitazar, a Novel PPAR Pan‐Agonist, and Metformin Hydrochloride in Healthy Subjects

Study on Drug‐Drug Interactions Between Chiglitazar, a Novel PPAR Pan‐Agonist, and Metformin... 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 (AUC0‐48 h) of CHI was similar following administration alone or with MET (AUC0‐48h, 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 (Cmax) of CHI was reduced during coadministration, as its 90%CI of the GMR was slightly outside the acceptance range for bioequivalence (Cmax, 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 (AUC0‐48 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%; Cmax, 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Clinical Pharmacology in Drug Development Wiley

Study on Drug‐Drug Interactions Between Chiglitazar, a Novel PPAR Pan‐Agonist, and Metformin Hydrochloride in Healthy Subjects

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References (28)

Publisher
Wiley
Copyright
© American College of Clinical Pharmacology
eISSN
2160-7648
DOI
10.1002/cpdd.668
Publisher site
See Article on Publisher Site

Abstract

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 (AUC0‐48 h) of CHI was similar following administration alone or with MET (AUC0‐48h, 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 (Cmax) of CHI was reduced during coadministration, as its 90%CI of the GMR was slightly outside the acceptance range for bioequivalence (Cmax, 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 (AUC0‐48 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%; Cmax, 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.

Journal

Clinical Pharmacology in Drug DevelopmentWiley

Published: Oct 1, 2019

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