- 2026-05-08
- Drug design, development and therapy 20
Study Design
- Type
- Clinical Trial
- Population
- healthy Chinese participants
- Methods
- Phase I study; single oral dose of empagliflozin (10 mg), atorvastatin (20 mg), and valsartan (160 mg) on Day 1; chiglitazar (48 mg) once daily from Day 5 to Day 9; on Day 10, last single dose of chiglitazar with one of the three drugs; pharmacokinetic parameters calculated using non-compartmental analysis and mixed-effects models
- Blinding
- Open-label
- Duration
- 9 days (Day 1 to Day 9 dosing, Day 10 co-administration)
Background and objectives
This study aimed to characterize the drug-drug interactions (DDIs) between chiglitazar and three commonly prescribed organic anion transporting polypeptides (OATP) 1B1/1B3 substrates (empagliflozin, atorvastatin, and valsartan) in healthy Chinese participants.Methods
In this Phase I study, healthy participants received a single oral dose of empagliflozin (10 mg), atorvastatin (20 mg), and valsartan (160 mg) on Day 1 and an oral dose of chiglitazar (48 mg) once daily from Day 5 to Day 9. On Day 10, participants received the last single dose of chiglitazar (48 mg), concurrently with a single dose of either empagliflozin (10 mg), atorvastatin (20 mg), or valsartan (160 mg). Pharmacokinetic (PK) parameters were calculated using non-compartmental analysis and the possible DDIs were statistically evaluated by mixed-effects models.Results
Chiglitazar exposure was not significantly changed when co-administrated with empagliflozin, atorvastatin, or valsartan. As a perpetrator of DDI, co-administration of chiglitazar had a minimal effect on empagliflozin exposure, whereas it decreased valsartan area under the concentration-time curve (AUC) from time 0 to infinity (AUC0-inf) by 14.3% and maximum observed plasma concentration (Cmax) by 24.7%, respectively. Although co-administration of chiglitazar decreased atorvastatin AUC0-inf by 26.6% and Cmax by 26.9%, respectively, it had no effect on its primary metabolite, 2-hydroxy atorvastatin, with its AUC0-inf and Cmax decreasing by only 7.7% and 1.2%, respectively. For atorvastatin and valsartan, the 90% confidence intervals (CIs) for AUC0-inf and Cmax extended below the 80% lower bioequivalence limit. Although the reductions were unexpected, they were not considered clinically significant based on the therapeutic contexts.Conclusion
Although the PK interactions of chiglitazar with atorvastatin and valsartan led to exposure reductions that fell outside the standard bioequivalence limits, these reductions were not expected to have clinical significance. Therefore, chiglitazar can be co-administered with these OATP1B1/1B3 substrates without dose adjustments.Clinical trial registration
NCT05681273 (ClinicalTrials.gov).