Key result
A fixed-dose combination of amlodipine, losartan, and chlorthalidone was bioequivalent to its separate components, with 90% CIs for Cmax and AUC falling within the 0.80 to 1.25 range.
Why the study?
Hypertension is more effectively treated with coadministration of two or more antihypertensive drugs, prompting comparison of the pharmacokinetic profiles of an amlodipine, losartan, and chlorthalidone fixed-dose combination versus concurrent separate components.
Does a fixed-dose combination of amlodipine, losartan, and chlorthalidone have equivalent pharmacokinetics to the separate components in human subjects?
RCT (n=60)
open-label
randomized
Does a fixed-dose combination of amlodipine, losartan, and chlorthalidone have equivalent pharmacokinetics to the separate components in human subjects?
A single-pill fixed-dose combination of amlodipine, losartan, and chlorthalidone is bioequivalent to its individual components, offering a simplified regimen for hypertension management.
Hypertension is more effectively treated with coadministration of 2 or more antihypertensive drugs than with high-dose monotherapy. Therefore, calcium channel blockers, angiotensin II receptor blockers, and thiazides are coadministered to treat hypertension. The objective of this study was to compare the pharmacokinetic (PK) profiles of HCP1401, a fixed-dose combination of amlodipine 5 mg, losartan 100 mg, and chlorthalidone 25 mg, with the separate components (loose combination) of amlodipine/losartan 5/100 mg and chlorthalidone 25 mg. A randomized, open-label, single-dose, 2-way crossover study was conducted. Blood samples for amlodipine and chlorthalidone were collected for up to 144 hours after dosing, whereas those for losartan were collected up to 48 hours after dosing. The PK parameters of these drugs were calculated using a noncompartmental method. Sixty subjects completed the study. The geometric mean ratios and 90% confidence intervals of maximum plasma concentration and area under the concentration-time curve to the last measurable point for amlodipine, losartan, and chlorthalidone were within the conventional bioequivalence range of 0.80 to 1.25. There were no clinically significant changes in safety assessments, and the treatments were well tolerated. The PK characteristics and tolerability profiles of a single oral FDC of amlodipine, losartan, and chlorthalidone were equivalent to those of individual tablets in a loose combination.
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Jeon et al. (2021) conducted an RCT in Hypertension (n=60). HCP1401 (fixed-dose combination of amlodipine, losartan, and chlorthalidone) vs. separate components of amlodipine/losartan 5/100 mg and chlorthalidone 25 mg was evaluated on maximum plasma concentration and area under the concentration-time curve to the last measurable point. A fixed-dose combination of amlodipine, losartan, and chlorthalidone was bioequivalent to its separate components, with 90% CIs for Cmax and AUC falling within the 0.80 to 1.25 range.
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