The HM-APOLLO-301 and HM-APOLLO-302 phase III trials evaluated a single-pill ultra–low-dose combination of amlodipine 1.67 mg, losartan potassium 16.67 mg, and chlorthalidone 4.17 mg (LDC-ALC) versus standard-dose monotherapy. The results were published in the Journal of American College of Cardiology. 

Both multicenter, randomized, double-blind, active-controlled studies were conducted in South Korea. Adults (≥19 years) with systolic BP 140 to <180 mm Hg and diastolic BP <110 mm Hg after a 4-week placebo run-in were randomized to 8 weeks of treatment. The primary endpoint was systolic BP (SBP) reduction at week 8, assessed for noninferiority and then superiority.

In Study 301 (May 2022–June 2023), LDC-ALC demonstrated noninferiority to amlodipine (upper bound of one-sided 97.5% CI: 2.8 mm Hg [<3 mm Hg margin]) with similar SBP reduction (−19.1 vs −19.9 mm Hg; 95% CI −1.5 to 3.1; P=0.495). Diastolic BP reduction and BP control rates were similar.

In Study 302 (March–December 2024), LDC-ALC was noninferior and superior to losartan (−19.9 vs −16.4 mm Hg; 95% CI −6.6 to −0.2; P=0.037), with greater DBP reduction and higher BP control rates. Adverse events were comparable, with ≤1% withdrawals and no serious drug-related events.

LDC-ALC achieved BP reductions comparable to amlodipine and greater than losartan over eight weeks. Short-term tolerability was similar across groups.