TABLE 2.

Phase I-III clinical studies of hybutimibe.

Study type	Design and sample size	Population	Intervention	Follow-up duration	Key efficacy findings	Safety profile
Single-center first-in-human (dose-escalation study) (Altmann et al., 2004)	First-in-human, single-center, single- and multiple-ascending-dose and food-effect study; 5–10 hybutimibe-treated participants per single-dose cohort	Healthy volunteers	Single ascending doses (1, 3, 5, 10, 20, 30 mg) and multiple ascending doses (5, 10, 20 mg) of hybutimibe	Single dosing and 10-day repeated dosing	–	All adverse events were mild to moderate; no clinically significant laboratory abnormalities; most subjects had no adverse events
Phase I randomized, double-blind, placebo-controlled dose-escalation study	Randomized, double-blind, placebo-controlled, parallel-group Phase I study	Healthy adults in China and the United States	Single oral doses of 1–30 mg; repeated dosing with 5, 10, or 20 mg once daily for 10 days	10 days (treatment period)	–	Single and multiple doses were well tolerated; most adverse events were mild; overall safety favorable
Phase II multicenter, randomized, double-blind, placebo- and active-controlled study (Liao et al., 2021)	Multicenter, randomized, double-blind, placebo- and positive-controlled, parallel-group Phase II study	Patients with primary hyperlipidemia	Hybutimibe ≥5 mg once daily	8 weeks	Significant reductions in LDL-C, TC, non-HDL-C, and ApoB; no significant effect on TG	Overall well tolerated; most adverse events were mild; elevated liver enzymes and gastrointestinal reactions were infrequent; severe adverse events were rare (1.03%); no drug-related serious adverse events
Phase III multicenter monotherapy study (Ruan et al., 2014)	Multicenter, randomized, double-blind, placebo-controlled, parallel-group Phase III study; n = 373	Patients with primary hypercholesterolemia	Hybutimibe monotherapy	12-week placebo-controlled period plus 40-week extension; 52 weeks in total	Significant LDL-C reduction; lipid-lowering effect sustained; treatment well tolerated	Low incidence of adverse events; most were mild; withdrawal rate <5%; no new safety signals
Phase III multicenter randomized, double-blind combination-therapy study (Qi et al., 2022a)	Multicenter, randomized, double-blind, placebo-controlled, parallel-group Phase III study; n = 255	Patients with hypercholesterolemia and ASCVD	Hybutimibe 20 mg plus atorvastatin 10 mg versus atorvastatin 20 mg	12 weeks	Mean LDL-C changes from baseline at week 12 were −16.39% and −6.75%, respectively (P < 0.0001)	Adverse-event incidence low; no serious drug-related events; discontinuation rate low; safety profile consistent with Phase III data
Phase III multicenter monotherapy or combination therapy study (Schwartz et al., 2018)	Multicenter, randomized, double-blind, double-dummy, parallel-controlled Phase III study; n = 727	Patients with primary hypercholesterolemia	Hybutimibe monotherapy or combination with atorvastatin	12-week treatment period plus 40-week long-term evaluation; 52 weeks in total	Combination therapy further improved LDL-C reduction compared with monotherapy	No new drug-related severe adverse events within 52 weeks; overall tolerability excellent