Efficacy and safety of various doses of hybutimibe monotherapy or in combination with atorvastatin for primary hypercholesterolemia: a multicenter, randomized, double-blind, double-dummy, parallel-controlled phase Ⅲ clinical trial.
10.3760/cma.j.cn112148-20230105-00009
- Author:
Si Yu CAI
1
;
Xiang GU
2
;
Pei Jing LIU
3
;
Rong Shan LI
4
;
Jian Jun JIANG
5
;
Shui Ping ZHAO
6
;
Wei YAO
7
;
Yi Nong JIANG
8
;
Yue Hui YIN
9
;
Bo YU
10
;
Zu Yi YUAN
11
;
Jian An WANG
1
Author Information
1. Department of Cardiology, The Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou 310009, China.
2. Department of Cardiology, Subei People's Hospital of Jiangsu Province, Yangzhou 225001, China.
3. Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, China.
4. Department of Cardiology, Liuzhou People's Hospital, Liuzhou 545026, China.
5. Department of Cardiology, Taizhou Hospital of Zhejiang Province, Taizhou 317000, China.
6. Department of Cardiology, the Second Xiangya Hospital of Central South University, Changsha 410011, China.
7. Department of Cardiology, Tianjin Medical University General Hospital, Tianjin 300052, China.
8. Department of Cardiology, the First Affiliated Hospital of Dalian Medical University, Dalian 116011, China.
9. Department of Cardiology, the Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
10. Department of Cardiology, the Second Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
11. Department of Cardiology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
- Publication Type:Journal Article
- MeSH:
Male;
Humans;
Middle Aged;
Atorvastatin/therapeutic use*;
Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use*;
Hypercholesterolemia/drug therapy*;
Cholesterol, LDL/therapeutic use*;
Anticholesteremic Agents/therapeutic use*;
Treatment Outcome;
Triglycerides;
Apolipoproteins B/therapeutic use*;
Double-Blind Method;
Pyrroles/therapeutic use*
- From:
Chinese Journal of Cardiology
2023;51(2):180-187
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To evaluate the efficacy and safety of hybutimibe monotherapy or in combination with atorvastatin in the treatment of primary hypercholesterolemia. Methods: This was a multicenter, randomized, double-blind, double-dummy, parallel-controlled phase Ⅲ clinical trial of patients with untreated primary hypercholesterolemia from 41 centers in China between August 2015 and April 2019. Patients were randomly assigned, at a ratio of 1∶1∶1∶1∶1∶1, to the atorvastatin 10 mg group (group A), hybutimibe 20 mg group (group B), hybutimibe 20 mg plus atorvastatin 10 mg group (group C), hybutimibe 10 mg group (group D), hybutimibe 10 mg plus atorvastatin 10 mg group (group E), and placebo group (group F). After a dietary run-in period for at least 4 weeks, all patients were administered orally once a day according to their groups. The treatment period was 12 weeks after the first dose of the study drug, and efficacy and safety were evaluated at weeks 2, 4, 8, and 12. After the treatment period, patients voluntarily entered the long-term safety evaluation period and continued the assigned treatment (those in group F were randomly assigned to group B or D), with 40 weeks' observation. The primary endpoint was the percent change in low density lipoprotein cholesterol (LDL-C) from baseline at week 12. Secondary endpoints included the percent changes in high density lipoprotein cholesterol (HDL-C), triglyceride (TG), apolipoprotein B (Apo B) at week 12 and changes of the four above-mentioned lipid indicators at weeks 18, 24, 38, and 52. Safety was evaluated during the whole treatment period. Results: Totally, 727 patients were included in the treatment period with a mean age of (55.0±9.3) years old, including 253 males. No statistical differences were observed among the groups in demographics, comorbidities, and baseline blood lipid levels. At week 12, the percent changes in LDL-C were significantly different among groups A to F (all P<0.01). Compared to atorvastatin alone, hybutimibe combined with atorvastatin could further improve LDL-C, TG, and Apo B (all P<0.05). Furthermore, there was no significant difference in percent changes in LDL-C at week 12 between group C and group E (P=0.991 7). During the long-term evaluation period, there were intergroup statistical differences in changes of LDL-C, TG and Apo B at 18, 24, 38, and 52 weeks from baseline among the statins group (group A), hybutimibe group (groups B, D, and F), and combination group (groups C and E) (all P<0.01), with the best effect observed in the combination group. The incidence of adverse events was 64.2% in the statins group, 61.7% in the hybutimibe group, and 71.0% in the combination group during the long-term evaluation period. No treatment-related serious adverse events or adverse events leading to death occurred during the 52-week study period. Conclusions: Hybutimibe combined with atorvastatin showed confirmatory efficacy in patients with untreated primary hypercholesterolemia, which could further enhance the efficacy on the basis of atorvastatin monotherapy, with a good overall safety profile.
