{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Yoon J"],"funding":["Boehringer Ingelheim"],"pagination":["319-328"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11088545"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["44(5)"],"pubmed_abstract":["BACKGROUND AND OBJECTIVES: BI 1358894, a novel small-molecule inhibitor of transient receptor potential canonical ion channels, is under development for treatment of major depressive disorder. Phase I trials assessing the safety and pharmacokinetics of BI 1358894 in Caucasian male healthy volunteers (HVs) have been performed. This Phase I, double-blind, placebo-controlled, parallel-group trial assessed the safety, tolerability and pharmacokinetics of BI 1358894 in Japanese male HVs.<h4>Methods</h4>Male HVs were randomized to receive oral BI 1358894 (n = 18) or placebo (n = 6) after a high-fat, high-calorie meal within three dose groups (50 mg, 100 mg, 200 mg), administered sequentially in dose-ascending order. The primary endpoint was number of HVs with drug-related adverse events (DRAEs). Secondary endpoints were the pharmacokinetic parameters of BI 1358894.<h4>Results</h4>Overall, 24 male HVs entered the trial [mean (standard deviation) age: 30.0 (7.6) years]. DRAEs occurred in 3/18 HVs (BI 1358894 100 mg group: one HV experienced dizziness and headache; BI 1358894 200 mg group: one HV experienced headache, another reported sleep disorder). BI 1358894 exposure increased dose dependently and proportionally, peaking 4-6 h after administration before declining in a multiphasic manner with a terminal elimination half-life of ~70 h in the 50 mg and 100 mg dose groups, and 203 h in the 200 mg dose group.<h4>Conclusion</h4>BI 1358894 was well tolerated with a favorable pharmacokinetic profile in Japanese male HVs, similar to findings from a previous study in Caucasian male HVs.<h4>Trial registration</h4>ClinicalTrials.gov (NCT03875001; 08-Mar-2019)."],"journal":["Clinical drug investigation"],"pubmed_title":["Safety, Tolerability, and Pharmacokinetics of Oral BI 1358894 in Healthy Japanese Male Volunteers."],"pmcid":["PMC11088545"],"funding_grant_id":["1402-0008"],"pubmed_authors":["Yoon J","Sharma V","Harada A"],"additional_accession":[]},"is_claimable":false,"name":"Safety, Tolerability, and Pharmacokinetics of Oral BI 1358894 in Healthy Japanese Male Volunteers.","description":"BACKGROUND AND OBJECTIVES: BI 1358894, a novel small-molecule inhibitor of transient receptor potential canonical ion channels, is under development for treatment of major depressive disorder. Phase I trials assessing the safety and pharmacokinetics of BI 1358894 in Caucasian male healthy volunteers (HVs) have been performed. This Phase I, double-blind, placebo-controlled, parallel-group trial assessed the safety, tolerability and pharmacokinetics of BI 1358894 in Japanese male HVs.<h4>Methods</h4>Male HVs were randomized to receive oral BI 1358894 (n = 18) or placebo (n = 6) after a high-fat, high-calorie meal within three dose groups (50 mg, 100 mg, 200 mg), administered sequentially in dose-ascending order. The primary endpoint was number of HVs with drug-related adverse events (DRAEs). Secondary endpoints were the pharmacokinetic parameters of BI 1358894.<h4>Results</h4>Overall, 24 male HVs entered the trial [mean (standard deviation) age: 30.0 (7.6) years]. DRAEs occurred in 3/18 HVs (BI 1358894 100 mg group: one HV experienced dizziness and headache; BI 1358894 200 mg group: one HV experienced headache, another reported sleep disorder). BI 1358894 exposure increased dose dependently and proportionally, peaking 4-6 h after administration before declining in a multiphasic manner with a terminal elimination half-life of ~70 h in the 50 mg and 100 mg dose groups, and 203 h in the 200 mg dose group.<h4>Conclusion</h4>BI 1358894 was well tolerated with a favorable pharmacokinetic profile in Japanese male HVs, similar to findings from a previous study in Caucasian male HVs.<h4>Trial registration</h4>ClinicalTrials.gov (NCT03875001; 08-Mar-2019).","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 May","modification":"2026-04-08T19:49:42.878Z","creation":"2026-04-08T14:31:19.514Z"},"accession":"S-EPMC11088545","cross_references":{"pubmed":["38656736"],"doi":["10.1007/s40261-024-01357-z"]}}