{"title":"磷酸二酯酶5型抑制剂DDCI-01在健康受试者中的安全性和药代动力学评价","authors":"Qian Li, Shen-Shen Huang, Dong-Chuan Zhang, Wei-Yi Zhang, Yi-Min Mao, Rui Chen, Zhi-Cheng Jing","doi":"10.1007/s40262-025-01491-7","DOIUrl":null,"url":null,"abstract":"<p><strong>Aim: </strong>The aim of this study was to evaluate the safety, tolerability, and pharmacokinetics of single escalating oral doses of DDCI-01 (a novel, highly selective, long-acting phosphodiesterase type 5 inhibitor) administered via capsules to healthy volunteers.</p><p><strong>Methods: </strong>This randomized, double-blind, placebo-controlled, single ascending dosing, Phase Ia clinical study involved 52 healthy volunteers who were randomized (3:1 ratio) to receive a single oral dose of DDCI-01 (1.25, 2.5, 5, 10, 20, 40, or 60 mg) or a placebo. Adverse events and pharmacokinetic parameters were evaluated after 14 days post-administration.</p><p><strong>Results: </strong>Within the studied dose range, DDCI-01 was safe and tolerable. Mild adverse events incidence was > 10% in all 39 volunteers receiving DDCI-01: myalgia (eight cases, 20.51%) and spontaneous penile erection (four cases, 10.26%). Drug exposure (C<sub>max</sub>, AUC<sub>0-t</sub>, and AUC<sub>0-inf</sub>) increased with increasing dosage; however, no linear correlation was observed between drug exposure and dosage. The drug exposure increase was less than the expected dose-proportional increase. Terminal half-life of DDCI-01 ranged between 35.5 and 40.6 hours, whereas the values of apparent clearance (CL/F) and apparent volume (V<sub>z</sub>/F) were in the range of 1.1-3.0 L/h and 59-175 L, respectively. Both CL/F and V<sub>z</sub>/F increased with increasing doses of DDCI-01.</p><p><strong>Conclusions: </strong>DDCI-01 demonstrated favorable safety and pharmacokinetic profiles within the dose range. The findings of this first-in-human study support further research for the indications of DDCI-01, such as pulmonary arterial hypertension and erectile dysfunction.</p><p><strong>Registration: </strong>Chinese Center for Drug Evaluation (CDE) registry number CTR20201564. The date of registration: August 3, 2020.</p>","PeriodicalId":10405,"journal":{"name":"Clinical Pharmacokinetics","volume":" ","pages":""},"PeriodicalIF":4.6000,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Evaluation of Safety and Pharmacokinetics of DDCI-01, a Phosphodiesterase Type 5 Inhibitor, in Healthy Participants.\",\"authors\":\"Qian Li, Shen-Shen Huang, Dong-Chuan Zhang, Wei-Yi Zhang, Yi-Min Mao, Rui Chen, Zhi-Cheng Jing\",\"doi\":\"10.1007/s40262-025-01491-7\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Aim: </strong>The aim of this study was to evaluate the safety, tolerability, and pharmacokinetics of single escalating oral doses of DDCI-01 (a novel, highly selective, long-acting phosphodiesterase type 5 inhibitor) administered via capsules to healthy volunteers.</p><p><strong>Methods: </strong>This randomized, double-blind, placebo-controlled, single ascending dosing, Phase Ia clinical study involved 52 healthy volunteers who were randomized (3:1 ratio) to receive a single oral dose of DDCI-01 (1.25, 2.5, 5, 10, 20, 40, or 60 mg) or a placebo. Adverse events and pharmacokinetic parameters were evaluated after 14 days post-administration.</p><p><strong>Results: </strong>Within the studied dose range, DDCI-01 was safe and tolerable. Mild adverse events incidence was > 10% in all 39 volunteers receiving DDCI-01: myalgia (eight cases, 20.51%) and spontaneous penile erection (four cases, 10.26%). Drug exposure (C<sub>max</sub>, AUC<sub>0-t</sub>, and AUC<sub>0-inf</sub>) increased with increasing dosage; however, no linear correlation was observed between drug exposure and dosage. The drug exposure increase was less than the expected dose-proportional increase. Terminal half-life of DDCI-01 ranged between 35.5 and 40.6 hours, whereas the values of apparent clearance (CL/F) and apparent volume (V<sub>z</sub>/F) were in the range of 1.1-3.0 L/h and 59-175 L, respectively. Both CL/F and V<sub>z</sub>/F increased with increasing doses of DDCI-01.</p><p><strong>Conclusions: </strong>DDCI-01 demonstrated favorable safety and pharmacokinetic profiles within the dose range. The findings of this first-in-human study support further research for the indications of DDCI-01, such as pulmonary arterial hypertension and erectile dysfunction.</p><p><strong>Registration: </strong>Chinese Center for Drug Evaluation (CDE) registry number CTR20201564. The date of registration: August 3, 2020.</p>\",\"PeriodicalId\":10405,\"journal\":{\"name\":\"Clinical Pharmacokinetics\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":4.6000,\"publicationDate\":\"2025-03-06\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical Pharmacokinetics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s40262-025-01491-7\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical Pharmacokinetics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s40262-025-01491-7","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Evaluation of Safety and Pharmacokinetics of DDCI-01, a Phosphodiesterase Type 5 Inhibitor, in Healthy Participants.
Aim: The aim of this study was to evaluate the safety, tolerability, and pharmacokinetics of single escalating oral doses of DDCI-01 (a novel, highly selective, long-acting phosphodiesterase type 5 inhibitor) administered via capsules to healthy volunteers.
Methods: This randomized, double-blind, placebo-controlled, single ascending dosing, Phase Ia clinical study involved 52 healthy volunteers who were randomized (3:1 ratio) to receive a single oral dose of DDCI-01 (1.25, 2.5, 5, 10, 20, 40, or 60 mg) or a placebo. Adverse events and pharmacokinetic parameters were evaluated after 14 days post-administration.
Results: Within the studied dose range, DDCI-01 was safe and tolerable. Mild adverse events incidence was > 10% in all 39 volunteers receiving DDCI-01: myalgia (eight cases, 20.51%) and spontaneous penile erection (four cases, 10.26%). Drug exposure (Cmax, AUC0-t, and AUC0-inf) increased with increasing dosage; however, no linear correlation was observed between drug exposure and dosage. The drug exposure increase was less than the expected dose-proportional increase. Terminal half-life of DDCI-01 ranged between 35.5 and 40.6 hours, whereas the values of apparent clearance (CL/F) and apparent volume (Vz/F) were in the range of 1.1-3.0 L/h and 59-175 L, respectively. Both CL/F and Vz/F increased with increasing doses of DDCI-01.
Conclusions: DDCI-01 demonstrated favorable safety and pharmacokinetic profiles within the dose range. The findings of this first-in-human study support further research for the indications of DDCI-01, such as pulmonary arterial hypertension and erectile dysfunction.
Registration: Chinese Center for Drug Evaluation (CDE) registry number CTR20201564. The date of registration: August 3, 2020.
期刊介绍：
Clinical Pharmacokinetics promotes the continuing development of clinical pharmacokinetics and pharmacodynamics for the improvement of drug therapy, and for furthering postgraduate education in clinical pharmacology and therapeutics.
Pharmacokinetics, the study of drug disposition in the body, is an integral part of drug development and rational use. Knowledge and application of pharmacokinetic principles leads to accelerated drug development, cost effective drug use and a reduced frequency of adverse effects and drug interactions.
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