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 (C max , AUC 0-t , and AUC 0-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 (V z /F) were in the range of 1.1-3.0 L/h and 59-175 L, respectively. Both CL/F and V z /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., Competing Interests: Declarations. Funding: The study was funded by Chongqing Dikang Erle Pharmaceutical Co. Ltd. Conflict of interest: DZ and WZ were Chongqing Dikang Erle Pharmaceutical Co. Ltd. employees at the time the study was conducted. All the authors have no competing interests in relation to the work described. Contribution statement: RC and ZJ designed the study. QL, SH, and YM recruited patients and were responsible for the informed consent form signing process. SH and YM followed up with patients. QL, DZ, and WZ conducted the data analysis. QL and SH wrote the first draft of the manuscript, and RC and ZJ edited the manuscript. RC and ZJ are the guarantors of this work and, as such, had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Data availability: The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions. Ethics approval: Ethics Committee of Peking Union Medical College Hospital (Approval number HS2020053). Consent to participate: Written, informed consent was obtained from all participants. Consent for publication: Not applicable. Code availability: Not applicable., (© 2025. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)