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Aim <p>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> Methods <p>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&#xa0;mg) or a placebo. Adverse events and pharmacokinetic parameters were evaluated after 14 days post-administration.</p> Results <p>Within the studied dose range, DDCI-01 was safe and tolerable. Mild adverse events incidence was &gt; 10% in all 39 volunteers receiving DDCI-01: myalgia (eight cases, 20.51%) and spontaneous penile erection (four cases, 10.26%). Drug exposure (<i>C</i><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 (<i>V</i><sub>z</sub>/<i>F</i>) were in the range of 1.1–3.0 L/h and 59–175&#xa0;L, respectively. Both CL/F and <i>V</i><sub>z</sub>/<i>F</i> increased with increasing doses of DDCI-01.</p> Conclusions <p>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> Registration <p>Chinese Center for Drug Evaluation (CDE) registry number CTR20201564. The date of registration: August 3, 2020.</p>

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Evaluation of Safety and Pharmacokinetics of DDCI-01, a Phosphodiesterase Type 5 Inhibitor, in Healthy Participants

  • 期刊论文

  • 发表日期：

    2025年3月6日

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  • Qian Li,
  • Shen-Shen Huang,
  • Dong-Chuan Zhang,
  • Wei-Yi Zhang,
  • Yi-min Mao,
  • Rui Chen,
  • Zhi-Cheng Jing

摘要

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.