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.
