Patient allocation and interventions
The PLAN statistical procedure in SAS9.4 software was used to randomly allocate the patients to interventions and interventions to blocks in a 3:1 ratio for each dose group (nine patients to receive ZSP1601 and three patients to receive placebo in block randomization). The randomization sequence was generated by an independent statistician. A sheet with the information regarding the allocation and identification numbers was placed in an envelope, which was then sealed. During the study, investigators, participants, sponsors and any combination of them are unaware of allocation of the treatment drug.ZSP1601 tablets (two dosage forms: 25 mg and 100 mg) were obtained from Guangdong Raynovent Biotech Co., Ltd (Guangzhou, Guangdong, China). This clinical trial consisted of three dose cohorts with multiple doses of ZSP1601, including 50 mg once daily (QD), 50 mg twice daily (BID) (time interval of 12 ± 2 h), and 100 mg BID (time interval of 12 ± 2 h). Each cohort included twelve patients, of which nine patients were treated with ZSP1601 50 mg QD, 50 mg BID, or 100 mg BID, and three patients received matching placebo orally once or twice daily for 28 days. Patient compliance was monitored in this study. Briefly, at the research center, two researchers were responsible for the study medication administration at a fixed time. Before discharge from the research center, patients were instructed to take the study medication at home and record the medication status. At each time when the study subject returned to the research center for a visit, the researchers verified the medication status. Immediately upon completion of the 28-day treatment, patients received treatment-free follow-up for 14 days.