Tolerability, exposure and pharmacokinetics in healthy subjects of a Chinese herbal medicine MaZiRenWan (MZRW): Study protocol for a randomized open-labelled, three-arm phase 0/1 clinical trial

Introduction The formula of MaZiRenWan (MZRW) has been commonly used in Chinese medicine to treat constipation. Our previous studies have showed benefits in terms of increased bowel movement, relief in the severity of constipation and straining of evacuation when compared with placebo. However, the lack of studies on its safety, tolerability, system exposure and pharmacokinetics making it difficult to obtain a consistent picture of its mechanism of action. Methods/design This is a randomized, open-labelled, three-arm phase 0/1 clinical trial. After the run-in period, eligible healthy subjects will be randomized assigned in a ratio of 1:1:1 to receive 5.0 g, 7.5 g, 10 g q.d. of MZRW. The primary outcome will be the number of participants with adverse events as a measurement of safety and tolerability among three doses of MZRW. Secondary outcome will be the clearness of pharmacokinetic parameters of main active ingredients in human sample, include the area under the plasma concentration-time curve (AUC), the peak plasma concentration of an ingredient after administration (C_max), the time to reach C_max (t_max), the elimination half-life (t_1/2) and clearance (CL). Ethics and dissemination The study was approved by Hong Kong Baptist University Ethics Committee on the Use of Human Subjects for Teaching and Research (Approval no. HASC/13-14/0017) and was registered with an identifier (NCT02359396) in Clinical Trial.gov. The potential risks incurred by study participants will be reported to the public and the study results will be released to the investigators, patients and the general medical community.