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A phase I study of M875(single-dose study and food-effect study)

A phase I study of M875(single-dose study and food-effect study)

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(1) Single-dose study This study was conducted in 40 healthy Japanese adult subjects aged 20 to 45 years. (2) Food-effect study This study was conducted in 6 healthy Japanese adult subjects aged 20 to 45 years.

(1) Single-dose study Of the 114 subjects who provided written informed consent to participate in the study, 40 were enrolled and received the investigational drug (active drug [M875T2 or M875T3] or placebo tablet [M875T4]). The breakdown of enrolled subjects was as follows: Step 1 (dose: 15 mg) included 6 subjects receiving the active drug (M875T2) and 2 receiving the placebo tablet (M875T4); Step 1 (dose: 30 mg) included 6 subjects receiving the active drug (M875T3) and 2 receiving the placebo tablet (M875T4); Step 2 (dose: 60 mg): 6 subjects received the active drug (M875T3), 2 subjects received the placebo tablet (M875T4), Step 3 (dose: 120 mg): 6 subjects received the active drug (M875T3), 2 subjects received the placebo tablet (M875T4), Step 4 (dose: 180 mg): 6 subjects administered active drug (M875T3), 2 subjects administered placebo tablets (M875T4). In this trial, no subjects violated step transition criteria or discontinued participation; all enrolled subjects completed the trial. (2) Food -effect study Of the 17 subjects who provided written informed consent to participate in the trial, the 6 registered subjects were assigned to Groups A and B (3 subjects each) and administered the investigational drug (M875T3). In this trial, there were no discontinuations, and all registered subjects completed the trial.

(1) Single-dose Study In the single-dose study, 8 adverse events were observed in 8 subjects; all were non-serious and mild. The breakdown of adverse events was 4 events in 4 of 30 subjects (13.3%) in the active-drug group and 4 events in 4 of 10 subjects (40%) in the placebo group.Among the adverse events, events for which the investigator could not rule out a relationship with the study drug (side effects) were observed in 1 placebo-treated subject (10.0%) and 1 active drug-treated subject (3.3%). All recovered without treatment. No deaths, serious adverse events, adverse events leading to discontinuation, or other significant adverse events were observed. Furthermore, no notable abnormalities were observed in clinical laboratory tests or physiological examinations beyond those reported as adverse events. (2) Food-effect study In the food effect study, adverse events were observed in 1 of 6 subjects (16.7%) receiving the investigational drug. The adverse events that occurred were non-serious and mild. No side effects were observed in the food effect study. No deaths, serious adverse events, adverse events leading to discontinuation, or other important adverse events were observed. Furthermore, no noteworthy abnormalities were observed in clinical laboratory parameters or physiological tests.

(1)Single-dose Study To evaluate dose proportionality, linear regression analysis (power model) was conducted using logarithmically transformed pharmacokinetic parameters (Cmax, AUC0-t, and AUC0-inf)for the four components (Cepharanthine, Isotetrandrine, Cycleanine, and Berbamine). The results (95% CI) of the linear regression analysis (power model) using logarithmic transformations of the pharmacokinetic parameters for the four components are shown in 2-1, Other Attachments 1 (Table 1). For isotetrandrine, cycleanine, and berbamine, no dose proportionality was observed for any of the pharmacokinetic parameters (Cmax, AUC0-t, and AUC0-inf). For cepharanthine, although no dose proportionality was observed for Cmax and AUC0-t, a tendency for AUC0-inf to increase in proportion to the dose was observed. In addition, for pharmacokinetic parameters other than Cmax, AUC0-t, and AUC0-inf, a Kruskal-Wallis test was conducted for Tmax between doses, a one-way analysis of ANOVA was conducted for MRT0-t and CL/F between doses, and a one-way analysis of ANOVA was conducted for t1/2 for reference. The results (p-values) of the Kruskal-Wallis test and one-way ANOVA for the four components are shown in 2-1 and Other Attachments1(Table 2). Dose proportionality was observed for Tmax in all four components. For CL/F, dose proportionality was observed for Cepharanthine and Cycleanine, but uniformity was exhibited across doses for Isotetrandrine and Berbamine. For all four compounds, MRT0-t and t1/2 showed uniformity across doses. (2)Food-effect study A summary of the pharmacokinetic parameters for the four components is presented in Section 2-1, Other Attachments 1 [Table 3]. Results of the food effect study showed that plasma drug concentrations of the four components (Cepharanthine, Isotetrandrine, Cycleanine, Berbamine) exhibited similar trends following both fasting and postprandial administration. Similarly, urinary excretion rates for the four components also showed comparable trends between fasting and postprandial administration. Analysis of variance for the pharmacokinetic parameters of Cepharanthine (Cmax, AUC0-inf, Tmax, and t1/2) showed no significant interaction effects for Cmax, AUC0-inf, and t1/2 (group or carryover effect), administration method , and timing. For Tmax, significant differences were observed for the variability factors administration method and timing, but no significant difference was observed for group or carryover effect. Therefore, for Cepharanthine, Cmax, AUC0-inf, and t1/2 were not affected by differences in administration method (fasting or postprandial administration), but Tmax was suggested to be affected by differences in administration method. Analysis of variance for pharmacokinetic parameters (Cmax, AUC0-inf, Tmax, and t1/2)of isotetrandrine showed no significant differences for Cmax and t1/2 based on either group or carryover effect or administration method, and timing. For AUC0-inf, a significant difference was observed for the variable Administration Method, but no significant differences were observed for Group or Carryover Effect or Period. For Tmax, a significant difference was observed for the variable administration method, but no significant differences were observed for group or carryover effect or period. Therefore, for Isotetrandrine, Cmax and t1/2 were not affected by differences in administration method (fasting vs. postprandial), but AUC0-inf and Tmax were suggested to be affected by differences in administration method. Analysis of variance for pharmacokinetic parameters (Cmax, AUC0-inf, Tmax, and t1/2)of Cyclanine showed no significant differences in Cmax, Tmax, and t1/2 for group or carryover effect No significant differences were observed for any of the variation factors:group or carryover effect, administration method, or timing. For AUC0-inf, a significant difference was observed for the variable timing , but no significant differences were observed for group or carryover effect or administration method. Therefore, for Berbamine, it was suggested that none of the pharmacokinetic parameters (Cmax, AUC0-inf, Tmax, and t1/2) were affected by differences in administration method (fasting vs. after a meal). Analysis of variance for pharmacokinetic parameters (Cmax, AUC0-inf, Tmax, and t1/2) in Berbamine showed no significant interaction effects for Cmax, AUC0-inf, Tmax, or t1/2, timing, and timing. Therefore, Berbamine demonstrated that none of the pharmacokinetic parameters-Cmax, AUC0-inf, Tmax, or t1/2 were affected by differences in administration method (fasting versus postprandial).

In single-dose studies, no dose proportionality was observed for any pharmacokinetic parameters of excluding cepharanthine . For cepharanthine, AUC0-inf showed a tendency to increase in proportion to the dose. While Tmax exhibited dose proportionality for all components, t1/2 remained consistent across dose levels.The results of the food effect study, food effect is not shown in all components.The safety of both trials has been confirmed.

July. 01, 2026

No

https://jrct.mhlw.go.jp/latest-detail/jRCT2071240065

Fujimoto Souichi

Medisa Shinyaku Inc.

5-2-27, Miyahara, Yodogawa-Ku, Osaka-Shi, Osaka

fujimoto.medisa@sawai.co.jp

Fujimoto Souichi

Medisa Shinyaku Inc.

5-2-27, Miyahara, Yodogawa-Ku, Osaka-Shi, Osaka

+81-6-6150-1107

fujimoto.medisa@sawai.co.jp

Complete

Oct. 02, 2024

Interventional

randomized controlled trial

double blind

placebo control

parallel assignment

other

(1)Japanese healthy adult male aged 20 or older and younger than 45 years at the time of signing informed consent.
(2) Persons who weighs between 50 kg and 80 kg.
(3)Body mass index(BMI) (Weight (kg)/(Height (m))2)between 18.5 and 25.0 (rounded down to the second decimal place)
(4)Persons who are judged by the principal investigator, etc. to be eligible as subjects for this study, taking into consideration the results of the screening test.
(5)Persons who are able to undergo the medical examinations and tests specified in the study protocol and report subjective symptoms, etc., in accordance with the compliance requirements during participation in the clinical trial.

(1)Persons with gastrointestinal, heart, liver, kidney, blood, or other diseases that may affect pharmacokinetics and safety, or with a history of such diseases.
(2)Persons with an ALT greater than 45 U/L on the screening test.
(3)Persons with WPW syndrome, complete right bundle branch block, or Brugada syndrome determined by 12-lead ECG in the screening test(including automatic device determination).
(4)Persons with a history of major surgery in the gastrointestinal tract area, such as gastrectomy, gastrointestinal suture, or intestinal resection (appendicectomy and inguinal hernia repair are acceptable).
(5)Persons with drug hypersensitivity or allergy to drugs.
(6)Alcohol or drug dependent persons.
(7)Received cephalantin within 12 weeks prior to study drug administration.
(8)Persons who participated in another clinical trial and received another investigational drug within 12 weeks prior to the administration of the investigational drug (in case of clinical trials of health food products, this is defined as within 4 weeks prior to the administration of the investigational drug).
(9)Persons from whom at least 200 mL or 400 mL of blood samples (e.g., blood donation) had been collected within 4 or 12 weeks prior to administration of the investigational drug, or who had donated blood component within 2 weeks prior to administration of the investigational drug.
(10)Persons with a confirmed positive immunological test in the screening test.
(11)Persons who are judged to be ineligible to participate in the clinical trial by the principal investigator, etc.

Male

Oral lichen planus

Single-dose study:Drug administration
Single oral dose of actual drug (M875T2 or M875T3) or placebo (M875T4) with 200 mL of water after fasting for at least 10 hours.
Food-effect study:Drug administration
Fasting: Single oral dose of M875T3 with 200 mL of water after fasting for at least 10 hours.
Postprandial dose: A single oral dose of the actual drug (M875T3) with 200 mL of water within 10 minutes after a high-fat meal consumed within 20 minutes.

Pharmacokinetics and safety

+81-92-283-7701

Aug. 29, 2024

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