A Study of the Safety, Tolerability and Pharmacokinetics of HMPL-523
Condition: Rheumatoid Arthritis (RA)
MeSH terms: Arthritis; Arthritis, Rheumatoid
Study type: Interventional
Phase: Phase 1

Summary: 
      The primary objective of this study is to assess the safety and tolerability of a single dose
      of up to 800 mg in Part A (evaluated in planned steps of 5, 20, 50, 100, 200, 300 mg under
      fasted conditions, followed by 300, 400, 600 and 800 mg HMPL-523 under fed conditions of a
      standard meal, followed by multiple doses of 200, 300, 400 and 500 mg of HMPL-523 in Part B,
      in healthy male volunteers.

      The secondary objective is to determine the pharmacokinetic profile of single (Part A) and
      multiple (Part B) oral doses of HMPL-523 in healthy male volunteers and to determine the
      preliminary effect of food (Part C）
    

Detailed description: 
      This is a Phase I study with 3 parts:

      Part A: Double blind, randomized, placebo-controlled, dose-escalating, single dose study in
      healthy volunteers.

      Part B: Double blind, randomized, placebo-controlled, dose-escalating, multiple dose study in
      healthy volunteers.

      Part C: Open labeled, single dose, cross-over, preliminary food effect study in healthy
      volunteers.

      Number of subjects:

      Part A: 80 healthy volunteers (10 cohorts of 8 subjects) Part B: About 40 healthy volunteers
      (5 cohorts of 8 subjects) In Part B, the multiple doses are 200(Cohort B1), 300(Cohort B2),
      400(Cohort B3), and 500 mg(Cohort B4) and 8 subjects will be enrolled in each cohort. At dose
      200mg, additional cohort (Cohort B1a) with 8 subjects needs to be enrolled based on the
      clinical data (safety, tolerability, available PK data and clinical laboratory values). The
      decision is made jointly by the Principal Investigator and the sponsor. Within each cohort, 6
      subjects will receive HMPL-523 and 2 subjects will receive placebo Part C: 6 healthy
      volunteers (1 cohort; all will receive HMPL-523 100 mg).

      Treatments:

      -Part A: Single Ascending Dose.Subjects will receive a single dose of up to 800 mg HMPL-523
      or matching placebo during Day 1. The planned dose levels are: 5, 20, 50,100, 200, 300 mg
      under fasted conditions, followed by 300, 400, 600, 800 mg under fed conditions with a
      standard meal, according to the randomization schedule. Dose levels may be repeated, reduced
      or administered as a split dose if deemed appropriate by the Principal Investigator and
      Sponsor's medical Expert.

      For Cohort 1 a sentinel group (1 HMPL-523 and 1 placebo) will be dosed at 5 mg HMPL-523, 24
      hours prior to the planned dosing of the remaining six subjects. Dosing of the remaining six
      will be based on investigator judgment. The decision to dose escalate will be made jointly by
      the Principal Investigator and the sponsor based on the clinical data (safety, tolerability,
      available PK data and clinical laboratory values).

      -Part B: Multiple Ascending Dose (MAD). Part B of the study has been designed to assess the
      effects of multiple ascending doses of HMPL-523 in healthy volunteers. The total daily doses
      and dosing regimen for Part B have been determined as 200, 300,400 and 500 mg based on the
      review of safety and PK data from Part A, made jointly by the Principal Investigator and the
      sponsor. The dose will be the same or less than one already administered to participants in
      Part A. Because dog has similar protein binding to humans, we will closely monitor the
      clinical safety and laboratory result when the AUC is getting to 2085 h*ng/mL, which is the
      NOAEL AUC in dogs. Further dose escalation will be based on clinical safety and discussion
      between the sponsor and the investigators.

      Part C: Preliminary Food Effect Study. Part C of the study has been designed to preliminarily
      assess the effect of food on the pharmacokinetics of HMPL-523 in healthy volunteers. Subjects
      will first receive a single dose of HMPL-523 100mg under fasted conditions (Period 1) and
      then following a washout period of 7 days, will receive a single dose of HMPL-523 100mg after
      consuming a standard high fat breakfast (fed conditions) (Period 2). Part C may be conducted
      at any time, provided 100 mg has been deemed safe in Part A.

      Safety data:

      The following safety evaluations will be performed during the study: Adverse events, physical
      examination, clinical safety laboratory (hematology, clinical chemistry, urinalysis), body
      weight, oral temperature, triplicate blood pressure and heart rate , and ECG .
    

Intervention name(s): HMPL-523; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): HMPL-523: Oral administration with a single dose of 5, 20, 50, 100, 200 and 300 mg in Part A, followed by multiple doses of selected strength in Part B Other Name: NA; Oral administration
Other intervention name(s): HMPL-523 acetate; HMPL-523 Placebo
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment