A Study of the Safety, Tolerability and Pharmacokinetics of HMPL-523

Rheumatoid Arthritis (RA) Clinical Trial

Official title: A Phase I, Randomized, Double Blind, Placebo-controlled, Dose-escalating Study of the Safety, Tolerability and Pharmacokinetics of Single and Repeat Doses of HMPL-523

Status Completed

Clinical Trial 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）

Clinical Trial 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 . ;

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis, Rheumatoid
• Rheumatoid Arthritis (RA)

• NCT number: NCT02105129
• Study type: Interventional
• Source: Hutchison Medipharma Limited
• Status: Completed
• Phase: Phase 1
• Start date: May 2014
• Completion date: December 2015