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