A Study of HMPL-689 in Healthy Volunteers

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and tolerability of a single dose of HMPL-689 in healthy volunteers To determine the pharmacokinetic profile of single oral doses of HMPL-689 in healthy volunteers

Detailed Description
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Subjects will receive a single dose of HMPL-689 or matching placebo during Day 1. The planned dose levels are: 1, 2.5, 5, 10, 20, 25 and 30 mg (about 7 cohorts of 8 subjects). In each dose cohort, 8 subjects will be randomized to receive HMPL-689 (6 subjects) or placebo (2 subjects) under fed condition with a standard meal. For the first dose Cohort (1 mg), a sentinel group of 2 subjects (1 HMPL-689 and 1 placebo) will be dosed 24 hours prior to the planned dosing of the remaining six subjects. The decision of dose escalation or study termination 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). Any dose level may be repeated, reduced or split into 2 doses if deemed appropriate by the Principal Investigator and Sponsor's medical Expert.

Official Title
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A Phase I,Randomized,Double Blinded,Placebo-controlled,Dose-escalating Study of the Safety,Tolerability and Pharmacokinetics of HMPL-689 in Healthy Volunteers

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: HMPL-689
* Drug: HMPL-689 placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent must be obtained in writing for all subjects before enrollment into the study Healthy male subjects aged 18 to 45 years inclusive at the time of screening Body mass index ≥19.0 and ≤ 30.0 kg/m2 Willing to comply with the contraceptive requirements of the study and must not donate sperm during the study or for 3 months afterwards. Subjects must agree to use a condom or to abstain from sexual intercourse throughout the trial and for 30 days afterwards Exclusion Criteria: Family history of premature Coronary Heart Disease History of immunosuppression or opportunistic infections or receipt of a live virus vaccination within the 3 months prior to screening Clinically significant abnormalities as determined by medical history physical examination, or laboratory test, especially for liver and renal function Clinically significant findings in ECG, blood pressure and heart rate, as determined by the Clinical Investigator Subjects at risk for tuberculosis (TB), which is defined as: Current clinical or laboratory evidence of active TB History of TB A positive QuantiFERON® test at screening or within 6 months prior to Day 1 Any medical condition requiring regular use of medication Exposure to prescription medications within 30 days prior to Day 1 Exposure to any other medication, including over-the-counter medications, herbal remedies and vitamins 14 days prior to first dose (except for paracetamol) Participation in another clinical trial with any investigational drug within 30 days of Day 1 Treatment in the previous 3 months with any drug known to have a well-defined potential for toxicity to a major organ Current smoker of more than 10 cigarettes or equivalent/ day prior to commencing the study and unable to completely stop smoking during the study Symptoms of a clinically significant illness in the 3 months before the study Presence or sequelae of gastrointestinal, liver or kidney disease, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs Chronic constipation or diarrhea, irritable bowel syndrome, inflammatory bowel disease, hemorrhoids or anal diseases with regular or recent presence of blood in feces History of significant allergic disease (e.g. allergic to medications) and acute phase of allergic rhinitis in the previous 2 weeks before randomization/ enrollment or any food allergy Clinically significant history of liver disease, including cirrhosis, current alcohol abuse, or current known active infection with HIV, hepatitis B virus (HBV), or hepatitis C virus (HCV) Current evidence of drug abuse or history of drug abuse within one year before randomization/ enrollment Mental condition rendering the subject incapable to understand the nature, scope, and possible consequences of the study Unlikely to comply with the clinical study protocol; e.g. uncooperative attitude, inability to return for follow-up visits, and improbability of completing the study Subject is the investigator or any sub-investigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the protocol

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Health Services Research
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HMPL-689<br>Subjects will receive a single dose of HMPL-689 or matching placebo on Day 1. The planned dose levels in ascending order are: 1, 2.5, 5, 10, 20, 25 and 30 mg (7 dose cohorts with 8 subjects in each cohort). Within each cohort, randomization ratio of 3:1 is followed to dose 6 subjects with HMPL-689 and 2 subjects with placebo. | Drug: HMPL-689<br>* selective PI3Kδ inhibitor<br>* Other names: Huchison Medipharma;|
| Placebo Comparator: HMPL-689 placebo<br>Subjects will receive a single dose of HMPL-689 or matching placebo on Day 1. The planned dose levels in ascending order are: 1, 2.5, 5, 10, 20, 25 and 30 mg (7 dose cohorts with 8 subjects in each cohort). Within each cohort, randomization ratio of 3:1 is followed to dose 6 subjects with HMPL-689 and 2 subjects with placebo. | Drug: HMPL-689 placebo<br>* placebo of HMPL-689<br>* Other names: Huchison Medipharma;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| dose limited toxicities evaluated with NCI CTCAE v4.03 | Incidence of dose limited toxicities and associated dose of HMPL-689 | within 28 days after the first dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| maximum plasma concentration calculated with Blood samples | Blood samples will be taken to measure the levels of study drug | within 29 days after the first dose | 
| time to reach maximum concentration calculated with Blood samples | Blood samples will be taken to measure the levels of study drug | within 29 days after the first dose |