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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
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| HMPL-689 | Experimental | 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. |
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| HMPL-689 placebo | Placebo Comparator | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| HMPL-689 | Drug | selective PI3Kδ inhibitor |
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| 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 |
| 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 |
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Inclusion Criteria:
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:
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
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| Name | Affiliation | Role |
|---|---|---|
| Jason Lickliter | Nucleus Network Ltd | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Nucleus Network | Melbourne | Victoria | 3001 | Australia |
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| HMPL-689 placebo | Drug | placebo of HMPL-689 |
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Blood samples will be taken to measure the levels of study drug
| within 29 days after the first dose |