A Phase I, Randomized, Placebo-Controlled Study to Assess the Safety, Tolerability, and Pharmacokinetics of single oral dose of HMPL-689 in Healthy Adult Participants
A Phase I, Randomized, Double-Blind, Placebo-Controlled, Dose Escalation Study of the Safety, Tolerability, and Pharmacokinetics of HMPL-689 in Healthy Adult Volunteers
INC Research Australia Pty Ltd
56 participants
Mar 23, 2016
Interventional
Conditions
Summary
This study aims to assess the safety, tolerability and pharmacokinetics of HMPL-689 in healthy adult volunteers. Who is it for? You may be eligible to join this study if you are a healthy adult aged between 18 and 45 years. Study details This study is evaluating safety of a new drug known as HMPL-689, that could be used for treatment of autoimmune diseases and B-cell mediated malignancies, in healthy adults. Participants will receive a single dose of HMPL-689 or matching placebo on Day 1 of their admission into the Phase 1 unit. 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 conditions with a standard meal. For the first dose cohort (1 mg), a group of 2 subjects (1 HMPL-689 and 1 placebo) will be dosed 24 hours prior to the planned dosing of the remaining 6 subjects. Decisions regarding escalation to the next dose or termination of the study 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) of each dose cohort. Any dose level maybe repeated or reduced if deemed appropriate by the Principal Investigator and Sponsor’s medical expert. The estimated study participation for each participant is approximately 5 weeks. Follow up and assessments performed over these 5 weeks include: a) Collection of medical history b) Alcohol breath testing c) Regular physical exams d) ECG and vital signs measurements e) Urine sample assessments for general heath, safety and testing for drugs of addiction f) Blood sample analysis for routine measurements including clinical laboratory safety testing and screening for HIV (AIDS virus), hepatitis and tuberculosis (TB) g) Semen sample analysis h) Pharmacokinetic blood sample collections to measure the amount of study drug in your blood i) Adverse events monitored throughout the treatment period j) Use of concomitant medications reviewed throughout the study
Eligibility
Inclusion Criteria4
- 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 greater than or equal to 19.0 and less than or equal to 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 Criteria22
- Family history of premature coronary artery 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 tests, especially for liver or renal function
- Clinically significant findings in ECG, blood pressure, and heart rate, as determined by the Investigator
- Subjects at risk for tuberculosis (TB), which is defined as:
- a. Current clinical or laboratory evidence of active TB
- b. History of TB
- c. A positive QuantiFERON (Registered Trademark) 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 Day1
- 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 the feces
- History of significant allergic disease (e.g. allergy 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 1 year before randomization/ enrollment
- Unlikely to comply with the clinical study protocol; e.g.,uncooperative attitude, inability to return for follow-up visits, and unlikely to complete 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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Interventions
Single oral dose of study drug (HMPL-689 or matching placebo) will be administered on Day 1 of participants' admission into the Phase 1 unit, 30 minutes after food intake (i.e., after consumption of a standard meal, approximately 240mL of water). Escalating double-blind doses of HMPL-689 or placebo will be administered in accordance with the randomization/enrollment schedule. The following cohorts are planned: Each cohort will consist of 8 participants, randomly assigned to HMPL-689 or placebo treatment in a ratio of 3:1 (i.e. 6 participants will receive HMPL-689 and 2 will receive matching placebo). The dose and dosing regimen have been selected as 1, 2.5, 5, 10, 20, 25 and 30 mg and will be carefully selected based on data from preceding cohorts. There will be 7 cohorts as below: Cohort 1: 1 mg (0.5mg capsule*2) Cohort 2: 2.5 mg (2.5mg capsule*1) Cohort 3: 5 mg (2.5mg capsule*2) Cohort 4: 10 mg (10mg capsule*1) Cohort 5: 20 mg (10mg capsule*2) Cohort 6: 25 mg (10mg capsule*2+2.5mg capsule*2) Cohort 7: 30 mg (10mg capsule*3)
Locations(1)
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ACTRN12616000451404