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Trial registered on ANZCTR


Registration number
ACTRN12616000451404
Ethics application status
Approved
Date submitted
23/03/2016
Date registered
7/04/2016
Date last updated
22/03/2017
Type of registration
Retrospectively registered

Titles & IDs
Public title
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
Scientific title
A Phase I, Randomized, Double-Blind, Placebo-Controlled, Dose Escalation
Study of the Safety, Tolerability, and Pharmacokinetics of HMPL-689 in Healthy Adult
Volunteers
Secondary ID [1] 288836 0
2015-689-00AU2
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
B-cell Non-Hodgkin Lymphomas 298116 0
Condition category
Condition code
Cancer 298281 298281 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 298282 298282 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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)
Intervention code [1] 294289 0
Treatment: Drugs
Comparator / control treatment
Study is placebo-controlled. Placebo is formulated as a matching HMPL-689 capsule for oral use.
Control group
Placebo

Outcomes
Primary outcome [1] 297768 0
To evaluate the safety and tolerability of a single dose of HMPL-689 in healthy adult volunteers. This outcome will be assessed by conducting regular ECG and vital signs (triplicate blood pressure, heart rate and oral body temperature) assessments, analysis of blood samples for laboratory safety tests (hematology, coagulation, clinical chemistry and creatine phosphokinase) and urinalysis, regular physical examinations, semen tests and regular review of adverse events and concomitant medication throughout the trial.
Timepoint [1] 297768 0
Safety and tolerability assessments are conducted at the following timepoints:
1. ECG and vital signs (triplicate blood pressure, heart rate and oral body temperature) measured on Days 1, 2, 3, 7, 15 and 28 of the study
2. Blood samples for laboratory safety tests (hematology, coagulation, clinical chemistry and creatine phosphokinase) and urinalysis conducted on Days 2, 3, 7, 15 and 28 of the study.
3. Physical examination conducted on Days 3, 7, 15 and 28 of the study.
4. Semen test conducted on Days 15 and 28 of the study.
5. Adverse event and concomitant medication review conducted from Days 1-28 of the study.
Secondary outcome [1] 322162 0
To determine the pharmacokinetic profile of single oral doses of HMPL-689 in healthy adult volunteers. This outcome will be assessed by collecting blood samples for pharmacokinetic analysis throughout the trial.
Timepoint [1] 322162 0
Blood samples for pharmacokinetic analysis will be collected at the following timepoints:
a) 30 mins prior to study drug administration
b) 30 mins after study drug administration
c) 1 hour after study drug administration
d) 2 hours after study drug administration
e) 4 hours after study drug administration
f) 6 hours after study drug administration
g) 8 hours after study drug administration
h) 12 hours after study drug administration
i) 24 hours after study drug administration
j) 36 hours after study drug administration
k) 48 hours after study drug administration
l) 72 hours after study drug administration
m) 96 hours after study drug administration
n) 144 hours after study drug administration

Eligibility
Key inclusion criteria
1. Informed consent must be obtained in writing for all subjects before enrollment into the study
2. Healthy male subjects aged 18 to 45 years inclusive at the time of screening
3. Body mass index greater than or equal to 19.0 and less than or equal to 30.0 kg/m2
4. 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.
Minimum age
18 Years
Maximum age
45 Years
Sex
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Family history of premature coronary artery disease
2. History of immunosuppression or opportunistic infections or receipt of a live virus vaccination within the 3 months prior to screening
3. Clinically significant abnormalities as determined by medical history, physical examination, or laboratory tests, especially for liver or renal function
4. Clinically significant findings in ECG, blood pressure, and heart rate, as determined by the Investigator
5. 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
6. Any medical condition requiring regular use of medication
7. Exposure to prescription medications within 30 days prior to Day1
8. Exposure to any other medication, including over-the-counter medications, herbal remedies, and vitamins 14 days prior to first dose (except for paracetamol)
9. Participation in another clinical trial with any investigational drug within 30 days of Day 1
10. Treatment in the previous 3 months with any drug known to have a well-defined potential for toxicity to a major organ
11. Current smoker of more than 10 cigarettes or equivalent/day prior to commencing the study and unable to completely stop smoking during the study
12. Symptoms of a clinically significant illness in the 3 months before the study
13. Presence or sequelae of gastrointestinal, liver, or kidney disease, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs
14. Chronic constipation or diarrhea, irritable bowel syndrome, inflammatory bowel disease, hemorrhoids, or anal diseases with regular or recent presence of blood in the feces
15. 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
16. 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)
17. Current evidence of drug abuse or history of drug abuse within 1 year before randomization/ enrollment
18. 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
19. 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Other
Other design features
Single ascending dose design
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis
Stastitical analyses will generally be descriptive in nature. Demographics and other baseline characteristics, enrollment, major protocol violations and discontinuations from the study will be summarized descriptively by dose group. For continuous variables, descriptive statistics will include the number of subjects (n), mean, standard deviation, median, minimum and maximum. For categorical variables, descriptive statistics will include the number and percentage of subjects in each category.
Sample Size Justification:
This is the first investigation of HMPL-689 in humans. The sample size is based on currently accepted standards for this type of investigation. Approximately 40-60 healthy adult male subjects will participate in the study .

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
23/03/2016
Date of last participant enrolment
Anticipated
1/07/2016
Actual
8/08/2016
Date of last data collection
Anticipated
Actual
16/10/2016
Sample size
Target
56
Accrual to date
Final
48
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 5481 0
Nucleus Network - Melbourne
Recruitment postcode(s) [1] 12966 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 293195 0
Commercial sector/Industry
Name [1] 293195 0
Hutchison MediPharma Ltd
Country [1] 293195 0
China
Primary sponsor type
Commercial sector/Industry
Name
INC Research Australia Pty Ltd
Address
159 Port Road Hindmarsh
South Australia 5007
Australia
Country
Australia
Secondary sponsor category [1] 291999 0
None
Name [1] 291999 0
Address [1] 291999 0
Country [1] 291999 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294683 0
The Alfred Hospital Ethics Committee
Ethics committee address [1] 294683 0
Office of Ethics and Research Governance Ground Floor, Linay Pavilion
The Alfred
PO Box 315 Prahran VIC 3181
Ethics committee country [1] 294683 0
Australia
Date submitted for ethics approval [1] 294683 0
11/01/2016
Approval date [1] 294683 0
26/02/2016
Ethics approval number [1] 294683 0
Project No: 9/16

Summary
Brief 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
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 64646 0
Dr Jason Lickliter
Address 64646 0
Nucleus Network
Level 5, Burnet Building, AMREP Precinct,
89 Commercial Road, Melbourne VIC 3004
Country 64646 0
Australia
Phone 64646 0
+61 3 9076 8960
Fax 64646 0
Email 64646 0
[email protected]
Contact person for public queries
Name 64647 0
Biljana Georgievska
Address 64647 0
Nucleus Network
Level 5, Burnet Building, AMREP Precinct,
89 Commercial Road, Melbourne VIC 3004
Country 64647 0
Australia
Phone 64647 0
1800 243 733
Fax 64647 0
Email 64647 0
[email protected]
Contact person for scientific queries
Name 64648 0
Biljana Georgievska
Address 64648 0
Nucleus Network
Level 5, Burnet Building, AMREP Precinct,
89 Commercial Road, Melbourne VIC 3004
Country 64648 0
Australia
Phone 64648 0
+61 3 9076 9017
Fax 64648 0
Email 64648 0
[email protected]

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No Supporting Document Provided



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