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Trial registered on ANZCTR


Registration number
ACTRN12618000582257
Ethics application status
Approved
Date submitted
10/04/2018
Date registered
16/04/2018
Date last updated
22/04/2020
Date data sharing statement initially provided
1/07/2019
Date results information initially provided
1/07/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
A Dose-Escalation Safety Study of Yindan Softgels in Healthy Subjects
Scientific title
A Dose-Escalation Safety Study of Yindan Softgels in Healthy Subjects
Secondary ID [1] 294330 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
unstable angina pectoris of coronary heart disease (CHD) 304926 0
carotid atherosclerosis 304927 0
ischemic stroke sequelae 304928 0
Condition category
Condition code
Cardiovascular 304253 304253 0 0
Coronary heart disease
Cardiovascular 304254 304254 0 0
Diseases of the vasculature and circulation including the lymphatic system
Stroke 304256 304256 0 0
Ischaemic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a MTD study to assess safety and tolerance and to determine the maximum tolerated dose of M8.
There are 5 dosing cohorts (2.4g (6 capsules), 4.8g (12 capsules), 7.2g (18 capsules), 9.6g (24 capsules), 12g (30 capsules), orally, single dose). Each cohort consists of 8 subjects who will be randomized to receive active (N=6) or placebo (N=2). Each subject will receive only one dose, starting with the initial dose of 2.4g (6 capsules).
If less than two subjects who have taken M8 experience a DLT or other safety related issue in a cohort, the next dose-escalation cohort will be enrolled after overall safety evaluation. Overall safety evaluation will be performed by the Safety Review Team (SRT), including investigators and Medical Monitor from the CRO and Sponsor, based on physical examination, ECG and laboratory assessments, including hematology, biochemistry, urinalysis and coagulation tests.
If the previous dose was not well tolerated, after reviewing the safety data, and discussions between the Investigators, Medical Monitors from CRO and Sponsor, the same dose level may be repeated. If this dose level is well tolerated, the study will continue to the next higher dose. If this dose level is not well tolerated again, the MTD is defined at the prior lower dose level and the dose escalation will be stopped.
Intervention code [1] 299252 0
Treatment: Drugs
Comparator / control treatment
2 of 8 subjects in each cohort will be administered with placebo.
It is a soft capsule made from corn starch, and adding non-active excipients: beeswax, soybean lecithin, soybean oil.
Control group
Placebo

Outcomes
Primary outcome [1] 303539 0
To evaluate the safety and tolerability of M8 as defined by numbers and severity of adverse events.
Overall safety evaluation will be performed by the Safety Review Team (SRT), including investigators and Medical Monitor from the CRO and Sponsor, based on physical examination, ECG and laboratory assessments, including hematology, biochemistry, urinalysis and coagulation tests.
Timepoint [1] 303539 0
Subjects will be allowed to leave the unit after all the 48 h assessments have been completed on Day 3 and will return for follow-up assessments on Day 5.
Physical examination will be performed at on Day 3 (48.0 h) and Day 5 post each dose.
Vital signs will be performed on Day 1 (0 h, 0.5 h, 1.0 h, 2.0 h, 6.0 h, 12.0 h), Day 2 (24.0 h, 36.0 h), Day 3 (48.0 h) and Day 5 post each dose.
12-lead ECG will be performed at 12.0 h (Day 1), 24.0 h (Day 2), 48.0 h (Day 3) and/or Day 5 if applicable post each dose.
Biochemistry, hematology, urinalysis, coagulation tests will be performed at 12.0 h (Day 1) and 48.0 h (Day 3) post each dose.
AE/SAE will be recorded or reported and the event shall be closely monitored up to its resolution.
Secondary outcome [1] 339239 0
No secondary outcome
Timepoint [1] 339239 0
No secondary outcome

Eligibility
Key inclusion criteria
1) Non-smoking male or female within the age range of 18 to 45 years.
2) Body Mass Index (BMI = weight/height2) greater than or equal to 18.0 kg/m2 and less than or equal to 30.0 kg/m2.
3) Healthy adult with no current medical problems or significant chronic diseases as determined by the investigators based on medical history, physical examination and laboratory assessments;
4) Female subjects who are surgically sterile for at least 6 months or who are willing to use at least two clinically or medically approved contraceptive methods for at least 28 days prior to the drug administration, during the study and up until 1 month after the drug administration to avoid pregnancy.
5) Availability of the subject for his/her study period and willingness of the subject to adhere to protocol requirements, as evidenced by a signed ICF.
Minimum age
18 Years
Maximum age
45 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Subjects meeting any one of the following criteria will be excluded from the
study:
1) Known history or presence of cardiac, pulmonary, gastrointestinal, endocrine, musculoskeletal, neurological, hematological, liver or kidney disease, unless deemed not clinically significant by the Investigators.
2) With a family history (1st degree relative) of heart attack or stroke diagnosed by clinical findings only.
3) Any history or evidence of psychiatric or psychological disease (including depression) unless deemed not clinically significant by the investigators.
4) Known history of frequent headaches or migraines occurred daily or several times per week.
5) Known history of serious head injuries, seizures, or of any eating disorders such as bulimia or anorexia nervosa.
6) Any clinically significant illness within 4 weeks prior to this study.
7) Known history or presence of food allergies (including lactose or gluten intolerance), or any condition known to interfere with the distribution, metabolism, or excretion of drugs.
8) Any history of severe allergic reaction (including drugs, food, insect bites, environmental allergens).
9) Subjects with a recent history (within 24 months prior to the screening visit) of alcoholism or known drug dependence, at the discretion of the investigator;
10) Known to have hepatitis or who are carrier of the hepatitis B (hepatitis B surface antigen, HBsAg positive), or hepatitis C (hepatitis C antibody positive), or HIV antigens and/or antibodies tests are positive;
11) Pregnancy or lactation;
12) Subjects with positive urine cotinine, urine drug screen and/or alcohol breath test;
13) Use of any prescription medication within 30 days preceding the drug administration of the study.
14) Use of any monoamine oxidase (MAO) inhibitor drugs such as phenelzine (Nardil®) or tranylcypromine (Parnate®) within 30 days preceding drug administration of this study and until 14 days after the drug administration.
15) Use of over-the-counter (OTC) medication or other herbal based drugs or dietary supplements (except for vitamin and protein shakes) within 30 days prior to the study drug administration (except for contraceptive products).
16) Participation in a clinical trial with an investigational drug within 30 days prior to dosing.
17) Who has donated blood within 56 days (8 weeks) prior to the study drug administration.
18) Who has participated as a plasma donor in a plasmapheresis program within 30 days prior to the study drug administration.
19) Intolerance to venipuncture.
20) In the opinion of the investigators, subjects with medical history or other factors which may interfere with the study.

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)
Sealed opaque envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software
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
Intervention assignment
Other
Other design features
Eligible subjects will be sequentially enrolled into 5 dosing cohorts. Each cohort consists of 8 subjects who will be randomized to receive active (N=6) or placebo (N=2). The study will start with the lowest dose level given to the first cohort of eight subjects. After satisfactory review of the available safety and toleration data, the next dose level will be processed if the previous dose was well tolerated. Not more than one dose group is allowed to be administered at one time.
Phase
Phase 1
Type of endpoint(s)
Safety
Statistical methods / analysis
Descriptive statistics will be performed for safety data (AE/SAE, 12-lead ECG, physical examinations, vital signs and laboratory tests). The current version of the MedDRA will be used to code all AEs.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 16538 0
Q-Pharm Pty - Clive Berghofer Research Centre (CBCRC) - Herston
Recruitment postcode(s) [1] 30094 0
4006 - Herston

Funding & Sponsors
Funding source category [1] 297643 0
Commercial sector/Industry
Name [1] 297643 0
Guizhou Bailing Group Pharmaceutical Co., Ltd.
Address [1] 297643 0
Xihang Ave. Anshun Economic and Technological Development Area, Guizhou, 561000
Country [1] 297643 0
China
Primary sponsor type
Commercial sector/Industry
Name
Axeon Research (Au) Pty Ltd.
Address
15 Burke Rd, Malvern East, Victoria, Australia, 3145
Country
Australia
Secondary sponsor category [1] 298229 0
None
Name [1] 298229 0
Address [1] 298229 0
Country [1] 298229 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298728 0
Bellberry Human Research Ethics Committee
Ethics committee address [1] 298728 0
129 Glen Osmond Road, Eastwood, South Australia 5063
Ethics committee country [1] 298728 0
Australia
Date submitted for ethics approval [1] 298728 0
04/10/2017
Approval date [1] 298728 0
26/02/2018
Ethics approval number [1] 298728 0
2017-09-680

Summary
Brief summary
The study is a single-center, double-blind, dose-escalation, single-dose design to assess safety and tolerance of M8 and to identify a dose range for phase II study and to determine the maximum tolerated dose (MTD) of M8. M8 is expected to be indicated for the treatment of unstable angina pectoris of coronary heart disease (CHD), carotid atherosclerosis, and ischemic stroke sequelae.
Forty (40) healthy subjects will be randomized with 5 dose level, 8 subjects per dose level (cohort). Eligible subjects will be sequentially enrolled into 5 dosing cohorts (2.4g (6 capsules), 4.8g (12 capsules), 7.2g (18 capsules), 9.6g (24 capsules), 12g (30 capsules), orally, single dose). The study will start with the lowest dose level given to the first cohort of eight subjects. Eligible subjects will be admitted to the unit on Day -1 and conduct all qualification assessments. Subjects will be allowed to leave the unit after all the 48 h assessments have been completed on Day 3 and will return for follow-up assessments on Day 5.
After satisfactory review of the available safety and toleration data, the next dose level will be processed if the previous dose was well tolerated. If the previous dose was not well tolerated, after reviewing the safety data, and discussions between the Investigators, Medical Monitors from CRO and Sponsor, the same dose level may be repeated. If this dose level is well tolerated, the study will continue to the next higher dose. If this dose level is not well tolerated again, the MTD is defined at the prior lower dose level and the dose escalation will be stopped.
Descriptive statistics will be performed for safety data (AE/SAE, 12-lead ECG, physical examinations, vital signs, and laboratory tests). The current version of the MedDRA will be used to code all AEs.
Update Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 78038 0
Dr Paul Griffin
Address 78038 0
Level 5, Clive Berghofer Cancer Research Centre, 300 Herston Road, Herston, Queensland, 4006
Country 78038 0
Australia
Phone 78038 0
+61 7 3845 3636
Fax 78038 0
Email 78038 0
P.Griffin@qpharm.com.au
Contact person for public queries
Name 78039 0
Ms Helen Han
Address 78039 0
Axeon Biomedicine Globalization CO., LTD
No.1 Tingjiang Road, Beichen District, Tianjin, 300410
Country 78039 0
China
Phone 78039 0
+86 22 8634 3704
Fax 78039 0
Email 78039 0
hanwei@axeon.org
Contact person for scientific queries
Name 78040 0
Dr Xuefeng Su
Address 78040 0
Axeon Research Corporation
9400 Key West Avenues, Rockville, Maryland, 20850.
Country 78040 0
United States of America
Phone 78040 0
+1 301 978 3908
Fax 78040 0
Email 78040 0
Xuefeng.Su@axeon-us.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
The study is the material for drug administration registration and should be kept confidential before IND submission.
What supporting documents are/will be available?
No other documents available
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
No
Results – basic reporting
Results – plain English summary