A Dose-Escalation Safety Study of Yindan Softgels in Healthy Subjects

• Register: ANZCTR
• Last refreshed on: 1 November 2021
• Main ID: ACTRN12618000582257
• Date of registration: 16/04/2018
• Prospective Registration: Yes
• Primary sponsor: Axeon Research (Au) Pty Ltd.
• 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
• Date of first enrolment: 13/09/2018
• Target sample size: 40
• Recruitment status: Completed
• URL: https://anzctr.org.au/ACTRN12618000582257.aspx
• Study type: Interventional
• Study design: Purpose: Treatment; Allocation: Randomised controlled trial; Masking: Blinded (masking used);Assignment: Other;Type of endpoint: Safety;
• Phase: Phase 1

Countries of recruitment

Australia

Contacts

• Name: Ms Tina He

• Name: Dr Xuefeng Su

Key inclusion & exclusion criteria

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.
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.

Age minimum: 18 Years
Age maximum: 45 Years
Gender: Both males and females

Health Condition(s) or Problem(s) studied

Stroke - Ischaemic

Cardiovascular - Coronary heart disease

Cardiovascular - Diseases of the vasculature and circulation including the lymphatic system

unstable angina pectoris of coronary heart disease (CHD);carotid atherosclerosis;ischemic stroke sequelae;
unstable angina pectoris of coronary heart disease (CHD)
carotid atherosclerosis
ischemic stroke sequelae

Intervention(s)

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.

Primary Outcome(s)

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.[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(s)

No secondary outcome[No secondary outcome]

Secondary ID(s)

Nil known

Source(s) of Monetary Support

Guizhou Bailing Group Pharmaceutical Co., Ltd.

Ethics review

Status: Approved
Approval date: 26/02/2018
Contact:

Bellberry Human Research Ethics Committee

Results

• Results available: Yes
• Date Posted: 01/07/2019
• Date Completed: 25/05/2019