A SAD/MAD Study to Evaluate the Safety, Tolerability, PK of MT200605 in Healthy Subjects

Shaanxi Micot Pharmaceutical Technology Co., Ltd.61 enrolled

Overview

The goal of this randomized, double-blind, placebo control, Phase I clinical trial is to evaluate the Safety, Tolerability, and Pharmacokinetics after Single Ascending Dose (SAD) and multiple Ascending Dose (MAD) of MT200605 for Injection in Healthy Subjects. The main questions it aims to answer are: 1. The safety and tolerability of MT200605 injection in health subjects 2. The Pharmacokinetic characteristic of MT200605 injction in health subjects The study aims to recruit 60 health subjects and participants will be randomly allocate to two stages (SAD and MAD) with 36 subjects in SAD and 24 subjects in MAD stages. The placebo will be used in this study, and the researchers will compare the placebo and test article to see if the MT200605 will be safe or well tolerated.

Shaanxi Micot Technology Co. Ltd. is developing MT200605, a novel investigational synthetic small molecule tyrosine kinase B (TrkB) receptor agonist to mimic brain-derived neurotrophic factor (BDNF). It can directly bind to TrkB receptor to exert strong neuroprotective and nutritional effects and used for the indication of Treatment of brain tissue damage after cerebral ischemia-reperfusion and nerve repair after ischemic stroke. The goal of this randomized, double-blind, placebo control, Phase I clinical trial is to evaluate the Safety, Tolerability, and Pharmacokinetics after Single Ascending Dose (SAD) and multiple Ascending Dose (MAD) of MT200605 for Injection in Healthy Subjects. The study was divided into two stages including 5 groups in SAD stage and 3 groups in MAD stage. 4 subjects were in the first corhort (C1) of SAD stage while the rest of the corhorts were 8 cases. The MT200605 and Placebo will be administrated by Intravenous injection.The dose level in SAD will be 0.15 (C1), 0.3(C2), 0.6(C3), 0.9(C4), and 1.2(C5) mg/kg. The dose level will be adjusted based on the safety and PK data of the completed SAD corhort. The dose level in MAD will be 0.3(C6), 0.6(C7), and 1.2(C8) mg/kg. The dose level will be adjusted based on the safety and PK data of the completed SAD and MAD corhort.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Interventions

MT200605 for InjectionDRUG

Two stages (SAD, MAD) were designed in this study. For SAD, the MT200605 will single Intravenous (IV) infusion for 1h with the dose level as 0.15 mg/kg、0.3 mg/kg、0.6 mg/kg、0.9 mg/kg、1.2 mg/kg. For MAD, the participants will IV infusion of the MT200605 for 7 days with 2 times per day under the dose level of 0.3 mg/kg、0.6 mg/kg、1.2 mg/kg. The dosing frequency will be Q12h. The drug/placebo in day 7 will be only administrated for 1 time on morning. The infusion duration will be 1h.

MT200605 PlaceboDRUG

Two stages (SAD, MAD) were designed in this study. For SAD, the MT200605 Placebo will single Intravenous (IV) infusion for 1h with the dose level as 0.15 mg/kg、0.3 mg/kg、0.6 mg/kg、0.9 mg/kg、1.2 mg/kg. For MAD, the participants will IV infusion of the MT200605 Placebo for 7 days with 2 times per day under the dose level of 0.3 mg/kg、0.6 mg/kg、1.2 mg/kg. The dosing frequency will be Q12h. The drug/placebo in day 7 will be only administrated for 1 time on morning. The infusion duration will be 1h.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 50 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: 1. Male or female, ≥ 18 and ≤ 50 years of age with BMI ≥ 18.0 and ≤ 28.0 kg/m\^2 2. Healthy as defined by: 1. The absence of clinically significant illness and major surgery within 4 weeks prior to study drug administration. 2. The absence of clinically significant history of neurological, endocrine, cardiovascular, respiratory, hematological, immunological, psychiatric, gastrointestinal, renal, hepatic, and metabolic disease. 3. Participants have no fertility plan, no sperm or egg donation plan in the next 6 months and voluntarily use effective contraception; Female subjects with negative serum pregnancy test results. 4. Can understand the study process of the clinical trial, and provide the signed ICF of joinning the clinical trial. Exclusion Criteria: \- Participants will be excluded from the study if any of the following applies: 1. Any clinically significant abnormal finding at physical examination. 2. Clinically significant abnormal laboratory test results or positive serology test results for HBsAg, HCV antibody, or HIV antigen and antibody at screening, or active infections. 3. Positive pregnancy test or lactating female subject. 4. Positive results of urine drug screen and breath alcohol test. 5. History of significant allergic reactions (e.g., Immediate hypersensitivity, hypersensitivity, angioedema) to any drug that the Investigator judges to be clinically significant. 6. Clinically significant ECG abnormalities (QTcF ≥ 450 ms) or vital signs abnormalities (systolic BP lower than 90 or over 140 mmHg, diastolic BP lower than 50 or over 90 mmHg, HR less than 50 or over 100 bpm) at screening. 7. History of drug abuse within 1 year prior to screening or using of the recreational drugs (such as marijuana, cocaine, phencyclidine \[PCP\], opioid derivatives (including Morphine, buprenorphine, methadone) or amphetamine derivatives within 3 months prior to screening. 8. History of alcohol abuse within 1 year prior to screening or regular use of alcohol within 6 months prior to screening that exceeds 10 units for women or 15 units for men of alcohol per week (1 unit = 355 mL of 5% beer, or 150 mL of 12% wine, or 45 mL of 40% distilled alcohol). 9. Donation or loss of more than 500 mL blood within 2 months prior to study drug administration, or has received any blood, plasma, or platelet transfusions within 3 months prior to screening, or plans to donate blood during the study or within 3 months after the study. 10. Estimated glomerular filtration rate (eGFR) \<60 mL/min at screening (estimated with the MDRD equation). 11. Participants daily smoking of cigarettes amounts \> 5 prior to the 3 months of screening, or get used to usage of nicotine-containing products, or participants who is not accept forbidden of any cigarettes products. 12. Use of medications for the timeframes specified below, with the exception of medications exempted by the Investigator on a case-by-case basis because they are judged unlikely to affect the PK profile of the study drug or subject safety (e.g., topical drug products without significant systemic absorption): 1. Depot injection or implant within 3 months prior to the first dosing. 2. Any drug or substances known to be strong inhibitors or strong inducers of CYP3A4/5, transporters of P-gp (e.g. rifampin, St, John´s Wort) within 30 days prior to the first dosing 3. Usage of the prescription medications within 14 days prior to the first dosing. 4. Usage of the Over-the-counter (OTC) medications (other than ≤2 g/day paracetamol \[acetaminophen\] or ≤ 800 mg/day ibuprofen) and natural health products (including herbal remedies, homeopathic and traditional medicines, probiotics, food supplements such as vitamins, minerals, amino acids, essential fatty acids, and protein supplements used in sports) within 7 days prior to the first dosing. 13. Participants involved in the clinical trials of study drugs, marketed drug, medical devices within 90 days prior to the first dosing, or concomitant participation in an investigational study without drug or medical device administration. 14. Poor compliance or unable to comply with the relevant provisions of the research protocol, and any reason which, in the opinion of the Investigator, would prevent the subject from participating in the study.

Outcomes

Primary Outcomes

Adverse Events（AEs)

For SAD, AEs will be recorded and evaluated for their seriousness, severity, and relationship to the study drug.

Time frame: From the date of screening until the date of last follow-up visit or early termination and end of study, assessed up to 4 weeks.

Adverse Events（AEs)

For MAD, AEs will be recorded and evaluated for their seriousness, severity, and relationship to the study drug.

Time frame: From the date of screening until the date of last follow-up visit or early termination and end of study, assessed up to 4 weeks.

Vital signs (SAD)

Vital signs measurements including blood pressure \[BP\] in mmHG.

Time frame: From the date of screening until the date of last follow-up visit or early termination and end of study, assessed up to 4 weeks.

Vital signs (MAD)

Vital signs measurements including blood pressure \[BP\] in mmHG.

Time frame: From the date of screening until the date of last follow-up visit or early termination and end of study, assessed up to 4 weeks.

Vital signs (SAD)

Vital signs measurements including pulse rate \[PR\] in beats/minute.