A Randomized, Double-blind, Placebo Control, Phase 1 Clinical Trial to Evaluate the Safety, Tolerability, and Pharmacokinetics After Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD) of MT200605 for Injection in Healthy Subjects.
Overview
- Phase
- Phase 1
- Intervention
- MT200605 for Injection
- Conditions
- Healthy
- Sponsor
- Shaanxi Micot Technology Limited Company
- Enrollment
- 61
- Locations
- 1
- Primary Endpoint
- Adverse Events（AEs)
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
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:
- The safety and tolerability of MT200605 injection in health subjects
- 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.
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male or female, ≥ 18 and ≤ 50 years of age with BMI ≥ 18.0 and ≤ 28.0 kg/m\^2
- •Healthy as defined by:
- •The absence of clinically significant illness and major surgery within 4 weeks prior to study drug administration.
- •The absence of clinically significant history of neurological, endocrine, cardiovascular, respiratory, hematological, immunological, psychiatric, gastrointestinal, renal, hepatic, and metabolic disease.
- •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.
- •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:
- •Any clinically significant abnormal finding at physical examination.
- •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.
- •Positive pregnancy test or lactating female subject.
- •Positive results of urine drug screen and breath alcohol test.
- •History of significant allergic reactions (e.g., Immediate hypersensitivity, hypersensitivity, angioedema) to any drug that the Investigator judges to be clinically significant.
- •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.
- •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.
- •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).
- •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.
Arms & Interventions
MT200605 for injection
The Single Ascending Dose (SAD) and Muliple Ascending Dose (MAD) stages were built up in the study. The MT200605 in SAD and MAD following Intravenous Infusion Administration by using infusion pump in Healthy Subjects.
Intervention: MT200605 for Injection
MT200605 Placebo
The Single Ascending Dose (SAD) and Muliple Ascending Dose (MAD) stages were built up in the study. The MT200605 Placebo in SAD and MAD following Intravenous Infusion Administration by using infusion pump in Healthy Subjects.
Intervention: MT200605 Placebo
Outcomes
Primary Outcomes
Adverse Events（AEs)
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.
For MAD, AEs will be recorded and evaluated for their seriousness, severity, and relationship to the study drug.
12-lead electrocardiogram (ECG) recordings (MAD)
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
The ECG QTc Interval will be used to evaluate and monitor the participants.
Physical examinations-Head (SAD)
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
A thorough physical examination will be performed at SAD stage, including head examination，the descriptive name of scale （inspection，palpation） will be used to report this outcome measure.
Physical examinations-Eyes (SAD)
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
A thorough physical examination will be performed at SAD stage, including eyes examination，the descriptive name of scale （inspection） will be used to report this outcome measure.
Vital signs (SAD)
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 measurements including axillaty temperature \[AT\] in Celsius (°C).
Vital signs (MAD)
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 measurements including axillaty temperature \[AT\] in Celsius (°C).
12-lead electrocardiogram (ECG) recordings (SAD)
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
The ECG QTc Interval will be used to evaluate and monitor the participants.
Physical examinations-Ears (SAD)
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
A thorough physical examination will be performed at SAD stage, including ears examination，the descriptive name of scale （auscultation） will be used to report this outcome measure.
Physical examinations-Nose (SAD)
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
A thorough physical examination will be performed at SAD stage, including nose examination，the descriptive name of scale （inspection，palpation） will be used to report this outcome measure.
Physical examinations-Abdomen (SAD)
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
A thorough physical examination will be performed at SAD stage, including Abdomen examination，the descriptive name of scale （palpation） will be used to report this outcome measure.
Physical examinations-throat (SAD)
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
A thorough physical examination will be performed at SAD stage, including throat examination，the descriptive name of scale （inspection） will be used to report this outcome measure.
Physical examinations-lung (MAD)
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
A simple physical examination will be performed at MAD stage, including lung examination, the descriptive name of scale （palpation，percussion，auscultation） will be used to report this outcome measure.
Physical examinations-Cardiovascular (MAD)
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
A simple physical examination will be performed at MAD stage, including Cardiovascular examination，the descriptive name of scale（inspection, palpation, percussion, and asking for Anamnesis）will be used to report this outcome measure.
Clinical laboratory test-Urinalysis (SAD)
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
The Urinalysis will be performed, the urine albumin-to-creatinine ratio (UACR) will be calculated.
Clinical laboratory test-hematology (MAD)
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
The hematology testing will be performed, the Hemoglobin will be evaluated
Physical examinations-lung (SAD)
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
A thorough physical examination will be performed at SAD stage, including lung examination, the descriptive name of scale （palpation，percussion，auscultation） will be used to report this outcome measure.
Physical examinations-neck (SAD)
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
A thorough physical examination will be performed at SAD stage, including neck examination, the descriptive name of scale （inspection，palpation） will be used to report this outcome measure.
Physical examinations-Abdomen (MAD)
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
A simple physical examination will be performed at MAD stage, including Abdomen examination，the descriptive name of scale （palpation） will be used to report this outcome measure.
Physical examinations-skin (MAD)
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
A simple physical examination will be performed at MAD stage, including skin examination, the descriptive name of scale （inspection，palpation） will be used to report this outcome measure.
Clinical laboratory test-hematology (SAD)
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
The hematology testing will be performed,the Hemoglobin will be evaluated
Physical examinations-skin (SAD)
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
A thorough physical examination will be performed at SAD stage, including skin examination, the descriptive name of scale （inspection，palpation） will be used to report this outcome measure.
Physical examinations-Musculoskeletal (SAD)
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
A thorough physical examination will be performed at SAD stage, including musculoskeletal examination，the descriptive name of scale（inspection，palpation，percussion） will be used to report this outcome measure.
Physical examinations-Cardiovascular (SAD)
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
A thorough physical examination will be performed at SAD stage, including Cardiovascular examination，the descriptive name of scale（inspection, palpation, percussion, and asking for Anamnesis）will be used to report this outcome measure.
Physical examinations-neurological (SAD)
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
A thorough physical examination will be performed at SAD stage, including neurological examination，the descriptive name of scale（palpation, percussion）will be used to report this outcome measure.
Clinical laboratory test-Cardiac Enzymes (SAD)
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
The Urinalysis will be performed, the TnI will be evaluated.
Clinical laboratory test-biochemistry (SAD)
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
The biochemistry testing will be performed, the serum creatinine will be evaluated
Clinical laboratory test-Coagulation (SAD)
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
The Urinalysis will be performed, the INR will be evaluated.
Clinical laboratory test-biochemistry (MAD)
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
The biochemistry testing will be performed, the serum creatinine will be evaluated
Clinical laboratory test-Urinalysis (MAD)
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
The Urinalysis will be performed, the urine albumin-to-creatinine ratio (UACR) will be calculated.
Clinical laboratory test-Cardiac Enzymes (MAD)
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
The Urinalysis will be performed, the TnI will be evaluated.
Clinical laboratory test-Coagulation (MAD)
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
The Urinalysis will be performed, the INR will be evaluated.
Secondary Outcomes
- Plasma PK of free MT200605 and total MT200605 (MAD)(Up to 2 Days.)
- Urine PK of free MT200605 and total MT200605 (unconjugated MT200605 and total MT200605 after enzymatic hydrolysisof MT200605 glucuronide conjugate metabolits by β-glucuronidase) (SAD)(Up to 2 Days (the urine PK analysis only for 4th Corhort at SAD stage))
- Plasma PK of free MT200605 and total MT200605 (SAD)(Up to 2 Days.)
- Urine PK of free MT200605 and total MT200605 (SAD)(Up to 2 Days (the urine PK analysis only for 4th Corhort at SAD stage))