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The Tolerability, Safety, and PK Characteristics of SIM1910-09 in Healthy Chinese Volunteers

Primary Purpose

Acute Ischemic Stroke, Cerebral Edema

Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
SIM1910-09
Placebo
Sponsored by
Jiangsu Simcere Pharmaceutical Co., Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Ischemic Stroke focused on measuring brain edema, Acute ischemic stroke

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  1. Chinese male or female healthy volunteers;
  2. The subject fully understood the purpose, procedure, requirements, study period and potential risks of the study, and have signed the informed consent form (ICF);
  3. Age 18-50 years (including the boundary value) at the date of signing ICF ;
  4. The weight of Male subjects is no less than 50 kg, the one of female subjects no less than 45 kg, and body mass index (BMI) should be in the range of 19-28 kg/m2 (including the boundary value)

Exclusion Criteria:

  1. Those who participated in blood donation with blood donation volume ≥400 mL within 3 months prior to the first drug administration, or those who received blood transfusion;
  2. Those who have a history of clinically significant drug allergy or allergic reaction, as determined by the investigator, and is known to be allergic to the study drug or any of the ingredients in the study drug;
  3. Those who have a history of drug addiction and/or alcohol abuse, or positive result in drugs and alcohol screening test, or have had a history of drug abuse in the past five years or have used drugs in the three months before screening; or positive result in urine drug screening test during screening period;
  4. Alcohol and tobacco users (drinking more than 14 units of alcohol per week: 1 unit = 285 mL beer, or 25 mL spirits, or 100 mL wine; Smokers who smoke 5 or above cigarettes a day) and cannot abstain from smoking or alcohol during the trial period; Or positive result in urine cotinine test ;
  5. Fridericia method corrected QT interval (QTcF) > 450 msec in males or > 470 msec in female in 12-lead electrocardiogram;
  6. Those who have a definite disease history of important organs, such as nervous system, cardiovascular system, urinary system, digestive system, respiratory system, metabolic system and skeletal musculoskeletal system, which are not suitable for attending this study according to the investigator' judgement;
  7. Those who have undergone any surgery operation within 6 months prior to the first dose;
  8. Those who have taken hepatotoxic drugs (such as dapsone, erythromycin, fluconazole, ketoconazole, rifampicin) within 6 months before the first dose;
  9. Have taken any investigational drug within 3 months prior to the first dose;
  10. Have taken any prescription medicine or over-the-counter drug, any vitamin product, health care product or herbal medicine within 2 weeks prior to initial administration;
  11. Abnormalities in comprehensive physical examination (vital signs, physical examination, neurological examination), routine laboratory examination (blood routine, blood biochemistry, urine routine, coagulation function), 12-lead ECG, chest X-ray, cognitive function and other examinations, which are judged as clinically significant by investigators;
  12. Female subjects who are pregnant or in lactation, or who are unable to abstain from sex or unable to use effective non-pharmacological contraception during the study period and during 3 months after final dose, or who have had unprotected sexual intercourse in the 2 weeks prior to the first dose;
  13. The positive result in the Infectious disease screening (including HBSAG, HCV-AB, HIV-AB, syphilis antibody) ;
  14. Intake of grapefruit or grapefruits-containing products, foods or beverages containing caffeine, xanthine or alcohol within 48 hours prior to administration of the study drug; Or other factors of affecting drug absorption, distribution, metabolism, excretion.;
  15. Patients with a history of needle sickness or blood sickness, or resistance for blood collection or intolerance to venipuncture blood collection;
  16. Subjects with other inappropriate factors for attending this study judged by investigators.

Sites / Locations

  • Beijing Tiantan Hospital, Capital Medical UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

SIM1910-09

Placebo

Arm Description

This trial includes of 2 parts, Part A-single ascending doses and Part B- multiple ascending doses. Part A, there are 4 dose cohorts and each cohort will enroll 6 subjects to receive SIM1910-09. Part B, there are 3 dose cohorts and each cohort will enroll 6 subjects to receive SIM1910-09. The dose ascending will be determined by independent third party clinical physician. The next higher dose cohort could be initiated only if the stopping rules is not met.

This trial Includes of 2 parts, Part A-single ascending dose and Part B- multiple ascending dose. Part A, there are 4 dose cohorts and each cohort will enroll 2 subjects to receive placebo. Part B, there are 3 dose cohorts and each cohort will enroll 2 subjects to receive placebo. The dose ascending will be determined by independent third party clinical physician. The next higher dose cohort could be initiated only if the stopping rules is not met.

Outcomes

Primary Outcome Measures

the adverse events after single/multiple ascending dosing in healthy Chinese adult subjects
the number and the percentage of subjects with adverse event according to CTCAE V5.0
the clinically significant change from baseline of physical examinations after single/multiple ascending dosing in healthy Chinese adult subjects
the abnormal incidence of physicial assessment , including of the head, the neck, the chest, the abdomen, Musculoskeletal system, Superficial lymph node, the nervous system
the clinically significant change from baseline of the vital signs after single/multiple ascending dosing in healthy Chinese adult subjects
the abnormal incidence of the the body tempreture, the pulse rate, respiratory rate, the blood pressure
the clinically significant change from baseline of laboratory tests after single/multiple ascending dosing in healthy Chinese adult subjects
incidence of laboratory abnormalities, based on hematology, coagulation function, clinical chemistry, and urinalysis test results
the clinically significant change from baseline of 12-lead electrocardiograms after single/multiple ascending dosing in healthy Chinese adult subjects
the abnormal incidence of heart rate, PR, QT, QRS, QTcF based on the ECG recording

Secondary Outcome Measures

PK parameters: Peak Plasma Concentration (Cmax)
Maximum concentration of SIM1910-09 and SCR-6401 derived from plasma concentration-time profile (ng/mL)
PK parameters: Area under the plasma concentration versus time curve (AUC)
Maximum concentration of SIM1910-09 and SCR-6401 derived from plasma concentration-time profile (h*ng/mL)
PK parameters: Clearance (CL)
Clearance of SIM1910-09 derived from plasma concentration-time profile (mL/h/kg)
PK parameters: Half-life (t1/2)
Half-life of SIM1910-09 and SCR-6401 derived from plasma concentration-time profile (h)
PK parameters: Volume of distribution (V)
Volume of distribution of SIM1910-09 derived from plasma concentration-time profile (mL/kg)

Full Information

First Posted
November 18, 2021
Last Updated
January 7, 2022
Sponsor
Jiangsu Simcere Pharmaceutical Co., Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT05200728
Brief Title
The Tolerability, Safety, and PK Characteristics of SIM1910-09 in Healthy Chinese Volunteers
Official Title
A Single-center, Randomized, Double-blind, Placebo-controlled Phase I Clinical Study to Evaluate the Tolerability, Safety, and PK Characteristics of SIM1910-09 After Single/Multiple Dosing in Healthy Chinese Volunteers
Study Type
Interventional

2. Study Status

Record Verification Date
November 2021
Overall Recruitment Status
Recruiting
Study Start Date
December 2, 2021 (Actual)
Primary Completion Date
September 30, 2022 (Anticipated)
Study Completion Date
December 31, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Jiangsu Simcere Pharmaceutical Co., Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
This is a single-center, randomized, double-blind, placebo-controlled Phase I clinical study to evaluate the tolerability, safety, and pharmacokinetic characteristics of SIM1910-09 for injection after single/multiple dosing in healthy Chinese adult volunteers.
Detailed Description
This is a double-blind, randomized, placebo-controlled, sequential-group study with intravenously (IV) administered SIM1910-09 in healthy human subjects to assess the safety, tolerability and pharmacokinetic parameters, which include of single ascending dose part and multiple ascending doses part. The primary objectives of this study are to assess the safety and tolerability of SIM1910-09 in healthy subjects. Secondary objectives are to determine the pharmacokinetics of SIM1910-09 and SCR-6401 (primary metabolite) after administration of SIM1910-09. Exploratory objectives are to learn the inhibitory effect of SIM1910-09 and SCR-6401 on inflammation cytokine in ex vivo blood.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Ischemic Stroke, Cerebral Edema
Keywords
brain edema, Acute ischemic stroke

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
56 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
SIM1910-09
Arm Type
Experimental
Arm Description
This trial includes of 2 parts, Part A-single ascending doses and Part B- multiple ascending doses. Part A, there are 4 dose cohorts and each cohort will enroll 6 subjects to receive SIM1910-09. Part B, there are 3 dose cohorts and each cohort will enroll 6 subjects to receive SIM1910-09. The dose ascending will be determined by independent third party clinical physician. The next higher dose cohort could be initiated only if the stopping rules is not met.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
This trial Includes of 2 parts, Part A-single ascending dose and Part B- multiple ascending dose. Part A, there are 4 dose cohorts and each cohort will enroll 2 subjects to receive placebo. Part B, there are 3 dose cohorts and each cohort will enroll 2 subjects to receive placebo. The dose ascending will be determined by independent third party clinical physician. The next higher dose cohort could be initiated only if the stopping rules is not met.
Intervention Type
Drug
Intervention Name(s)
SIM1910-09
Other Intervention Name(s)
AER-271
Intervention Description
Part A-single ascending doses, SIM1910-09 will be administered by IV bolus infusion over a 30-min. The test doses are including of : 2mg/kg, 4mg/kg, 6mg/kg, 8mg/kg, which will be tested sequentially from low dose to high dose. Part B-multiple ascending doses, SIM1910-09 will be administered as an initial bolus dose over 30-min, plus subsequent continuous infusion over 72 hours, the test doses are including of : 4mg/kg IV bolus infusion+0.03mg/kg/h continuous infusion;4mg/kg IV bolus infusion+0.1mg/kg/h continuous infusion;4mg/kg IV bolus infusion+0.3mg/kg/h continuous infusion, which will be tested sequentially from low dose to high dose.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Part A-single ascending doses, placebo will be administered by IV bolus infusion over a 30-min. The test doses are including of : 2mg/kg, 4mg/kg, 6mg/kg, 8mg/kg, which will be tested sequentially from low dose to high dose. Part B-multiple ascending doses, placebo will be administered as an initial bolus dose over 30-min, plus subsequent continuous infusion over 72 hours, the test doses are including of : 4mg/kg IV bolus infusion+0.03mg/kg/h continuous infusion;4mg/kg IV bolus infusion+0.1mg/kg/h continuous infusion;4mg/kg IV bolus infusion+0.3mg/kg/h continuous infusion, which will be tested sequentially from low dose to high dose.
Primary Outcome Measure Information:
Title
the adverse events after single/multiple ascending dosing in healthy Chinese adult subjects
Description
the number and the percentage of subjects with adverse event according to CTCAE V5.0
Time Frame
7 days after final dose
Title
the clinically significant change from baseline of physical examinations after single/multiple ascending dosing in healthy Chinese adult subjects
Description
the abnormal incidence of physicial assessment , including of the head, the neck, the chest, the abdomen, Musculoskeletal system, Superficial lymph node, the nervous system
Time Frame
7 days after final dose
Title
the clinically significant change from baseline of the vital signs after single/multiple ascending dosing in healthy Chinese adult subjects
Description
the abnormal incidence of the the body tempreture, the pulse rate, respiratory rate, the blood pressure
Time Frame
7 days after final dose
Title
the clinically significant change from baseline of laboratory tests after single/multiple ascending dosing in healthy Chinese adult subjects
Description
incidence of laboratory abnormalities, based on hematology, coagulation function, clinical chemistry, and urinalysis test results
Time Frame
7 days after final dose
Title
the clinically significant change from baseline of 12-lead electrocardiograms after single/multiple ascending dosing in healthy Chinese adult subjects
Description
the abnormal incidence of heart rate, PR, QT, QRS, QTcF based on the ECG recording
Time Frame
7 days after final dose
Secondary Outcome Measure Information:
Title
PK parameters: Peak Plasma Concentration (Cmax)
Description
Maximum concentration of SIM1910-09 and SCR-6401 derived from plasma concentration-time profile (ng/mL)
Time Frame
Within 1-2 weeks of final blood sample collection
Title
PK parameters: Area under the plasma concentration versus time curve (AUC)
Description
Maximum concentration of SIM1910-09 and SCR-6401 derived from plasma concentration-time profile (h*ng/mL)
Time Frame
Within 1-2 weeks of final blood sample collection
Title
PK parameters: Clearance (CL)
Description
Clearance of SIM1910-09 derived from plasma concentration-time profile (mL/h/kg)
Time Frame
Within 1-2 weeks of final blood sample collection
Title
PK parameters: Half-life (t1/2)
Description
Half-life of SIM1910-09 and SCR-6401 derived from plasma concentration-time profile (h)
Time Frame
Within 1-2 weeks of final blood sample collection
Title
PK parameters: Volume of distribution (V)
Description
Volume of distribution of SIM1910-09 derived from plasma concentration-time profile (mL/kg)
Time Frame
Within 1-2 weeks of final blood sample collection
Other Pre-specified Outcome Measures:
Title
Exploratory outcome: The cytokines Concentrations of interleukin 1β (IL-1β)
Description
The cytokines Concentrations of IL-1β in ex-vivo blood after in-vitro stimulation and the blood sampling was token before and after single/multiple ascending dose
Time Frame
Within one week of final blood sample collection
Title
Exploratory outcome: The cytokines Concentrations of interleukin 6 (IL-6)
Description
The cytokines Concentrations of IL-6 in ex-vivo blood after in-vitro stimulation and the blood sampling was token before and after single/multiple ascending dose
Time Frame
Within one week of final blood sample collection
Title
Exploratory outcome: The cytokines Concentrations of tumor necrosis factor α (TNF-α)
Description
The cytokines Concentrations of TNF-α in ex-vivo blood after in-vitro stimulation and the blood sampling was token before and after single/multiple ascending dose
Time Frame
Within one week of final blood sample collection
Title
Exploratory outcome: The cytokines Concentrations of interferon γ (IFN-γ)
Description
The cytokines Concentrations of IFN-γ in ex-vivo blood after in-vitro stimulation and the blood sampling was token before and after single/multiple ascending dose
Time Frame
Within one week of final blood sample collection

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Chinese male or female healthy volunteers; The subject fully understood the purpose, procedure, requirements, study period and potential risks of the study, and have signed the informed consent form (ICF); Age 18-50 years (including the boundary value) at the date of signing ICF ; The weight of Male subjects is no less than 50 kg, the one of female subjects no less than 45 kg, and body mass index (BMI) should be in the range of 19-28 kg/m2 (including the boundary value) Exclusion Criteria: Those who participated in blood donation with blood donation volume ≥400 mL within 3 months prior to the first drug administration, or those who received blood transfusion; Those who have a history of clinically significant drug allergy or allergic reaction, as determined by the investigator, and is known to be allergic to the study drug or any of the ingredients in the study drug; Those who have a history of drug addiction and/or alcohol abuse, or positive result in drugs and alcohol screening test, or have had a history of drug abuse in the past five years or have used drugs in the three months before screening; or positive result in urine drug screening test during screening period; Alcohol and tobacco users (drinking more than 14 units of alcohol per week: 1 unit = 285 mL beer, or 25 mL spirits, or 100 mL wine; Smokers who smoke 5 or above cigarettes a day) and cannot abstain from smoking or alcohol during the trial period; Or positive result in urine cotinine test ; Fridericia method corrected QT interval (QTcF) > 450 msec in males or > 470 msec in female in 12-lead electrocardiogram; Those who have a definite disease history of important organs, such as nervous system, cardiovascular system, urinary system, digestive system, respiratory system, metabolic system and skeletal musculoskeletal system, which are not suitable for attending this study according to the investigator' judgement; Those who have undergone any surgery operation within 6 months prior to the first dose; Those who have taken hepatotoxic drugs (such as dapsone, erythromycin, fluconazole, ketoconazole, rifampicin) within 6 months before the first dose; Have taken any investigational drug within 3 months prior to the first dose; Have taken any prescription medicine or over-the-counter drug, any vitamin product, health care product or herbal medicine within 2 weeks prior to initial administration; Abnormalities in comprehensive physical examination (vital signs, physical examination, neurological examination), routine laboratory examination (blood routine, blood biochemistry, urine routine, coagulation function), 12-lead ECG, chest X-ray, cognitive function and other examinations, which are judged as clinically significant by investigators; Female subjects who are pregnant or in lactation, or who are unable to abstain from sex or unable to use effective non-pharmacological contraception during the study period and during 3 months after final dose, or who have had unprotected sexual intercourse in the 2 weeks prior to the first dose; The positive result in the Infectious disease screening (including HBSAG, HCV-AB, HIV-AB, syphilis antibody) ; Intake of grapefruit or grapefruits-containing products, foods or beverages containing caffeine, xanthine or alcohol within 48 hours prior to administration of the study drug; Or other factors of affecting drug absorption, distribution, metabolism, excretion.; Patients with a history of needle sickness or blood sickness, or resistance for blood collection or intolerance to venipuncture blood collection; Subjects with other inappropriate factors for attending this study judged by investigators.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ru Lin
Phone
86-15521381683
Email
ru.lin@cn.simcere.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yongjun Wang
Organizational Affiliation
Beijing Tiantan Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Beijing Tiantan Hospital, Capital Medical University
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100050
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yongjun Wang
Phone
010-59978538
Email
yongjunwang111@aliyun.com

12. IPD Sharing Statement

Learn more about this trial

The Tolerability, Safety, and PK Characteristics of SIM1910-09 in Healthy Chinese Volunteers

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