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出境医 / 临床实验 / A Randomized, Double-blind, Placebo-controlled, Sequential Single and Multiple Ascending Doses of YG1699

A Randomized, Double-blind, Placebo-controlled, Sequential Single and Multiple Ascending Doses of YG1699

Study Description
Brief Summary:
This is a randomized, double-blind, placebo-controlled, dose-escalation study to evaluate the safety, tolerability, and pharmacokinetics (PK) of YG1699 following single and multiple ascending oral dose administration.

Condition or disease Intervention/treatment Phase
Diabete Mellitus Drug: YG1699 Drug: Placebos Phase 1

Detailed Description:

This is a randomized, double-blind, placebo-controlled, dose-escalation study to evaluate the safety, tolerability, and pharmacokinetics (PK) of YG1699 following single and multiple ascending oral dose administration.

The study consists of 2 parts: Part 1, SAD dose-escalation; Part 2, MAD dose-escalation.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 64 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Single Ascending Dose and Multiple Ascending Dose
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: Double Blinded
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Placebo-controlled, Sequential Single and Multiple Ascending Doses (SAD/MAD) Study Following Oral Administration in Healthy Subjects to Evaluate the Safety, Tolerability, and Pharmacokinetics of YG1699
Actual Study Start Date : May 1, 2019
Actual Primary Completion Date : November 13, 2019
Actual Study Completion Date : November 13, 2019
Arms and Interventions
Arm Intervention/treatment
Experimental: SAD Cohort 1
5 mg YG1699 or Placebo
Drug: YG1699
YG1699 at Multiple Doses

Drug: Placebos
Placebos

Experimental: SAD Cohort 2
10 mg YG1699 or placebo
Drug: YG1699
YG1699 at Multiple Doses

Drug: Placebos
Placebos

Experimental: SAD Cohort 3
25 mg YG1699 or placebo
Drug: YG1699
YG1699 at Multiple Doses

Drug: Placebos
Placebos

Experimental: SAD Cohort 4
50 mg YG1699 or placebo
Drug: YG1699
YG1699 at Multiple Doses

Drug: Placebos
Placebos

Experimental: SAD Cohort 5
100 mg YG1699 or placebo
Drug: YG1699
YG1699 at Multiple Doses

Drug: Placebos
Placebos

Experimental: MAD Cohort 1
5 mg YG1699 or placebo
Drug: YG1699
YG1699 at Multiple Doses

Drug: Placebos
Placebos

Experimental: MAD Cohort 2
20 mg YG1699 or placebo
Drug: YG1699
YG1699 at Multiple Doses

Drug: Placebos
Placebos

Experimental: MAD Cohort 3
50 mg YG1699 or placebo
Drug: YG1699
YG1699 at Multiple Doses

Drug: Placebos
Placebos

Outcome Measures
Primary Outcome Measures :
  1. Adverse events will be evaluated [ Time Frame: 76 Days ]
    Safety and Tolerability of YG1699


Secondary Outcome Measures :
  1. Area Under the Curve [AUC] [ Time Frame: 76 Days ]
    area under the plasma drug concentration time curve from time 0 to T (AUC)

  2. maximum plasma concentration (Cmax) [ Time Frame: 76 days ]
    maximum plasma concentration


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Are capable of giving informed consent and complying with study procedures;
  2. Are between the ages of 18 and 55 years, inclusive;
  3. Female subjects have a negative urine pregnancy test result at screening and Day -1, and meet one of the following criteria:

    1. Using a medically acceptable form of birth control for at least 1 month prior to screening (3 months on oral contraceptives) [e.g., hormonal contraceptives (oral, patch, injectable or vaginal ring), implantable device (implantable rod or intrauterine device), or a double barrier (e.g., diaphragm, cervical cap, oral, patch or vaginal hormonal contraceptive, condom, spermicide, or sponge)]
    2. Surgically sterile for at least 3 months prior to screening by one of the following means:

      • Bilateral tubal ligation
      • Bilateral salpingectomy (with or without oophorectomy)
      • Surgical hysterectomy
      • Bilateral oophorectomy (with or without hysterectomy)
    3. Postmenopausal, defined as the following:

      • Last menstrual period greater than 12 months prior to screening
      • Postmenopausal status confirmed by serum FSH and estradiol levels at screening;
  4. Considered healthy by the Investigator, based on subject's reported medical history, full physical examination, clinical laboratory tests, 12-lead ECG, and vital signs;
  5. Normal renal function with estimated glomerular filtration rate (eGFR) of 60 ml/min/1.73m2 or greater and as deemed by the Investigator;
  6. Non-smoker and no more than 2 tobacco-containing including nicotine replacement products in last 6 months;
  7. Body mass index (BMI) of 18.0 to 30.0 kg/m2 inclusive and body weight not less than 50 kg;
  8. Willing and able to adhere to study restrictions and to be confined at the clinical research center.
  9. Male subjects with female partners of child bearing potential must agree to use condoms for the duration of the study and until 12 weeks after dosing with the study drug and must refrain from donating sperm for this same period.

Exclusion Criteria:

  1. Clinically significant history of gastrointestinal, cardiovascular, musculoskeletal, endocrine, hematologic, psychiatric, renal, hepatic, bronchopulmonary, neurologic, immunologic, lipid metabolism disorders, or drug hypersensitivity as determined by the Investigator;
  2. Known or suspected malignancy;
  3. History of pancreatitis or gall stones;
  4. History of unexplained syncope, symptomatic hypotension or hypoglycemia;
  5. Family history of long QTc syndrome;
  6. History of chronic diarrhea, malabsorption, unexplained weight loss, food allergies or intolerance;
  7. Poor venous access;
  8. Positive blood screen for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C antibody;
  9. Donated or lost >500ml of blood in the previous 3 months;
  10. Taken an investigational drug or participated in a clinical trial within 3 months (or 5 half-lives), whichever is longer;
  11. Taken any prescription medications within 14 days or 5 half-lives (whichever is longer) of the first dose of study drug;
  12. Hospital admission or major surgery within 6 months prior to screening;
  13. A history of prescription drug abuse, or illicit drug use within 9 months prior to screening;
  14. A history of alcohol abuse according to medical history within 9 months prior to screening;
  15. A positive screen for alcohol, drugs of abuse at screening or Day -1;
  16. An unwillingness or inability to comply with food and beverage restrictions during study participation;
  17. Use of over-the-counter (OTC) medication within 7 days, and herbal (including St John's Wort, herbal teas, garlic extracts) within 7 days prior to dosing (Note: Use of acetaminophen at < 2 g/day is permitted until 24 hours prior to dosing);
  18. Any condition or finding that in the Investigators opinion would put the subject or study conduct at risk if the subject were to participate in the study.
Contacts and Locations

Locations
Layout table for location information
United States, New Jersey
Frontage Labs
Secaucus, New Jersey, United States, 07094
Sponsors and Collaborators
Youngene Therapeutics Inc., Ltd.
Investigators
Layout table for investigator information
Study Director: Yalin Li, MD Youngene Therapeutics Inc., Ltd.
Tracking Information
First Submitted Date  ICMJE May 14, 2019
First Posted Date  ICMJE May 16, 2019
Last Update Posted Date January 11, 2021
Actual Study Start Date  ICMJE May 1, 2019
Actual Primary Completion Date November 13, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 15, 2019)
Adverse events will be evaluated [ Time Frame: 76 Days ]
Safety and Tolerability of YG1699
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 15, 2019)
  • Area Under the Curve [AUC] [ Time Frame: 76 Days ]
    area under the plasma drug concentration time curve from time 0 to T (AUC)
  • maximum plasma concentration (Cmax) [ Time Frame: 76 days ]
    maximum plasma concentration
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Randomized, Double-blind, Placebo-controlled, Sequential Single and Multiple Ascending Doses of YG1699
Official Title  ICMJE A Randomized, Double-blind, Placebo-controlled, Sequential Single and Multiple Ascending Doses (SAD/MAD) Study Following Oral Administration in Healthy Subjects to Evaluate the Safety, Tolerability, and Pharmacokinetics of YG1699
Brief Summary This is a randomized, double-blind, placebo-controlled, dose-escalation study to evaluate the safety, tolerability, and pharmacokinetics (PK) of YG1699 following single and multiple ascending oral dose administration.
Detailed Description

This is a randomized, double-blind, placebo-controlled, dose-escalation study to evaluate the safety, tolerability, and pharmacokinetics (PK) of YG1699 following single and multiple ascending oral dose administration.

The study consists of 2 parts: Part 1, SAD dose-escalation; Part 2, MAD dose-escalation.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:
Single Ascending Dose and Multiple Ascending Dose
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description:
Double Blinded
Primary Purpose: Treatment
Condition  ICMJE Diabete Mellitus
Intervention  ICMJE
  • Drug: YG1699
    YG1699 at Multiple Doses
  • Drug: Placebos
    Placebos
Study Arms  ICMJE
  • Experimental: SAD Cohort 1
    5 mg YG1699 or Placebo
    Interventions:
    • Drug: YG1699
    • Drug: Placebos
  • Experimental: SAD Cohort 2
    10 mg YG1699 or placebo
    Interventions:
    • Drug: YG1699
    • Drug: Placebos
  • Experimental: SAD Cohort 3
    25 mg YG1699 or placebo
    Interventions:
    • Drug: YG1699
    • Drug: Placebos
  • Experimental: SAD Cohort 4
    50 mg YG1699 or placebo
    Interventions:
    • Drug: YG1699
    • Drug: Placebos
  • Experimental: SAD Cohort 5
    100 mg YG1699 or placebo
    Interventions:
    • Drug: YG1699
    • Drug: Placebos
  • Experimental: MAD Cohort 1
    5 mg YG1699 or placebo
    Interventions:
    • Drug: YG1699
    • Drug: Placebos
  • Experimental: MAD Cohort 2
    20 mg YG1699 or placebo
    Interventions:
    • Drug: YG1699
    • Drug: Placebos
  • Experimental: MAD Cohort 3
    50 mg YG1699 or placebo
    Interventions:
    • Drug: YG1699
    • Drug: Placebos
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 15, 2019)
64
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE November 13, 2019
Actual Primary Completion Date November 13, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Are capable of giving informed consent and complying with study procedures;
  2. Are between the ages of 18 and 55 years, inclusive;
  3. Female subjects have a negative urine pregnancy test result at screening and Day -1, and meet one of the following criteria:

    1. Using a medically acceptable form of birth control for at least 1 month prior to screening (3 months on oral contraceptives) [e.g., hormonal contraceptives (oral, patch, injectable or vaginal ring), implantable device (implantable rod or intrauterine device), or a double barrier (e.g., diaphragm, cervical cap, oral, patch or vaginal hormonal contraceptive, condom, spermicide, or sponge)]
    2. Surgically sterile for at least 3 months prior to screening by one of the following means:

      • Bilateral tubal ligation
      • Bilateral salpingectomy (with or without oophorectomy)
      • Surgical hysterectomy
      • Bilateral oophorectomy (with or without hysterectomy)
    3. Postmenopausal, defined as the following:

      • Last menstrual period greater than 12 months prior to screening
      • Postmenopausal status confirmed by serum FSH and estradiol levels at screening;
  4. Considered healthy by the Investigator, based on subject's reported medical history, full physical examination, clinical laboratory tests, 12-lead ECG, and vital signs;
  5. Normal renal function with estimated glomerular filtration rate (eGFR) of 60 ml/min/1.73m2 or greater and as deemed by the Investigator;
  6. Non-smoker and no more than 2 tobacco-containing including nicotine replacement products in last 6 months;
  7. Body mass index (BMI) of 18.0 to 30.0 kg/m2 inclusive and body weight not less than 50 kg;
  8. Willing and able to adhere to study restrictions and to be confined at the clinical research center.
  9. Male subjects with female partners of child bearing potential must agree to use condoms for the duration of the study and until 12 weeks after dosing with the study drug and must refrain from donating sperm for this same period.

Exclusion Criteria:

  1. Clinically significant history of gastrointestinal, cardiovascular, musculoskeletal, endocrine, hematologic, psychiatric, renal, hepatic, bronchopulmonary, neurologic, immunologic, lipid metabolism disorders, or drug hypersensitivity as determined by the Investigator;
  2. Known or suspected malignancy;
  3. History of pancreatitis or gall stones;
  4. History of unexplained syncope, symptomatic hypotension or hypoglycemia;
  5. Family history of long QTc syndrome;
  6. History of chronic diarrhea, malabsorption, unexplained weight loss, food allergies or intolerance;
  7. Poor venous access;
  8. Positive blood screen for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C antibody;
  9. Donated or lost >500ml of blood in the previous 3 months;
  10. Taken an investigational drug or participated in a clinical trial within 3 months (or 5 half-lives), whichever is longer;
  11. Taken any prescription medications within 14 days or 5 half-lives (whichever is longer) of the first dose of study drug;
  12. Hospital admission or major surgery within 6 months prior to screening;
  13. A history of prescription drug abuse, or illicit drug use within 9 months prior to screening;
  14. A history of alcohol abuse according to medical history within 9 months prior to screening;
  15. A positive screen for alcohol, drugs of abuse at screening or Day -1;
  16. An unwillingness or inability to comply with food and beverage restrictions during study participation;
  17. Use of over-the-counter (OTC) medication within 7 days, and herbal (including St John's Wort, herbal teas, garlic extracts) within 7 days prior to dosing (Note: Use of acetaminophen at < 2 g/day is permitted until 24 hours prior to dosing);
  18. Any condition or finding that in the Investigators opinion would put the subject or study conduct at risk if the subject were to participate in the study.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 55 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03953092
Other Study ID Numbers  ICMJE YG1699 -01
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Youngene Therapeutics Inc., Ltd.
Study Sponsor  ICMJE Youngene Therapeutics Inc., Ltd.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Yalin Li, MD Youngene Therapeutics Inc., Ltd.
PRS Account Youngene Therapeutics Inc., Ltd.
Verification Date January 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP