Clinical trial NCT03953092: A Randomized, Double-blind, Placebo-controlled, Sequential Single and Multiple Ascending Doses of YG1699
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Diabete Mellitus
Keywords: Diabetes
Lead sponsor: Youngene Therapeutics Inc., Ltd.
Sponsor class: INDUSTRY
First posted: 2019-05-16
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Single Ascending Dose and Multiple Ascending Dose
Primary purpose: TREATMENT

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.

Eligibility 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.

Primary outcomes:
measure: Adverse events will be evaluated
timeFrame: 76 Days
Secondary outcomes:
measure: Area Under the Curve [AUC]
timeFrame: 76 Days
measure: maximum plasma concentration (Cmax)
timeFrame: 76 days
Other outcomes:
Locations:
city: Secaucus
country: United States
facility: Frontage Labs
state: New Jersey
Study officials:
affiliation: Youngene Therapeutics Inc., Ltd.
name: Yalin Li, MD
role: STUDY_DIRECTOR
References: