Clinical trial NCT03990090: A Study of TG103 in Chinese Healthy Adult Subjects
Official title: A Randomized, Double-blind, Placebo-controlled, Single Ascending Dose Phase Ia Study in Chinese Healthy Adult Subjects to Investigate the Safety, Tolerability and Pharmacokinetic of TG103
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: TG103
Pharmacokinetic
Pharmacodynamic
Safety
Tolerability
Lead sponsor: CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2019-06-18
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The main purposes of this study are to determine:

1. To assess the safety and tolerability of a single subcutaneous injection of different doses of TG103 in healthy Chinese adult subjects.
2. The pharmacokinetic and pharmacodynamic characteristics of a single subcutaneous injection of different doses of TG103 in healthy Chinese adult subjects were assessed.


Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years old and ≤ 65 years old, male or female;
* Medical history, physical examination, vital signs, 12-lead ECG and laboratory examination, imaging examination (thyroid color Doppler ultrasound, abdominal color Doppler ultrasound, chest X-ray) in the normal range, or not in the normal range but the researchers consider they have no clinical significance;
* The weighing no less than 50 kg in male subjects, and no less than 45 kg in female subjects , body mass index (BMI) between 18.9 and 27.9 kg/m2 (including boundary values)
* Fasting blood glucose is between 3.9-6.1 mmol/L (excluding the boundary value), and HbA1c is \<5.7%;
* Subjects must use reliable methods of contraception throughout the study period and avoid pregnancy in women or pregnancy in male subjects' partners at least 3 months after dosing;
* The subject is fully aware of the test content and possible adverse reactions, and has the ability to communicate properly with the researcher while complying with the research requirements;
* Voluntarily participate in the study and sign the informed consent form.

Exclusion Criteria:

* Have a history of severe drug or food allergies, or who may be allergic to the test drug by the investigator;
* Have serious history of pancreas, liver, kidney, gastrointestinal tract, cardiovascular, respiratory, hematological, central nervous system disease, etc.，or other important disease that have risks may endanger the safety of the subject or affect the absorption, metabolism, excretion, etc. of the study drug，or the investigator believes that the subject is not suitable for inclusion.
* Have undergone major surgery within 3 months prior to the trial, or have experienced severe infection within 4 weeks prior to the trial;
* Have diabetes, thyroid dysfunction or other endocrine diseases that may affect blood sugar metabolism;
* Individual or family history of medullary thyroid carcinoma (MTC) or type 2 multiple endocrine neoplasia, or other genetic diseases that are susceptible to medullary medullary cancer;
* Those with history of malignant tumors and mental illness, depression, anxiety, and epilepsy disease.
* Drugs and drug abusers in the past three years;
* Vaccination within 28 days prior to the trial or planned to be vaccinated within 1 week of receiving the study drug;
* Has one or more positive tests in Hepatitis B surface antigen, hepatitis C virus antibody, anti-human immunodeficiency virus antibody or anti- Treponema pallidum-specific antibody;
* Lost more than 400 ml of blood due to blood donation or other reasons within 3 months before the test;
* Apply a glucagon-like peptide-1(GLP-1 )analogue, a glucagon-like peptide-1(GLP-1 )receptor agonist, or any other incretin mimetic 1 month prior to the planned study drug, or other drugs that the investigator believes may affect the trial;
* Those who took prescription or similar over-the-counter medications within 1 month prior to the trial to promote weight loss (eg, orlistat, sibutramine, rimonabant, phenylpropanolamine or chlorpheniramine) ;
* Alcohol intake is more than 21 units of alcohol per week (male) / 14 units of alcohol per week(female) (1 unit ≈ 360mL beer, or 45mL spirits with 40% alcohol content, or 150mL wine) 3 months prior to the screening.
* Regular consumption of caffeine more than 600 mg per day in the past 3 months (1 cup of coffee contains about 100 mg of caffeine, 1 cup of tea contains about 30 mg of caffeine, and 1 can of Coke contains about 20 mg of caffeine);
* Those who have taken caffeinated products or drugs within 48 hours prior to the study;
* Taken more than 5 cigarettes per day in the past 3 months;
* The investigator considers that the subject's diet has a big difference in the ratio to normal protein, carbohydrate, and fat intake (eg, vegetarian)person;
* There are symptoms such as dermatitis or skin abnormalities at the site of administration;
* Participated in other drug studies within 3 months prior to the planned study drug or the time of the last test drug was less than 3 months prior to screening for the trial; or attempted to participate in other drug trials during the study;
* Pregnancy, lactation or blood human chorionic gonadotropin(HCG) positive in pregnancy test;
* Drug abuse screening, alcohol breath test positive;
* Failure to ensure full participation in the trial;
* Others who have been judged by the investigator that inappropriate to participate in the study.

Primary outcomes:
measure: Number of Participants with One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration
timeFrame: Baseline through Day 28
Secondary outcomes:
measure: Area under the plasma concentration versus time curve (AUC)
timeFrame: 0,0.25,1,4,6,8,12,24,36,48,60,72,96,144,192,264,336,648h
measure: Peak Plasma Concentration (Cmax)
timeFrame: 0,0.25,1,4,6,8,12,24,36,48,60,72,96,144,192,264,336,648h
measure: Time to maximum plasma concentration（Tmax）
timeFrame: 0,0.25,1,4,6,8,12,24,36,48,60,72,96,144,192,264,336,648hours
measure: Half time (t1/2)
timeFrame: 0,0.25,1,4,6,8,12,24,36,48,60,72,96,144,192,264,336,648hours
measure: Apparent clearance (CL/F)
timeFrame: 0,0.25,1,4,6,8,12,24,36,48,60,72,96,144,192,264,336,648hours
measure: Fasting blood glucose
timeFrame: 1,2,3,4,5,7days
measure: 2-hour postprandial blood glucose
timeFrame: 1,2,3,4,5,7days
measure: fasting insulin
timeFrame: -1,3days
measure: fasting glucagon
timeFrame: -1,3days
Other outcomes:
Locations:
city: Beijing
country: China
facility: China-Japan Friendship Hospital
state: Beijing
Study officials:
affiliation: China-Japan Friendship Hospital
name: jintong li
role: PRINCIPAL_INVESTIGATOR
affiliation: China-Japan Friendship Hospital
name: li chen
role: PRINCIPAL_INVESTIGATOR
References: