Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of JY09

Study Overview
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Brief Summary
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JY09 is a glucagon-like peptide-1 (GLP-1) mimetic generated by genetic fusion of a Exendin-4 dimer to human immunoglobulin Fc. In this Double-blind, randomized, placebo-controlled trial, 41 healthy subjects received placebo or escalating doses of JY09 on day 1 in the first cohort, and on days 1 and 22 in the following sequential cohort 2-4, and on days 1, 15, and 30 in the cohort 5: cohort 1: 0.3 mg; cohort 2: 0.3 + 0.7 mg; cohort 3: 0.7+1.5 mg; cohort 4: 0.7+3.0 mg; and cohort 5: 0.7 + 1.5 + 6.0 mg. The primary endpoints were the incidence of adverse events and serious adverse events related to JY09. Secondary endpoints included pharmacodynamics and pharmacokinetics parameters, as well as anti-JY09 antibody incidence and titers.

Official Title
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Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of JY09, a Long-acting Glucagon-like Peptide-1 Mimetic, in Healthy Subjects

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: JY09


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy subjects Male's mass is ≥50 kg, female's mass is ≥45 kg, have a body mass index between 18 and 26 kg/m^2 Subjects or their legal representative signed informed consent agree to use instruments of contraception from the time of the first dose until 6 months after the last dose of investigational drug, avoid pregnancy make yourself or your mate Able to keep good communication with investigator and comply with the requirements of the clinical trials Exclusion Criteria: Smokers,quitting time less than 3 months , or can't quit smoking during the trial Use of any prescription drugs within 4 weeks prior dosing, or over-the-counter medication (vitamins, herbal supplements, dietary supplements) within 2 weeks prior to dosing,or being treated for a direct lower gastrointestinal or using steroids Participation in any clinical investigation within 3 months prior to dosing Donation or loss of 400 mL or more of blood within 8 weeks prior to first dosing Significant illness within 2 weeks prior to dosing,and investigator judge doesn't fit to participate in this trial A history of clinical significance of abnormal ECG A history of diabetes, hyperuricemia and hyperlipidemia A history of acute or chronic bronchial spasms Have clinical significant gastrointestinal diseases Have serious, progressive, or uncontrolled organ or system diseases Abuse of drug or alcohol within 12 months before first dosing People who are pregnant, nursing mothers, or in the near future plan to be pregnant,or show pregnancy test positive before into group Subjects who, in the opinion of the investigator, are in any way unsuitable to participate in the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 0.3-mg<br>Eligible subjects received 0.3 mg placebo or JY09 on day 1 in this cohort | Drug: JY09<br>* Subcutaneous injection<br>* Other names: Placebo;|
| Experimental: Cohort 0.7-mg<br>Eligible subjects received 0.3 mg placebo or JY09 on days 1, and 0.7 mg placebo or JY09 on days 22 | Drug: JY09<br>* Subcutaneous injection<br>* Other names: Placebo;|
| Experimental: Cohort 1.5-mg<br>Eligible subjects received 0.7 mg placebo or JY09 on days 1, and 1.5 mg placebo or JY09 on days 22 | Drug: JY09<br>* Subcutaneous injection<br>* Other names: Placebo;|
| Experimental: Cohort 3.0-mg<br>Eligible subjects received 0.7 mg placebo or JY09 on days 1, and 3.0 mg placebo or JY09 on days 22 | Drug: JY09<br>* Subcutaneous injection<br>* Other names: Placebo;|
| Experimental: Cohort 6.0-mg<br>Eligible subjects received 0.7 mg placebo or JY09 on days 1, and 1.0 mg placebo or JY09 on days 15, and 6.0 mg placebo or JY09 on days 30 | Drug: JY09<br>* Subcutaneous injection<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events and serious adverse events related to JY09 |  | Up to day 21 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacodynamics parameters: Cmax | Average Cmax of each dose level | Up To day 42 | 
| Pharmacodynamics parameters: AUC | Average AUC follewing single dose of each doase level | Up to day 42 | 
| Pharmacodynamics parameters: Half-life | Average Half-life of each dose level | Up to day 42 | 
| Pharmacokinetics parameters | OGTT test was conducter predose and 5 days after the target dose in each cohorts | Day 5 | 
| Immunogenicity | Anti-JY09 antibody incidence at each dose level | Up To day 42 |