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This trial is conducted in china. The aim of the trial is as follows:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Exendin-4 Fc fusion protein (JY09) injection | Experimental | D22 received a single subcutaneous abdominal injection of 1.2 mg of JY09 injection after completion of PK blood sampling; D29 to D78 received continuous subcutaneous abdominal injections of 2.4 mg of JY09 injection in the morning, once weekly (total of 8 administrations). All doses were to be administered within 3 min. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Exendin-4 Fc fusion protein (JY09) injection | Drug | D22 received a single subcutaneous abdominal injection of 1.2 mg of JY09 injection after completion of PK blood sampling; D29, D36, D43, D50, D57, D64, D71, and D78 subjects returned to the study center to receive a subcutaneous abdominal injection of 2.4 mg of JY09 injection(total of 8 administrations).All doses were to be administered within 3 min. |
| Measure | Description | Time Frame |
|---|---|---|
| The Metformin Peak Concentration (Cmax ) | The peak concentration(Cmax） is the highest level of plasma concentration that occurs after administration.This parameter is an important index to reflect the absorption rate and degree of drug in vivo. | During a dosing interval (0-36 hours) after the last of 7 repeated doses of metformin without JY09 exposure (Day 4) and at JY09 steady state (Day 88) |
| Area under the Metformin blood concentration-time curve | AUC refers to the area under the drug time curve, which is the area surrounded by the pharmacokinetic blood concentration curve to the time axis. This parameter is an important index to evaluate the degree of drug absorption, reflecting the exposure characteristics of drugs in vivo. | During a dosing interval (0-36 hours) after the last of 7 repeated doses of metformin without JY09 exposure (Day 4) and at JY09 steady state (Day 88) |
| The Rosuvastatin Peak Concentration (Cmax ) | The peak concentration(Cmax） is the highest level of plasma concentration that occurs after administration.This parameter is an important index to reflect the absorption rate and degree of drug in vivo. | From time 0 to 96 hours after a single dose of Rosuvastatin without JY09 exposure (Day 8) and at JY09 steady state (Day 95) |
| Area under the Rosuvastatin blood concentration-time curve | Area under curve(AUC) refers to the area under the drug time curve, which is the area surrounded by the pharmacokinetic blood concentration curve to the time axis. This parameter is an important index to evaluate the degree of drug absorption, reflecting the exposure characteristics of drugs in vivo. | From time 0 to 96 hours after a single dose of Rosuvastatin without JY09 exposure (Day 8) and at JY09 steady state (Day 95) |
| The Digoxin Peak Concentration (Cmax ) |
| Measure | Description | Time Frame |
|---|---|---|
| Safety endpoint-Adverse events | All adverse medical events occurring after the subject receives the experimental drug, which may be manifested as symptoms, signs, diseases, or abnormalities in laboratory tests, but may not necessarily have a causal relationship with the experimental drug. | From baseline (Day -1) to follow-up (Day 123) |
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Effect Curve from time 0 to the last measurable concentration (AUEC0-t ) | AUEC0-t is a Pharmacodynamics -related endpoint for glucose, C-peptide and insulin in the Oral glucose tolerance test (OGTT),which reflects the amount of exposure to the effect. | From time 0 to 240 minutes after Oral glucose(Day21) and Oral glucose(Day84). |
Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Peking University Third Hospital drug clinical trial Institute | Beijing | Beijing Municipality | China |
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| Metformin Hydrochloride tablet | Drug | D1 to D4 continuous oral administration of 0.5 g metformin hydrochloride tablets twice daily (D4 was administered only in the morning, with a total of 7 administrations) for a washout period of 96 h;0.5 g metformin hydrochloride tablets orally twice a day continuously from D85 to D88 (D88 was given only in the morning, for a total of 7 doses). |
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| Rosuvastatin calcium tablets | Drug | D8 received a single oral administration of 10 mg of Rosuvastatin calcium tablets in the morning, with a washout period of 168 h,and 10 mg Rosuvastatin calcium tablets orally at 72 h ± 0.5 h (D95) after JY09 administration. |
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| Digoxin tablet | Drug | D15 received a single oral administration of 0.25 mg digoxin tablets in the morning, with a washout period of 168 h,oral 0.25 mg digoxin tablets 72 h±0.5 h after JY09 administration (D102) |
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The peak concentration(Cmax） is the highest level of plasma concentration that occurs after administration.This parameter is an important index to reflect the absorption rate and degree of drug in vivo.
| From time 0 to 168 hours after a single dose of Digoxin without JY09 exposure (Day 15) and at JY09 steady state (Day 102) |
| Baseline-corrected difference of Corrected QT interval after multiple subcutaneous injections of JY09 injection | Corrected QT interval is a QT interval adjusted by heart rate, which is an index of cardiac depolarization and repolarization | From time 0 to 72 hours after a single dose of JY09 (Day 22) and at JY09 steady state (Day 92) |
| Vital signs-Blood pressure |
Blood pressure includes systolic and diastolic blood pressure. |
| From baseline (Day -1) to follow-up (Day 123) |
| Vital signs-Pulse | Pulse refers to the pulsation formed in the arteries when the heart contracts, due to the flow of blood from the heart into the arteries. Pulse is one of the vital signs of human body, and it is an important index to measure heart rate and blood pressure. | From baseline (Day -1) to follow-up (Day 123) |
| Vital signs-Respiration | Respiration refers to the process of gas exchange between the body and the outside world. | From baseline (Day -1) to follow-up (Day 123) |
| Physical examination | Include general condition, skin, neck (including thyroid), head (including eyes, ears, nose, throat), chest, abdomen, back, lymph nodes, limbs, and nervous system. | From baseline (Day -1) to follow-up (Day 123) |
| Laboratory tests-Routine blood | Blood routine refers to the examination of blood conditions and diseases by observing the changes in the number and morphological distribution of blood cells. | From baseline (Day -1) to follow-up (Day 123) |
| Laboratory tests-Blood biochemistry | Blood biochemical examination can determine the content of sugars, lipids, hormones, ions and other substances in the blood, and provide help for the diagnosis and treatment of diseases. | From baseline (Day -1) to follow-up (Day 123) |
| Laboratory tests-Urine routine | Urine routine is of great significance not only for the observation of the curative effect of the diagnosis of urinary system diseases, but also for the diagnosis and prognosis of other system diseases. | From baseline (Day -1) to follow-up (Day 123) |
| Laboratory tests-coagulation function | The coagulation function test is mainly to find out whether the clotting factors in the patient's body are abnormal. | From baseline (Day -1) to follow-up (Day 123) |
| 12-lead electrocardiogram (ECG) | Electrocardiogram (ECG) is an objective index of the occurrence, propagation and recovery of cardiac excitation. It is used for the examination of various arrhythmias, ventricular and atrial hypertrophy, myocardial infarction, arrhythmia, myocardial ischemia and other diseases. | From baseline (Day -1) to follow-up (Day 123) |
| Immunogenicity | Immunogenicity refers to the performance that can cause an immune response, that is, the antigen can stimulate specific immune cells, so that immune cells activation, proliferation, differentiation, and eventually produce immune effecting substances antibodies and sensitized lymphocytes. | From baseline (Day -1) to follow-up (Day 123) |
| The Peak Effect Concentration(ECmax） |
ECmax is a Pharmacodynamics -related endpoint for glucose, C-peptide and insulin in the Oral glucose tolerance test (OGTT),which reflects the maximum effective concentration. |
| From time 0 to 240 minutes after Oral glucose(Day21) and Oral glucose(Day84). |
| Maximum Effect Time(ETmax ) | ETmax is a Pharmacodynamics -related endpoint for glucose, C-peptide and insulin in the Oral glucose tolerance test (OGTT),which reflects the time of the first maximum effect. | From time 0 to 240 minutes after Oral glucose(Day21) and Oral glucose(Day84). |
| (AUEC0-t after JY09 administration - AUEC0-t before JY09 administration)/AUEClast before JY09 administration ×100%(Δ%AUEC0-t) | Δ%AUEC0-t is a Pharmacodynamics -related endpoint for glucose, C-peptide and insulin in the Oral glucose tolerance test (OGTT), which reflects changes in the amount of effect exposure before and after administration. | From time 0 to 240 minutes after Oral glucose(Day21) and Oral glucose(Day84). |
| (post-administration Maximum Effect(Emax)- pre-administration Maximum Effect(Emax))/pre-administration Maximum Effect(Emax)×100%(Δ%Emax ) | Δ%Emax is a Pharmacodynamics -related endpoint for glucose, C-peptide and insulin in the Oral glucose tolerance test (OGTT), which reflects changes in maximum effects before and after administration. | From time 0 to 240 minutes after Oral glucose(Day21) and Oral glucose(Day84). |
| Body fat mass | Body fat mass refers to the amount of fat in a person's body. | Day19 or Day20,Day103 or Day104. |
| Body fat percentage | Body fat percentage refers to fat content as a percentage of total body weight. | Day19 or Day20,Day103 or Day104. |
| Fat-free weight | Fat-free weight refers to the body weight after the removal of fat, also known as lean body weight, is the weight of other body components other than fat. | Day19 or Day20,Day103 or Day104. |
| Skeletal muscle mass | Skeletal muscle mass is the percentage of skeletal muscle in the body, and can be used to determine health status. | Day19 or Day20,Day103 or Day104. |
| Waist-to-hip ratio | Waist-to-hip ratio is the ratio between waist and hip circumference and is an important indicator of central obesity. | Day19 or Day20,Day103 or Day104. |
| Visceral fat area | Visceral fat area is an indicator used to assess the degree of abdominal obesity in an individual, and it can be measured in a number of ways, such as CT (computed tomography) or MRI (magnetic resonance imaging). This area of adipose tissue around the abdomen is associated with the risk of a number of chronic diseases such as heart disease and diabetes. | Day19 or Day20,Day103 or Day104. |
| Pharmacodynamically relevant plasma endogenous markers（If necessary） | The investigator will use JY09 PK residual or backup plasma samples from this trial to assay efficacy-related endogenous marker concentrations to support individualized dosing of JY09. | From time 0 to 72 hours after a single dose of JY09 (Day 22) and at JY09 steady state (Day 92) and Day21，Day29，Day43，Day83 |
| Pharmacodynamically relevant plasma metabolomics(if necessary) | The investigator will use JY09 PK residual or backup plasma samples from this trial to assay efficacy-related metabolomics to support individualized dosing of JY09. | From time 0 to 72 hours after a single dose of JY09 (Day 22) and at JY09 steady state (Day 92) and Day21，Day29，Day43，Day83 |
| Blood Cell Genotype Characterization (if necessary) | Blood cell samples after centrifugation at each time point of the immunogenicity assay were retained for each subject so that they could be used for genotypic testing at a later stage, if necessary, to support individualized dosing of JY09. | Day21，Day29，Day43，Day83 |
| Bacteria genus | Species of bacteria in intestinal flora. | Day21 or Day22,Day84 or Day85 |
| Relative abundance | Relative abundance of genera and strains of bacteria | Day21 or Day22,Day84 or Day85 |
| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| D050177 | Overweight |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D001835 | Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D007267 | Injections |
| D008687 | Metformin |
| D000068718 | Rosuvastatin Calcium |
| D004077 | Digoxin |
| ID | Term |
|---|---|
| D004333 | Drug Administration Routes |
| D004358 | Drug Therapy |
| D013812 | Therapeutics |
| D001645 | Biguanides |
| D006146 | Guanidines |
| D000578 | Amidines |
| D009930 | Organic Chemicals |
| D013449 | Sulfonamides |
| D000577 | Amides |
| D005464 | Fluorobenzenes |
| D006845 | Hydrocarbons, Fluorinated |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D004071 | Digitalis Glycosides |
| D002298 | Cardenolides |
| D002301 | Cardiac Glycosides |
| D002297 | Cardanolides |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
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