Evaluation of the Effects of Exendin-4 Fc Fusion Protein (JY09) Injection on the Pharmacokinetic Profiles of Metformin Hydrochloride Tablets, Rosuvastatin Calcium Tablets, and Digoxin Tablets and on the QT Interval in Overweight Chinese Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 28
- 试验地点
- 1
- 主要终点
- The Metformin Peak Concentration (Cmax )
研究概览
简要总结
This trial is conducted in china. The aim of the trial is as follows:
- To assess the effect of multiple subcutaneous injections of JY09 injection on the pharmacokinetic (PK) profile of multiple oral doses of metformin hydrochloride tablets, a single oral dose of Rosuvastatin calcium tablets, or digoxin tablets in overweight Chinese subjects;
- To assess the effect of multiple subcutaneous injections of JY09 injection on QT interval in overweight Chinese subjects.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age: Overweight subjects with full capacity for civil behavior who are ≥ 18 years old and ≤ 45 years old (the ratio of the number of subjects of either sex is not less than 1/3).
- •Body weight: men ≥ 50.0 kg, women ≥ 45.0 kg, body mass index (BMI) ≥ 24.0 kg/m2 and ≤ 28.0 kg/m2 , BMI = weight (kg)/height (m2 ).
- •Those who do not plan to have children in the last 6 months, do not plan to donate sperm/eggs, and are willing to use effective contraception for 6 months after the end of dosing.
- •Fully understand the trial and possible adverse effects, have the ability to communicate normally with the investigator, as well as comply with study requirements, follow protocol procedures and limitations, and be able to visit on time.
- •Understand the content of the informed consent form, agree to participate in this trial and voluntarily sign the consent form.
排除标准
- •A clear history of central nervous system, cardiovascular system, renal, hepatic, pulmonary, metabolic, and musculoskeletal disorders or other notable diseases.
- •Individuals with gastrointestinal disorders, such as history of hepatobiliary disease, history of gastrointestinal disease, history of gastrointestinal surgery (except appendectomy) or history of chronic pancreatitis or idiopathic acute pancreatitis, and those with habitual diarrhea.
- •Previous tip-twisting ventricular tachycardia or other risk factors that can lead to malignant arrhythmias, or a family history of first-degree relatives (i.e., biological parents, siblings, or children) with short QT syndrome, long QT syndrome, unexplained sudden death, drowning, or sudden infant death syndrome in young adulthood (less than/equal to 40 years of age), or cardiac conduction block.
- •Have disorders of electrolyte metabolism such as hyperkalemia, hypokalemia, hypomagnesemia, hypomagnesemia, hypercalcemia or hypocalcemia.
- •If the results of vital signs (blood pressure, pulse, respiration, temperature) are abnormal and clinically significant, a retest is allowed to confirm the results if they are abnormal, and the abnormal values of each vital sign.
- •Physical examination, laboratory tests, 12-lead electrocardiogram (ECG), abdominal ultrasound, calcitonin and chest radiographs (orthopantomograms) suggesting the presence of abnormalities judged by the investigator to be clinically significant (retesting was allowed once).
- •Smokers who smoked an average of more than 5 cigarettes per day in the 3 months prior to screening or who could not give up smoking during their participation in the trial or who had a positive smoke test.
- •Those who have participated in other clinical trials as a subject within 3 months prior to screening.
- •Those who donated blood or blood products ≥400 mL within 3 months prior to screening.
- •Those who cannot tolerate venipuncture and have a history of needle and blood sickness.
研究组 & 干预措施
Exendin-4 Fc fusion protein (JY09) injection
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.
干预措施: Exendin-4 Fc fusion protein (JY09) injection (Drug)
Exendin-4 Fc fusion protein (JY09) injection
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.
干预措施: Metformin Hydrochloride tablet (Drug)
Exendin-4 Fc fusion protein (JY09) injection
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.
干预措施: Rosuvastatin calcium tablets (Drug)
Exendin-4 Fc fusion protein (JY09) injection
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.
干预措施: Digoxin tablet (Drug)
结局指标
主要结局
The Metformin Peak Concentration (Cmax )
时间窗: 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 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.
The Rosuvastatin Peak Concentration (Cmax )
时间窗: 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 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.
Area under the Metformin blood concentration-time curve
时间窗: 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)
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.
Area under the Rosuvastatin blood concentration-time curve
时间窗: 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 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.
The Digoxin Peak Concentration (Cmax )
时间窗: From time 0 to 168 hours after a single dose of Digoxin without JY09 exposure (Day 15) and at JY09 steady state (Day 102)
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.
Baseline-corrected difference of Corrected QT interval after multiple subcutaneous injections of JY09 injection
时间窗: From time 0 to 72 hours after a single dose of JY09 (Day 22) and at JY09 steady state (Day 92)
Corrected QT interval is a QT interval adjusted by heart rate, which is an index of cardiac depolarization and repolarization
次要结局
- Safety endpoint-Adverse events(From baseline (Day -1) to follow-up (Day 123))
- Vital signs-Pulse(From baseline (Day -1) to follow-up (Day 123))
- Immunogenicity(From baseline (Day -1) to follow-up (Day 123))
- Vital signs-Respiration(From baseline (Day -1) to follow-up (Day 123))
- Laboratory tests-coagulation function(From baseline (Day -1) to follow-up (Day 123))
- 12-lead electrocardiogram (ECG)(From baseline (Day -1) to follow-up (Day 123))
- Vital signs-Blood pressure(From baseline (Day -1) to follow-up (Day 123))
- Physical examination(From baseline (Day -1) to follow-up (Day 123))
- Laboratory tests-Blood biochemistry(From baseline (Day -1) to follow-up (Day 123))
- Laboratory tests-Urine routine(From baseline (Day -1) to follow-up (Day 123))
- Laboratory tests-Routine blood(From baseline (Day -1) to follow-up (Day 123))