A Phase 1, Open Label, Fixed Sequence Study to Evaluate the Effect of ECC5004 on the Single Dose Pharmacokinetics of Atorvastatin, Rosuvastatin, Digoxin and Midazolam in Healthy Participants
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- Rosuvastatin PK parameters: Cmax
研究概览
简要总结
This is a Phase 1, open-label, non-randomized, fixed sequence study designed to evaluate the effect of ECC5004 on single dose pharmacokinetics of Atorvastatin, Rosuvastatin, Digoxin and Midazolam in healthy participants.
详细描述
The study consists of four parts (Part A, Part B, optional Part C and optional Part D), each with approximately 16 healthy participants enrolled. Part A and optional Part C of the study will have the same study design with two treatment periods, except that ECC5004 will be administered at a higher dose level in the optional Part C. Part B and optional Part D of the study will have the same study design with five treatment periods, except that ECC5004 will be administered at a higher dose level in optional Part D. Rosuvastatin and Digoxin will be administered alone or in combination with EC5004 in Part A and optional Part C. Atorvastatin and Midazolam will be administered alone or in combination with ECC5004 in Part B and optional Part D. The conduct of Part C and Part D with an increased dose of ECC5004 may be conducted as optional parts.
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Male and female participants of non-childbearing potential (NCBP) between the ages of 18 to 65 years of age
- •BMI of 18.0 to 32.0 kg/m2
- •Female participants who are postmenopausal, confirmed by FSH test, or surgically sterile, confirmed by medical documentation, or agree to practice true abstinence
- •Male participants agree to use contraception, or agree to practice true abstinence
- •No clinically significant findings in physical examination, 12-lead electrocardiogram (ECG), vital sign measurements, clinical laboratory evaluations, concomitant medications, or medical/psychiatric history
- •Able to understand and sign and date informed consent
排除标准
- •Females who are pregnant, planning to become pregnant, or breastfeeding during the study or within 3 months after the study
- •Concomitant participation in any investigational study of any nature
- •Blood loss of non-physiological reasons ≥ 200 ml (i.e., trauma, blood collection, blood donation) within 2 months prior to the first dose of study treatment, or plan to donate blood during this trial and within 1 month after the last dose of study treatment
- •Serum calcitonin > 20 ng/L
- •Clinically relevant acute or chronic medical conditions or diseases of the cardiovascular, gastrointestinal, hepatic, renal, endocrine, pulmonary, neurologic, psychiatric, immune or dermatologic systems
- •Individual or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia 2 (MEN2), or suspected MTC
- •History of pancreatitis
- •Significant allergic reaction to active ingredients or excipients of the study drug
- •Any clinically significant abnormal findings in the participant's physical examination, laboratory tests, pregnancy test, urine drug screen, alcohol test, or medical history which in the opinion of the Investigator would prevent the participants from participating in the study
- •Used or plan to use any drugs or substances that can modulate the activity of CYP3A4 within at least 14 days prior to the first dose of study treatment until after their final follow up visit
- •Use of drugs with enzyme-inducing properties such as St. John's Wort within 3 weeks prior to the first dose of study treatment until after their final follow up visit
研究组 & 干预措施
Digoxin, Rosuvastatin, ECC5004 (Part A)
Part A consists of 2 treatment periods. Participants will receive Digoxin and Rosuvastatin administered alone in treatment period 1 and in combination with ECC5004 in treatment period 2.
干预措施: Rosuvastatin (Drug)
Digoxin, Rosuvastatin, ECC5004 (Part A)
Part A consists of 2 treatment periods. Participants will receive Digoxin and Rosuvastatin administered alone in treatment period 1 and in combination with ECC5004 in treatment period 2.
干预措施: Digoxin (Drug)
Digoxin, Rosuvastatin, ECC5004 (Part A)
Part A consists of 2 treatment periods. Participants will receive Digoxin and Rosuvastatin administered alone in treatment period 1 and in combination with ECC5004 in treatment period 2.
干预措施: ECC5004 (Drug)
Midazolam, Atorvastatin, ECC5004 (Part B)
Part B consists of 5 treatment periods. In treatment period 1, participants will receive Midazolam administered alone followed by treatment period 2 in which participants will receive Atorvastatin administered alone. In treatment period 3, participants will receive ECC5004 alone. In treatment period 4, participants will receive ECC5004 in combination with Midazolam. In treatment period 5, ECC5004 will be administered alone and co-administered with Atorvastatin.
干预措施: ECC5004 (Drug)
Midazolam, Atorvastatin, ECC5004 (Part B)
Part B consists of 5 treatment periods. In treatment period 1, participants will receive Midazolam administered alone followed by treatment period 2 in which participants will receive Atorvastatin administered alone. In treatment period 3, participants will receive ECC5004 alone. In treatment period 4, participants will receive ECC5004 in combination with Midazolam. In treatment period 5, ECC5004 will be administered alone and co-administered with Atorvastatin.
干预措施: Midazolam (Drug)
Midazolam, Atorvastatin, ECC5004 (Part B)
Part B consists of 5 treatment periods. In treatment period 1, participants will receive Midazolam administered alone followed by treatment period 2 in which participants will receive Atorvastatin administered alone. In treatment period 3, participants will receive ECC5004 alone. In treatment period 4, participants will receive ECC5004 in combination with Midazolam. In treatment period 5, ECC5004 will be administered alone and co-administered with Atorvastatin.
干预措施: Atorvastatin (Drug)
Digoxin, Rosuvastatin, ECC5004 (optional Part C)
Optional Part C consists of 2 treatment periods. Participants will receive Digoxin and Rosuvastatin administered alone in treatment period 1 and in combination with ECC5004 in treatment period 2.
干预措施: ECC5004 (Drug)
Digoxin, Rosuvastatin, ECC5004 (optional Part C)
Optional Part C consists of 2 treatment periods. Participants will receive Digoxin and Rosuvastatin administered alone in treatment period 1 and in combination with ECC5004 in treatment period 2.
干预措施: Rosuvastatin (Drug)
Digoxin, Rosuvastatin, ECC5004 (optional Part C)
Optional Part C consists of 2 treatment periods. Participants will receive Digoxin and Rosuvastatin administered alone in treatment period 1 and in combination with ECC5004 in treatment period 2.
干预措施: Digoxin (Drug)
Midazolam, Atorvastatin, ECC5004 (optional Part D)
Optional Part D consists of 5 treatment periods. In treatment period 1, participants will receive Midazolam administered alone followed by treatment period 2 in which participants will receive Atorvastatin administered alone. In treatment period 3, participants will receive ECC5004 alone. In treatment period 4, participants will receive ECC5004 in combination with Midazolam. In treatment period 5, ECC5004 will be administered alone and co-administered with Atorvastatin.
干预措施: ECC5004 (Drug)
Midazolam, Atorvastatin, ECC5004 (optional Part D)
Optional Part D consists of 5 treatment periods. In treatment period 1, participants will receive Midazolam administered alone followed by treatment period 2 in which participants will receive Atorvastatin administered alone. In treatment period 3, participants will receive ECC5004 alone. In treatment period 4, participants will receive ECC5004 in combination with Midazolam. In treatment period 5, ECC5004 will be administered alone and co-administered with Atorvastatin.
干预措施: Midazolam (Drug)
Midazolam, Atorvastatin, ECC5004 (optional Part D)
Optional Part D consists of 5 treatment periods. In treatment period 1, participants will receive Midazolam administered alone followed by treatment period 2 in which participants will receive Atorvastatin administered alone. In treatment period 3, participants will receive ECC5004 alone. In treatment period 4, participants will receive ECC5004 in combination with Midazolam. In treatment period 5, ECC5004 will be administered alone and co-administered with Atorvastatin.
干预措施: Atorvastatin (Drug)
结局指标
主要结局
Rosuvastatin PK parameters: Cmax
时间窗: Part A and optional Part C: up to Day 11
Maximum observed plasma concentration
Atorvastatin PK parameters: AUC(0-tlast)
时间窗: Part B and optional Part D: up to Day 34
Area under the Plasma Concentration-Time Curve from Time 0 to the Last Measurable Non Zero Concentration
Rosuvastatin PK parameters: AUC(0-tlast)
时间窗: Part A and optional Part C: up to Day 11
Area under the Plasma Concentration-Time Curve from Time 0 to the Last Measurable Non Zero Concentration
Rosuvastatin PK parameters: AUC(0-inf)
时间窗: Part A and optional Part C: up to Day 11
Area under the Plasma Concentration-Time Curve from Time 0 Extrapolated to Infinity
Midazolam PK parameters: Cmax
时间窗: Part B and optional Part D: up to Day 34
Maximum observed plasma concentration
Atorvastatin PK parameters: AUC(0-inf)
时间窗: Part B and optional Part D: up to Day 34
Area under the Plasma Concentration-Time Curve from Time 0 Extrapolated to Infinity
Midazolam PK parameters: AUC(0-tlast)
时间窗: Part B and optional Part D: up to Day 34
Area under the Plasma Concentration-Time Curve from Time 0 to the Last Measurable Non Zero Concentration
Atorvastatin PK parameters: Cmax
时间窗: Part B and optional Part D: up to Day 34
Maximum observed plasma concentration
Digoxin PK parameters: AUC(0-tlast)
时间窗: Part A and optional Part C: up to Day 11
Area under the Plasma Concentration-Time Curve from Time 0 to the Last Measurable Non Zero Concentration
Digoxin PK parameters: Cmax
时间窗: Part A and optional Part C: up to Day 11
Maximum observed plasma concentration
Digoxin PK parameters: AUC(0-inf)
时间窗: Part A and optional Part C: up to Day 11
Area under the Plasma Concentration-Time Curve from Time 0 Extrapolated to Infinity
Midazolam PK parameters: AUC(0-inf)
时间窗: Part B and optional Part D: up to Day 34
Area under the Plasma Concentration-Time Curve from Time 0 Extrapolated to Infinity
次要结局
- ECC5004 Safety parameters: Number of participants with adverse events (AEs)(Part A and optional Part C: up to Day 16; Part B and optional Part D: up to Day 40)
- Rosuvastatin safety parameters: Number of participants with physical examination abnormalities(Part A and optional Part C: up to Day 16)
- ECC5004 PK parameters: Ctau(Part A and optional Part C: up to Day 11; Part B and optional Part D: up to Day 34)
- Atorvastatin safety parameters: Number of participants with electrocardiogram (ECG)(Part B and optional Part D: up to Day 40)
- Atorvastatin safety parameters: Number of participants with physical examination abnormalities(Part B and optional Part D: up to Day 40)
- Digoxin safety parameters: Number of participants with vital sign abnormalities(Part A and optional Part C: up to Day 16)
- Digoxin safety parameters: Number of participants with electrocardiogram (ECG) abnormalities(Part A and optional Part C: up to Day 16)
- Midazolam safety parameters: Number of participants with adverse events (AEs)(Part B and optional Part D: up to Day 40)
- Midazolam safety parameters: Number of participants with electrocardiogram (ECG) abnormalities(Part B and optional Part D: up to Day 40)
- Rosuvastatin safety parameters: Number of participants with adverse events (AEs)(Part A and optional Part C: up to Day 16)
- Rosuvastatin safety parameters: Number of participants with clinical laboratory abnormalities(Part A and optional Part C: up to Day 16)
- Digoxin safety parameters: Number of participants with clinical laboratory abnormalities(Part A and optional Part C: up to Day 16)
- Midazolam safety parameters: Number of participants with physical examination abnormalities(Part B and optional Part D: up to Day 40)
- ECC5004 Safety parameters: Number of participants with vital sign abnormalities(Part A and optional Part C: up to Day 16; Part B and optional Part D: up to Day 40)
- ECC5004 Safety parameters: Number of participants with physical examination abnormalities(Part A and optional Part C: up to Day 16; Part B and optional Part D: up to Day 40)
- Atorvastatin safety parameters: Number of participants with vital sign abnormalities(Part B and optional Part D: up to Day 40)
- Atorvastatin safety parameters: Number of participants with clinical laboratory abnormalities(Part B and optional Part D: up to Day 40)
- Rosuvastatin safety parameters: Number of participants with electrocardiogram (ECG) abnormalities(Part A and optional Part C: up to Day 16)
- Digoxin safety parameters: Number of participants with physical examination abnormalities(Part A and optional Part C: up to Day 16)
- Midazolam safety parameters: Number of participants with vital sign abnormalities(Part B and optional Part D: up to Day 40)
- Midazolam safety parameters: Number of participants with clinical laboratory abnormalities(Part B and optional Part D: up to Day 40)
- ECC5004 PK parameters: AUC(0-24)(Part A and optional Part C: up to Day 11; Part B and optional Part D: up to Day 34)
- ECC5004 PK parameters: CL/F(Part A and optional Part C: up to Day 11; Part B and optional Part D: up to Day 34)
- ECC5004 Safety parameters: Number of participants with electrocardiogram (ECG) abnormalities(Part A and optional Part C: up to Day 16; Part B and optional Part D: up to Day 40)
- ECC5004 Safety parameters: Number of participants with clinical laboratory abnormalities(Part A and optional Part C: up to Day 16; Part B and optional Part D: up to Day 40)
- Atorvastatin safety parameters: Number of participants with adverse events (AEs)(Part B and optional Part D: up to Day 40)
- Rosuvastatin safety parameters: Number of participants with vital sign abnormalities(Part A and optional Part C: up to Day 16)
- Digoxin safety parameters: Number of participants with adverse events (AEs)(Part A and optional Part C: up to Day 16)
- ECC5004 PK parameters: AUC (0-τ)(Part A and optional Part C: up to Day 11; Part B and optional Part D: up to Day 34)
- ECC5004 PK parameters: tmax(Part A and optional Part C: up to Day 11; Part B and optional Part D: up to Day 34)
- ECC5004 PK parameters: t1/2(Part A and optional Part C: up to Day 11; Part B and optional Part D: up to Day 34)