A Phase I, Randomised, Single-blind, Placebo-controlled, Single and Repeated Dose-escalation Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AZD5004 in Healthy Japanese Participants and With Type 2 Diabetes Mellitus
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 35
- 试验地点
- 1
- 主要终点
- PartA: Number of participants with adverse events (AEs) and serious adverse events (SAEs)
研究概览
简要总结
This Phase I study will gather important information on the safety, tolerability, pharmacokinetics and pharmacodynamics of AZD5004 in both healthy Japanese participants and Japanese participants with T2DM.
详细描述
This is a placebo-controlled study to assess the safety, efficacy, tolerability, and PK of single and repeated dosing of AZD5004 compared with placebo.
Participants who are eligible according to the inclusion/exclusion criteria will be randomized to receive AZD5004 or matching placebo.
The study will comprise:
- A Screening Period of maximum 28 days.
- A Treatment Period of 1 day(Part A) or 105 days (Part B).
- A final Follow-up Visit approximately 7 days(Part A) or 14 days(Part B) after the last study intervention administration.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Japanese men or women, and 18-65 years of age inclusive, at the time of signing the informed consent.
- •Inclusion Criteria for Part A:
- •HbA1c ≤ 6.0%.
- •Body weight ≥ 50.0 kg and BMI within the range 18.0-32.0 kg/m
- •Inclusion Criteria for Part B:
- •HbA1c ≥ 6.5% and ≤ 10.5%.
- •Not on any other diabetic medications.
- •Body weight ≥ 60.0 kg and BMI within the range 24.0-35.0 kg/m2
排除标准
- •Has a clinically relevant acute or chronic medical condition or disease.
- •History of acute pancreatitis and chronic pancreatitis, gallstones.
- •Abnormal renal function.
- •Known clinically significant gastric emptying abnormality
- •Significant hepatic disease.
- •Uncontrolled thyroid disease
研究组 & 干预措施
Part A-AZD5004
Participants will receive AZD5004 orally.
干预措施: AZD5004(Part A) (Drug)
Part A-Placebo
Participants will receive matching Placebo orally.
干预措施: Placebo(Part A) (Drug)
Part B-AZD5004
Participants will receive AZD5004 orally.
干预措施: AZD5004(Part B) (Drug)
Part B-Placebo
Participants will receive matching Placebo orally.
干预措施: Placebo(Part B) (Drug)
结局指标
主要结局
PartA: Number of participants with adverse events (AEs) and serious adverse events (SAEs)
时间窗: From screening (Day -28) to last follow up visit (Day 8)
To assess the safety and tolerability of AZD5004 following single oral doses in healthy participants.
PartB: Number of participants with adverse events (AEs) and serious adverse events (SAEs)
时间窗: From screening (Day -28) to last follow up visit (Day 119 )
To assess the safety and tolerability of AZD5004 following multiple oral ascending doses in participants with T2DM.
次要结局
- PartB: AUC0-4 for glucose, insulin and C-peptide for MMTT(From Day 1 to Day 105)
- PartB: Absolute change from baseline to Day 105 in fasting plasma glucose(From Day 1 to Day 105)
- PartB: % change from baseline to Day 105 in HOMA-IR(From Day 1 to Day 105)
- PartB: The proportion of time in hyperglycaemia /hypoglycaemia over the last 7-day intervals at each dose level in CGM(From Day 1 to Day 106)
- PartB: % change from baseline to Day 105 in body weight (kg)(From Day 1 to Day 105)
- PartB: % change from baseline to Day 105 in waist circumference (cm)(From Day 1 to Day 105)
- PartA: Area under the Plasma Concentration vs. Time Curve(AUC0-24)(From Day 1 to Day 6)
- PartA: Area under the Plasma Concentration vs. Time Curve from Zero until the Time of the Last Concentration above the Limit of Quantification(AUC0-tlast)(From Day 1 to Day 6)
- PartA: Area under the Plasma Concentration vs. Time Curve from Zero to Infinity(AUC0-inf)(From Day 1 to Day 6)
- PartA: Maximum Observed Plasma Concentration(Cmax)(From Day 1 to Day 6)
- PartA: Plasma Concentration at 24 Hours Post-Dose(C24h)(From Day 1 to Day 6)
- PartA: Time of Occurrence of Maximum Plasma Concentration(tmax)(From Day 1 to Day 6)
- PartA: Lag Time before Observation of Quantifiable Analyte Concentrations in Plasma(tlag)(From Day 1 to Day 6)
- PartA: Half-Life(t1/2)(From Day 1 to Day 6)
- PartA: Last measurable Non-Zero Concentration(Clast)(From Day 1 to Day 6)
- PartA: Last measurable Non-Zero ConcentrationTime to Last Detectable Concentration(tlast)(From Day 1 to Day 6)
- PartA: Apparent Oral Clearance(CL/F)(From Day 1 to Day 6)
- PartA: Cumulative Urinary Excretion(Ae)(From Day 1 to Day 6)
- PartA: Clearance(CLR)(From Day 1 to Day 6)
- PartB: Area under the Plasma Concentration vs. Time Curve(AUC0-24)(Day 1)
- PartB: Maximum Observed Plasma Concentration(Cmax)(Day 1, Day 49, Day 63, Day 77, Day91, Day105)
- PartB: Plasma Concentration at 24 Hours Post-Dose(C24h)(Day 1)
- PartB: Time of Occurrence of Maximum Plasma Concentration(tmax)(Day 1, Day 49, Day 63, Day 77, Day91, Day105)
- PartB: Lag Time before Observation of Quantifiable Analyte Concentrations in Plasma(tlag)(Day 1)
- PartB: Area under the Plasma Concentration vs. Time Curve over the Dosing Interval(AUC0-τ)(Day 49, Day 63, Day 77, Day 91, Day 105)
- PartB: Observed Concentration at the End of the Dosing Interval(Cτ)(Day 49, Day 63, Day 77, Day 91, Day 105)
- PartB: Half-Life(t1/2)(Day 49, Day 63, Day 77, Day 91, Day 105)
- PartB: Apparent Oral Clearance(CL/F)(Day 49, Day 63, Day 77, Day 91, Day 105)
- PartB: Cumulative Urinary Excretion(Ae)(Day 105)
- PartB: Clearance(CLR)(Day 105)