An Open-label, Fixed-sequence, Two-part Study to Assess the Effect of AZD5004 on the Pharmacokinetics of Mitiglinide and Pioglitazone in Healthy Participants
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 32
- 试验地点
- 1
- 主要终点
- Area under concentration-time curve from time 0 to infinity (AUCinf)
研究概览
简要总结
The purpose of the study is to assess the effect of AZD5004 on the pharmacokinetics (PK) of mitiglinide and pioglitazone in healthy participants.
详细描述
This is an open-label, fixed-sequence, two-part study of mitiglinide (Part A) and pioglitazone (Part B) in healthy participants. Part A will assess the PK of mitiglinide when administered alone and in combination with AZD5004 while Part B will assess the PK of pioglitazone when administered alone and in combination of AZD5004.
Both parts are independent and non-sequential to each other.
Each study part will comprise of:
- A screening period of maximum 28 days.
- Four sequential treatment periods during which the participants will receive the study interventions.
- A final follow-up visit
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Participants with suitable veins for cannulation or repeated venipuncture.
- •All females must have a negative serum pregnancy test at the Screening Visit and on admission to the study site.
- •Females of childbearing potential must agree to use a highly effective contraception method from enrollment.
- •Male Participants, if heterosexually active, must practice true abstinence or use condoms during the trial and their female partners of childbearing potential must use additional effective contraception during the trial.
- •Body Mass Index (BMI) between 18 and 35 kg/m² and weigh at least 50 kg.
排除标准
- •History of any clinically important disease or disorder which may put the participant at risk or influence the results, including:
- •Clinically significant inflammatory bowel disease, gastroparesis, severe disease, or surgery affecting the upper gastrointestinal (GI) tract
- •Cardiovascular disease
- •Neuromuscular or neurogenic disease
- •Type 1 or type 2 diabetes mellitus
- •History of acute pancreatitis, chronic pancreatitis, gallstones, or elevation in serum lipase/pancreatic amylase.
- •History of clinically significant cardiovascular, dermatological, respiratory, neurological, psychiatric or GI disease disorder.
- •History of malignant neoplastic disease.
- •History or presence of GI disease or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
- •Any clinically important illness, medical/surgical procedure, or trauma.
- •Any clinically important abnormalities in clinical chemistry, hematology, coagulation, or urinalysis results.
- •Basal calcitonin level ≥ 35 ng/L or history/family history of medullary thyroid cancer or multiple endocrine neoplasia type 2 (MEN2).
- •Uncontrolled thyroid disease.
- •Any positive result on screening for serum human immunodeficiency virus (HIV).
- •Known or suspected history of alcohol or drug abuse or excessive intake of alcohol.
- •History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity to drugs with a similar chemical structure or class to AZD5004, or to mitiglinide and/or pioglitazone.
- •Participants who have previously received AZD5004.
研究组 & 干预措施
Part A: Mitiglinide + AZD5004
In Period 1, participants receive a single dose of mitiglinide on Day 1, followed by single doses of AZD5004 Dose A once daily from Days 3-9, then single doses of AZD5004 Dose B once daily from Days 10-16. In Period 2, participants receive single dose of mitiglinide co-administered with single dose of AZD5004 Dose B on Day 17, followed by a single dose of AZD5004 Dose B on Day 18, then single doses of AZD5004 Dose C once daily from Days 19-25, followed by single doses of AZD5004 Dose D once daily from Days 26-32. In Period 3, participants receive single dose of mitiglinide co-administered with single dose of AZD5004 Dose D on Day 33, followed by a single dose of AZD5004 Dose D on Day 34, then single doses of AZD5004 Dose E once daily from Days 35-41. In Period 4, participants receive single dose of mitiglinide co-administered with single dose of AZD5004 Dose E on Day 42, followed by a single dose of AZD5004 Dose E on Day 43.
干预措施: AZD5004 (Drug)
Part A: Mitiglinide + AZD5004
In Period 1, participants receive a single dose of mitiglinide on Day 1, followed by single doses of AZD5004 Dose A once daily from Days 3-9, then single doses of AZD5004 Dose B once daily from Days 10-16. In Period 2, participants receive single dose of mitiglinide co-administered with single dose of AZD5004 Dose B on Day 17, followed by a single dose of AZD5004 Dose B on Day 18, then single doses of AZD5004 Dose C once daily from Days 19-25, followed by single doses of AZD5004 Dose D once daily from Days 26-32. In Period 3, participants receive single dose of mitiglinide co-administered with single dose of AZD5004 Dose D on Day 33, followed by a single dose of AZD5004 Dose D on Day 34, then single doses of AZD5004 Dose E once daily from Days 35-41. In Period 4, participants receive single dose of mitiglinide co-administered with single dose of AZD5004 Dose E on Day 42, followed by a single dose of AZD5004 Dose E on Day 43.
干预措施: Mitiglinide (Drug)
Part B: Pioglitazone + AZD5004
In Period 1, participants receive a single dose of pioglitazone on Day 1, followed by single doses of AZD5004 Dose A once daily from Days 8-14, then single doses of AZD5004 Dose B once daily from Days 15-21. In Period 2, participants receive single dose of pioglitazone co-administered with single dose of AZD5004 Dose B on Day 22, followed by single doses of AZD5004 Dose B once daily from Days 23-28, then single doses of AZD5004 Dose C once daily from Days 29-35, followed by single doses of AZD5004 Dose D once daily from Days 36-42. In Period 3, participants receive single dose of pioglitazone co-administered with single dose of AZD5004 Dose D on Day 43, followed by single doses of AZD5004 Dose D once daily from Days 44-49, then single doses of AZD5004 Dose E once daily from Days 50-56. In Period 4, participants receive single dose of pioglitazone co-administered with single dose of AZD5004 Dose E on Day 57, followed by single doses of AZD5004 Dose E once daily from Days 58-63.
干预措施: Pioglitazone (Drug)
Part B: Pioglitazone + AZD5004
In Period 1, participants receive a single dose of pioglitazone on Day 1, followed by single doses of AZD5004 Dose A once daily from Days 8-14, then single doses of AZD5004 Dose B once daily from Days 15-21. In Period 2, participants receive single dose of pioglitazone co-administered with single dose of AZD5004 Dose B on Day 22, followed by single doses of AZD5004 Dose B once daily from Days 23-28, then single doses of AZD5004 Dose C once daily from Days 29-35, followed by single doses of AZD5004 Dose D once daily from Days 36-42. In Period 3, participants receive single dose of pioglitazone co-administered with single dose of AZD5004 Dose D on Day 43, followed by single doses of AZD5004 Dose D once daily from Days 44-49, then single doses of AZD5004 Dose E once daily from Days 50-56. In Period 4, participants receive single dose of pioglitazone co-administered with single dose of AZD5004 Dose E on Day 57, followed by single doses of AZD5004 Dose E once daily from Days 58-63.
干预措施: AZD5004 (Drug)
结局指标
主要结局
Area under concentration-time curve from time 0 to infinity (AUCinf)
时间窗: Part A: From Day 1 to Day 50; Part B: From Day 1 to Day 70
To assess the effect of AZD5004 on the PK (AUCinf) of mitiglinide and pioglitazone in healthy participants
Area under concentration-curve from time 0 to the last quantifiable concentration (AUClast)
时间窗: Part A: From Day 1 to Day 50; Part B: From Day 1 to Day 70
To assess the effect of AZD5004 on the PK (AUClast) of mitiglinide and pioglitazone in healthy participants
Maximum observed drug concentration (Cmax)
时间窗: Part A: From Day 1 to Day 50; Part B: From Day 1 to Day 70
To assess the effect of AZD5004 on the PK (Cmax) of mitiglinide and pioglitazone in healthy participants
次要结局
- Number of participants with adverse events (AEs) and AE of special interest (AESI)(Part A: Up to follow-up visit [Day 54 (± 3 days)]; Part B: Up to follow-up visit [Day 74 (± 3 days)])
- Terminal elimination half-life (t½λz)(Part A: From Day 1 to Day 50; Part B: From Day 1 to Day 70)
- Terminal rate constant (λz)(Part A: From Day 1 to Day 50; Part B: From Day 1 to Day 70)
- Time to reach maximum observed concentration (tmax)(Part A: From Day 1 to Day 50; Part B: From Day 1 to Day 70)
- Part A: Ratio of mitiglinide + AZD5004 to mitiglinide (alone) based on AUCinf (RAUCinf)(From Day 1 to Day 50)
- Part A: Ratio of mitiglinide + AZD5004 to mitiglinide (alone) based on AUClast (RAUClast)(From Day 1 to Day 50)
- Part A: Ratio of mitiglinide + AZD5004 to mitiglinide (alone) based on Cmax (RCmax)(From Day 1 to Day 50)
- Part B: Ratio of pioglitazone + AZD5004 to pioglitazone (alone) based on AUCinf (RAUCinf)(From Day 1 to Day 70)
- Part B: Ratio of pioglitazone + AZD5004 to pioglitazone (alone) based on AUClast (RAUClast)(From Day 1 to Day 70)
- Part B: Ratio of pioglitazone + AZD5004 to pioglitazone (alone) based on Cmax (RCmax)(From Day 1 to Day 70)