An Open-label, Randomized, Parallel Group, Four/Five Period, Eight Treatment Cross-over, Single Oral Dose Study to Assess the Relative Bioavailability of Different Formulations of AZD9977 and Dapagliflozin and Influence of Food in Selected Formulations in Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Maximum observed plasma (peak) drug concentration (Cmax)
研究概览
简要总结
The primary purpose of the study is to evaluate relative bioavailability of AZD9977 and dapagliflozin and compare the plasma concentration time profiles after dosing with different capsule formulations containing both AZD9977 and dapagliflozin or solely dapagliflozin, the AZD9977 capsule, and dapagliflozin tablet under fasted conditions.
详细描述
The study will be conducted at 2 study centers in Germany.
Eligible participants will be randomized to one of the 8 treatment sequences (4 unique sequences to Group 1 and 4 unique sequences to Group 2). In Group 1, participants will receive 5 single dose treatments, while in Group 2 participants will receive 4 single dose treatments.
Below treatments A, B, C, D and E will be given to participants in Group 1 and treatments A, F, G and H will be given to participants in Group 2 in randomized order:
- Treatment A: AZD9977 Dose A + 10 mg dapagliflozin tablet, fasted
- Treatment B: AZD9977 Dose A + 10 mg dapagliflozin capsule 1, fasted
- Treatment C: AZD9977 Dose A + 10 mg dapagliflozin capsule 1, fed
- Treatment D: AZD9977 Dose A + 10 mg dapagliflozin capsule 2, fasted
- Treatment E: AZD9977 Dose A + 10 mg dapagliflozin capsule 2, fed
- Treatment F: AZD9977 Dose A + 10 mg dapagliflozin capsule 3, fasted
- Treatment G: AZD9977 Dose A + 10 mg dapagliflozin capsule 4, fasted
- Treatment H: 10 mg dapagliflozin capsule, fasted
The study will comprise of the following:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy participants of non-childbearing potential with suitable veins for cannulation or repeated venipuncture at screening
- •Females must have a negative pregnancy test at the screening Visit and a negative urine pregnancy test at admission to the study center, must not be lactating and must be of non childbearing potential
- •Have a body mass index between 18 and 29.9 kg/m^2, inclusive, and weigh at least 50 kg and no more than 100 kg, inclusive, at screening
排除标准
- •History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the participant at risk because of participation in the study, or influence the results or the subject's ability to participate in the study
- •History or presence of gastrointestinal, hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs
- •Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of investigational medicinal product (IMP).
- •Any clinically significant abnormalities in clinical chemistry, hematology, or urinalysis results at screening, as judged by the Investigator
- •Any clinically significant abnormal findings in vital signs, and 12-lead electrocardiogram as judged by the Investigator
- •Any positive result on screening for serum hepatitis B surface antigen or anti-hemoglobin antibody, hepatitis C antibody, and human immunodeficiency virus antibody
- •Has received another new chemical entity (defined as a compound which has not been approved for marketing) within 3 months (or 5 half lives, whichever is longer) of the first administration of IMP in this study
- •Plasma donation within 1 month of screening or any blood donation/loss more than 500 mL during the 3 months prior to screening
- •History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity or history of hypersensitivity to drugs with a similar chemical structure or class to AZD9977 or dapagliflozin
- •Current smokers or those who have smoked or used nicotine products (including e cigarettes) within the 3 months prior to screening
- •Participant has a positive test result for Severe acute respiratory syndrome coronavirus 2 reverse transcriptase polymerase chain reaction at admission
- •Use of drugs with enzyme-inducing properties such as St John's Wort within 3 weeks prior to the first administration of IMP
- •Use of any prescribed or non prescribed medication including antacids, analgesics, hormone replacement therapy, herbal remedies, megadose vitamins and minerals during the 2 weeks prior to the first administration of IMP or longer if the medication has a long half life
- •Participants who have previously received AZD9977 or dapagliflozin
- •Judgment by the Investigators that the participant should not participate in the study if they have any ongoing or recent minor medical complaints
- •Participants who cannot communicate reliably with the Investigator and/or is not able to read, speak and understand the German language
- •Participant has clinical signs and symptoms consistent with corona virus disease 2019 (COVID-19), or confirmed infection by appropriate laboratory test within the last 4 weeks prior to screening or on first admission
- •History of severe COVID-19 infection (hospitalization, extracorporeal membrane oxygenation, mechanically ventilated) as judged by the Investigator
研究组 & 干预措施
Group 1: Treatment Sequence ABECD
Participants will receive a single oral dose of Treatments A, B, E, C, and D in Treatment periods 1 to 5 on Day 1 of the study.
干预措施: Treatment A (Drug)
Group 1: Treatment Sequence ABECD
Participants will receive a single oral dose of Treatments A, B, E, C, and D in Treatment periods 1 to 5 on Day 1 of the study.
干预措施: Treatment B (Drug)
Group 1: Treatment Sequence ABECD
Participants will receive a single oral dose of Treatments A, B, E, C, and D in Treatment periods 1 to 5 on Day 1 of the study.
干预措施: Treatment C (Drug)
Group 1: Treatment Sequence ABECD
Participants will receive a single oral dose of Treatments A, B, E, C, and D in Treatment periods 1 to 5 on Day 1 of the study.
干预措施: Treatment D (Drug)
Group 1: Treatment Sequence ABECD
Participants will receive a single oral dose of Treatments A, B, E, C, and D in Treatment periods 1 to 5 on Day 1 of the study.
干预措施: Treatment E (Drug)
Group 1: Treatment Sequence BACED
Participants will receive a single oral dose of Treatments B, A, C, E, and D in Treatment periods 1 to 5 on Day 1 of the study.
干预措施: Treatment A (Drug)
Group 1: Treatment Sequence BACED
Participants will receive a single oral dose of Treatments B, A, C, E, and D in Treatment periods 1 to 5 on Day 1 of the study.
干预措施: Treatment B (Drug)
Group 1: Treatment Sequence BACED
Participants will receive a single oral dose of Treatments B, A, C, E, and D in Treatment periods 1 to 5 on Day 1 of the study.
干预措施: Treatment C (Drug)
Group 1: Treatment Sequence BACED
Participants will receive a single oral dose of Treatments B, A, C, E, and D in Treatment periods 1 to 5 on Day 1 of the study.
干预措施: Treatment D (Drug)
Group 1: Treatment Sequence BACED
Participants will receive a single oral dose of Treatments B, A, C, E, and D in Treatment periods 1 to 5 on Day 1 of the study.
干预措施: Treatment E (Drug)
Group 1: Treatment Sequence CDBEA
Participants will receive a single oral dose of Treatments C, D, B, E, and A in Treatment periods 1 to 5 on Day 1 of the study.
干预措施: Treatment A (Drug)
Group 1: Treatment Sequence CDBEA
Participants will receive a single oral dose of Treatments C, D, B, E, and A in Treatment periods 1 to 5 on Day 1 of the study.
干预措施: Treatment B (Drug)
Group 1: Treatment Sequence CDBEA
Participants will receive a single oral dose of Treatments C, D, B, E, and A in Treatment periods 1 to 5 on Day 1 of the study.
干预措施: Treatment C (Drug)
Group 1: Treatment Sequence CDBEA
Participants will receive a single oral dose of Treatments C, D, B, E, and A in Treatment periods 1 to 5 on Day 1 of the study.
干预措施: Treatment D (Drug)
Group 1: Treatment Sequence CDBEA
Participants will receive a single oral dose of Treatments C, D, B, E, and A in Treatment periods 1 to 5 on Day 1 of the study.
干预措施: Treatment E (Drug)
Group 1: Treatment Sequence EADBC
Participants will receive a single oral dose of Treatments E, A, D, B, and C in Treatment periods 1 to 5 on Day 1 of the study.
干预措施: Treatment A (Drug)
Group 1: Treatment Sequence EADBC
Participants will receive a single oral dose of Treatments E, A, D, B, and C in Treatment periods 1 to 5 on Day 1 of the study.
干预措施: Treatment B (Drug)
Group 1: Treatment Sequence EADBC
Participants will receive a single oral dose of Treatments E, A, D, B, and C in Treatment periods 1 to 5 on Day 1 of the study.
干预措施: Treatment C (Drug)
Group 1: Treatment Sequence EADBC
Participants will receive a single oral dose of Treatments E, A, D, B, and C in Treatment periods 1 to 5 on Day 1 of the study.
干预措施: Treatment D (Drug)
Group 1: Treatment Sequence EADBC
Participants will receive a single oral dose of Treatments E, A, D, B, and C in Treatment periods 1 to 5 on Day 1 of the study.
干预措施: Treatment E (Drug)
Group 2: Treatment Sequence AFHG
Participants will receive a single oral dose of Treatments A, F, H, and G in Treatment periods 1 to 4 on Day 1 of the study.
干预措施: Treatment A (Drug)
Group 2: Treatment Sequence AFHG
Participants will receive a single oral dose of Treatments A, F, H, and G in Treatment periods 1 to 4 on Day 1 of the study.
干预措施: Treatment F (Drug)
Group 2: Treatment Sequence AFHG
Participants will receive a single oral dose of Treatments A, F, H, and G in Treatment periods 1 to 4 on Day 1 of the study.
干预措施: Treatment G (Drug)
Group 2: Treatment Sequence AFHG
Participants will receive a single oral dose of Treatments A, F, H, and G in Treatment periods 1 to 4 on Day 1 of the study.
干预措施: Treatment H (Drug)
Group 2: Treatment Sequence FGAH
Participants will receive a single oral dose of Treatments F, G, A, and H in Treatment periods 1 to 4 on Day 1 of the study.
干预措施: Treatment A (Drug)
Group 2: Treatment Sequence FGAH
Participants will receive a single oral dose of Treatments F, G, A, and H in Treatment periods 1 to 4 on Day 1 of the study.
干预措施: Treatment F (Drug)
Group 2: Treatment Sequence FGAH
Participants will receive a single oral dose of Treatments F, G, A, and H in Treatment periods 1 to 4 on Day 1 of the study.
干预措施: Treatment G (Drug)
Group 2: Treatment Sequence FGAH
Participants will receive a single oral dose of Treatments F, G, A, and H in Treatment periods 1 to 4 on Day 1 of the study.
干预措施: Treatment H (Drug)
Group 2: Treatment Sequence GHFA
Participants will receive a single oral dose of Treatments G, H, F, and A in Treatment periods 1 to 4 on Day 1 of the study.
干预措施: Treatment A (Drug)
Group 2: Treatment Sequence GHFA
Participants will receive a single oral dose of Treatments G, H, F, and A in Treatment periods 1 to 4 on Day 1 of the study.
干预措施: Treatment F (Drug)
Group 2: Treatment Sequence GHFA
Participants will receive a single oral dose of Treatments G, H, F, and A in Treatment periods 1 to 4 on Day 1 of the study.
干预措施: Treatment G (Drug)
Group 2: Treatment Sequence GHFA
Participants will receive a single oral dose of Treatments G, H, F, and A in Treatment periods 1 to 4 on Day 1 of the study.
干预措施: Treatment H (Drug)
Group 2: Treatment Sequence HAGF
Participants will receive a single oral dose of Treatments H, A, G, and F in Treatment periods 1 to 4 on Day 1 of the study.
干预措施: Treatment A (Drug)
Group 2: Treatment Sequence HAGF
Participants will receive a single oral dose of Treatments H, A, G, and F in Treatment periods 1 to 4 on Day 1 of the study.
干预措施: Treatment F (Drug)
Group 2: Treatment Sequence HAGF
Participants will receive a single oral dose of Treatments H, A, G, and F in Treatment periods 1 to 4 on Day 1 of the study.
干预措施: Treatment G (Drug)
Group 2: Treatment Sequence HAGF
Participants will receive a single oral dose of Treatments H, A, G, and F in Treatment periods 1 to 4 on Day 1 of the study.
干预措施: Treatment H (Drug)
结局指标
主要结局
Maximum observed plasma (peak) drug concentration (Cmax)
时间窗: Day 1 until Day 4 of each Treatment Period (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48 and 72 hours post-dose)
Evaluation of Cmax of AZD9977 and dapagliflozin, after dosing with different capsule formulations containing both AZD9977 and dapagliflozin or solely dapagliflozin, the AZD9977 capsule, and dapagliflozin tablet under fasted conditions.
Area under the plasma concentration time curve from zero to the last quantifiable concentration (AUClast)
时间窗: Day 1 until Day 4 of each Treatment Period (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48 and 72 hours post-dose)
Evaluation of AUClast of AZD9977 and dapagliflozin, after dosing with different capsule formulations containing both AZD9977 and dapagliflozin or solely dapagliflozin, the AZD9977 capsule, and dapagliflozin tablet under fasted conditions.
Area under plasma concentration time curve from zero to infinity (AUCinf)
时间窗: Day 1 until Day 4 of each Treatment Period (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48 and 72 hours post-dose)
Evaluation of AUCinf of AZD9977 and dapagliflozin, after dosing with different capsule formulations containing both AZD9977 and dapagliflozin or solely dapagliflozin, the AZD9977 capsule, and dapagliflozin tablet under fasted conditions.
Drug concentration in plasma at 24 hours post-dose (C24)
时间窗: Day 1 until Day 4 of each Treatment Period (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48 and 72 hours post-dose)
Evaluation of C24 of AZD9977 and dapagliflozin, after dosing with different capsule formulations containing both AZD9977 and dapagliflozin or solely dapagliflozin, the AZD9977 capsule, and dapagliflozin tablet under fasted conditions.
次要结局
- AUClast of AZD9977 and dapagliflozin(Day 1 until Day 4 of each Treatment Period (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48 and 72 hours post-dose))
- AUCinf of AZD9977(Day 1 until Day 4 of each Treatment Period (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48 and 72 hours post-dose))
- Cmax of AZD9977 and dapagliflozin(Day 1 until Day 4 of each Treatment Period (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48 and 72 hours post-dose))
- Cmax of AZD9977(Day 1 until Day 4 of each Treatment Period (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48 and 72 hours post-dose))
- C24 of dapagliflozin(Day 1 until Day 4 of each Treatment Period (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48 and 72 hours post-dose))
- AUCinf of AZD9977 and dapagliflozin(Day 1 until Day 4 of each Treatment Period (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48 and 72 hours post-dose))
- AUCinf of dapagliflozin(Day 1 until Day 4 of each Treatment Period (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48 and 72 hours post-dose))
- AUClast of AZD9977(Day 1 until Day 4 of each Treatment Period (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48 and 72 hours post-dose))
- C24 of AZD9977(Day 1 until Day 4 of each Treatment Period (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48 and 72 hours post-dose))
- C24 of AZD9977 and dapagliflozin(Day 1 until Day 4 of each Treatment Period (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48 and 72 hours post-dose))
- AUClast of dapagliflozin(Day 1 until Day 4 of each Treatment Period (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48 and 72 hours post-dose))
- Cmax of dapagliflozin(Day 1 until Day 4 of each Treatment Period (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48 and 72 hours post-dose))
- Number of participants with adverse events(From screening until follow-up visit (5 to 7 days post final dose))