A Single-centre, Randomised, Double-blind, Placebo-controlled, Four-Way Crossover Phase I Thorough QTc Study to Investigate the Effect on QTcF of Single Doses of Baxdrostat Compared With Placebo, Using Open-label Moxifloxacin as a Positive Control, in Healthy Participants
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 28
- 试验地点
- 1
- 主要终点
- Placebo corrected change from baseline in QTcF (ΔΔQTcF)
研究概览
简要总结
This study will assess the effect of single oral doses of baxdrostat on the ECG interval measured from the onset of the QRS complex to the end of the T wave (QT) interval corrected for HR using Fridericia's formula (QTcF) compared to placebo using a concentration-QTcF analysis, and with moxifloxacin as positive control, in healthy participants.
详细描述
This is a randomised, placebo-controlled, double-blind, 4-way crossover TQT study to assess the effect of single oral doses of baxdrostat on the QTcF compared to placebo using a concentration-QTcF analysis, and with open-label moxifloxacin as positive control, in 28 healthy participants, performed at a single clinical unit.
The study will comprise of:
- a screening period of maximum 28 days,
- four treatment periods during which participants will be resident at the Clinical Unit from Treatment Period Day -1 until at least 48 hours after dosing (Treatment Period Day 3).
- a final Follow-up Visit within 7 to 10 days following discharge after Visit 5
Participants will each receive a single dose of all treatments in a cross-over design over 4 treatment periods. Participants will be randomised to 1 of 4 treatment sequences with equal allocation regarded as a Williams design of order 4.
Treatment Periods will be separated by a washout period of at least 7 days but no more than 9 days.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
This study is double-blinded with regard to treatment (baxdrostat or placebo), for all placebo-controlled dose groups (groups where placebo and active substance is given in a cohort, ie, the sponsor, the investigator, all clinical staff involved in the clinical study (except for the unblinded pharmacist), the participants, and the study monitor will remain blinded, unless safety concerns or a regulatory requirement necessitate unblinding). Moxifloxacin will be administered as an open-label positive control in this study.
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
- •Females must have a negative pregnancy test.
- •Have a Basal Metabolic index (BMI) between 19 and 30 kg/m2 inclusive and weigh at least 50 kg.
排除标准
- •History of any clinically significant disease or disorder.
- •History or presence of gastrointestinal, hepatic, or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
- •History of additional risk factors for Torsade de Pointes.
- •History of neoplastic disease.
- •Family history of sudden cardiac death.
- •Any skin condition likely to interfere with ECG electrode placement or adhesion.
- •Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of drug.
- •Any clinically significant abnormalities at screening and first admission in rhythm, conduction, or morphology of the 12-lead resting ECG and any clinically important abnormalities in the 12-lead ECG as considered by the investigator.
- •Participant has clinical signs and symptoms consistent with COVID-
- •Current smokers or those who have smoked or used nicotine products (including e-cigarettes) within the 3 months prior to screening.
- •Positive screen for drugs of abuse, alcohol or cotinine at screening or on each admission to the Clinical Unit.
- •Participants who have previously received Baxdrostat.
- •Participants with any special dietary restrictions such as participants who are lactose intolerant or are vegetarians/vegans.
- •Participants who cannot communicate reliably with the investigator and/or are not able to read, speak, and understand the local language.
- •Vulnerable participants, eg, kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order.
研究组 & 干预措施
Treatment Sequence ABCD
Dummy sequence according to CSP: Participants will receive a single dose of all 4 treatments (ABCD) in a crossover design with a washout period of at least 7 days between each study dose administration.
干预措施: Moxifloxacin (Drug)
Treatment Sequence CADB
Dummy sequence according to CSP: Participants will receive a single dose of all 4 treatments (CADB) in a crossover design with a washout period of at least 7 days between each study dose administration.
干预措施: Moxifloxacin (Drug)
Treatment Sequence ABCD
Dummy sequence according to CSP: Participants will receive a single dose of all 4 treatments (ABCD) in a crossover design with a washout period of at least 7 days between each study dose administration.
干预措施: Baxdrostat (Drug)
Treatment Sequence ABCD
Dummy sequence according to CSP: Participants will receive a single dose of all 4 treatments (ABCD) in a crossover design with a washout period of at least 7 days between each study dose administration.
干预措施: Placebo (Drug)
Treatment Sequence BDAC
Dummy sequence according to CSP: Participants will receive a single dose of all 4 treatments (BDAC) in a crossover design with a washout period of at least 7 days between each study dose administration.
干预措施: Baxdrostat (Drug)
Treatment Sequence BDAC
Dummy sequence according to CSP: Participants will receive a single dose of all 4 treatments (BDAC) in a crossover design with a washout period of at least 7 days between each study dose administration.
干预措施: Placebo (Drug)
Treatment Sequence BDAC
Dummy sequence according to CSP: Participants will receive a single dose of all 4 treatments (BDAC) in a crossover design with a washout period of at least 7 days between each study dose administration.
干预措施: Moxifloxacin (Drug)
Treatment Sequence CADB
Dummy sequence according to CSP: Participants will receive a single dose of all 4 treatments (CADB) in a crossover design with a washout period of at least 7 days between each study dose administration.
干预措施: Baxdrostat (Drug)
Treatment Sequence CADB
Dummy sequence according to CSP: Participants will receive a single dose of all 4 treatments (CADB) in a crossover design with a washout period of at least 7 days between each study dose administration.
干预措施: Placebo (Drug)
Treatment Sequence DCBA
Dummy sequence according to CSP: Participants will receive a single dose of all 4 treatments (DCBA) in a crossover design with a washout period of at least 7 days between each study dose administration.
干预措施: Baxdrostat (Drug)
Treatment Sequence DCBA
Dummy sequence according to CSP: Participants will receive a single dose of all 4 treatments (DCBA) in a crossover design with a washout period of at least 7 days between each study dose administration.
干预措施: Placebo (Drug)
Treatment Sequence DCBA
Dummy sequence according to CSP: Participants will receive a single dose of all 4 treatments (DCBA) in a crossover design with a washout period of at least 7 days between each study dose administration.
干预措施: Moxifloxacin (Drug)
结局指标
主要结局
Placebo corrected change from baseline in QTcF (ΔΔQTcF)
时间窗: Visit 2,3, 4 and 5:- Day 1: Pre-dose, 0.5, 1, 1.5, 2,3,4,5,6, 8 and 12 hour (h); Day 2: 24 and 36 h post-dose; Day 3: 48 h post dose
The effect of single doses of baxdrostat on QTcF compared to placebo using a concentration-QTcF analysis will be assessed.
次要结局
- Change from baseline in RR interval (ΔRR)(Visit 2,3, 4 and 5:- Day 1: Pre-dose, 0.5, 1, 1.5, 2,3,4,5,6, 8 and 12 hour (h); Day 2: 24 and 36 h post-dose; Day 3: 48 h post dose)
- Change from baseline in QRS interval (ΔQRS)(Visit 2,3, 4 and 5:- Day 1: Pre-dose, 0.5, 1, 1.5, 2,3,4,5,6, 8 and 12 hour (h); Day 2: 24 and 36 h post-dose; Day 3: 48 h post dose)
- Number of participants with significant change in QRS interval(Day 1 to Day 3)
- Number of participants with significant change in QT interval(Day 1 to Day 3)
- Number of participants with significant change in HR(Day 1 to Day 3)
- Placebo corrected change from baseline in HR (ΔΔHR)(Visit 2,3, 4 and 5:- Day 1: Pre-dose, 0.5, 1, 1.5, 2,3,4,5,6, 8 and 12 hour (h); Day 2: 24 and 36 h post-dose; Day 3: 48 h post dose)
- Placebo corrected change from baseline in PR interval (ΔΔPR)(Visit 2,3, 4 and 5:- Day 1: Pre-dose, 0.5, 1, 1.5, 2,3,4,5,6, 8 and 12 hour (h); Day 2: 24 and 36 h post-dose; Day 3: 48 h post dose)
- Placebo corrected change from baseline in QRS (ΔΔQRS)(Visit 2,3, 4 and 5:- Day 1: Pre-dose, 0.5, 1, 1.5, 2,3,4,5,6, 8 and 12 hour (h); Day 2: 24 and 36 h post-dose; Day 3: 48 h post dose)
- AUCinf of Baxdrostat(Day 1 to Day 3)
- RR interval(Visit 2,3, 4 and 5:- Day 1: Pre-dose, 0.5, 1, 1.5, 2,3,4,5,6, 8 and 12 hour (h); Day 2: 24 and 36 h post-dose; Day 3: 48 h post dose)
- QRS interval(Visit 2,3, 4 and 5:- Day 1: Pre-dose, 0.5, 1, 1.5, 2,3,4,5,6, 8 and 12 hour (h); Day 2: 24 and 36 h post-dose; Day 3: 48 h post dose)
- Change from baseline in QT interval (ΔQT)(Visit 2,3, 4 and 5:- Day 1: Pre-dose, 0.5, 1, 1.5, 2,3,4,5,6, 8 and 12 hour (h); Day 2: 24 and 36 h post-dose; Day 3: 48 h post dose)
- Number of participants with significant change in QTcF(Day 1 to Day 3)
- Time to reach peak or maximum observed concentration (Tmax) of baxdrostat(Day 1 to Day 3)
- Number of participants with Adverse events of special interest(Day 1 to last day of follow-up (approximately 7 to 10 days after the last dose))
- Heart Rate (HR)(Visit 2,3, 4 and 5:- Day 1: Pre-dose, 0.5, 1, 1.5, 2,3,4,5,6, 8 and 12 hour (h); Day 2: 24 and 36 h post-dose; Day 3: 48 h post dose)
- Change from baseline in Heart rate (ΔHR)(Visit 2,3, 4 and 5:- Day 1: Pre-dose, 0.5, 1, 1.5, 2,3,4,5,6, 8 and 12 hour (h); Day 2: 24 and 36 h post-dose; Day 3: 48 h post dose)
- PR interval(Visit 2,3, 4 and 5:- Day 1: Pre-dose, 0.5, 1, 1.5, 2,3,4,5,6, 8 and 12 hour (h); Day 2: 24 and 36 h post-dose; Day 3: 48 h post dose)
- QT interval(Visit 2,3, 4 and 5:- Day 1: Pre-dose, 0.5, 1, 1.5, 2,3,4,5,6, 8 and 12 hour (h); Day 2: 24 and 36 h post-dose; Day 3: 48 h post dose)
- Change from baseline in PR interval (ΔPR)(Visit 2,3, 4 and 5:- Day 1: Pre-dose, 0.5, 1, 1.5, 2,3,4,5,6, 8 and 12 hour (h); Day 2: 24 and 36 h post-dose; Day 3: 48 h post dose)
- Change from baseline in QTcF (ΔQTcF)(Visit 2,3, 4 and 5:- Day 1: Pre-dose, 0.5, 1, 1.5, 2,3,4,5,6, 8 and 12 hour (h); Day 2: 24 and 36 h post-dose; Day 3: 48 h post dose)
- Number of participants with significant change in RR interval(Day 1 to Day 3)
- Number of participants with significant change in PR interval(Day 1 to Day 3)
- Placebo corrected change from baseline in RR interval (ΔΔRR)(Visit 2,3, 4 and 5:- Day 1: Pre-dose, 0.5, 1, 1.5, 2,3,4,5,6, 8 and 12 hour (h); Day 2: 24 and 36 h post-dose; Day 3: 48 h post dose)
- AUClast of Baxdrostat(Day 1 to Day 3)
- Maximum observed plasma peak concentration (Cmax) of baxdrostat(Day 1 to Day 3)
- Number of participants with Adverse Events (AEs)(Day 1 to last day of follow-up (approximately 7 to 10 days after the last dose))
- Number of treatment-emergent changes in U-waves presence and morphology(Day 1 to Day 3)
- Number of treatment-emergent changes in T-wave morphology(Day 1 to Day 3)