Healthy Participants
Conditions
Keywords
Aldosterone synthase inhibitor, QT/QTc interval, Moxifloxacin
Brief summary
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.
Detailed description
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.
Interventions
DRUGBaxdrostat
Participants will receive baxdrostat as two separate doses.
DRUGPlacebo
Participants will receive baxdrostat matching placebo.
DRUGMoxifloxacin
Participants will receive a single dose moxifloxacin
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* 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.
Exclusion criteria
* 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-19. * 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Placebo corrected change from baseline in QTcF (ΔΔQTcF) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | The effect of baxdrostat on HR will be assessed. |
| 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 | The effect of baxdrostat on RR interval will be assessed. |
| 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 | The effect of baxdrostat on QRS interval will be assessed. |
| 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 | The effect of baxdrostat on HR will be assessed. |
| 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 | The effect of baxdrostat on QT interval will be assessed. |
| 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 | The effect of baxdrostat on ΔRR interval will be assessed. |
| 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 | The effect of baxdrostat on ΔPR interval will be assessed. |
| 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 | The effect of baxdrostat on ΔQRS interval will be assessed. |
| 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 | The effect of baxdrostat on ΔQTcF will be assessed. |
| 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 | The effect of baxdrostat on ΔQT interval will be assessed. |
| Number of participants with significant change in QTcF | Day 1 to Day 3 | The presence of categorical outliers for QTcF after baxdrostat administration will be assessed. |
| Number of participants with significant change in PR interval | Day 1 to Day 3 | The presence of categorical outliers for PR interval after baxdrostat administration will be assessed. |
| Number of participants with significant change in QRS interval | Day 1 to Day 3 | The presence of categorical outliers for QRS interval after baxdrostat administration will be assessed. |
| Number of participants with significant change in RR interval | Day 1 to Day 3 | The presence of categorical outliers for RR interval after baxdrostat administration will be assessed. |
| 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 | The effect of baxdrostat on PR interval will be assessed. |
| Number of participants with significant change in HR | Day 1 to Day 3 | The presence of categorical outliers for HR after baxdrostat administration will be assessed. |
| 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 | The effect of baxdrostat on ΔΔHR will be assessed. |
| 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 | The effect of baxdrostat on ΔΔRR interval will be assessed. |
| 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 | The effect of baxdrostat on ΔΔPR interval will be assessed. |
| 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 | The effect of baxdrostat on ΔΔQRS interval will be assessed. |
| AUClast of Baxdrostat | Day 1 to Day 3 | The PK of baxdrostat will be assessed. |
| AUCinf of Baxdrostat | Day 1 to Day 3 | The PK of baxdrostat will be assessed. |
| Maximum observed plasma peak concentration (Cmax) of baxdrostat | Day 1 to Day 3 | The PK of baxdrostat will be assessed. |
| Time to reach peak or maximum observed concentration (Tmax) of baxdrostat | Day 1 to Day 3 | The PK of baxdrostat will be assessed. |
| Number of participants with Adverse Events (AEs) | Day 1 to last day of follow-up (approximately 7 to 10 days after the last dose) | The safety and tolerability of baxdrostat will be assessed. |
| 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) | The safety and tolerability of baxdrostat will be assessed. For this clinical study, AESIs include the following: hyperkalaemia, hyponatraemia, and hypotension events that require intervention. |
| Number of treatment-emergent changes in T-wave morphology | Day 1 to Day 3 | Morphological changes in the T-wave after baxdrostat administration will be assessed. |
| Number of treatment-emergent changes in U-waves presence and morphology | Day 1 to Day 3 | Morphological changes in the U wave after baxdrostat administration will be assessed. |
| Number of participants with significant change in QT interval | Day 1 to Day 3 | The presence of categorical outliers for QT interval after baxdrostat administration will be assessed. |
Countries
Germany
Outcome results
None listed