A Study to Investigate the Effect on QTcF of Baxdrostat Compared With Placebo, Using Moxifloxacin as a Positive Control, in Healthy Participants

Healthy Participants Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT06194032
• Other study ID #: D6970C00004
• Status: Completed
• Phase: Phase 1
• Start date: February 29, 2024
• Est. completion date: May 13, 2024

Study information

• Verified date: May 2024
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: May 13, 2024
• Est. primary completion date: May 13, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy Participants

Intervention

Drug:
• Baxdrostat
Participants will receive baxdrostat as two separate doses.
• Placebo
Participants will receive baxdrostat matching placebo.
• Moxifloxacin
Participants will receive a single dose moxifloxacin

Locations

Country	Name	City	State
Germany	Research Site	Berlin

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Placebo corrected change from baseline in QTcF (??QTcF)	The effect of single doses of baxdrostat on QTcF compared to placebo using a concentration-QTcF analysis will be assessed.	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
Secondary	Heart Rate (HR)	The effect of baxdrostat on HR will be assessed.	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
Secondary	RR interval	The effect of baxdrostat on RR interval will be assessed.	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
Secondary	PR interval	The effect of baxdrostat on PR interval will be assessed.	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
Secondary	QRS interval	The effect of baxdrostat on QRS interval will be assessed.	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
Secondary	Change from baseline in Heart rate (?HR)	The effect of baxdrostat on HR will be assessed.	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
Secondary	QT interval	The effect of baxdrostat on QT interval will be assessed.	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
Secondary	Change from baseline in RR interval (?RR)	The effect of baxdrostat on ?RR interval will be assessed.	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
Secondary	Change from baseline in PR interval (?PR)	The effect of baxdrostat on ?PR interval will be assessed.	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
Secondary	Change from baseline in QRS interval (?QRS)	The effect of baxdrostat on ?QRS interval will be assessed.	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
Secondary	Change from baseline in QTcF (?QTcF)	The effect of baxdrostat on ?QTcF will be assessed.	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
Secondary	Change from baseline in QT interval (?QT)	The effect of baxdrostat on ?QT interval will be assessed.	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
Secondary	Number of participants with significant change in QTcF	The presence of categorical outliers for QTcF after baxdrostat administration will be assessed.	Day 1 to Day 3
Secondary	Number of participants with significant change in PR interval	The presence of categorical outliers for PR interval after baxdrostat administration will be assessed.	Day 1 to Day 3
Secondary	Number of participants with significant change in QRS interval	The presence of categorical outliers for QRS interval after baxdrostat administration will be assessed.	Day 1 to Day 3
Secondary	Number of participants with significant change in RR interval	The presence of categorical outliers for RR interval after baxdrostat administration will be assessed.	Day 1 to Day 3
Secondary	Number of participants with significant change in QT interval	The presence of categorical outliers for QT interval after baxdrostat administration will be assessed.	Day 1 to Day 3
Secondary	Number of participants with significant change in HR	The presence of categorical outliers for HR after baxdrostat administration will be assessed.	Day 1 to Day 3
Secondary	Placebo corrected change from baseline in HR (??HR)	The effect of baxdrostat on ??HR will be assessed.	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
Secondary	Placebo corrected change from baseline in RR interval (??RR)	The effect of baxdrostat on ??RR interval will be assessed.	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
Secondary	Placebo corrected change from baseline in PR interval (??PR)	The effect of baxdrostat on ??PR interval will be assessed.	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
Secondary	Placebo corrected change from baseline in QRS (??QRS)	The effect of baxdrostat on ??QRS interval will be assessed.	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
Secondary	AUClast of Baxdrostat	The PK of baxdrostat will be assessed.	Day 1 to Day 3
Secondary	AUCinf of Baxdrostat	The PK of baxdrostat will be assessed.	Day 1 to Day 3
Secondary	Maximum observed plasma peak concentration (Cmax) of baxdrostat	The PK of baxdrostat will be assessed.	Day 1 to Day 3
Secondary	Time to reach peak or maximum observed concentration (Tmax) of baxdrostat	The PK of baxdrostat will be assessed.	Day 1 to Day 3
Secondary	Number of participants with Adverse Events (AEs)	The safety and tolerability of baxdrostat will be assessed.	Day 1 to last day of follow-up (approximately 7 to 10 days after the last dose)
Secondary	Number of participants with Adverse events of special interest	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.	Day 1 to last day of follow-up (approximately 7 to 10 days after the last dose)
Secondary	Number of treatment-emergent changes in T-wave morphology	Morphological changes in the T-wave after baxdrostat administration will be assessed.	Day 1 to Day 3
Secondary	Number of treatment-emergent changes in U-waves presence and morphology	Morphological changes in the U wave after baxdrostat administration will be assessed.	Day 1 to Day 3