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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Participants
• Intervention / Treatment: Drug: Baxdrostat; Drug: Placebo; Drug: Moxifloxacin

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.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 14050
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Baxdrostat; Participants will receive baxdrostat as two separate doses.; Drug: Placebo; Participants will receive baxdrostat matching placebo.; Drug: Moxifloxacin; Participants will receive a single dose moxifloxacin
Experimental: 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.	Drug: Baxdrostat; Participants will receive baxdrostat as two separate doses.; Drug: Placebo; Participants will receive baxdrostat matching placebo.; Drug: Moxifloxacin; Participants will receive a single dose moxifloxacin
Experimental: 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.	Drug: Baxdrostat; Participants will receive baxdrostat as two separate doses.; Drug: Placebo; Participants will receive baxdrostat matching placebo.; Drug: Moxifloxacin; Participants will receive a single dose moxifloxacin
Experimental: 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.	Drug: Baxdrostat; Participants will receive baxdrostat as two separate doses.; Drug: Placebo; Participants will receive baxdrostat matching placebo.; Drug: Moxifloxacin; Participants will receive a single dose moxifloxacin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Placebo corrected change from baseline in QTcF (ΔΔQTcF)	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
Change from baseline in Heart rate (ΔHR)	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
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
Change from baseline in RR interval (ΔRR)	The effect of baxdrostat on ΔRR 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
Change from baseline in PR interval (ΔPR)	The effect of baxdrostat on ΔPR 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
Change from baseline in QRS interval (ΔQRS)	The effect of baxdrostat on ΔQRS 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
Change from baseline in QTcF (ΔQTcF)	The effect of baxdrostat on ΔQTcF 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
Change from baseline in QT interval (ΔQT)	The effect of baxdrostat on ΔQT 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
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
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
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
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
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
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
Placebo corrected change from baseline in HR (ΔΔHR)	The effect of baxdrostat on ΔΔHR 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
Placebo corrected change from baseline in RR interval (ΔΔRR)	The effect of baxdrostat on ΔΔRR 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
Placebo corrected change from baseline in PR interval (ΔΔPR)	The effect of baxdrostat on ΔΔPR 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
Placebo corrected change from baseline in QRS (ΔΔQRS)	The effect of baxdrostat on ΔΔQRS 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
AUClast of Baxdrostat	The PK of baxdrostat will be assessed.	Day 1 to Day 3
AUCinf of Baxdrostat	The PK of baxdrostat will be assessed.	Day 1 to Day 3
Maximum observed plasma peak concentration (Cmax) of baxdrostat	The PK of baxdrostat will be assessed.	Day 1 to Day 3
Time to reach peak or maximum observed concentration (Tmax) of baxdrostat	The PK of baxdrostat will be assessed.	Day 1 to Day 3
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)
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)
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
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

Collaborators and Investigators

• Sponsor: AstraZeneca

Publications and helpful links

Helpful Links

• D6970C00004_Redacted_CSR Synopsis
• Results posted on AZCT.com

Study record dates

Study Major Dates

• Study Start (Actual): February 29, 2024
• Primary Completion (Actual): May 13, 2024
• Study Completion (Actual): May 13, 2024

Study Registration Dates

• First Submitted: December 21, 2023
• First Submitted That Met QC Criteria: December 21, 2023
• First Posted (Actual): January 8, 2024

Study Record Updates

• Last Update Posted (Actual): April 25, 2025
• Last Update Submitted That Met QC Criteria: April 23, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Moxifloxacin; QT/QTc interval; Aldosterone synthase inhibitor
• Additional Relevant MeSH Terms: Anti-Bacterial Agents; Anti-Infective Agents; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Topoisomerase Inhibitors; Topoisomerase II Inhibitors; Moxifloxacin
• Other Study ID Numbers: D6970C00004; 2023-506108-23-00 (Registry Identifier: CTIS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. "Yes", indicates that AZ are accepting requests for IPD, but this does not mean all requests will be approved.
• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA Data-Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes