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

AstraZeneca

Status and phase: Completed; Phase 1

Conditions: Healthy Participants

Treatments: Drug: Baxdrostat; Drug: Moxifloxacin; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT06194032

2023-506108-23-00 (Registry Identifier)

D6970C00004

Details and patient eligibility

About

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.

Full 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.

Enrollment: 28 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

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28 participants in 4 patient groups

Treatment Sequence ABCD

Experimental group

Description:

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.

Treatment:

Drug: Placebo

Drug: Moxifloxacin

Drug: Baxdrostat

Treatment Sequence BDAC

Experimental group

Description:

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.

Treatment:

Drug: Placebo

Drug: Moxifloxacin

Drug: Baxdrostat

Treatment Sequence CADB

Experimental group

Description:

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.

Treatment:

Drug: Placebo

Drug: Moxifloxacin

Drug: Baxdrostat

Treatment Sequence DCBA

Experimental group

Description:

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.

Treatment:

Drug: Placebo

Drug: Moxifloxacin

Drug: Baxdrostat