Clinical trial NCT06194032: A Study to Investigate the Effect on QTcF of Baxdrostat Compared With Placebo, Using Moxifloxacin as a Positive Control, in Healthy Participants
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Participants
Keywords: Aldosterone synthase inhibitor
QT/QTc interval
Moxifloxacin
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2024-01-08
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Placebo corrected change from baseline in QTcF (ΔΔQTcF)
timeFrame: 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 outcomes:
measure: Heart Rate (HR)
timeFrame: 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
measure: RR interval
timeFrame: 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
measure: PR interval
timeFrame: 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
measure: QRS interval
timeFrame: 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
measure: Change from baseline in Heart rate (ΔHR)
timeFrame: 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
measure: QT interval
timeFrame: 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
measure: Change from baseline in RR interval (ΔRR)
timeFrame: 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
measure: Change from baseline in PR interval (ΔPR)
timeFrame: 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
measure: Change from baseline in QRS interval (ΔQRS)
timeFrame: 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
measure: Change from baseline in QTcF (ΔQTcF)
timeFrame: 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
measure: Change from baseline in QT interval (ΔQT)
timeFrame: 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
measure: Number of participants with significant change in QTcF
timeFrame: Day 1 to Day 3
measure: Number of participants with significant change in PR interval
timeFrame: Day 1 to Day 3
measure: Number of participants with significant change in QRS interval
timeFrame: Day 1 to Day 3
measure: Number of participants with significant change in RR interval
timeFrame: Day 1 to Day 3
measure: Number of participants with significant change in QT interval
timeFrame: Day 1 to Day 3
measure: Number of participants with significant change in HR
timeFrame: Day 1 to Day 3
measure: Placebo corrected change from baseline in HR (ΔΔHR)
timeFrame: 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
measure: Placebo corrected change from baseline in RR interval (ΔΔRR)
timeFrame: 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
measure: Placebo corrected change from baseline in PR interval (ΔΔPR)
timeFrame: 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
measure: Placebo corrected change from baseline in QRS (ΔΔQRS)
timeFrame: 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
measure: AUClast of Baxdrostat
timeFrame: Day 1 to Day 3
measure: AUCinf of Baxdrostat
timeFrame: Day 1 to Day 3
measure: Maximum observed plasma peak concentration (Cmax) of baxdrostat
timeFrame: Day 1 to Day 3
measure: Time to reach peak or maximum observed concentration (Tmax) of baxdrostat
timeFrame: Day 1 to Day 3
measure: Number of participants with Adverse Events (AEs)
timeFrame: Day 1 to last day of follow-up (approximately 7 to 10 days after the last dose)
measure: Number of participants with Adverse events of special interest
timeFrame: Day 1 to last day of follow-up (approximately 7 to 10 days after the last dose)
measure: Number of treatment-emergent changes in T-wave morphology
timeFrame: Day 1 to Day 3
measure: Number of treatment-emergent changes in U-waves presence and morphology
timeFrame: Day 1 to Day 3
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Research Site
Study officials:
References: