A Study to Investigate the Pharmacokinetics of Baxdrostat When Given Alone and in Combination With Itraconazole in Healthy Participants

Healthy Participants Clinical Trial

Official title:

An Open-label, Fixed Sequence Study in Healthy Participants to Assess the Pharmacokinetics of Baxdrostat When Administered Alone and in Combination With Itraconazole

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06357520
• Other study ID #: D6970C00005
• Status: Recruiting
• Phase: Phase 1
• Start date: April 16, 2024
• Est. completion date: June 6, 2024

Study information

• Verified date: April 2024
• Source: AstraZeneca
• Contact: AstraZeneca Clinical Study Information Center
• Phone: 1-877-240-9479
• Email: information.center[@]astrazeneca.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The main purpose of this study is to assess the effect of itraconazole on the pharmacokinetic (PK) of baxdrostat.

Description:

This study will be an open-label, 3-period fixed sequence study conducted at a single Clinical Unit. The study will comprise of: - A Screening Period of maximum 28 days - Period 1: Period 1 will start from Day -1 to Day 6 (followed by pharmacokinetic (PK) sampling of baxdrostat). Baxdrostat administration on Day 1 to Day 6 - Period 2: Period 2 will start from Day 6 (after the last PK sample in period 1) to Day 8. Itraconazole administration on Days 6 to 8 (twice a day [BID] on Day 6 and once daily [QD] on Days 7 and 8) - Period 3: Period 3 will start from Day 9 to Day 17. Baxdrostat administration on Day 9 and itraconazole administration on Days 9 to 16 QD - A Final Follow-up Visit at 7 to 14 days after the last baxdrostat PK sample in Period 3 All participants will receive 2 single doses of baxdrostat and 12 doses of itraconazole, under fed conditions.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 14
• Est. completion date: June 6, 2024
• Est. primary completion date: June 6, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• Healthy male and/or female participants of non-childbearing potential aged 18 to 55 years with suitable veins for cannulation or repeated venipuncture.
• All female participants must have a negative pregnancy test at the Screening Visit and on admission to the Clinical Unit (Study Day -1).
• Have a body mass index between 18 and 32 kilograms per meter square (kg/m2) inclusive and weigh greater than or equal to (>=) 50 kilograms (kg) and less than or equal to <=) 120 kg.

Exclusion Criteria:

• History of any clinically important disease or disorder which, in the opinion of the principal investigator (PI), may either put the participant at risk because of participation in the study, or influence the results or the participant's ability to participate in the study.
• 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 drug-related hepatic toxicity.
• Any clinically important illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of study intervention.
• History of any treatment with QT prolongation drugs.
• History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity, as judged by the PI or history of hypersensitivity to drugs with a similar chemical structure or class to baxdrostat or itraconazole.
• Participants who have previously received baxdrostat.

Related Conditions & MeSH terms

• Healthy Participants

Intervention

Drug:
• Baxdrostat
Baxdrostat tablet will be administered orally.
• Itraconazole
Itraconazole capsule will be administered orally.

Locations

Country	Name	City	State
United States	Research Site	Brooklyn	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area Under Plasma Concentration-Time Curve From Time Zero To Infinity (AUCinf)	The effect of itraconazole on the PK (AUCinf) of baxdrostat will be assessed.	Period 1: Days 1 to 6 (pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96, and 120 hours post-dose); Period 3: Days 9 to 17 (pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, and 192 hours)
Primary	Maximum Observed Plasma Drug Concentration (Cmax)	The effect of itraconazole on the PK (Cmax) of baxdrostat will be assessed.	Period 1: Days 1 to 6 (pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96, and 120 hours post-dose); Period 3: Days 9 to 17 (pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, and 192 hours)
Secondary	Extrapolated Area Under The Curve From Tlast to Infinity (AUCextr)	The PK (AUCextr) of baxdrostat when baxdrostat is administered alone or in combination with itraconazole will be evaluated.	Period 1: Days 1 to 6 (pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96, and 120 hours post-dose); Period 3: Days 9 to 17 (pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, and 192 hours)
Secondary	Area Under Plasma Concentration Curve from Time Zero to the Last Quantifiable Concentration (AUClast)	The PK (AUClast) of baxdrostat when baxdrostat is administered alone or in combination with itraconazole will be evaluated.	Period 1: Days 1 to 6 (pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96, and 120 hours post-dose); Period 3: Days 9 to 17 (pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, and 192 hours)
Secondary	Apparent Total Body Clearance (CL/F)	The PK (CL/F) of baxdrostat when baxdrostat is administered alone or in combination with itraconazole will be evaluated.	Period 1: Days 1 to 6 (pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96, and 120 hours post-dose); Period 3: Days 9 to 17 (pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, and 192 hours)
Secondary	Apparent Volume Of Distribution Based On The Terminal Phase (Vz/F)	The PK (Vz/F) of baxdrostat when baxdrostat is administered alone or in combination with itraconazole will be evaluated.	Period 1: Days 1 to 6 (pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96, and 120 hours post-dose); Period 3: Days 9 to 17 (pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, and 192 hours)
Secondary	Terminal Elimination Half-life (t1/2?z)	The PK (t1/2?z) of baxdrostat when baxdrostat is administered alone or in combination with itraconazole will be evaluated.	Period 1: Days 1 to 6 (pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96, and 120 hours post-dose); Period 3: Days 9 to 17 (pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, and 192 hours)
Secondary	Terminal Rate Constant (?z)	The PK (?z) of baxdrostat when baxdrostat is administered alone or in combination with itraconazole will be evaluated.	Period 1: Days 1 to 6 (pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96, and 120 hours post-dose); Period 3: Days 9 to 17 (pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, and 192 hours)
Secondary	Mean Residence Time (MRTinf)	The PK (MRTinf) of baxdrostat when baxdrostat is administered alone or in combination with itraconazole will be evaluated.	Period 1: Days 1 to 6 (pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96, and 120 hours post-dose); Period 3: Days 9 to 17 (pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, and 192 hours)
Secondary	Time To Reach Maximum Observed Concentration (tmax)	The PK (tmax) of baxdrostat when baxdrostat is administered alone or in combination with itraconazole will be evaluated.	Period 1: Days 1 to 6 (pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96, and 120 hours post-dose); Period 3: Days 9 to 17 (pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, and 192 hours)
Secondary	Ratio of Baxdrostat (Baxdrostat + Itraconazole) to Baxdrostat (Alone) Based on Maximum Plasma Concentration (RCmax)	The PK (RCmax) of baxdrostat when baxdrostat is administered alone or in combination with itraconazole will be evaluated.	Period 1: Days 1 to 6 (pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96, and 120 hours post-dose); Period 3: Days 9 to 17 (pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, and 192 hours)
Secondary	Ratio of Baxdrostat (Baxdrostat + Itraconazole) to Baxdrostat (Alone) Based on AUClast (RAUClast)	The PK (RAUClast) of baxdrostat when baxdrostat is administered alone or in combination with itraconazole will be evaluated.	Period 1: Days 1 to 6 (pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96, and 120 hours post-dose); Period 3: Days 9 to 17 (pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, and 192 hours)
Secondary	Ratio of Baxdrostat (Baxdrostat + Itraconazole) to Baxdrostat (Alone) Based on AUCinf (RAUCinf)	The PK (RAUCinf) of baxdrostat when baxdrostat is administered alone or in combination with itraconazole will be evaluated.	Period 1: Days 1 to 6 (pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96, and 120 hours post-dose); Period 3: Days 9 to 17 (pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, and 192 hours)
Secondary	Number of Participants with Adverse Events	The safety and tolerability of baxdrostat alone and in combination with itraconazole will be assessed.	Up to 8 weeks