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

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

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

Study Overview

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

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Brooklyn, Maryland, United States, 21225
      • Research Site

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Baxdrostat and Itraconazole; Participants will receive single dose of baxdrostat tablet orally on Day 1 in Period 1, followed by itraconazole capsule orally twice a day on Day 6 and once daily on Days 7 to 8 in Period 2, and then single dose of baxdrostat tablet orally on Day 9 with itraconazole capsule orally once daily on Days 9 to 16 in Period 3.	Drug: Baxdrostat; Baxdrostat tablet will be administered orally.; Other Names: CIN-107; Drug: Itraconazole; Itraconazole capsule will be administered orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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)
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)
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)
Terminal Elimination Half-life (t1/2λz)	The PK (t1/2λz) 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)
Terminal Rate Constant (λz)	The PK (λz) 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)
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)
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)
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)
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)
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)
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

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): April 16, 2024
• Primary Completion (Actual): June 17, 2024
• Study Completion (Actual): June 17, 2024

Study Registration Dates

• First Submitted: April 5, 2024
• First Submitted That Met QC Criteria: April 5, 2024
• First Posted (Actual): April 10, 2024

Study Record Updates

• Last Update Posted (Actual): July 3, 2024
• Last Update Submitted That Met QC Criteria: July 2, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Itraconazole
• Other Study ID Numbers: D6970C00005

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