Phase 1 Study to Determine the Metabolism and Clearance of Baxdrostat

A Phase 1, Open-Label Study Of The Absorption, Metabolism, And Excretion Of [14C]-Baxdrostat Following A Single Oral Dose In Healthy Male Subjects

This was a Phase 1, open-label, single dose study in healthy male subjects. The goals of this clinical trial were to determine how baxdrostat might be absorbed and metabolized using radioactive [14C] labeled baxdrostat. Subjects were administered a single oral dose of 10 mg containing approximately 100 μCi of [14C] baxdrostat. Subjects were to be confined to the study site for 9 to 15 days for blood, urine, and feces collections.

Study Overview

• Status: Completed
• Conditions: Hypertension
• Intervention / Treatment: Drug: baxdrostat

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53704
      • Labcorp Clinical Research Unit

Participation Criteria

Eligibility Criteria

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

Description

Subjects must meet the following inclusion criteria:

• Be males of any race between 18 and 55 years of age
• Have a body mass index between 18.0 and 32.0 kg/m2
• Be in good health, determined by no clinically significant findings from medical history
• Have normal renal function, defined as estimated GFR ≥70 mL/min/1.73 m2
• Agree to use contraception
• Be able to comprehend and willing to sign an ICF and to abide by the study restrictions
• Have a history of a minimum of 1 bowel movement per day
• Agree to refrain from donation of sperm from check-in until 90 days after discharge

Main Exclusion Criteria:

• Significant history or clinical manifestation of any diseases as determined by the investigator
• Prolonged QTcF (>450 msec)
• Confirmed (eg, 2 consecutive measurements) systolic BP >140 or <90 mmHg, diastolic BP >90 or <50 mmHg, and pulse rate >100 or <45 beats per minute (bpm).
• Postural tachycardia (ie, >30 bpm upon standing) or orthostatic hypotension (ie, a fall in systolic BP of ≥20 mmHg or diastolic BP of ≥10 mmHg upon standing).
• Serum potassium >upper limit of normal (5.3 mmol/L; ULN) of the reference range and serum sodium <lower limit of normal (135 mmol/L) of the reference range
• Aspartate aminotransferase, alanine aminotransferase, or total bilirubin values >1.2 × ULN.
• A known history of porphyria, myopathy, or active liver disease
• Use of any prescription medications
• Corticosteroid use (systemic or extensive topical use) within 3 months prior to dosing
• Subjects who have participated in more than 3 radiolabeled drug studies in the last 12 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• 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: 10 mg [14C]-bexdrostat; single oral dose of 10 mg baxdrostat containing 100 μCi of [14C] baxdrostat	Drug: baxdrostat; a blood pressure lowering drug, oral dose; Other Names: CIN-107

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total radioactivity recovery in urine and feces following administration of [14C] baxdrostat.	Measurement of total radioactivity recovery in urine and feces to determine the routes, rates of elimination, and mass balance of total radioactivity from [14C] baxdrostat.	1 to 15 days after dosing
Area under the curve [AUC] of baxdrostat and its primary metabolite (CIN-107M) following administration of [14C] baxdrostat to healthy male subjects.	Area under the curve (AUC)0-∞ and AUC0-last will be determined for baxdrostat and CIN-107M in plasma.	1 to 15 days after dosing
Cumulative baxdrostat and CIN-107M excreted in urine and fraction of baxdrostat renally excreted following administration of [14C] baxdrostat to healthy subjects.	Determining cumulative amount of baxdrostat and CIN-107M excreted in urine, clearance of baxdrostat and CIN-107M, and fraction of dose excreted renally (baxdrostat only).	1 to 15 days after dosing
Maximum concentration [Cmax] for baxdrostat and CIN-107M in plasma.	Cmax will be determined based on measurement of baxdrostat and CIN-107M in plasma.	1 to 15 days after dosing
Time to maximum concentration [Tmax] for baxdrostat and CIN-107M in plasma.	Tmax will be determined based on measurement of baxdrostat and CIN-107M in plasma.	1 to 15 days after dosing
Terminal elimination half-life (t1/2) for baxdrostat and CIN-107M in plasma.	t1/2 for baxdrostat and CIN-107M in plasma will be determined based on measurement of baxdrostat and CIN-107M in plasma.	1 to 15 days after dosing

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quantitative metabolic profiles of baxdrostat in plasma and excreta.	To determine, where possible, the quantitative metabolite profiles in plasma, urine, and feces after [14C]-baxdrostat	1 to 15 days after dosing
Identification of baxdrostat metabolites in plasma and excreta.	To determine, where possible, the chemical structure of major metabolites in plasma, urine, and feces after [14C]-baxdrostat	1 to 15 days after dosing
Incidence of treatment emergent adverse events following administration of [14C] baxdrostat.	Incidence of adverse events will be used to assess the safety and tolerability of [14C] baxdrostat when administered to healthy subjects.	1 to 15 days after dosing

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: Nicholas Siebers, MD Siebers, MD, Labcorp Clinical Research Unit, Madison, Wisconsin, USA 53704

Publications and helpful links

Helpful Links

• CSR Synopsis Redacted

Study record dates

Study Major Dates

• Study Start (Actual): November 18, 2021
• Primary Completion (Actual): January 15, 2022
• Study Completion (Actual): January 15, 2022

Study Registration Dates

• First Submitted: July 3, 2023
• First Submitted That Met QC Criteria: July 18, 2023
• First Posted (Actual): July 27, 2023

Study Record Updates

• Last Update Posted (Actual): August 15, 2023
• Last Update Submitted That Met QC Criteria: August 11, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: pharmacokinetics (PK); metabolism; baxdrostat
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension
• Other Study ID Numbers: CIN-107-117

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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No