Phase 1 Study to Determine the Metabolism and Clearance of Baxdrostat

Phase 1

Completed

• Conditions: Hypertension
• Interventions: Drug: baxdrostat

• Registration Number: NCT05961384
• Lead Sponsor: AstraZeneca

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2021-11-18
• Primary Completion: 2022-01-15
• Study Completion: 2022-01-15
• Study First Submitted: 2023-07-03
• Study First Submitted QC: 2023-07-18
• Study First Posted: 2023-07-27
• Status Verified: 2023-08
• Last Update Submitted: 2023-08-11
• Last Update Posted: 2023-08-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 8

Inclusion Criteria

Not provided

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
10 mg [14C]-bexdrostat	baxdrostat	single oral dose of 10 mg baxdrostat containing 100 μCi of \[14C\] baxdrostat

Primary Outcome Measures

Name	Time	Method
Area under the curve [AUC] of baxdrostat and its primary metabolite (CIN-107M) following administration of [14C] baxdrostat to healthy male subjects.	1 to 15 days after dosing	Area under the curve (AUC)0-∞ and AUC0-last will be determined for baxdrostat and CIN-107M in plasma.
Total radioactivity recovery in urine and feces following administration of [14C] baxdrostat.	1 to 15 days after dosing	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.
Cumulative baxdrostat and CIN-107M excreted in urine and fraction of baxdrostat renally excreted following administration of [14C] baxdrostat to healthy subjects.	1 to 15 days after dosing	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).
Maximum concentration [Cmax] for baxdrostat and CIN-107M in plasma.	1 to 15 days after dosing	Cmax will be determined based on measurement of baxdrostat and CIN-107M in plasma.
Time to maximum concentration [Tmax] for baxdrostat and CIN-107M in plasma.	1 to 15 days after dosing	Tmax will be determined based on measurement of baxdrostat and CIN-107M in plasma.
Terminal elimination half-life (t1/2) for baxdrostat and CIN-107M in plasma.	1 to 15 days after dosing	t1/2 for baxdrostat and CIN-107M in plasma will be determined based on measurement of baxdrostat and CIN-107M in plasma.

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Labcorp Clinical Research Unit; 🇺🇸 Madison, Wisconsin, United States