Phase 1 Study to Determine the Metabolism and Clearance of Baxdrostat

Study Overview
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Brief Summary
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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.

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

Conditions
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Hypertension

Intervention / Treatment
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* Drug: baxdrostat


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 10 mg [14C]-bexdrostat<br>single oral dose of 10 mg baxdrostat containing 100 μCi of [14C] baxdrostat | Drug: baxdrostat<br>* a blood pressure lowering drug, oral dose<br>* Other names: CIN-107;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pharmacokinetics (PK), metabolism, baxdrostat