Phase 1 Study to Determine the Metabolism and Clearance of Baxdrostat

Hypertension Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05961384
• Other study ID #: CIN-107-117
• Status: Completed
• Phase: Phase 1
• Start date: November 18, 2021
• Est. completion date: January 15, 2022

Study information

• Verified date: August 2023
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: January 15, 2022
• Est. primary completion date: January 15, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Hypertension

Intervention

Drug:
• baxdrostat
a blood pressure lowering drug, oral dose

Locations

Country	Name	City	State
United States	Labcorp Clinical Research Unit	Madison	Wisconsin

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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)0-8 and AUC0-last will be determined for baxdrostat and CIN-107M in plasma.	1 to 15 days after dosing
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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

External Links

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