Clinical trial NCT05961384: Phase 1 Study to Determine the Metabolism and Clearance of Baxdrostat
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hypertension
Keywords: pharmacokinetics (PK)
metabolism
baxdrostat
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2023-07-27
Enrollment: 8
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Total radioactivity recovery in urine and feces following administration of [14C] baxdrostat.
timeFrame: 1 to 15 days after dosing
measure: Area under the curve [AUC] of baxdrostat and its primary metabolite (CIN-107M) following administration of [14C] baxdrostat to healthy male subjects.
timeFrame: 1 to 15 days after dosing
measure: Cumulative baxdrostat and CIN-107M excreted in urine and fraction of baxdrostat renally excreted following administration of [14C] baxdrostat to healthy subjects.
timeFrame: 1 to 15 days after dosing
measure: Maximum concentration [Cmax] for baxdrostat and CIN-107M in plasma.
timeFrame: 1 to 15 days after dosing
measure: Time to maximum concentration [Tmax] for baxdrostat and CIN-107M in plasma.
timeFrame: 1 to 15 days after dosing
measure: Terminal elimination half-life (t1/2) for baxdrostat and CIN-107M in plasma.
timeFrame: 1 to 15 days after dosing
Secondary outcomes:
measure: Quantitative metabolic profiles of baxdrostat in plasma and excreta.
timeFrame: 1 to 15 days after dosing
measure: Identification of baxdrostat metabolites in plasma and excreta.
timeFrame: 1 to 15 days after dosing
measure: Incidence of treatment emergent adverse events following administration of [14C] baxdrostat.
timeFrame: 1 to 15 days after dosing
Other outcomes:
Locations:
city: Madison
country: United States
facility: Labcorp Clinical Research Unit
state: Wisconsin
Study officials:
affiliation: Labcorp Clinical Research Unit, Madison, Wisconsin, USA 53704
name: Nicholas Siebers, MD Siebers, MD
role: PRINCIPAL_INVESTIGATOR
References: