Hypertension
Conditions
Keywords
pharmacokinetics (PK), metabolism, baxdrostat
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.
Interventions
DRUGbaxdrostat
a blood pressure lowering drug, oral dose
Sponsors
AstraZeneca
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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. |
| 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 |
Countries
United States
Outcome results
None listed