Phase 1 Study to Determine the Metabolism and Clearance of Baxdrostat

NCT05961384 | Completed Phase 1 FDA Drug

• 1 other identifier: CIN-107-117
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

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.

Conditions

Hypertension

Keywords

pharmacokinetics (PK); metabolism; baxdrostat

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (3)

• Quantitative metabolic profiles of baxdrostat in plasma and excreta.

  1 to 15 days after dosing

• Identification of baxdrostat metabolites in plasma and excreta.

  1 to 15 days after dosing

• Incidence of treatment emergent adverse events following administration of [14C] baxdrostat.

  1 to 15 days after dosing

Study Arms (1)

10 mg [14C]-bexdrostat

EXPERIMENTAL

single oral dose of 10 mg baxdrostat containing 100 μCi of \[14C\] baxdrostat

Drug: baxdrostat

Interventions

baxdrostat DRUG

a blood pressure lowering drug, oral dose

Also known as: CIN-107

10 mg [14C]-bexdrostat

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Labcorp Clinical Research Unit

Madison, Wisconsin, 53704, United States

Location

Related Links

• CSR Synopsis Redacted

MeSH Terms

Conditions

Hypertension

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Study Officials

• Nicholas Siebers, MD Siebers, MD

  Labcorp Clinical Research Unit, Madison, Wisconsin, USA 53704

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 3, 2023
• First Posted: July 27, 2023
• Study Start: November 18, 2021
• Primary Completion: January 15, 2022
• Study Completion: January 15, 2022
• Last Updated: August 15, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA Data-Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Locations

US (1)