Baxdrostat Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Study in a Japanese Population

NCT05966324 | Completed Phase 1 FDA Drug

• 1 other identifier: CIN-107-126
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this study is to compare the characteristics of baxdrostat (CIN-107) in terms of baxdrostat levels over time in the blood in healthy Japanese and Caucasian volunteer participants.

Conditions

Hypertension

Keywords

hypertension; Japanese; PK; baxdrostat

Outcome Measures

Primary Outcomes (6)

• Incidence of treatment emergent adverse events following single and multiple doses of baxdrostat in healthy Japanese and Caucasian participants versus placebo recipients.

  Safety and tolerability will be assessed by comparison of number of treatment emergent adverse events between groups.

  0 to 19 days after dosing

• Area under the curve (AUC) for baxdrostat and the CIN-107-M metabolite after single and multiple oral doses of baxdrostat in healthy Japanese subjects.

  AUC \[0 to 24 hours, 0 to last quantifiable concentration, and 0 to infinity of baxdrostat\] will be determined for baxdrostat and the CIN-107M metabolite for Japanese participants in each of each of the 3 dose groups of baxdrostat.

  0 to 15 days after dosing

• Maximum Plasma Concentration [Cmax] of baxdrostat and the CIN-107-M metabolite after single and multiple oral doses of baxdrostat in healthy Japanese subjects.

  Cmax will be determined for baxdrostat and the CIN-107M metabolite for Japanese participants in each of each of the 3 dose groups of baxdrostat.

  0 to 15 days after dosing

• Plasma aldosterone levels following single and multiple oral doses of baxdrostat in healthy Japanese subjects.

  Plasma aldosterone levels will be determined for baxdrostat and the CIN-107M metabolite for Japanese participants in each of each of the 3 dose groups of baxdrostat.

  0 to 15 days after dosing

• Time to Maximum Plasma Concentration [Tmax] of baxdrostat and the CIN-107-M metabolite after single and multiple oral doses of baxdrostat in healthy Japanese subjects.

  Tmax will be determined for baxdrostat and the CIN-107M metabolite for Japanese participants in each of each of the 3 dose groups of baxdrostat.

  0 to 15 days after dosing

• Terminal elimination half-life of baxdrostat and the CIN-107-M metabolite after single and multiple oral doses of baxdrostat in healthy Japanese subjects.

  Terminal elimination half-life will be determined for baxdrostat and the CIN-107M metabolite for Japanese participants in each of each of the 3 dose groups of baxdrostat.

  0 to 15 days after dosing

Study Arms (4)

Cohort 1

EXPERIMENTAL

Oral tablet dose of baxdrostat 1 mg or placebo, administered as a single dose (Day 1) and multiple doses (once daily \[QD\] for 5 days, Days 6 - 10) to Japanese subjects

Drug: baxdrostat

Cohort 2

EXPERIMENTAL

Oral tablet dose of baxdrostat 3 mg or placebo, administered as a single dose (Day 1) and multiple doses (QD for 5 days, Days 6 - 10) to Japanese subjects

Drug: baxdrostat

Cohort 3

EXPERIMENTAL

Oral tablet dose of baxdrostat 3 mg or placebo, administered as a single dose (Day 1) and multiple doses (QD for 5 days, Days 6 - 10) to Caucasian subjects

Drug: baxdrostat

Cohort 4

EXPERIMENTAL

Oral tablet dose of baxdrostat 10 mg or placebo, administered as a single dose (Day 1) and multiple doses (QD for 5 days, Days 6 - 10) to Japanese subjects

Drug: baxdrostat

Interventions

baxdrostat DRUG

Baxdrostat is an aldosterone synthase inhibitor

Also known as: CIN-107

Cohort 1; Cohort 2; Cohort 3; Cohort 4

Eligibility Criteria

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

You may qualify if:

• Male or female subjects, 18 to 55 years of age, inclusive.
• Demographics as follows:
• Japanese subjects must have been born in Japan, with both biological parents and all 4 biological grandparents of Japanese descent, have lived outside of Japan for \< 10 years, and have not significantly changed his or her diet since leaving Japan (eg, still mainly eating a "Japanese" diet), OR
• Caucasian ancestry (Cohort 3)
• Healthy status as defined by absence of evidence of any active or chronic disease following a detailed medical and surgical history, a complete physical examination including vital signs, 12-lead ECG, and laboratory assessments (hematology, chemistry, serology, and urinalysis).
• A BMI between 18 - 30 kg/m2, inclusive.
• Females may be of nonchildbearing or childbearing potential. Females of nonchildbearing potential are postmenopausal or surgically sterile. Females of nonchildbearing potential are exempt from the dual contraception requirement.
• Females of childbearing potential may be included, provided the subject agrees to continuously use dual methods of contraception from 1 month prior through 90 days after study drug administration.
• Able to participate and willing to give written informed consent and to comply with the study restrictions.

You may not qualify if:

• Any clinically relevant history or the presence of respiratory, renal, hepatic, gastrointestinal, hematological, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, allergic, ophthalmological disease or connective tissue disease, cancer or cirrhosis.
• A history of clinically significant drug hypersensitivity.
• Subjects with clinically significant symptoms of an infectious illness (bacterial, viral, or parasitic) within 5 days of the first dose or a history of recurrent infections.
• History of alcohol abuse, illicit drug use, physical dependence to any opioid, or any history of drug abuse or addiction (including soft drugs like cannabis products) within 6 months of screening.
• Nicotine users unable or unwilling to restrict nicotine usage to the equivalent of 5 cigarettes daily during the study and to not smoke during the in-clinic stays. (Nicotine-containing products include cigarettes, chewing tobacco, snuff, nicotine patches, electronic cigarettes, vaping devices, etc.)
• Positive result for HIV-1 or HIV-2, hepatitis C virus (HCV), or HBsAg at screening.
• Confirmed (based on the average of ≥ 3 blood pressure measurements) sustained systolic blood pressure \> 140 or \< 90 mmHg, and diastolic blood pressure \> 90 or \< 45 mmHg, and pulse rate \> 100 or \< 40 bpm.
• Personal or family history of congenital long QT syndrome or QTcF values \> 450 msec in males or \> 470 msec in females.
• Screening or baseline ECGs with QRS and/or T-wave judged by the Investigator to be unfavorable for a consistently accurate QT measurement (ie, neuromuscular artifact that cannot be readily eliminated, arrhythmias, indistinct QRS onset, low amplitude T-wave, merged T- and U-waves, prominent U-waves, etc.)
• Screening or baseline ECG with clinically significant abnormalities such as atrial fibrillation, atrial flutter, complete bundle branch block, Wolf-Parkinson-White Syndrome, or cardiac pacemaker, as judged by the Investigator.
• Clinically significant abnormalities in laboratory test results (including hepatic and renal panels, complete blood count, chemistry panel, and urinalysis) at screening or prior to dosing. The Medical Monitor may be consulted to discuss questionable abnormalities. Laboratory values that are not clinically significant, in the Investigator's opinion, may be allowable. In addition, subjects with the following will be excluded from the study (regardless of significance):
• red blood cell count \< 0.75 x lower limit of normal (LLN)
• white blood cell count \< 0.75 x LLN
• hemoglobin \< 0.75 x LLN
• aspartate transaminase \> 1.25 x upper limit of normal (ULN)

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Anaheim Clinical Trials

Anaheim, California, 92801, United States

Location

Related Links

• Redacted CSR Synopsis

MeSH Terms

Conditions

Hypertension

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Study Officials

• Peter J Winkle, MD

  ICON Clinical Research LLC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The study included 4 cohorts and each cohort consisted of 10 subjects, randomized 4:1 (active:placebo).
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This was a single and multiple oral dose study of the safety/tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) in healthy Japanese subjects compared with a cohort of healthy Caucasian subjects. total of 41 subjects were enrolled in this study: 31 Japanese subjects and 10 Caucasian subjects. The study included 4 cohorts and each cohort consisted of 10 subjects, randomized 4:1 (active:placebo). The Japanese cohorts (Cohorts 1, 2, and 4) were performed in parallel. The Caucasian cohort (Cohort 3) was performed after Cohort 2 was complete so that the Caucasian subjects could be matched by certain demographic factors.

Study Record Dates

• First Submitted: July 4, 2023
• First Posted: July 28, 2023
• Study Start: July 5, 2022
• Primary Completion: September 20, 2022
• Study Completion: September 20, 2022
• Last Updated: August 14, 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)