Study With CIN-107 Following Multiple Oral Ascending Doses in Healthy Subjects

NCT05500820 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: CIN-107-111
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized, double-blind, study to assess the safety, tolerability, PK, and PD of multiple oral doses of CIN-107 when administered to healthy adult subjects.

Conditions

Hypertension

Keywords

pharmacokinetics (PK), metabolism, baxdrostat

Outcome Measures

Primary Outcomes (20)

• Maximum plasma concentration (Cmax)

  This PK parameter will be determined for CIN-107, its primary metabolite (CIN-107-M), and any other measured metabolites using plasma concentration data and following the first and last doses of CIN-107, as the data permit.

  up to Day 15

• Time to maximum plasma concentration (Tmax)

  This PK parameter will be determined for CIN-107, its primary metabolite (CIN-107-M), and any other measured metabolites using plasma concentration data and following the first and last doses of CIN-107, as the data permit.

  up to Day 15

• Area under the curve from time 0 to the time of last quantifiable plasma concentration (AUC[0-last])

  This PK parameter will be determined for CIN-107, its primary metabolite (CIN-107-M), and any other measured metabolites using plasma concentration data following the final dose of CIN-107, as the data permit.

  up to Day 15

• Area under the curve from time 0 to infinity

  This PK parameter will be determined for CIN-107, its primary metabolite (CIN-107-M), and any other measured metabolites using plasma concentration data following the final dose of CIN-107, as the data permit.

  up to Day 15

• Area under the curve over a dosing interval (tau)

  This PK parameter will be determined for CIN-107, its primary metabolite (CIN-107-M), and any other measured metabolites using plasma concentration data following the final dose of CIN-107, as the data permit.

  up to Day 15

• Area under the plasma concentration-time curve (AUC) from time 0 to 24 hours

  This PK parameter will be determined for CIN-107, its primary metabolite (CIN-107-M), and any other measured metabolites using plasma concentration data and following the first dose of CIN-107, as the data permit.

  up to Day 2

• Percent of AUC extrapolated

  This PK parameter will be determined for CIN-107, its primary metabolite (CIN-107-M), and any other measured metabolites using plasma concentration data following the final dose of CIN-107, as the data permit.

  up to Day 15

• Terminal phase elimination half-life

  This PK parameter will be determined for CIN-107, its primary metabolite (CIN-107-M), and any other measured metabolites using plasma concentration data following the final dose of CIN-107, as the data permit.

  up to Day 15

• Apparent plasma clearance

  This PK parameter will be determined for CIN-107 using plasma concentration data.

  up to Day 15

• Apparent volume of distribution

  This PK parameter will be determined for CIN-107 using plasma concentration data.

  Up to Day 15

• The cumulative amount of CIN-107 and CIN-107-M excreted in the urine (Ae)

  This PK parameter will be calculated using the urine concentrations of CIN-107 and its primary metabolite (CIN-107-M)

  up to Day 15

• Renal clearance (CLR Calculated as Ae/AUC) of CIN-107 and CIN-107-M

  This PK parameter will be calculated using the urine concentrations of CIN-107 and its primary metabolite (CIN-107-M)

  up to Day 15

• Fraction of the dose excreted renally (fe)

  This PK parameter will be calculated using the urine concentrations of CIN-107

  up to Day 15

• Number of patients experiencing adverse events (AEs)

  up to Day 15

• Number of patients experiencing adverse drug reactions

  up to Day 15

• Number of patients experiencing serious adverse events (SAEs)

  up to Day 15

• Plasma concentration of aldosterone

  up to Day 15

• Plasma renin activity

  up to Day 15

• Plasma concentration of cortisol (free and total)

  up to Day 15

• Plasma concentration of ACTH (Adrenocorticotropic hormone)

  up to Day 15

Study Arms (10)

Cohort 1: 2.5 mg CIN-107

EXPERIMENTAL

Subjects on a low salt diet

Drug: CIN-107

Cohort 2: 5.0 mg CIN-107

EXPERIMENTAL

Subjects on a low salt diet

Drug: CIN-107

Cohort 3: 1.5 mg CIN-107

EXPERIMENTAL

Subjects on a normal salt diet

Drug: CIN-107

Cohort 4: 2.5 mg CIN-107

EXPERIMENTAL

Subjects on a normal salt diet

Drug: CIN-107

Cohort 5: 0.5 mg CIN-107

EXPERIMENTAL

Subjects on a normal salt diet

Drug: CIN-107

Cohort 1: 2.5 mg matching placebo

PLACEBO COMPARATOR

Subjects on a low salt diet

Drug: Matching Placebo

Cohort 2: 5.0 mg matching placebo

PLACEBO COMPARATOR

Subjects on a low salt diet

Drug: Matching Placebo

Cohort 3: 1.5 mg matching placebo

PLACEBO COMPARATOR

Subjects on a normal salt diet

Drug: Matching Placebo

Cohort 4: 2.5 mg matching placebo

PLACEBO COMPARATOR

Subjects on a normal salt diet

Drug: Matching Placebo

Cohort 5: 0.5 mg matching placebo

PLACEBO COMPARATOR

Subjects on a normal salt diet

Drug: Matching Placebo

Interventions

CIN-107 DRUG

A repeat oral dose of CIN-107 once daily for 10 days.

Also known as: baxdrostat

Cohort 1: 2.5 mg CIN-107; Cohort 2: 5.0 mg CIN-107; Cohort 3: 1.5 mg CIN-107; Cohort 4: 2.5 mg CIN-107; Cohort 5: 0.5 mg CIN-107

Matching Placebo DRUG

A repeat oral dose of matching placebo once daily for 10 days.

Cohort 1: 2.5 mg matching placebo; Cohort 2: 5.0 mg matching placebo; Cohort 3: 1.5 mg matching placebo; Cohort 4: 2.5 mg matching placebo; Cohort 5: 0.5 mg matching placebo

Eligibility Criteria

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

You may qualify if:

• Healthy subjects between the ages of 18 and 55 years, inclusive, in good health based on medical and psychiatric history, physical examination, ECG, orthostatic vital signs, and routine laboratory tests (blood chemistry, hematology, coagulation, and urinalysis).
• Body mass index (BMI) between 18 and 30 kg/m2, inclusive.
• Nonsmokers who have not used nicotine-containing products for at least 6 months prior to the Screening Visit.

You may not qualify if:

• Actively participating in an experimental therapy study; received experimental therapy with a small molecule within 30 days of Day 1, or 5 half-lives, whichever is longer; or received experimental therapy with a large molecule within 90 days of Day 1, or 5 half-lives, whichever is longer.
• A personal or family history of long QT syndrome, Torsades de Pointes, or other complex ventricular arrhythmias, or family history of sudden death.
• History of, or current, clinically significant arrhythmias as judged by the Investigator, including ventricular tachycardia, ventricular fibrillation, or atrial fibrillation.
• Prolonged QTcF (\>450 msec) based on the average of triplicate ECGs.
• Seated blood pressure higher than 150/90 mmHg or lower than 90/50 mmHg.
• Resting heart rate higher than 100 bpm or lower than 50 bpm , sinus node dysfunction, or clinically significant heart block.
• Temperature (T) greater than 37.6o C (99.68o F, measured orally), and respiration rate less than 12 and greater than 20 breaths/minute.
• Postural tachycardia (ie \>30 bpm upon standing) or orthostatic hypotension (ie, a fall in systolic blood pressure (SBP) of ≥20 mm Hg or DBP of ≥ 10 mm Hg when a person assumes a standing position).
• Serum potassium \> upper limit of normal of the reference range (ULN) and serum sodium \< lower limit of normal of the reference range (LLN).
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) values \> 1.2 ULN.
• Positive for human immunodeficiency virus (HIV) antibody, hepatitis C virus (HCV) antibody, or Hepatitis B surface antigen (HBsAg).
• A known history of porphyria, myopathy, or an active liver disease.
• Positive drug or alcohol test result or a history of alcoholism or drug abuse within 2 years prior to the first dose of study drug as defined by the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition: DSM-IV.
• Typical consumption of ≥14 alcoholic drinks weekly.
• Surgical procedures within 4 weeks of check-in or planned elective surgery during the study period.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Medpace Clinical Pharmacology Unit

Cincinnati, Ohio, 45227, United States

Location

Related Publications (1)

• Freeman MW, Bond M, Murphy B, Hui J, Isaacsohn J. Results from a phase 1, randomized, double-blind, multiple ascending dose study characterizing the pharmacokinetics and demonstrating the safety and selectivity of the aldosterone synthase inhibitor baxdrostat in healthy volunteers. Hypertens Res. 2023 Jan;46(1):108-118. doi: 10.1038/s41440-022-01070-4. Epub 2022 Oct 20.

  PMID: 36266539 BACKGROUND

Related Links

• Redacted CSR Synopsis

MeSH Terms

Conditions

Hypertension

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Study Officials

• Leela Vrishabhendra, MD

  Medpace Clinical Pharmacology Unit

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 12, 2022
• First Posted: August 15, 2022
• Study Start: December 19, 2019
• Primary Completion: April 3, 2020
• Study Completion: April 3, 2020
• 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)