Study to Evaluate the Pharmacokinetics of CIN-107 in Subjects With Varying Degrees of Renal Function

NCT05470725 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: CIN-107-113
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 2

Brief Summary

This is a Phase 1, open-label, parallel-group study in subjects with varying degrees of renal function to assess the safety, tolerability, and Pharmacokinetics of a single 10 mg oral dose of CIN-107.

Conditions

Hypertension

Outcome Measures

Primary Outcomes (14)

• 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, as the data permit.

  up to Day 8

• 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, as the data permit.

  up to Day 8

• 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, as the data permit.

  up to Day 8

• Area under the curve from time 0 to infinity (AUC[0-inf])

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

  up to Day 8

• 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, as the data permit.

  up to Day 8

• 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, as the data permit.

  up to Day 8

• Apparent plasma clearance (CL/F)

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

  up to Day 8

• Apparent volume of distribution

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

  up to Day 8

• 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 8

• Renal clearance (CLR) of CIN-107 and CIN-107-M of CIN-107 and CIN-107-M

  Calculated as Ae/AUC. This PK parameter will be calculated using the urine concentrations of CIN-107 and its primary metabolite (CIN-107-M)

  up to Day 8

• The fraction of the dose excreted renally

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

  up to Day 8

• Number of patients experiencing adverse events (AEs)

  up to Day 11

• Number of patients experiencing adverse drug reactions

  up to Day 11

• Number of patients experiencing serious adverse events (SAEs)

  up to Day 11

Study Arms (3)

Control (normal renal function or mild renal impairment)

EXPERIMENTAL

Estimated glomerular filtration rate (eGFR) ≥60 mL/min

Drug: CIN-107

Moderate to severe renal impairment

EXPERIMENTAL

eGFR 15 to 59 mL/min

Drug: CIN-107

Kidney failure

EXPERIMENTAL

eGFR \<15 mL/min, including: * Subjects not on dialysis; and * Subjects on dialysis, with study drug administration on a non-dialysis day

Drug: CIN-107

Interventions

CIN-107 DRUG

A single 10 mg CIN-107 oral dose (2 X 5 mg tablets).

Also known as: baxdrostat

Control (normal renal function or mild renal impairment); Kidney failure; Moderate to severe renal impairment

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects in stable health based on medical and psychiatric history, physical examination, ECG, vital signs (seated and orthostatic), and routine laboratory tests (chemistry, hematology, coagulation, and urinalysis); Note: Underlying medical conditions consistent with the population under study are acceptable if the subject's condition is considered stable by the Investigator. For renally impaired subjects, their renal status must be stable for a minimum of 3 months prior to screening.
• Does not use nicotine-containing products at all or smokes \<10 cigarettes/day (approximately \<half pack/day);
• Body mass index (BMI) between 18 and 40 kg/m2, inclusive;

You may not qualify if:

• Active participation in another experimental therapy study of a small molecule other than CIN-107 within 30 days prior to Day 1 or 5 half-lives, whichever is longer; or received a large molecule within 90 days prior to Day 1 or 5 half-lives, whichever is longer;
• History of prior organ transplant or planned transplant within 6 months of screening;
• 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, chronic persistent atrial fibrillation, sinus node dysfunction, or clinically significant heart block. Subjects with minor forms of ectopy (eg, premature atrial contractions) are not necessarily excluded;
• Prolonged QTcF (\>450 msec for males or \>470 msec for females) based on the average of triplicate ECGs;
• Evidence of any of the following clinical measurements:
• Seated systolic BP \>160 mmHg and/or diastolic BP \>100 mmHg, or systolic BP \<90 mmHg and/or diastolic BP \<50 mmHg;
• Resting heart rate \>100 beats per minute (bpm) or \<50 bpm;
• Oral temperature \>37.6°C (\>99.68°F);
• Respiration rate 20 breaths/minute;
• Postural tachycardia (ie, an increase in heart rate \>30 bpm upon standing from a seated position);
• Orthostatic hypotension (ie, a fall in systolic BP ≥20 mmHg or diastolic BP ≥10 mmHg upon standing from a seated position);
• Clinically significant abnormal serum potassium \>upper limit of normal of the reference range (ULN);
• Clinically significant abnormal serum sodium 1.5 x ULN;
• Aspartate aminotransferase or alanine aminotransferase values \>1.5 x ULN

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (2)

Orlando Clinical Research Center

Orlando, Florida, 32809, United States

Location

Genesis Clinical Trials

Tampa, Florida, 33603, United States

Location

Related Links

• Redacted CSR Synopsis

MeSH Terms

Conditions

Hypertension

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 20, 2022
• First Posted: July 22, 2022
• Study Start: January 12, 2021
• Primary Completion: April 30, 2021
• Study Completion: April 30, 2021
• 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 (2)