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

A Phase 1, Open-Label, Single-Dose, Parallel-Group Study to Evaluate the Pharmacokinetics of CIN-107 in Subjects With Varying Degrees of Renal Function

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.

Study Overview

• Status: Completed
• Conditions: Hypertension
• Intervention / Treatment: Drug: CIN-107

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Orlando, Florida, United States, 32809
      • Orlando Clinical Research Center
    • Tampa, Florida, United States, 33603
      • Genesis Clinical Trials

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• 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;

Exclusion Criteria:

• 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:

  1. Seated systolic BP >160 mmHg and/or diastolic BP >100 mmHg, or systolic BP <90 mmHg and/or diastolic BP <50 mmHg;
  2. Resting heart rate >100 beats per minute (bpm) or <50 bpm;
  3. Oral temperature >37.6°C (>99.68°F);
  4. Respiration rate 20 breaths/minute;
  5. Postural tachycardia (ie, an increase in heart rate >30 bpm upon standing from a seated position);
  6. Orthostatic hypotension (ie, a fall in systolic BP ≥20 mmHg or diastolic BP ≥10 mmHg upon standing from a seated position);
  7. Clinically significant abnormal serum potassium >upper limit of normal of the reference range (ULN);
  8. Clinically significant abnormal serum sodium 1.5 x ULN;
  9. Aspartate aminotransferase or alanine aminotransferase values >1.5 x ULN
  10. Total bilirubin >2 x ULN, unless due to Gilbert's syndrome;
  11. Positive test for HIV antibody, hepatitis C virus (HCV) RNA, hepatitis B surface antigen (HBsAg), or SARS-CoV-2 RNA; or
• History of porphyria, myopathy, or active liver disease;
• Inadequate venous access;
• Current treatment with weight loss medication or prior weight loss surgery (eg, gastric bypass surgery);
• Use of a strong inducer of CYP3A4 within 28 days prior to the dose of study drug;
• Corticosteroid use (systemic or extensive topical use) within 3 months prior to study drug dosing;
• Positive drug or alcohol test result without medical explanation or a history of alcoholism or drug abuse within 2 years prior to study drug dosing as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition;
• Typical consumption of ≥14 alcoholic drinks weekly;
• Surgical procedures within 4 weeks prior to study drug dosing or planned elective surgery during the study period;
• Any clinically significant illness within 4 weeks prior to study drug dosing, unless deemed not clinically significant by the Investigator;
• Pregnant, breastfeeding, or planning to become pregnant during the study;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Control (normal renal function or mild renal impairment); Estimated glomerular filtration rate (eGFR) ≥60 mL/min	Drug: CIN-107; A single 10 mg CIN-107 oral dose (2 X 5 mg tablets).; Other Names: baxdrostat
Experimental: Moderate to severe renal impairment; eGFR 15 to 59 mL/min	Drug: CIN-107; A single 10 mg CIN-107 oral dose (2 X 5 mg tablets).; Other Names: baxdrostat
Experimental: Kidney failure; 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; A single 10 mg CIN-107 oral dose (2 X 5 mg tablets).; Other Names: baxdrostat

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: AstraZeneca

Publications and helpful links

Helpful Links

• Redacted CSR Synopsis

Study record dates

Study Major Dates

• Study Start (Actual): January 12, 2021
• Primary Completion (Actual): April 30, 2021
• Study Completion (Actual): April 30, 2021

Study Registration Dates

• First Submitted: July 20, 2022
• First Submitted That Met QC Criteria: July 20, 2022
• First Posted (Actual): July 22, 2022

Study Record Updates

• Last Update Posted (Actual): August 14, 2023
• Last Update Submitted That Met QC Criteria: August 9, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension
• Other Study ID Numbers: CIN-107-113

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. "Yes", indicates that AZ are accepting requests for IPD, but this does not mean all requests will be approved.
• IPD Sharing 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.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No