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

Hypertension Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05470725
• Other study ID #: CIN-107-113
• Status: Completed
• Phase: Phase 1
• Start date: January 12, 2021
• Est. completion date: April 30, 2021

Study information

• Verified date: August 2023
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. completion date: April 30, 2021
• Est. primary completion date: April 30, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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;

Related Conditions & MeSH terms

• Hypertension

Intervention

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

Locations

Country	Name	City	State
United States	Orlando Clinical Research Center	Orlando	Florida
United States	Genesis Clinical Trials	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	Apparent plasma clearance (CL/F)	This PK parameter will be determined for CIN-107 using plasma concentration data.	up to Day 8
Primary	Apparent volume of distribution	This PK parameter will be determined for CIN-107 using plasma concentration data.	up to Day 8
Primary	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
Primary	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
Primary	The fraction of the dose excreted renally	This PK parameter will be calculated using the urine concentrations of CIN-107	up to Day 8
Primary	Number of patients experiencing adverse events (AEs)		up to Day 11
Primary	Number of patients experiencing adverse drug reactions		up to Day 11
Primary	Number of patients experiencing serious adverse events (SAEs)		up to Day 11

External Links

•   Redacted CSR Synopsis