Study to Evaluate the Effect of CIN-107 on the Pharmacokinetics of the MATE Substrate, Metformin, in Healthy Subjects

Hypertension Clinical Trial

Official title:

A Randomized, Open-Label, Two-Period, Crossover Study to Evaluate the Effect of CIN-107 on the Pharmacokinetics of the MATE Substrate, Metformin, in Healthy Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05526690
• Other study ID #: CIN-107-114
• Status: Completed
• Phase: Phase 1
• Start date: October 28, 2020
• Est. completion date: December 12, 2020

Study information

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

Clinical Trial Summary

This is a randomized, open-label, two-period, crossover Phase 1 to assess the impact of CIN-107 on the pharmacokinetics (PK) of metformin and the safety and tolerability of coadministration of CIN-107 and metformin as compared to metformin alone.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: December 12, 2020
• Est. primary completion date: December 12, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• Healthy subjects between the ages of 18 and 55 years, inclusive, at Screening;

• Body mass index between 18 and 30 kg/m2, inclusive;

• In good health based on medical/surgical and psychiatric history, physical examination, electrocardiogram (ECG), vital signs (seated and orthostatic), and routine laboratory tests (serum chemistry, hematology, and urinalysis);

• Normal renal function, defined as estimated glomerular filtration rate =85 mL/min/1.73 m2 at Screening and Day -1;

• Nonsmokers who have not used nicotine-containing products (ie, cigarettes, nicotine patch, nicotine chewing gum, or electronic cigarettes) for at least 6 months prior to Screening;

Exclusion Criteria:

• Actively participating in an experimental therapy study; received experimental therapy with a small molecule other than CIN-107 within 30 days of the first dose of study drug or 5 half-lives, whichever is longer; or received experimental therapy with a large molecule within 90 days of the first dose of study drug or 5 half-lives, whichever is longer;

• A personal or family history of long QT syndrome, Torsades de Pointes, 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, atrial fibrillation, sinus node dysfunction, or clinically significant heart block. Subjects with minor forms of ectopy (eg, premature atrial contractions) are not necessarily excluded and may be discussed with the Medical Monitor for inclusion;

• Prolonged QT interval corrected by Fridericia's formula (>450 msec);

• Seated systolic blood pressure (BP) >140 mmHg and/or diastolic BP >90 mmHg or systolic BP <90 mmHg and/or diastolic BP <50 mmHg;

• Postural tachycardia (ie, >30 bpm upon standing) or orthostatic hypotension (ie, a fall in systolic BP =20 mmHg or diastolic BP =10 mmHg upon standing);

• Serum potassium >upper limit of normal (ULN) of the reference range and serum sodium <lower limit of normal of the reference range;

• Aspartate aminotransferase, alanine aminotransferase, or total bilirubin values >1.2 × ULN;

• Positive for human immunodeficiency virus antibody, hepatitis C virus antibody, hepatitis B surface antigen, or severe acute respiratory syndrome coronavirus 2 RNA;

• Evidence or history of any clinically significant immunologic, hematologic, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, musculoskeletal, hepatic, psychiatric, neurologic, or allergic (including clinically significant or multiple drug allergies) disease; surgical conditions; cancer (with the exception of basal or squamous cell carcinoma of the skin and cancer that has resolved or has been in remission for >5 years prior to Screening); or any condition that, in the Investigator's opinion, may confound study procedures or results, impact subject safety, or interfere with the absorption, distribution, metabolism, or excretion of the study drug (appendectomy allowed, cholecystectomy prohibited);

• Typical consumption of =14 alcoholic drinks weekly; Note: 1 drink of alcohol is equivalent to ½ pint of beer (285 mL), 1 glass of spirits (25 mL), or 1 glass of wine (125 mL).

• Surgical procedures within 4 weeks prior to Check-In (other than minor cosmetic surgery or minor dental procedures) or planned elective surgery during the treatment period;

Related Conditions & MeSH terms

• Hypertension

Intervention

Drug:
• Metformin
1000 mg dose of immediate-release metformin
• CIN-107
10 mg dose of CIN-107

Locations

Country	Name	City	State
United States	Medpace Clinical Pharmacology Unit	Cincinnati	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Country where clinical trial is conducted

United States, 

References & Publications (1)

Freeman MW, Bond M, Murphy B, Hui J, Isaacsohn J. Results From a Randomized, Open-Label, Crossover Study Evaluating the Effect of the Aldosterone Synthase Inhibitor Baxdrostat on the Pharmacokinetics of Metformin in Healthy Human Subjects. Am J Cardiovasc Drugs. 2023 May;23(3):277-286. doi: 10.1007/s40256-023-00572-x. Epub 2023 Feb 15. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum plasma concentration (Cmax)	This plasma PK parameter will be determined for CIN-107, its primary metabolite (CIN-107-M), and any other measured metabolites.	Up to day 3
Primary	Time to Cmax (Tmax)	This plasma PK parameter will be determined for CIN-107, its primary metabolite (CIN-107-M), and any other measured metabolites.	Up to day 3
Primary	Area under the concentration-time curve (AUC) from time 0 to 72 hours	This plasma PK parameter will be determined for CIN-107, its primary metabolite (CIN-107-M), and any other measured metabolites.	Up to day 3
Primary	Maximum plasma concentration (Cmax) of metformin	This plasma PK parameter will be determined for metformin.	Up to day 3
Primary	Time to Cmax (Tmax) of metformin	This plasma PK parameter will be determined for metformin.	Up to day 3
Primary	AUC from time 0 to the time of last quantifiable plasma concentration of metformin	This plasma PK parameter will be determined for metformin.	Up to day 3
Primary	AUC from time 0 to infinity of metformin	This plasma PK parameter will be determined for metformin.	Up to day 3
Primary	Percent of AUC extrapolated of metformin	This plasma PK parameter will be determined for metformin.	Up to day 3
Primary	Terminal phase elimination half-life of metformin	This plasma PK parameter will be determined for metformin.	Up to day 3
Primary	Cumulative amount of metformin excreted in the urine (Ae) of metformin	This urine PK parameter will be determined for metformin.	Up to day 3
Primary	Renal clearance (calculated as Ae/AUC) of metformin	This urine PK parameter will be determined for metformin.	Up to day 3
Primary	Fraction of the dose excreted renally of metformin	This urine PK parameter will be determined for metformin.	Up to day 3

External Links

•   Redacted CSR Synopsis