Clinical trial NCT05526690: Study to Evaluate the Effect of CIN-107 on the Pharmacokinetics of the MATE Substrate, Metformin, in Healthy Subjects
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hypertension
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2022-09-02
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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;

Primary outcomes:
measure: Maximum plasma concentration (Cmax)
timeFrame: Up to day 3
measure: Time to Cmax (Tmax)
timeFrame: Up to day 3
measure: Area under the concentration-time curve (AUC) from time 0 to 72 hours
timeFrame: Up to day 3
measure: Maximum plasma concentration (Cmax) of metformin
timeFrame: Up to day 3
measure: Time to Cmax (Tmax) of metformin
timeFrame: Up to day 3
measure: AUC from time 0 to the time of last quantifiable plasma concentration of metformin
timeFrame: Up to day 3
measure: AUC from time 0 to infinity of metformin
timeFrame: Up to day 3
measure: Percent of AUC extrapolated of metformin
timeFrame: Up to day 3
measure: Terminal phase elimination half-life of metformin
timeFrame: Up to day 3
measure: Cumulative amount of metformin excreted in the urine (Ae) of metformin
timeFrame: Up to day 3
measure: Renal clearance (calculated as Ae/AUC) of metformin
timeFrame: Up to day 3
measure: Fraction of the dose excreted renally of metformin
timeFrame: Up to day 3
Secondary outcomes:
Other outcomes:
Locations:
city: Cincinnati
country: United States
facility: Medpace Clinical Pharmacology Unit
state: Ohio
Study officials:
affiliation: Medpace Clinical Pharmacology Unit
name: Leela Leela Vrishabhendra, MD, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.