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

NCT05526690 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: CIN-107-114
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

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.

Conditions

Hypertension

Outcome Measures

Primary Outcomes (12)

• 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

• 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

• 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

• Maximum plasma concentration (Cmax) of metformin

  This plasma PK parameter will be determined for metformin.

  Up to day 3

• Time to Cmax (Tmax) of metformin

  This plasma PK parameter will be determined for metformin.

  Up to day 3

• 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

• AUC from time 0 to infinity of metformin

  This plasma PK parameter will be determined for metformin.

  Up to day 3

• Percent of AUC extrapolated of metformin

  This plasma PK parameter will be determined for metformin.

  Up to day 3

• Terminal phase elimination half-life of metformin

  This plasma PK parameter will be determined for metformin.

  Up to day 3

• Cumulative amount of metformin excreted in the urine (Ae) of metformin

  This urine PK parameter will be determined for metformin.

  Up to day 3

• Renal clearance (calculated as Ae/AUC) of metformin

  This urine PK parameter will be determined for metformin.

  Up to day 3

• Fraction of the dose excreted renally of metformin

  This urine PK parameter will be determined for metformin.

  Up to day 3

Study Arms (2)

Treatment A: Immediate-release metformin

ACTIVE COMPARATOR

Treatment A: single 1000 mg dose of immediate-release metformin Subjects will be randomly assigned to 1 of 2 sequences: AB or BA. * Treatment A: a single 1000 mg dose of immediate-release metformin; and * Treatment B: a single 1000 mg dose of immediate-release metformin coadministered with a 10 mg dose of CIN-107. All study medication will be administered at 8:00 AM (±2 hours). There will be a minimum 10-day washout between administration of study drug in each treatment period.

Drug: Metformin

Treatment B: Immediate-release metformin coadministered with a CIN-107

EXPERIMENTAL

Treatment B: a single 1000 mg dose of immediate-release metformin coadministered with a 10 mg dose of CIN-107 Subjects will be randomly assigned to 1 of 2 sequences: AB or BA. * Treatment A: a single 1000 mg dose of immediate-release metformin; and * Treatment B: a single 1000 mg dose of immediate-release metformin coadministered with a 10 mg dose of CIN-107. All study medication will be administered at 8:00 AM (±2 hours). For Treatment B, the dose of CIN-107 will be administered 2 hours prior to the dose of metformin. There will be a minimum 10-day washout between administration of study drug in each treatment period.

Drug: Metformin; Drug: CIN-107

Interventions

Metformin DRUG

1000 mg dose of immediate-release metformin

Treatment A: Immediate-release metformin; Treatment B: Immediate-release metformin coadministered with a CIN-107

CIN-107 DRUG

10 mg dose of CIN-107

Treatment B: Immediate-release metformin coadministered with a CIN-107

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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;

You may not qualify if:

• 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;
• 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;

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Medpace Clinical Pharmacology Unit

Cincinnati, Ohio, 45227, United States

Location

Related 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.

  PMID: 36790596 BACKGROUND

Related Links

• Redacted CSR Synopsis

MeSH Terms

Conditions

Hypertension

Interventions

Metformin

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Leela Leela Vrishabhendra, MD, MD

  Medpace Clinical Pharmacology Unit

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: August 31, 2022
• First Posted: September 2, 2022
• Study Start: October 28, 2020
• Primary Completion: December 12, 2020
• Study Completion: December 12, 2020
• 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 (1)