NCT04448821

Brief Summary

The aim of the study is to evaluate the effect of nilotinib on the pharmacokinetics and pharmacodynamics of metformin in healthy male adults

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
16

participants targeted

Target at below P25 for phase_1 healthy

Timeline
Completed

Started Jul 2020

Shorter than P25 for phase_1 healthy

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

June 24, 2020

Completed
2 days until next milestone

First Posted

Study publicly available on registry

June 26, 2020

Completed
27 days until next milestone

Study Start

First participant enrolled

July 23, 2020

Completed
2 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 7, 2020

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 7, 2020

Completed
Last Updated

November 4, 2020

Status Verified

November 1, 2020

Enrollment Period

2 months

First QC Date

June 24, 2020

Last Update Submit

November 3, 2020

Conditions

Healthy

Outcome Measures

Primary Outcomes (4)

  • Cmax

    maximum concentration

    24 hours post-dose

  • AUCinf

    Area under the concentration-time curve from time of administration extrapolated to infinity

    24 hours post-dose

  • Gmax

    maximum glucose level during oral glucose tolerance test

    3 hours from 2 hour post-dose

  • AUGC

    Area under the concentration-time curve during oral glucose tolerance test

    3 hours from 2 hour post-dose

Secondary Outcomes (1)

  • Taste test

    7 hour post-dose

Study Arms (2)

Sequence A

EXPERIMENTAL

Period 1: metformin; Period 2: metformin + nilotinib

Drug: MetforminDrug: Metformin + Nilotinib

Sequence B

EXPERIMENTAL

Period 1: metformin + nilotinib; Period 2: metformin

Drug: MetforminDrug: Metformin + Nilotinib

Interventions

MetforminDRUG

Single administration of metformin

Sequence ASequence B
Metformin + NilotinibDRUG

Coadministration of metformin and nilotinib

Sequence ASequence B

Eligibility Criteria

Age19 Years - 50 Years
Sexmale(Gender-based eligibility)
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • Healthy male subjects between the ages of 19 and 50 years
  • Subjects with body mass index (BMI) between 18.5 and 29.9 kg/m2 and weight more than 50 kg
  • Subjects who agree with performing contraception during the study
  • Subjects who provides written informed consent

You may not qualify if:

  • Subjects who have a current or prior history of cardiovascular, respiratory, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, skin, psychiatric, or neurological diseases that is clinically significant
  • Subjects who have clinically significant allergic history or allergy to metformin, nilotinib, or other components of drug
  • Subjects with history of galactose intolerance, lapp lactase deficiency, or glucose-galactose malabsorption
  • Subjects with hypokalemia or hypomagnesemia at screening
  • Subjects with QTcF \> 450 or clinically significant findings on 12-lead ECG at screening
  • Subjects with fasting plasma glucose lower than 70 mg/dL or upper than 126 mg/dL at screening
  • Subjects who have history of gastrointestinal surgery
  • Subjects with creatinine clearance ≤ 60mL/min at screening
  • Subjects with AST or ALT ≥ 2-folds of upper normal limit
  • Subjects who reports less than 12 points on taste test at screening
  • Subjects who have administrated drugs that are known to cause significant drug-drug interaction with investigational drugs within 2 weeks prior to dosing
  • Whole blood donation within 60 days prior to dosing, or apheresis donation within 20 days prior to dosing, or received blood donation within 30 days prior to dosing
  • Subjects who participated in a previous clinical trial within 6 months prior to dosing
  • Subjects with a history of alcohol abuse
  • Subjects who are determined as unsuitable for clinical trial participation by investigator's decision

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Korea University Guro Hospital

Seoul, Guro-gu, 08308, South Korea

Location

Related Publications (9)

  • Graham GG, Punt J, Arora M, Day RO, Doogue MP, Duong JK, Furlong TJ, Greenfield JR, Greenup LC, Kirkpatrick CM, Ray JE, Timmins P, Williams KM. Clinical pharmacokinetics of metformin. Clin Pharmacokinet. 2011 Feb;50(2):81-98. doi: 10.2165/11534750-000000000-00000.

    PMID: 21241070BACKGROUND

  • Chen EC, Liang X, Yee SW, Geier EG, Stocker SL, Chen L, Giacomini KM. Targeted disruption of organic cation transporter 3 attenuates the pharmacologic response to metformin. Mol Pharmacol. 2015 Jul;88(1):75-83. doi: 10.1124/mol.114.096776. Epub 2015 Apr 28.

    PMID: 25920679BACKGROUND

  • Kwon EY, Chung JY, Park HJ, Kim BM, Kim M, Choi JH. OCT3 promoter haplotype is associated with metformin pharmacokinetics in Koreans. Sci Rep. 2018 Nov 16;8(1):16965. doi: 10.1038/s41598-018-35322-6.

    PMID: 30446679BACKGROUND

  • Lapczuk-Romanska J, Busch D, Gieruszczak E, Drozdzik A, Piotrowska K, Kowalczyk R, Oswald S, Drozdzik M. Membrane Transporters in Human Parotid Gland-Targeted Proteomics Approach. Int J Mol Sci. 2019 Sep 28;20(19):4825. doi: 10.3390/ijms20194825.

    PMID: 31569384BACKGROUND

  • Lee N, Duan H, Hebert MF, Liang CJ, Rice KM, Wang J. Taste of a pill: organic cation transporter-3 (OCT3) mediates metformin accumulation and secretion in salivary glands. J Biol Chem. 2014 Sep 26;289(39):27055-27064. doi: 10.1074/jbc.M114.570564. Epub 2014 Aug 8.

    PMID: 25107910BACKGROUND

  • Minematsu T, Giacomini KM. Interactions of tyrosine kinase inhibitors with organic cation transporters and multidrug and toxic compound extrusion proteins. Mol Cancer Ther. 2011 Mar;10(3):531-9. doi: 10.1158/1535-7163.MCT-10-0731. Epub 2011 Jan 20.

    PMID: 21252289BACKGROUND

  • Rhee SJ, Choi Y, Lee S, Oh J, Kim SJ, Yoon SH, Cho JY, Yu KS. Pharmacokinetic and pharmacodynamic interactions between metformin and a novel dipeptidyl peptidase-4 inhibitor, evogliptin, in healthy subjects. Drug Des Devel Ther. 2016 Aug 10;10:2525-34. doi: 10.2147/DDDT.S110712. eCollection 2016.

    PMID: 27570447BACKGROUND

  • Jang K, Chung H, Yoon JS, Moon SJ, Yoon SH, Yu KS, Kim K, Chung JY. Pharmacokinetics, Safety, and Tolerability of Metformin in Healthy Elderly Subjects. J Clin Pharmacol. 2016 Sep;56(9):1104-10. doi: 10.1002/jcph.699. Epub 2016 Feb 22.

    PMID: 26710683BACKGROUND

  • Hwang CS, Kim JW, Al Sharhan SS, Kim JW, Cho HJ, Yoon JH, Kim CH. Development of a Gustatory Function Test for Clinical Application in Korean Subjects. Yonsei Med J. 2018 Mar;59(2):325-330. doi: 10.3349/ymj.2018.59.2.325.

    PMID: 29436203BACKGROUND

MeSH Terms

Interventions

Metforminnilotinib

Intervention Hierarchy (Ancestors)

BiguanidesGuanidinesAmidinesOrganic Chemicals

Study Officials

  • Hyewon Chung, MD, PhD

    Clinical Assistant Professor

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Clinical Assistant Professor

Study Record Dates

First Submitted

June 24, 2020

First Posted

June 26, 2020

Study Start

July 23, 2020

Primary Completion

September 7, 2020

Study Completion

September 7, 2020

Last Updated

November 4, 2020

Record last verified: 2020-11

Locations

KR(1)