A Clinical Trial to Evaluate the Effect of Nilotinib on the PK/PD of Meformin

Healthy Clinical Trial

Official title:

A Clinical Trial to Evaluate the Effect of Nilotinib on the Pharmacokinetics and Pharmacodynamics of Metformin in Healthy Male Adults

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04448821
• Other study ID #: NM-DDI
• Status: Completed
• Phase: Phase 1
• Start date: July 23, 2020
• Est. completion date: September 7, 2020

Study information

• Verified date: November 2020
• Source: Korea University Guro Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

Pharmacokinetics and pharmacodynamics of metformin without coadministration of nilotinib will be compared with those after administration of nilotinib.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: September 7, 2020
• Est. primary completion date: September 7, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 19 Years to 50 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• Metformin
Single administration of metformin
• Metformin + Nilotinib
Coadministration of metformin and nilotinib

Locations

Country	Name	City	State
Korea, Republic of	Korea University Guro Hospital	Seoul	Guro-gu

Sponsors (1)

Lead Sponsor	Collaborator
Hyewon Chung

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (9)

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. — View Citation

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. Review. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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). pii: E4825. doi: 10.3390/ijms20194825. — View Citation

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):27055-64. doi: 10.1074/jbc.M114.570564. Epub 2014 Aug 8. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cmax	maximum concentration	24 hours post-dose
Primary	AUCinf	Area under the concentration-time curve from time of administration extrapolated to infinity	24 hours post-dose
Primary	Gmax	maximum glucose level during oral glucose tolerance test	3 hours from 2 hour post-dose
Primary	AUGC	Area under the concentration-time curve during oral glucose tolerance test	3 hours from 2 hour post-dose
Secondary	Taste test		7 hour post-dose