Interaction Between Omeprazole and Gliclazide in CYP2C19 Normal/ Ultrarapid Metabolisers

Diabetes Mellitus, Type 2 Clinical Trial

— INTERGLIKOM  

Official title:

Interaction Between Omeprazole and Gliclazide in CYP2C19 Normal/ Ultrarapid Metabolisers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04198948
• Other study ID #: 0101-3678/18
• Secondary ID: 209943/Z/17/Z
• Status: Completed
• Phase: Phase 1
• Start date: March 4, 2019
• Est. completion date: August 5, 2019

Study information

• Verified date: July 2021
• Source: University of Sarajevo
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Proton pump inhibitors (PPIs) are treatment of choice for different gastrointestinal disorders common in type 2 diabetes. Sulfonylureas (SUs) are anti-diabetes agents particularly widely used in developing countries. Gliclazide, a recommended SU drug, is metabolised in part by CYP2C19, the main enzyme responsible for the PPI metabolism.

A randomised, placebo-controlled, two-sequence, two-period crossover study will be performed to explore whether gliclazide pharmacokinetics (PK) and pharmacodynamics (PD) are altered upon co-administration with omeprazole. Sixteen healthy volunteers, CYP2C19 extensive/ultrarapid metabolisers (EM/UM), will receive placebo or omeprazole alone for 4 days, and concomitantly with single dose of gliclazide on day 5. Plasma concentration of gliclazide will be measured for 24 hours, and plasma glucose and insulin levels up to 12 hours after gliclazide administration.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: August 5, 2019
• Est. primary completion date: August 5, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 30 Years

Eligibility

Inclusion Criteria:

• Men

• Age 18-30 years

• Non-smokers

• CYP2C19 extensive/ultrarapid metabolisers

Exclusion Criteria:

• medical history of hepatic, renal, gastrointestinal and hematologic disease or any acute or chronic disease, or drug allergy to sulfonylureas or PPIs or history of drug abuse

• abnormalities in physical examination, ECG and routine clinical laboratory tests (including fasting blood glucose concentration)

• medication use during the 14 days prior and during the study period

• grapefruit, grapefruit juice, alcohol, beverages or food containing methylxanthines use during 72 h prior and during the study period

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2

Intervention

Drug:
• Omeprazole
Omeprazole (20 mg) will be administered orally once daily for 5 days in one of the two treatment periods.
• Placebo oral tablet
Placebo will be administered orally once daily for 5 days in one of the two treatment periods.
• Gliclazide
Gliclazide (40 mg) will be administered orally once, concomitantly with omeprazole or placebo on day 5.

Locations

Country	Name	City	State
Bosnia and Herzegovina	General Hospital Prim. Dr. Abdulah Nakas	Sarajevo

Sponsors (4)

Lead Sponsor	Collaborator
University of Sarajevo	General Hospital Prim. Dr. Abdulah Nakas, University of Dundee, Wellcome Trust

Country where clinical trial is conducted

Bosnia and Herzegovina, 

References & Publications (9)

Dujic T, Zhou K, Donnelly LA, Leese G, Palmer CNA, Pearson ER. Interaction between variants in the CYP2C9 and POR genes and the risk of sulfonylurea-induced hypoglycaemia: A GoDARTS Study. Diabetes Obes Metab. 2018 Jan;20(1):211-214. doi: 10.1111/dom.13046. Epub 2017 Aug 25. — View Citation

Furuta T, Iwaki T, Umemura K. Influences of different proton pump inhibitors on the anti-platelet function of clopidogrel in relation to CYP2C19 genotypes. Br J Clin Pharmacol. 2010 Sep;70(3):383-92. doi: 10.1111/j.1365-2125.2010.03717.x. — View Citation

Kalra S, Aamir AH, Raza A, Das AK, Azad Khan AK, Shrestha D, Qureshi MF, Md Fariduddin, Pathan MF, Jawad F, Bhattarai J, Tandon N, Somasundaram N, Katulanda P, Sahay R, Dhungel S, Bajaj S, Chowdhury S, Ghosh S, Madhu SV, Ahmed T, Bulughapitiya U. Place of sulfonylureas in the management of type 2 diabetes mellitus in South Asia: A consensus statement. Indian J Endocrinol Metab. 2015 Sep-Oct;19(5):577-96. doi: 10.4103/2230-8210.163171. Review. — View Citation

Schopman JE, Simon AC, Hoefnagel SJ, Hoekstra JB, Scholten RJ, Holleman F. The incidence of mild and severe hypoglycaemia in patients with type 2 diabetes mellitus treated with sulfonylureas: a systematic review and meta-analysis. Diabetes Metab Res Rev. 2014 Jan;30(1):11-22. doi: 10.1002/dmrr.2470. Review. — View Citation

Semiz S, Dujic T, Ostanek B, Prnjavorac B, Bego T, Malenica M, Marc J, Causevic A. Analysis of CYP2C9*2, CYP2C19*2, and CYP2D6*4 polymorphisms in patients with type 2 diabetes mellitus. Bosn J Basic Med Sci. 2010 Nov;10(4):287-91. — View Citation

Shao H, Ren XM, Liu NF, Chen GM, Li WL, Zhai ZH, Wang DW. Influence of CYP2C9 and CYP2C19 genetic polymorphisms on pharmacokinetics and pharmacodynamics of gliclazide in healthy Chinese Han volunteers. J Clin Pharm Ther. 2010 Jun;35(3):351-60. doi: 10.1111/j.1365-2710.2009.01134.x. — View Citation

Sun XM, Tan JC, Zhu Y, Lin L. Association between diabetes mellitus and gastroesophageal reflux disease: A meta-analysis. World J Gastroenterol. 2015 Mar 14;21(10):3085-92. doi: 10.3748/wjg.v21.i10.3085. Review. — View Citation

Wedemeyer RS, Blume H. Pharmacokinetic drug interaction profiles of proton pump inhibitors: an update. Drug Saf. 2014 Apr;37(4):201-11. doi: 10.1007/s40264-014-0144-0. Review. — View Citation

Zhang Y, Si D, Chen X, Lin N, Guo Y, Zhou H, Zhong D. Influence of CYP2C9 and CYP2C19 genetic polymorphisms on pharmacokinetics of gliclazide MR in Chinese subjects. Br J Clin Pharmacol. 2007 Jul;64(1):67-74. Epub 2007 Feb 12. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Gliclazide AUC	Area under the concentration-time curve (AUC) up to the last concentration measured	24 hours
Secondary	Glucose	Change in glucose concentration - incremental area under the glucose concentration-time curve from 0 to 12 h	12 hours
Secondary	Insulin	Change in insulin concentration - incremental area under the insulin concentration-time curve from 0 to 12 h	12 hours