Interaction Between Omeprazole and Gliclazide in CYP2C19 Normal/ Ultrarapid Metabolisers

NCT ID: NCT04198948

Last Updated: 2021-08-18

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

15 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-03-04

Study Completion Date

2019-08-05

Brief Summary

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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.

Detailed Description

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Conditions

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Diabetes Mellitus, Type 2

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

SINGLE

Participants

Study Groups

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Omeprazole, Then Placebo

Healthy volunteers, CYP2C19 extensive/ultrarapid metabolisers, will receive 20 mg of omeprazole alone for 4 days, and concomitantly with single dose of gliclazide on day 5. After a wash-out period, they will receive placebo under same conditions in a cross-over manner.

Group Type EXPERIMENTAL

Omeprazole

Intervention Type DRUG

Omeprazole (20 mg) will be administered orally once daily for 5 days in one of the two treatment periods.

Placebo oral tablet

Intervention Type DRUG

Placebo will be administered orally once daily for 5 days in one of the two treatment periods.

Gliclazide

Intervention Type DRUG

Gliclazide (40 mg) will be administered orally once, concomitantly with omeprazole or placebo on day 5.

Placebo, Then Omeprazole

Healthy volunteers, CYP2C19 extensive/ultrarapid metabolisers, will receive placebo alone for 4 days, and concomitantly with single dose of gliclazide on day 5. After a wash-out period, they will receive omeprazole under same conditions in a cross-over manner.

Group Type EXPERIMENTAL

Omeprazole

Intervention Type DRUG

Omeprazole (20 mg) will be administered orally once daily for 5 days in one of the two treatment periods.

Placebo oral tablet

Intervention Type DRUG

Placebo will be administered orally once daily for 5 days in one of the two treatment periods.

Gliclazide

Intervention Type DRUG

Gliclazide (40 mg) will be administered orally once, concomitantly with omeprazole or placebo on day 5.

Interventions

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Omeprazole

Omeprazole (20 mg) will be administered orally once daily for 5 days in one of the two treatment periods.

Intervention Type DRUG

Placebo oral tablet

Placebo will be administered orally once daily for 5 days in one of the two treatment periods.

Intervention Type DRUG

Gliclazide

Gliclazide (40 mg) will be administered orally once, concomitantly with omeprazole or placebo on day 5.

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

30 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

Yes

Sponsors

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General Hospital Prim. Dr. Abdulah Nakas

OTHER

Sponsor Role collaborator

University of Dundee

OTHER

Sponsor Role collaborator

Wellcome Trust

OTHER

Sponsor Role collaborator

University of Sarajevo

OTHER

Sponsor Role lead

Responsible Party

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Tanja Dujic, PhD

Associate Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Tanja Dujic, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Sarajevo

Aida Kulo Cesic, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Sarajevo

Locations

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General Hospital Prim. Dr. Abdulah Nakas

Sarajevo, , Bosnia and Herzegovina

Site Status

Countries

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Bosnia and Herzegovina

References

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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.

Reference Type BACKGROUND
PMID: 26425465 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24030920 (View on PubMed)

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. doi: 10.1111/j.1365-2125.2007.02846.x. Epub 2007 Feb 12.

Reference Type BACKGROUND
PMID: 17298483 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20831536 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25780309 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20716239 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28656666 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24550106 (View on PubMed)

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. doi: 10.17305/bjbms.2010.2662.

Reference Type BACKGROUND
PMID: 21108610 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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209943/Z/17/Z

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

0101-3678/18

Identifier Type: -

Identifier Source: org_study_id

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