Interaction Between Omeprazole and Gliclazide in CYP2C19 Normal/ Ultrarapid Metabolisers (INTERGLIKOM)

University of Sarajevo

Status and phase: Completed; Phase 1

Conditions: Diabetes Mellitus, Type 2

Treatments: Drug: Omeprazole; Drug: Gliclazide; Drug: Placebo oral tablet

Study type: Interventional

Funder types: Other

Identifiers

NCT04198948

209943/Z/17/Z (Other Grant/Funding Number)

0101-3678/18

Details and patient eligibility

About

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.

Enrollment: 15 patients

Sex: Male

Ages: 18 to 30 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Single Blind

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15 participants in 2 patient groups

Omeprazole, Then Placebo

Experimental group

Description:

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.

Treatment:

Drug: Gliclazide

Drug: Placebo oral tablet

Drug: Omeprazole

Placebo, Then Omeprazole

Experimental group

Description:

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.

Treatment:

Drug: Gliclazide

Drug: Placebo oral tablet

Drug: Omeprazole