Interaction Between Omeprazole and Gliclazide in CYP2C19 Normal/ Ultrarapid Metabolisers

Phase 1

Completed

• Conditions: Diabetes Mellitus, Type 2
• Interventions: Drug: Omeprazole; Drug: Placebo oral tablet; Drug: Gliclazide

• Registration Number: NCT04198948
• Lead Sponsor: University of Sarajevo

Brief 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.

Detailed Description

Not available

Study Timeline

• Study Start: 2019-03-04
• Primary Completion: 2019-08-05
• Study Completion: 2019-08-05
• Study First Submitted: 2019-12-11
• Study First Submitted QC: 2019-12-11
• Study First Posted: 2019-12-13
• Results First Submitted: 2021-06-23
• Results First Submitted QC: 2021-06-23
• Status Verified: 2021-07
• Results First Posted: 2021-07-15
• Last Update Submitted: 2021-07-19
• Last Update Posted: 2021-08-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 15

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Placebo, Then Omeprazole	Placebo oral tablet	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.
Omeprazole, Then Placebo	Placebo oral tablet	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.
Omeprazole, Then Placebo	Omeprazole	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.
Omeprazole, Then Placebo	Gliclazide	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.
Placebo, Then Omeprazole	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.
Placebo, Then Omeprazole	Gliclazide	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.

Primary Outcome Measures

Name	Time	Method
Gliclazide AUC	24 hours	Area under the concentration-time curve (AUC) up to the last concentration measured

Secondary Outcome Measures

Name	Time	Method
Insulin	12 hours	Change in insulin concentration - incremental area under the insulin concentration-time curve from 0 to 12 h
Glucose	12 hours	Change in glucose concentration - incremental area under the glucose concentration-time curve from 0 to 12 h

Trial Locations

Locations (1)

General Hospital Prim. Dr. Abdulah Nakas; 🇧🇦 Sarajevo, Bosnia and Herzegovina