Interaction Between Omeprazole and Gliclazide in CYP2C19 Normal/ Ultrarapid Metabolisers

Study Overview
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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.

Official Title
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Interaction Between Omeprazole and Gliclazide in CYP2C19 Normal/ Ultrarapid Metabolisers

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Omeprazole
* Drug: Placebo oral tablet
* Drug: Gliclazide


Participation Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 30 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Omeprazole, Then Placebo<br>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. | Drug: Omeprazole<br>* Omeprazole (20 mg) will be administered orally once daily for 5 days in one of the two treatment periods.<br>Drug: Placebo oral tablet<br>* Placebo will be administered orally once daily for 5 days in one of the two treatment periods.<br>Drug: Gliclazide<br>* Gliclazide (40 mg) will be administered orally once, concomitantly with omeprazole or placebo on day 5.<br>|
| Experimental: Placebo, Then Omeprazole<br>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. | Drug: Omeprazole<br>* Omeprazole (20 mg) will be administered orally once daily for 5 days in one of the two treatment periods.<br>Drug: Placebo oral tablet<br>* Placebo will be administered orally once daily for 5 days in one of the two treatment periods.<br>Drug: Gliclazide<br>* Gliclazide (40 mg) will be administered orally once, concomitantly with omeprazole or placebo on day 5.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gliclazide AUC | Area under the concentration-time curve (AUC) up to the last concentration measured | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glucose | Change in glucose concentration - incremental area under the glucose concentration-time curve from 0 to 12 h | 12 hours | 
| Insulin | Change in insulin concentration - incremental area under the insulin concentration-time curve from 0 to 12 h | 12 hours |