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| ID | Type | Description | Link |
|---|---|---|---|
| 209943/Z/17/Z | Other Grant/Funding Number | Wellcome Trust |
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| Name | Class |
|---|---|
| General Hospital Prim. Dr. Abdulah Nakas | OTHER |
| University of Dundee | OTHER |
| Wellcome Trust | OTHER |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Omeprazole, Then Placebo | Experimental | 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 | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Omeprazole | Drug | Omeprazole (20 mg) will be administered orally once daily for 5 days in one of the two treatment periods. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Gliclazide AUC | Area under the concentration-time curve (AUC) up to the last concentration measured | 24 hours |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Tanja Dujic, PhD | University of Sarajevo | Principal Investigator |
| Aida Kulo Cesic, PhD | University of Sarajevo | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| General Hospital Prim. Dr. Abdulah Nakas | Sarajevo | 71000 | Bosnia and Herzegovina |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26425465 | Background | 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. | |
| 24030920 |
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Data may be shared with researchers who provide a methodologically sound proposal.
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From 23 individuals, CYP2C19 EM/UM metabolisers, 16 were available for further health status assessment. One participant did not meet inclusion criteria and a total of 15 volunteers were randomised.
A total of 37 volunteers were recruited in the period between March 4th, 2019 and May 29th, 2019. On May 30th, 2019, volunteers were screened for CYP2C19 genotype status at the General Hospital in Sarajevo, B&H.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. 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. |
| FG001 | 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. 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| First Period |
| |||||||||||||
| Wash-out (10 Days) |
| |||||||||||||
| Second Period |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Gliclazide AUC | Area under the concentration-time curve (AUC) up to the last concentration measured | A total of 14 participants who completed both study periods were included in the analysis. | Posted | Geometric Mean | 95% Confidence Interval | μgh/mL | 24 hours |
|
Five days for each intervention.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Gliclazide + Omeprazole | Participants received 20 mg of omeprazole alone for 4 days, and concomitantly with single dose of gliclazide on day 5. |
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Participants received half of the 80 mg gliclazide tablet registered as an immediate-release formulation in Bosnia and Herzegovina (Diprian®, Hemofarm d.o.o. Banja Luka, B&H). However, the concentration-time profiles showed modified-release pattern and incomplete elimination within 24h; thus Cmax, tmax, t1/2, and AUC0-∞ could not be determined. The obtained PK profiles were used at the end for validation of physiologically based pharmacokinetic simulation of omeprazole-gliclazide interaction.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Associate Professor Tanja Dujic, PhD | University of Sarajevo | +38733586194 | tanja.dujic@ffsa.unsa.ba |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Sep 14, 2018 | Jun 23, 2021 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D009853 | Omeprazole |
| D005907 | Gliclazide |
| ID | Term |
|---|---|
| D053799 | 2-Pyridinylmethylsulfinylbenzimidazoles |
| D013454 | Sulfoxides |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
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| Placebo oral tablet | Drug | Placebo will be administered orally once daily for 5 days in one of the two treatment periods. |
|
| Gliclazide | Drug | Gliclazide (40 mg) will be administered orally once, concomitantly with omeprazole or placebo on day 5. |
|
| 12 hours |
| Background |
| 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. |
| 17298483 | Background | 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. |
| 20831536 | Background | 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. |
| 25780309 | Background | 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. |
| 20716239 | Background | 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. |
| 28656666 | Background | 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. |
| 24550106 | Background | 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. |
| 21108610 | Background | 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. |
| NOT COMPLETED |
|
| NOT COMPLETED |
|
| BG001 | 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. 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. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Weight | Mean | Standard Deviation | kilograms |
|
| Units | Counts |
|---|---|
| Participants |
|
|
|
| Secondary | Glucose | Change in glucose concentration - incremental area under the glucose concentration-time curve from 0 to 12 h | A total of 14 participants who completed both study periods were included in the analysis. | Posted | Mean | Standard Deviation | mmol x h/L | 12 hours |
|
|
|
|
| Secondary | Insulin | Change in insulin concentration - incremental area under the insulin concentration-time curve from 0 to 12 h | A total of 14 participants who completed both study periods were included in the analysis. | Posted | Mean | Standard Deviation | mIU x h/L | 12 hours |
|
|
|
|
| 0 |
| 15 |
| 0 |
| 15 |
| 0 |
| 15 |
| EG001 | Gliclazide + Placebo | Participants received placebo alone for 4 days, and concomitantly with single dose of gliclazide on day 5. | 0 | 15 | 0 | 15 | 0 | 15 |
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| D004700 | Endocrine System Diseases |
| D011725 |
| Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D001562 | Benzimidazoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D000096926 | Benzenesulfonamides |
| D013449 | Sulfonamides |
| D000577 | Amides |
| D013453 | Sulfonylurea Compounds |
| D014508 | Urea |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D013450 | Sulfones |