Diabetes Mellitus, Type 2Phase 1INTERGLIKOMNCT04198948

Interaction Between Omeprazole and Gliclazide in CYP2C19 Normal/ Ultrarapid Metabolisers

A Phase 1 study testing Omeprazole and Gliclazide in people with Diabetes Mellitus, Type 2, run by University of Sarajevo at 1 site in Bosnia and Herzegovina.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial 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. Read more about this study

Who is it for?: Ages 18 to 30 years, men onlyHealthy volunteers can take part
Conditions the study is for: Diabetes Mellitus, Type 2
What is being tested?: Omeprazole and Gliclazide
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 15 participants
Where: 1 siteBosnia and Herzegovina
Study dates: 4 Mar 2019to 5 Aug 2019
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 30 years
Men only
Healthy volunteers accepted
Adult

Who may be able to join

Men
Age 18-30 years
Non-smokers
CYP2C19 extensive/ultrarapid metabolisers

Who cannot join

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 locations and contacts

1 site in 1 country.

Bosnia and Herzegovina1 site

General Hospital Prim. Dr. Abdulah Nakas
Sarajevo, 71000

Other trials in Bosnia and Herzegovina

About this study

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.

Conditions: Diabetes Mellitus, Type 2
Being tested: Omeprazole, Placebo oral tablet, Gliclazide
Medical subject headings: Diabetes Mellitus, Type 2

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

OmeprazoleDrug
Omeprazole (20 mg) will be administered orally once daily for 5 days in one of the two treatment periods.
Placebo oral tabletDrug
Placebo will be administered orally once daily for 5 days in one of the two treatment periods.
GliclazideDrug
Gliclazide (40 mg) will be administered orally once, concomitantly with omeprazole or placebo on day 5.

Study groups in NCT04198948
Study group	Role	What they receive
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. Receives: Drug: Omeprazole; Drug: Placebo oral tablet; Drug: Gliclazide
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. Receives: Drug: Omeprazole; Drug: Placebo oral tablet; Drug: Gliclazide

What is being measured

The primary outcome is the main question the study is designed to answer.

Gliclazide AUC
Area under the concentration-time curve (AUC) up to the last concentration measured
Measured: 24 hours

Secondary outcomes (2)

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

4 Mar 20195 Aug 2019

First posted13 Dec 2019
Study start4 Mar 2019
Primary completion5 Aug 2019
Study completion5 Aug 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (9)Papers the sponsor has linked to this study.
Other trials for Diabetes Mellitus, Type 2Studies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Basic science
Allocation: Randomised
Intervention model: Crossover
Masking: Single blind
Who is masked: Participant
Enrolment: 15 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04198948
Sponsor's protocol ID: 0101-3678/18
Other IDs: 209943/Z/17/Z
Acronym: INTERGLIKOM
Status last verified: Jul 2021
First submitted: 11 Dec 2019
Last updated: 18 Aug 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: Yes: Data may be shared with researchers who provide a methodologically sound proposal.

Publications

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.
PubMed 26425465
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.
PubMed 24030920
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.
PubMed 17298483
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.
PubMed 20831536
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.
PubMed 25780309
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.
PubMed 20716239
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.
PubMed 28656666
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.
PubMed 24550106
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.
PubMed 21108610

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 18 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Interaction Between Omeprazole and Gliclazide in CYP2C19 Normal/ Ultrarapid Metabolisers
ClinicalTrials.gov ID: NCT04198948
Acronym / sponsor ID: INTERGLIKOM / 0101-3678/18
Conditions: Diabetes Mellitus, Type 2
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 15 participants (actual)
Lead sponsor: University of SarajevoUniversity, hospital or other
Collaborators: General Hospital Prim. dr. Abdulah Nakaš, University of Dundee, Wellcome Trust
Study start: 4 Mar 2019 (actual)
Primary completion: 5 Aug 2019 (actual)
Study completion: 5 Aug 2019 (actual)
First posted: 13 Dec 2019 (actual)
Results: Posted 15 Jul 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Basic science
Allocation: Randomised
Intervention model: Crossover
Masking: Single blind (participant)
Number of arms: 2

Arm	Type	Receives
Omeprazole, Then Placebo	Experimental	Drug: Omeprazole, Drug: Placebo oral tablet, Drug: GliclazideHealthy 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	Drug: Omeprazole, Drug: Placebo oral tablet, Drug: GliclazideHealthy 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.

Who may qualify

Ages: 18 to 30 years
Sex: Male only
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (4 listed)

Men
Age 18-30 years
Non-smokers
CYP2C19 extensive/ultrarapid metabolisers

Key exclusion criteria (4 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
OmeprazoleOmeprazole (20 mg) will be administered orally once daily for 5 days in one of the two treatment periods.	Drug	Omeprazole, Then Placebo, Placebo, Then Omeprazole
Placebo oral tabletPlacebo will be administered orally once daily for 5 days in one of the two treatment periods.	Drug	Omeprazole, Then Placebo, Placebo, Then Omeprazole
GliclazideGliclazide (40 mg) will be administered orally once, concomitantly with omeprazole or placebo on day 5.	Drug	Omeprazole, Then Placebo, Placebo, Then Omeprazole

Primary outcome

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

2 secondary outcomes

Glucose
Time frame: 12 hours
Insulin
Time frame: 12 hours

Results and safety

Results posted to the registry on 15 Jul 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Omeprazole, Then Placebo	7	7
Placebo, Then Omeprazole	8	8

Primary outcome: Gliclazide AUC

Time frame: 24 hours. Geometric mean (95% Confidence Interval). Unit: μgh/mL

Measure	Gliclazide + Omeprazole n = 14	Gliclazide + Placebo n = 14
Value	3.73 (2.81 to 4.93)	3.29 (2.65 to 4.09)

Gliclazide + Omeprazole vs Gliclazide + Placebo: Geometric least square mean ratio: 1.13 (90% CI 0.86 to 1.48)

Population analysed: A total of 14 participants who completed both study periods were included in the analysis.

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: Five days for each intervention.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Gliclazide + Omeprazole	0 of 15 (0%)	0 of 15 (0%)	0 of 15
Gliclazide + Placebo	0 of 15 (0%)	0 of 15 (0%)	0 of 15

Limitations and caveats (from the sponsor): 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.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 18 Aug 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 26425465Kalra 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.
Background: PubMed 24030920Schopman 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.
Background: PubMed 17298483Zhang 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.
Background: PubMed 20831536Shao 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.
Background: PubMed 25780309Sun 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.
Background: PubMed 20716239Furuta 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.
Background: PubMed 28656666Dujic 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.
Background: PubMed 24550106Wedemeyer 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.
Background: PubMed 21108610Semiz 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.
Individual participant dataSharing planned: Yes. Data may be shared with researchers who provide a methodologically sound proposal.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Tanja Dujic, PhD principal investigator

University of Sarajevo

Aida Kulo Cesic, PhD principal investigator

University of Sarajevo

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Omeprazole and Gliclazide in people with Diabetes Mellitus, Type 2, run by University of Sarajevo at 1 site in Bosnia and Herzegovina.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Bosnia and Herzegovina. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 Jul 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Gliclazide AUC (time frame: 24 hours). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04198948, which also lists 9 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Aug 2021; AzTrials last refreshed its copy on 6 Nov 2026.