Comparative Bioavailability StudyPhase 1NCT05437783
Influence of Ethnicity and ABCB1 Gene Polymorphism on the Pharmacokinetics of Azithromycin in Healthy Bangladeshi Volunteers
A Phase 1 study testing Azithromycin Dihydrate in people with Comparative Bioavailability Study, run by Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh at 1 site in Bangladesh.
Trial summary
It is well recognized that different patients respond in different ways to the same medication. These differences are often greater among members of a population than they are within the same person at different times (or between monozygotic twins). Read more about this study
- Who is it for?
- Ages 20 to 25 yearsHealthy volunteers can take part
- Conditions the study is for
- Comparative Bioavailability Study
- What is being tested?
- Azithromycin Dihydrate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteBangladesh
- Study dates
- 1 Jan 2020to 1 Jul 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 20 to 25 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
None listed.
Who cannot join
- Liver cirrhosis.
- Chronic renal failure. .
- History of gastrectomy.
- History of drug abuse within the past 5 years.
- Treatment with an investigational drug within 3 months preceding the first dose of investigational product.
- Screening supine BP ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic), following at least 5 minutes of rest. If BP is ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic), the BP should be repeated 2 more times and the average of the 3 BP values should be used to determine the subject's eligibility.
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- Screening supine 12-lead ECG demonstrating a corrected QT (QTc) interval >450 msec or a QRS complex >120 msec. If QTc exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be repeated 2 more times and the average of the 3 QTc or QRS values should be used to determine the subject's eligibility.
- Female subjects who are breastfeeding or with positive pregnancy test at Screening and during the study period.
- Use of prescription or nonprescription drugs, dietary supplements and herbal medicines within 14 days prior to Screening.
- Blood donation (excluding plasma donations) or loss of blood of approximately 450 mL or more within 3 months prior to Screening.
- 111. History of hypersensitivity to azithromycin or any components of its formulation.
- 112. Use of special diet (including dragon fruit, grape fruit juice, mango, citrus, etc.), strenuous activities or other factors that may affect the disposition of the study medication within 14 days prior to Screening.
- 13. Use of chocolate, food or beverages containing caffeine or xanthine within 48 hours prior to dosing.
- 14. Use of products containing alcohol within 48 hours prior to dosing. 15. History of HIV, hepatitis B, or hepatitis C; positive testing for HIV, HBsAg, HCVAb..
- 16. Schizophrenia or other psychiatric illness..
- -
Trial locations and contacts
1 site in 1 country.
Bangladesh1 site, 1 recruiting
- Recruiting
Bangabandhu Sheikh Mujib Medical University
Dhaka, 1205
Registrar, 01684144656, registrar@bsmmu.edu.bd
About this study
Official title: Influence of Ethnicity and ABCB1 Gene Polymorphism on the Pharmacokinetics of Azithromycin in Healthy Bangladeshi Volunteers: A Preliminary Study.
It is well recognized that different patients respond in different ways to the same medication. These differences are often greater among members of a population than they are within the same person at different times (or between monozygotic twins). The existence of large population differences with small interpatient variability is consistent with inheritance as a determinant of drug response; it is estimated that genetics can account for 20 to 95 percent of variability in drug disposition and effects. Azithromycin is frequently used worldwide irrespective of gender or ethnic populations therefore, to investigate the impact of gender and ABCB1 gene polymorphism holds clinical significance. As a correlation between azithromycin high plasma level and cardiac arrhythmia also exists . If we can prove the variation of pharmacokinetics of azithromycin due to ethnic differences and ABCB1 polymorphism dose adjustment can be done.
No relevant study regarding this has been done before in Bangladesh. Therefore, this preliminary study would be of great benefit to formulate the individualized doses regiment design which may improve the efficacy of drug while reducing adverse reaction. At the same time, Genotyping may prove an essential tool for individualized treatment by optimizing the drug dosage for an individual's genetic variability. Further study regarding pharmacogenetics of various drugs may be possible in our country in the future .The present study design to investigate the influence of ethnic difference and gene polymorphism on the pharmacokinetics of azithromycin in Bangladeshi Bangalee and Bangladeshi minor ethnic volunteers.
Read the detailed description
Individual variation in drug response is a major problem in clinical practices and drug development which ranges from therapeutic failure to adverse drug reaction as drug reaction in multidrug therapy. Pharmacogenetic is relevant in this aspect and mainly concern with the study of genetic variation, which influence individuals' responses to drug. Again, polymorphism (variation) in the genes which are involved in encoding drug metabolizing enzymes, transporters of drug and ion channels can play role in the adverse drug reaction in an individual or can interfere with the therapeutic efficacy. For this reason, now-a-days concept of drug treatment is changed from 'right drug for the right person' to 'right dose for the right person at right time'. The human multidrug resistance gene ATP-binding cassette (ABCB1) codes for P-glycoprotein(P-gp), an important membrane-bound efflux transporter known to confer anticancer drug resistance as well as affect the pharmacokinetics of many drugs and xenobiotics. A number of single nucleotide polymorphisms (SNPs) have been identified throughout the ABCB1 gene that may have effect on P-gp expression levels and functions. Some studies shown an association between ABCB1 gene polymorphism on the pharmacokinetics of azithromycin. Genetic studies to explain this topic is uncommon. On this context, this proposed preliminary study is therefore to investigate the impact of ethnic difference and ABCB1 gene polymorphism on the pharmacokinetics of azithromycin among Bangladeshi people. This study will be a single dose open level comparative pharmacokinetic study, which will be conducted in the department of Pharmacology, BSMMU with the collaboration of Department of Anatomy, BSMMU and Bandarban Sadar Hospital, Bandarban. In this study healthy Bangladeshi volunteers will be divided into two arms-Bangladeshi Bengalese and Bangladeshi minor ethnics residing Chittagong Hill Tracts area, a total of 30 healthy volunteers of aged 20-25 will be provided 500mg oral azithromycin tablet and blood samples will be collected before drug administration (oh) and continuing at time points ,0.5 1.0, 2.0, 3.0, 4.0, 6.0, 8.0, 12.0, 24.0, 48.0, 72.0 h post dosing.2ml peripheral blood will be collected from each subject to determine the ABC1B gene polymorphism. This proposed study we would attempt to establish a High-Performance liquid Chromatography (HPLC) method to determine the azithromycin in plasma, in order to evaluate the bioavailability of azithromycin. Specific Genotypic polymorphism ABCB1 gene would be determine by Polymerase Chain Reaction-Restriction fragmentation Length Polymorphism Analysis (RFLP-PCR). After estimation of azithromycin and genotyping ABCB1 gene polymorphism, statistical analysis will be done to compare those values.
- Conditions
- Comparative Bioavailability Study
- Being tested
- Azithromycin Dihydrate
- Keywords
- Azithromycin, ABCB1 Gene, Pharmacokinetics, Single Nucleotide Polymorphism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Azithromycin DihydrateDrug
Also called Azithromycin
exclusively hospitalized at Bandarban Sadar hospital, Bandarban, Bangladesh. Participants will be fasting overnight for 10 h, all subjects will receive a single oral dose of 500mg of azithromycin with 250 ml of water. Drug intake will be ensured by direct supervision. Standardized meals will be served 4 and 10 h after dosing. Venous blood sample will be collected at multiple timepoints beginning before drug administration (0h) and containing at timepoints 1.0,2.0,3.0,4.0,6.0,8.0,12.0,24.0,48.0 and 72.0h post dosing. Two ml peripheral blood will be collected from each subject for genetic study.
| Study group | Role | What they receive |
|---|---|---|
| Healthy Bangladeshi Bangalee volunteers | Active comparator | Bangladeshi bangalee participants will be fasting overnight for 10 h, all subjects will receive a single oral dose of 500mg of azithromycin with 250 ml of water. Drug intake will be ensured by direct supervision. Standardized meals will be served 4 and 10 h after dosing. Venous blood sample will be collected at multiple timepoints beginning before drug administration (0h) and containing at timepoints 1.0,2.0,3.0,4.0,6.0,8.0,12.0,24.0,48.0 and 72.0h post dosing. Two ml peripheral blood will be collected from each subject for genetic study. Receives: Drug: Azithromycin Dihydrate |
| Healthy Bangladeshi minor ethnics volunteers | Active comparator | Bangladeshi minor ethnics participants will be fasting overnight for 10 h, all subjects will receive a single oral dose of 500mg of azithromycin with 250 ml of water. Drug intake will be ensured by direct supervision. Standardized meals will be served 4 and 10 h after dosing. Venous blood sample will be collected at multiple timepoints beginning before drug administration (0h) and containing at timepoints 1.0,2.0,3.0,4.0,6.0,8.0,12.0,24.0,48.0 and 72.0h post dosing. Two ml peripheral blood will be collected from each subject for genetic study. Receives: Drug: Azithromycin Dihydrate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cmax
Maximum observed plasma concentration of Azithromycin
Measured: [pre -dose(baseline) and day 1, day 2, day 3 post dose as designed time intervals.
AUC0-t
Area under the plasma concentration-time curve from time 0 to time t
Measured: [pre -dose(baseline) and day 1, day 2, day 3 post dose as designed time intervals.
AUC0-inf
Area under the plasma concentration-time curve from time 0 to infinity
Measured: [pre -dose(baseline) and day 1, day 2, day 3 post dose as designed time intervals.
Secondary outcomes (3)
Tmax
Time of maximum plasma concentration of azithromycin
Measured: [pre -dose(baseline) and day 1, day 2, day 3 post dose as designed time intervals.
t1/2
Elimination half life
Measured: [pre -dose(baseline) and day 1, day 2, day 3 post dose as designed time intervals.
Identification of genotypic of polymorphism of the gene ABCB1coding for P-gp.
To investigate the existence of a relation between single nucleotide polymorphism of ABCB1 and plasma concentration of azithromycin
Measured: 2.o hours of post dosing.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jun 2022
- Study start1 Jan 2020
- Primary completion1 Jul 2022 (estimated)
- Study completion1 Jul 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Comparative Bioavailability StudyStudies 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
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr. Zakia Sultana Ahmed, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05437783
- Sponsor's protocol ID
- BSMMU/2022/933
- Status last verified
- Jun 2022
- First submitted
- 18 Jun 2022
- Last updated
- 29 Jun 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Influence of Ethnicity and ABCB1 Gene Polymorphism on the Pharmacokinetics of Azithromycin in Healthy Bangladeshi Volunteers: A Preliminary Study.
- ClinicalTrials.gov ID
- NCT05437783
- Acronym / sponsor ID
- BSMMU/2022/933
- Conditions
- Comparative Bioavailability Study
- Keywords
- Azithromycin, ABCB1 Gene, Pharmacokinetics, Single Nucleotide Polymorphism
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- Bangabandhu Sheikh Mujib Medical University, Dhaka, BangladeshUniversity, hospital or other
- Study start
- 1 Jan 2020 (actual)
- Primary completion
- 1 Jul 2022 (estimated)
- Study completion
- 1 Jul 2022 (estimated)
- First posted
- 29 Jun 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
It is well recognized that different patients respond in different ways to the same medication. These differences are often greater among members of a population than they are within the same person at different times (or between monozygotic twins). The existence of large population differences with small interpatient variability is consistent with inheritance as a determinant of drug response; it is estimated that genetics can account for 20 to 95 percent of variability in drug disposition and effects. Azithromycin is frequently used worldwide irrespective of gender or ethnic populations therefore, to investigate the impact of gender and ABCB1 gene polymorphism holds clinical significance. As a correlation between azithromycin high plasma level and cardiac arrhythmia also exists . If we can prove the variation of pharmacokinetics of azithromycin due to ethnic differences and ABCB1 polymorphism dose adjustment can be done.
No relevant study regarding this has been done before in Bangladesh. Therefore, this preliminary study would be of great benefit to formulate the individualized doses regiment design which may improve the efficacy of drug while reducing adverse reaction. At the same time, Genotyping may prove an essential tool for individualized treatment by optimizing the drug dosage for an individual's genetic variability. Further study regarding pharmacogenetics of various drugs may be possible in our country in the future .The present study design to investigate the influence of ethnic difference and gene polymorphism on the pharmacokinetics of azithromycin in Bangladeshi Bangalee and Bangladeshi minor ethnic volunteers.
Detailed description
Individual variation in drug response is a major problem in clinical practices and drug development which ranges from therapeutic failure to adverse drug reaction as drug reaction in multidrug therapy. Pharmacogenetic is relevant in this aspect and mainly concern with the study of genetic variation, which influence individuals' responses to drug. Again, polymorphism (variation) in the genes which are involved in encoding drug metabolizing enzymes, transporters of drug and ion channels can play role in the adverse drug reaction in an individual or can interfere with the therapeutic efficacy. For this reason, now-a-days concept of drug treatment is changed from 'right drug for the right person' to 'right dose for the right person at right time'. The human multidrug resistance gene ATP-binding cassette (ABCB1) codes for P-glycoprotein(P-gp), an important membrane-bound efflux transporter known to confer anticancer drug resistance as well as affect the pharmacokinetics of many drugs and xenobiotics. A number of single nucleotide polymorphisms (SNPs) have been identified throughout the ABCB1 gene that may have effect on P-gp expression levels and functions. Some studies shown an association between ABCB1 gene polymorphism on the pharmacokinetics of azithromycin. Genetic studies to explain this topic is uncommon. On this context, this proposed preliminary study is therefore to investigate the impact of ethnic difference and ABCB1 gene polymorphism on the pharmacokinetics of azithromycin among Bangladeshi people. This study will be a single dose open level comparative pharmacokinetic study, which will be conducted in the department of Pharmacology, BSMMU with the collaboration of Department of Anatomy, BSMMU and Bandarban Sadar Hospital, Bandarban. In this study healthy Bangladeshi volunteers will be divided into two arms-Bangladeshi Bengalese and Bangladeshi minor ethnics residing Chittagong Hill Tracts area, a total of 30 healthy volunteers of aged 20-25 will be provided 500mg oral azithromycin tablet and blood samples will be collected before drug administration (oh) and continuing at time points ,0.5 1.0, 2.0, 3.0, 4.0, 6.0, 8.0, 12.0, 24.0, 48.0, 72.0 h post dosing.2ml peripheral blood will be collected from each subject to determine the ABC1B gene polymorphism. This proposed study we would attempt to establish a High-Performance liquid Chromatography (HPLC) method to determine the azithromycin in plasma, in order to evaluate the bioavailability of azithromycin. Specific Genotypic polymorphism ABCB1 gene would be determine by Polymerase Chain Reaction-Restriction fragmentation Length Polymorphism Analysis (RFLP-PCR). After estimation of azithromycin and genotyping ABCB1 gene polymorphism, statistical analysis will be done to compare those values.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Healthy Bangladeshi Bangalee volunteers | Active comparator | Drug: Azithromycin DihydrateBangladeshi bangalee participants will be fasting overnight for 10 h, all subjects will receive a single oral dose of 500mg of azithromycin with 250 ml of water. Drug intake will be ensured by direct supervision. Standardized meals will be served 4 and 10 h after dosing. Venous blood sample will be collected at multiple timepoints beginning before drug administration (0h) and containing at timepoints 1.0,2.0,3.0,4.0,6.0,8.0,12.0,24.0,48.0 and 72.0h post dosing. Two ml peripheral blood will be collected from each subject for genetic study. |
| Healthy Bangladeshi minor ethnics volunteers | Active comparator | Drug: Azithromycin DihydrateBangladeshi minor ethnics participants will be fasting overnight for 10 h, all subjects will receive a single oral dose of 500mg of azithromycin with 250 ml of water. Drug intake will be ensured by direct supervision. Standardized meals will be served 4 and 10 h after dosing. Venous blood sample will be collected at multiple timepoints beginning before drug administration (0h) and containing at timepoints 1.0,2.0,3.0,4.0,6.0,8.0,12.0,24.0,48.0 and 72.0h post dosing. Two ml peripheral blood will be collected from each subject for genetic study. |
Who may qualify
- Ages
- 20 to 25 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (0 listed)
Key exclusion criteria (16 listed)
- Liver cirrhosis.
- Chronic renal failure. .
- History of gastrectomy.
- History of drug abuse within the past 5 years.
- Treatment with an investigational drug within 3 months preceding the first dose of investigational product.
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 |
|---|---|---|
| Azithromycin DihydrateAlso: Azithromycinexclusively hospitalized at Bandarban Sadar hospital, Bandarban, Bangladesh. Participants will be fasting overnight for 10 h, all subjects will receive a single oral dose of 500mg of azithromycin with 250 ml of water. Drug intake will be ensured by direct supervision. Standardized meals will be served 4 and 10 h after dosing. Venous blood sample will be collected at multiple timepoints beginning before drug administration (0h) and containing at timepoints 1.0,2.0,3.0,4.0,6.0,8.0,12.0,24.0,48.0 and 72.0h post dosing. Two ml peripheral blood will be collected from each subject for genetic study. | Drug | Healthy Bangladeshi Bangalee volunteers, Healthy Bangladeshi minor ethnics volunteers |
Primary outcome
Cmax
Time frame: [pre -dose(baseline) and day 1, day 2, day 3 post dose as designed time intervals.
Maximum observed plasma concentration of Azithromycin
AUC0-t
Time frame: [pre -dose(baseline) and day 1, day 2, day 3 post dose as designed time intervals.
Area under the plasma concentration-time curve from time 0 to time t
AUC0-inf
Time frame: [pre -dose(baseline) and day 1, day 2, day 3 post dose as designed time intervals.
Area under the plasma concentration-time curve from time 0 to infinity
3 secondary outcomes
Tmax
Time frame: [pre -dose(baseline) and day 1, day 2, day 3 post dose as designed time intervals.
t1/2
Time frame: [pre -dose(baseline) and day 1, day 2, day 3 post dose as designed time intervals.
Identification of genotypic of polymorphism of the gene ABCB1coding for P-gp.
Time frame: 2.o hours of post dosing.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jun 2022.
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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.
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 Azithromycin Dihydrate in people with Comparative Bioavailability Study, run by Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh at 1 site in Bangladesh.
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 0 inclusion and 16 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: status not confirmed, as of the sponsor's last update on 29 Jun 2022. 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 Bangladesh. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Dr. Zakia Sultana Ahmed, MBBS, MD (01726375926, zakiasrabon@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cmax (time frame: [pre -dose(baseline) and day 1, day 2, day 3 post dose as designed time intervals.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 29 Jun 2022.