Healthy VolunteersPhase 1CYP_IVPONCT03366974
Assessment of Change in CYP3A Activity by Route of Administration Using Metabolic Markers in Healthy Male Volunteers
A Phase 1 study testing Midazolam, Clarithromycin and Grapefruit juice in people with Healthy Volunteers, run by Seoul National University Hospital at 1 site in South Korea.
Trial summary
The study objective is to evaluate and validate of endogenous markers for the assessment of change in CYP3A activity by route of administration in Korean healthy subjects using metabolomics. In addition, we aim to screen novel endogenous marker, which could determine the total or intestinal CYP activity. Read more about this study
- Who is it for?
- Ages 19 to 50 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Healthy Volunteers
- What is being tested?
- Midazolam, Clarithromycin and Grapefruit juice
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteSouth Korea
- Study dates
- 28 Dec 2017to 12 Dec 2018
- 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 19 to 50 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Age: Between 19 to 50 years of age
- Weight: Within 17 - 28 of Body Mass Index (BMI)
- Subject who are reliable and willing to make themselves available during the study period, and subject who are willing to follow the study protocol, and give their written informed consent voluntarily.
Who cannot join
- History of hypersensitive reaction to medication (midazolam, aspirin, NSAID, antibiotics, benzodiazepine, erythromycin, macrolide)
- History of significant clinical illness needs medical caution, including cardiovascular, immunologic, hematologic, neuropsychiatric, respiratory, gastrointestinal, hepatic, or renal disease or other chronic disease history or evidence of drug abuse
- Subjects with evidence or a history of gastrointestinal disease (e.g, gastritis, Chron's disease) or with history of gastrointestinal surgery (except simple appendectomy or herniorrhaphy) that may affect assessment of PK characteristics of study drug
- Any of the following ECG abnormalities: QTcF > 450 msec
- History of apnea
- Subjects with genetic problems such as galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption
Show all 17Show fewer
- Subject whose systolic blood pressure is over 150 mmHg or below 90 mmHg and diastolic blood pressure is over 100 mmHg or below 50 mmHg
- Subjects with a history of drug abuse or a positive urine screening for drug abuse
- Subjects who have participated in any other clinical trial within three months prior to study drug administration
- Use any prescriptive medication, Korean traditional medication not considered acceptable by the clinical investigator during the last 14 days period before first dosing, or use any medication not considered acceptable by the clinical investigator during the last 7 days period before first dosing (if used medication is considered acceptable by investigator, patients can be included)
- Subjects who have donated a unit of whole blood within two months or blood components within one month prior to study drug administration
- Subjects who consume more than 21 units of alcohol per week (1 unit = 10 g of pure alcohol) or who are unable to abstain from drinking during the admission period
- Smokers (except for those who had quit for at least three months before the first administration of the IP)
- Subjects who consume or are unable to abstain from products containing grapefruit during study period
- Subjects who consume or are unable to abstain from products containing caffeine during study period
- Subjects who are positive for Hepatitis B, Hepatitis C, and HIV
- Subject who judged not eligible for study participation by investigator
Trial locations and contacts
1 site in 1 country.
About this study
The study objective is to evaluate and validate of endogenous markers for the assessment of change in CYP3A activity by route of administration in Korean healthy subjects using metabolomics. In addition, we aim to screen novel endogenous marker, which could determine the total or intestinal CYP activity.
Read the detailed description
This study is an open-label, one-sequence, three-period study. A total of 16 healthy male subjects will be enrolled. In period 1, subjects will be administered midazolam IV 1 mg, and co-administration of midazolam IV 1mg and grapefruit juice 500 mL. In period 2, subjects will be administered midazolam PO 5 mg, and co-administration of midazolam PO 5mg and grapefruit juice 500 mL. In period 3, subjects will be administered clarithromycin 500 mg for 3-days in b.i.d regimen prior to admission. Subjects will be administered midazolam IV 1mg and PO 5mg after admission.
- Conditions
- Healthy Volunteers
- Being tested
- Midazolam, Clarithromycin, Grapefruit juice
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MidazolamDrug
Midazolam 5 mg PO, Midazolam 1 mg IV
ClarithromycinDrug
Clarithromycin 500 mg bid
Grapefruit juiceDietary supplement
Grapefruit juice 500 mL
| Study group | Role | What they receive |
|---|---|---|
| CYP inhibition + IV/PO midazolam | Experimental | Period 1: Administration of Midazolam (IV) on day 1, Co-administration of Midazolam (IV) and Grapefruit juice on day 2
Period 2: Administration of Midazolam (PO) on day 8, Co-administration of Midazolam (PO) and Grapefruit juice on day 9
Period 3: Self-administration of Clarithromycin (PO) bid regimen on day 12-14, Co-administration of Midazolam (IV) and Clarithromycin (PO) on day 15, Co-administration of Midazolam (PO) and Clarithromycin (PO) on day 16 Receives: Drug: Midazolam; Drug: Clarithromycin; Dietary Supplement: Grapefruit juice |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area under the curve of midazolam (AUClast)
Pharmacokinetics of midazolam
Measured: Up to 12 hours after midazolam administration
Metabolic ratio of steroids
endogenous metabolite profiles such as steroid (6beta-hydroxy-cortisol/cortisol, 6beta-hydroxy-cortisone/cortisone)
Measured: Up to 12 hours before/after midazolam administration
Clearance (CL) of midazolam
Pharmacokinetics of midazolam
Measured: Up to 12 hours after midazolam administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Dec 2017
- Study start28 Dec 2017
- Primary completion13 Feb 2018
- Study completion12 Dec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Healthy VolunteersStudies of the same condition, open and under way.
- More trials run by Seoul National University HospitalThe sponsor's other registered studies.
- 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
- Not applicable
- Intervention model
- Single group
- Model description
- An open-label, one-sequence, three-period study
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Seoul National University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Joo-Youn Cho, Seoul National University Hospital
- Investigators
- Joo-Youn Cho, Principal investigator, Seoul National University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03366974
- Sponsor's protocol ID
- CYP_IVPO
- Acronym
- CYP_IVPO
- Status last verified
- Oct 2022
- First submitted
- 4 Dec 2017
- Last updated
- 27 Oct 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessment of Change in CYP3A Activity by Route of Administration Using Metabolic Markers in Healthy Male Volunteers
- ClinicalTrials.gov ID
- NCT03366974
- Acronym / sponsor ID
- CYP_IVPO / CYP_IVPO
- Conditions
- Healthy Volunteers
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Seoul National University HospitalUniversity, hospital or other
- Study start
- 28 Dec 2017 (actual)
- Primary completion
- 13 Feb 2018 (actual)
- Study completion
- 12 Dec 2018 (actual)
- First posted
- 8 Dec 2017 (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.
The study objective is to evaluate and validate of endogenous markers for the assessment of change in CYP3A activity by route of administration in Korean healthy subjects using metabolomics. In addition, we aim to screen novel endogenous marker, which could determine the total or intestinal CYP activity.
Detailed description
This study is an open-label, one-sequence, three-period study. A total of 16 healthy male subjects will be enrolled. In period 1, subjects will be administered midazolam IV 1 mg, and co-administration of midazolam IV 1mg and grapefruit juice 500 mL. In period 2, subjects will be administered midazolam PO 5 mg, and co-administration of midazolam PO 5mg and grapefruit juice 500 mL. In period 3, subjects will be administered clarithromycin 500 mg for 3-days in b.i.d regimen prior to admission. Subjects will be administered midazolam IV 1mg and PO 5mg after admission.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- An open-label, one-sequence, three-period study
| Arm | Type | Receives |
|---|---|---|
| CYP inhibition + IV/PO midazolam | Experimental | Drug: Midazolam, Drug: Clarithromycin, Dietary Supplement: Grapefruit juicePeriod 1: Administration of Midazolam (IV) on day 1, Co-administration of Midazolam (IV) and Grapefruit juice on day 2 Period 2: Administration of Midazolam (PO) on day 8, Co-administration of Midazolam (PO) and Grapefruit juice on day 9 Period 3: Self-administration of Clarithromycin (PO) bid regimen on day 12-14, Co-administration of Midazolam (IV) and Clarithromycin (PO) on day 15, Co-administration of Midazolam (PO) and Clarithromycin (PO) on day 16 |
Who may qualify
- Ages
- 19 to 50 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Age: Between 19 to 50 years of age
- Weight: Within 17 - 28 of Body Mass Index (BMI)
- Subject who are reliable and willing to make themselves available during the study period, and subject who are willing to follow the study protocol, and give their written informed consent voluntarily.
Key exclusion criteria (17 listed)
- History of hypersensitive reaction to medication (midazolam, aspirin, NSAID, antibiotics, benzodiazepine, erythromycin, macrolide)
- History of significant clinical illness needs medical caution, including cardiovascular, immunologic, hematologic, neuropsychiatric, respiratory, gastrointestinal, hepatic, or renal disease or other chronic disease history or evidence of drug abuse
- Subjects with evidence or a history of gastrointestinal disease (e.g, gastritis, Chron's disease) or with history of gastrointestinal surgery (except simple appendectomy or herniorrhaphy) that may affect assessment of PK characteristics of study drug
- Any of the following ECG abnormalities: QTcF > 450 msec
- History of apnea
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 |
|---|---|---|
| MidazolamMidazolam 5 mg PO, Midazolam 1 mg IV | Drug | CYP inhibition + IV/PO midazolam |
| ClarithromycinClarithromycin 500 mg bid | Drug | CYP inhibition + IV/PO midazolam |
| Grapefruit juiceGrapefruit juice 500 mL | Dietary supplement | CYP inhibition + IV/PO midazolam |
Primary outcome
Area under the curve of midazolam (AUClast)
Time frame: Up to 12 hours after midazolam administration
Pharmacokinetics of midazolam
Metabolic ratio of steroids
Time frame: Up to 12 hours before/after midazolam administration
endogenous metabolite profiles such as steroid (6beta-hydroxy-cortisol/cortisol, 6beta-hydroxy-cortisone/cortisone)
Clearance (CL) of midazolam
Time frame: Up to 12 hours after midazolam administration
Pharmacokinetics of midazolam
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Oct 2022.
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Screening Protocol
Pain
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.
Joo-Youn Cho principal investigator
Seoul National University Hospital
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 Midazolam, Clarithromycin and Grapefruit juice in people with Healthy Volunteers, run by Seoul National University Hospital at 1 site in South Korea.
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 3 inclusion and 17 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 27 Oct 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 South Korea. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Area under the curve of midazolam (AUClast) (time frame: Up to 12 hours after midazolam administration). 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 27 Oct 2022.