Pharmacokinetics of MirabegronPhase 1NCT01478490
To Compare Blood and Urine Concentrations of Mirabegron (YM178) in Healthy Poor or Extensive Metabolizers for CYP2D6 and to Assess the Effect of Mirabegron on the Metabolism of Metoprolol
A Phase 1 study testing mirabegron and metoprolol in people with Pharmacokinetics of Mirabegron and Healthy Subjects, run by Astellas Pharma Inc at 1 site in Netherlands.
Trial summary
The study aims to compare blood and urine concentrations of mirabegron (YM178) in healthy poor or extensive metabolizers for CYP2D6 and to evaluate if blood levels of metoprolol change whilst being dosed at the same time with daily miragebron. Read more about this study
- Who is it for?
- Ages 18 to 55 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Pharmacokinetics of Mirabegron, Healthy Subjects
- What is being tested?
- mirabegron and metoprolol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 1 siteNetherlands
- Study dates
- Sep 2002to Nov 2002
- 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 18 to 55 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- For Part I:
- Subject genotyped and phenotyped for CYP2D6
- Body weight between 60 and 100 kg and Body Mass Index less than or equal to 30 kg/m2
- For Part II:
- Subject genotyped and phenotyped as extensive metaboliser for CYP2D6
- Body weight between 60 and 100 kg and Body Mass Index less than or equal to 30 kg/m2
Who cannot join
- Known or suspected hypersensitivity to β-adrenergic receptor agonists or constituents of the formulations used
- Any clinically significant history of asthma, eczema, any other allergic condition or previous severe hypersensitivity to any drug
- Any clinically significant history of upper gastrointestinal symptoms (such as nausea, vomiting, abdominal discomfort or upset, or heartburn) in the 4 weeks prior to admission to the Research Unit
- Any clinically significant history of any other disease or disorder - gastrointestinal, cardiovascular, respiratory, renal, hepatic, neurological, dermatological, psychiatric or metabolic
- Any clinically significant abnormality following the investigator's review of the pre-study physical examination, ECG and clinical laboratory tests
- QTc intervals of >430 msec
Show all 10Show fewer
- Abnormal pulse rate measurement (<40 or >90 bpm) taken by manual counting at the pre-study visit after subject has been resting in supine position for 5 min
- Abnormal blood pressure measurements taken at the pre-study visit after subject has been resting in supine position for 5 min as follows: systolic blood pressure <95 or >160 mmHg; diastolic blood pressure <40 or >95 mmHg
- Positive orthostatic test at screening i.e. any symptoms of dizziness, light-headedness etc. and/or a fall of ≥ 20 mmHg in systolic blood pressure after 2 min standing (preceded by 5 min. supine rest) and/or an increase in pulse rate of ≥ 20 bpm
- Regular use of any prescribed or OTC drugs except paracetamol up to 3 g/day, in the 4 weeks prior to admission to the Research Unit OR any use of such drugs in the 2 weeks prior to admission to the Research Unit
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
PRA International (former Pharma Bio-Research)
Zuidlaren, 9471 GP
About this study
Official title: An Open Label, One-sequence, Parallel Study to Compare the Single Dose Pharmacokinetics of YM178 in Healthy Poor or Extensive Metabolisers for CYP2D6 and to Assess the Effect of Multiple Doses of YM178 on the Metabolism of the Model Substrate Metoprolol
The study aims to compare blood and urine concentrations of mirabegron (YM178) in healthy poor or extensive metabolizers for CYP2D6 and to evaluate if blood levels of metoprolol change whilst being dosed at the same time with daily miragebron.
Read the detailed description
The study is an open label, single center study. All subjects are genotyped for CYP2D6 before the study. Genotype expression is confirmed by dextromethorphan phenotyping.
Part I: The pharmacokinetic profile of a single dose of YM178 is compared in 8 healthy male subjects genotyped and phenotyped as poor metaboliser (PM) for CYP2D6 and in 8 healthy male subjects genotyped and phenotyped as extensive metaboliser (EM) for CYP2D6.
Part II: The effect of YM178 on the model substrate of CYP2D6 metoprolol is evaluated, using a cross-over design, in 12 healthy male subjects genotyped and phenotyped as EM for CYP2D6.
- Conditions
- Pharmacokinetics of Mirabegron, Healthy Subjects
- Being tested
- mirabegron, metoprolol
- Keywords
- Pharmacokinetics,, Mirabegron, Metoprolol, CYP2D6, Phase 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
mirabegronDrug
Also called YM178
oral
metoprololDrug
oral
| Study group | Role | What they receive |
|---|---|---|
| Treatment Arm 1A | Experimental | mirabegron, poor metabolizers Receives: Drug: mirabegron |
| Treatment Arm 1B | Experimental | mirabegron, extensive metabolizers Receives: Drug: mirabegron |
| Treatment Arm 2 | Experimental | mirabegron/metoprolol Receives: Drug: mirabegron; Drug: metoprolol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pharmacokinetics of mirabegron assessed by plasma concentration
Primary outcome measure for Part 1
Measured: Pre-dose until 72 hours after dosing
Secondary outcomes (1)
Pharmacokinetics of metoprolol assessed by plasma concentration
Primary outcome measure for Part 2
Measured: Pre-dose until 48 hours after dosing
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Nov 2011 (estimated)
- Study startSep 2002
- Primary completionNov 2002
- Study completionNov 2002
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pharmacokinetics of MirabegronStudies 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
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- Astellas Pharma Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Study Manager, Study chair, Astellas Pharma Europe B.V.Principal Investigator, Principal investigator, Pharma Bio-Research Group B.V., Zuidlaren, The Netherlands
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01478490
- Sponsor's protocol ID
- 178-CL-005
- Status last verified
- Nov 2011
- First submitted
- 21 Nov 2011
- Last updated
- 10 Apr 2014
- Results posted
- No
- Data monitoring committee
- No
Publications
Krauwinkel W, Dickinson J, Schaddelee M, Meijer J, Tretter R, van de Wetering J, Strabach G, van Gelderen M. The effect of mirabegron, a potent and selective beta3-adrenoceptor agonist, on the pharmacokinetics of CYP2D6 substrates desipramine and metoprolol. Eur J Drug Metab Pharmacokinet. 2014 Mar;39(1):43-52. doi: 10.1007/s13318-013-0133-1. Epub 2013 Jun 1.
PubMed 23728524
Study at a glance
From the registry record, last updated by the sponsor on 10 Apr 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label, One-sequence, Parallel Study to Compare the Single Dose Pharmacokinetics of YM178 in Healthy Poor or Extensive Metabolisers for CYP2D6 and to Assess the Effect of Multiple Doses of YM178 on the Metabolism of the Model Substrate Metoprolol
- ClinicalTrials.gov ID
- NCT01478490
- Acronym / sponsor ID
- 178-CL-005
- Conditions
- Pharmacokinetics of Mirabegron, Healthy Subjects
- Keywords
- Pharmacokinetics,, Mirabegron, Metoprolol, CYP2D6, Phase 1
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- Astellas Pharma IncIndustry (pharma, biotech, devices)
- Study start
- Sep 2002
- Primary completion
- Nov 2002 (actual)
- Study completion
- Nov 2002 (actual)
- First posted
- 23 Nov 2011 (estimated)
- 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 aims to compare blood and urine concentrations of mirabegron (YM178) in healthy poor or extensive metabolizers for CYP2D6 and to evaluate if blood levels of metoprolol change whilst being dosed at the same time with daily miragebron.
Detailed description
The study is an open label, single center study. All subjects are genotyped for CYP2D6 before the study. Genotype expression is confirmed by dextromethorphan phenotyping.
Part I: The pharmacokinetic profile of a single dose of YM178 is compared in 8 healthy male subjects genotyped and phenotyped as poor metaboliser (PM) for CYP2D6 and in 8 healthy male subjects genotyped and phenotyped as extensive metaboliser (EM) for CYP2D6.
Part II: The effect of YM178 on the model substrate of CYP2D6 metoprolol is evaluated, using a cross-over design, in 12 healthy male subjects genotyped and phenotyped as EM for CYP2D6.
Study design
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Treatment Arm 1A | Experimental | Drug: mirabegronmirabegron, poor metabolizers |
| Treatment Arm 1B | Experimental | Drug: mirabegronmirabegron, extensive metabolizers |
| Treatment Arm 2 | Experimental | Drug: mirabegron, Drug: metoprololmirabegron/metoprolol |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Subject genotyped and phenotyped for CYP2D6
- Body weight between 60 and 100 kg and Body Mass Index less than or equal to 30 kg/m2
- Subject genotyped and phenotyped as extensive metaboliser for CYP2D6
- Body weight between 60 and 100 kg and Body Mass Index less than or equal to 30 kg/m2
Key exclusion criteria (10 listed)
- Known or suspected hypersensitivity to β-adrenergic receptor agonists or constituents of the formulations used
- Any clinically significant history of asthma, eczema, any other allergic condition or previous severe hypersensitivity to any drug
- Any clinically significant history of upper gastrointestinal symptoms (such as nausea, vomiting, abdominal discomfort or upset, or heartburn) in the 4 weeks prior to admission to the Research Unit
- Any clinically significant history of any other disease or disorder - gastrointestinal, cardiovascular, respiratory, renal, hepatic, neurological, dermatological, psychiatric or metabolic
- Any clinically significant abnormality following the investigator's review of the pre-study physical examination, ECG and clinical laboratory tests
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 |
|---|---|---|
| mirabegronAlso: YM178oral | Drug | Treatment Arm 1A, Treatment Arm 1B, Treatment Arm 2 |
| metoprololoral | Drug | Treatment Arm 2 |
Primary outcome
Pharmacokinetics of mirabegron assessed by plasma concentration
Time frame: Pre-dose until 72 hours after dosing
Primary outcome measure for Part 1
1 secondary outcome
Pharmacokinetics of metoprolol assessed by plasma concentration
Time frame: Pre-dose until 48 hours after dosing
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 10 Apr 2014.
- Background: PubMed 23728524Krauwinkel W, Dickinson J, Schaddelee M, Meijer J, Tretter R, van de Wetering J, Strabach G, van Gelderen M. The effect of mirabegron, a potent and selective beta3-adrenoceptor agonist, on the pharmacokinetics of CYP2D6 substrates desipramine and metoprolol. Eur J Drug Metab Pharmacokinet. 2014 Mar;39(1):43-52. doi: 10.1007/s13318-013-0133-1. Epub 2013 Jun 1.
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.
Clinical Study Manager study chair
Astellas Pharma Europe B.V.
Principal Investigator principal investigator
Pharma Bio-Research Group B.V., Zuidlaren, The Netherlands
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 mirabegron and metoprolol in people with Pharmacokinetics of Mirabegron and Healthy Subjects, run by Astellas Pharma Inc at 1 site in Netherlands.
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 6 inclusion and 10 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 10 Apr 2014. 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 Netherlands. 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?
Pharmacokinetics of mirabegron assessed by plasma concentration (time frame: Pre-dose until 72 hours after dosing). 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 NCT01478490, which also lists 1 linked publication.
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 10 Apr 2014.