HealthyPhase 1NCT02217514
Effects of BI 44370 TA Orally Applied as Tablets on the Pharmacokinetics of Orally Administered Midazolam Solution in Healthy Volunteers
A Phase 1 study testing Midazolam, BI 44370 low dose and BI 44370 medium dose in people with Healthy, run by Boehringer Ingelheim.
Trial summary
Evaluation of the long-term (48 h) and short-term (1 h) effects of BI 44370 BS on the pharmacokinetics of midazolam as marker of a possible inhibition of CYP 3A4; safety and tolerability. Read more about this study
- Who is it for?
- Ages 21 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Midazolam, BI 44370 low dose and BI 44370 medium dose
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- No sites listed yet
- Study dates
- Feb 2008to Mar 2008
- 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 21 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy males and females according to the following criteria: Based upon a complete medical history, including the physical examination, vital signs (BP, PR), 12-lead ECG, clinical laboratory tests
- Age ≥21 and Age ≤50 years
- BMI ≥18.5 and BMI ≤29.9 kg/m2 (Body Mass Index)
- Signed and dated written informed consent prior to admission to the study in accordance with Good clinical practice (GCP) and the local legislation.
Who cannot join
- Any finding of the medical examination (including Blood Pressure (BP), Pulse Rate (PR) and Electrocardiogram (ECG)) deviating from normal and of clinical relevance
- Any evidence of a clinically relevant concomitant disease
- Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
- Surgery of the gastrointestinal tract (except appendectomy)
- Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders
- History of relevant orthostatic hypotension, fainting spells or blackouts
Show all 28Show fewer
- Chronic or relevant acute infections
- History of relevant allergy/hypersensitivity (including allergy to drug or its excipients)
- Intake of drugs with a long half-life (> 24 hours) within at least one month or less than 10 half-lives of the respective drug prior to administration or during the trial
- Use of drugs which might reasonably influence the results of the trial or that prolong the QT/QTc interval based on the knowledge at the time of protocol preparation within 10 days prior to administration or during the trial
- Participation in another trial with an investigational drug within 30 days prior to administration or during the trial
- Smoker (> 10 cigarettes or > 3 cigars or > 3 pipes/day)
- Inability to refrain from smoking on trial days
- Alcohol abuse (more than 60 g/day)
- Drug abuse
- Blood donation (more than 100 mL within four weeks prior to administration or during the trial)
- Excessive physical activities (within one week prior to administration or during the trial)
- Any laboratory value outside the reference range that is of clinical relevance
- Inability to comply with dietary regimen of trial site
- A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval >470 ms);
- A history of additional risk factors for Torsade de Pointes (TdP) (e.g., heart failure, hypokalemia, family history of Long QT Syndrome)
- For Male Subjects:
- Not willing to use adequate contraception (condom use plus another form of contraception e.g. spermicide, oral contraceptive taken by female partner, sterilisation, intrauterine device (IUD)) during the whole study period from the time of the first intake of study drug until three months after the last intake
- For Female Subjects:
- Pregnancy
- Positive pregnancy test
- No adequate contraception (adequate contraception e.g. sterilisation, intrauterine pessary (IUP), oral contraceptives)
- Inability to maintain this adequate contraception during the whole study period during the whole study period from the time of the first intake of study drug until one month after the last intake
About this study
Official title: Effects of 100 mg and 500 mg BI 44370 TA Orally Applied as 50 mg Tablets on the Pharmacokinetics of 2 mg Orally Administered Midazolam Solution. An Open-label, Randomised, Parallel Group, Fixed-sequence Study With Intraindividual Comparison of Midazolam Pharmacokinetics With and Without BI 44370 TA
Evaluation of the long-term (48 h) and short-term (1 h) effects of BI 44370 BS on the pharmacokinetics of midazolam as marker of a possible inhibition of CYP 3A4; safety and tolerability.
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MidazolamDrug
Also called Dormicum®
BI 44370 low doseDrug
BI 44370 medium doseDrug
BI 44370 high doseDrug
| Study group | Role | What they receive |
|---|---|---|
| Treatment sequence 1 in male subjects | Experimental | Midazolam alone and 1 h after low dose BI44370BS in male subjects Receives: Drug: Midazolam; Drug: BI 44370 low dose |
| Treatment sequence 1 in female subjects | Experimental | Midazolam alone and 1 h after low dose BI44370BS followed by medium dose BI 44370 in an additional visit in female subjects Receives: Drug: Midazolam; Drug: BI 44370 low dose; Drug: BI 44370 medium dose |
| Treatment sequence 2 | Experimental | Midazolam before and 48 h after high dose BI44370BS Receives: Drug: Midazolam; Drug: BI 44370 high dose |
| Treatment sequence 3 | Experimental | Midazolam before and 24 h after high dose BI44370BS Receives: Drug: Midazolam; Drug: BI 44370 high dose |
| Treatment sequence 4 | Experimental | Midazolam before and 1 h after high dose BI44370BS Receives: Drug: Midazolam; Drug: BI 44370 high dose |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cmax (maximum concentration of midazolam in plasma)
Measured: up to 24 hours after drug administration
AUC0-tz (area under the concentration-time curve of midazolam in plasma over the time interval from 0 to the time of the last quantifiable data point)
Measured: up to 24 hours after drug administration
AUC0-infinity (area under the concentration-time curve of midazolam in plasma over the time interval from 0 extrapolated to infinity)
Measured: up to 24 hours after drug administration
Secondary outcomes (17)
Cmax (maximum measured concentration of the analyte in plasma)
Measured: Up to 48 hours after drug administration
tmax (time from dosing to maximum measured concentration)
Measured: up to 48 hours after drug administration
AUC0-∞ (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity)
Measured: up to 48 hours after drug administration
%AUCtz-∞ (the percentage of the AUC0-∞ that is obtained by extrapolation)
Measured: up to 48 hours after drug administration
AUC0-tz (area under the concentration-time curve of the analyte in plasma in plasma over the time interval from 0 to the time of the last quantifiable data point)
Measured: up to 48 hours after drug administration
AUCt1-t2 (Area under the concentration-time curve of the analyte in plasma over the time interval t1 to t2)
Measured: up to 48 hours after drug administration
λz (terminal rate constant in plasma)
Measured: up to 48 hours after drug administration
t1/2 (terminal half-life of the analyte in plasma)
Measured: up to 48 hours after drug administration
MRTp.o. (mean residence time of the analyte in the body after oral administration)
Measured: up to 48 hours after drug administration
CL/F (total/apparent clearance of the analyte in plasma after extravascular administration)
Measured: up to 48 hours after drug administration
Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose)
Measured: up to 48 hours after drug administration
ratio of AUC0-∞ 1-OH-midazolam / AUC0-∞ midazolam
Measured: up to 48 hours after drug administration
Aet1-t2 (amount of BI 44370 BS eliminated in urine from the time point t1 to time point t2)
Measured: up to 24 hours after drug administration
fet1-t2 (fraction of BI 44370 BS eliminated in urine from time point t1 to time point t2)
Measured: up to 24 hours after drug administration
CLR,t1-t2 (renal clearance of BI 44370 BS from the time point t1 until the time point t2)
Measured: up to 24 hours after drug administration
Number of patients with adverse events
Measured: up to 8 days after last drug administration
Assessment of tolerability by investigator on a 4-point scale
Measured: up to 8 days after last drug administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Aug 2014 (estimated)
- Study startFeb 2008
- Primary completionMar 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HealthyStudies of the same condition, open and under way.
- More trials run by Boehringer IngelheimThe 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boehringer Ingelheim
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02217514
- Sponsor's protocol ID
- 1246.3
- Status last verified
- Aug 2014
- First submitted
- 13 Aug 2014
- Last updated
- 15 Aug 2014
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Aug 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of 100 mg and 500 mg BI 44370 TA Orally Applied as 50 mg Tablets on the Pharmacokinetics of 2 mg Orally Administered Midazolam Solution. An Open-label, Randomised, Parallel Group, Fixed-sequence Study With Intraindividual Comparison of Midazolam Pharmacokinetics With and Without BI 44370 TA
- ClinicalTrials.gov ID
- NCT02217514
- Acronym / sponsor ID
- 1246.3
- Conditions
- Healthy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- Boehringer IngelheimIndustry (pharma, biotech, devices)
- Study start
- Feb 2008
- Primary completion
- Mar 2008 (actual)
- First posted
- 15 Aug 2014 (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.
Evaluation of the long-term (48 h) and short-term (1 h) effects of BI 44370 BS on the pharmacokinetics of midazolam as marker of a possible inhibition of CYP 3A4; safety and tolerability.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Treatment sequence 1 in male subjects | Experimental | Drug: Midazolam, Drug: BI 44370 low doseMidazolam alone and 1 h after low dose BI44370BS in male subjects |
| Treatment sequence 1 in female subjects | Experimental | Drug: Midazolam, Drug: BI 44370 low dose, Drug: BI 44370 medium doseMidazolam alone and 1 h after low dose BI44370BS followed by medium dose BI 44370 in an additional visit in female subjects |
| Treatment sequence 2 | Experimental | Drug: Midazolam, Drug: BI 44370 high doseMidazolam before and 48 h after high dose BI44370BS |
| Treatment sequence 3 | Experimental | Drug: Midazolam, Drug: BI 44370 high doseMidazolam before and 24 h after high dose BI44370BS |
| Treatment sequence 4 | Experimental | Drug: Midazolam, Drug: BI 44370 high doseMidazolam before and 1 h after high dose BI44370BS |
Who may qualify
- Ages
- 21 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Healthy males and females according to the following criteria: Based upon a complete medical history, including the physical examination, vital signs (BP, PR), 12-lead ECG, clinical laboratory tests
- Age ≥21 and Age ≤50 years
- BMI ≥18.5 and BMI ≤29.9 kg/m2 (Body Mass Index)
- Signed and dated written informed consent prior to admission to the study in accordance with Good clinical practice (GCP) and the local legislation.
Key exclusion criteria (28 listed)
- Any finding of the medical examination (including Blood Pressure (BP), Pulse Rate (PR) and Electrocardiogram (ECG)) deviating from normal and of clinical relevance
- Any evidence of a clinically relevant concomitant disease
- Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
- Surgery of the gastrointestinal tract (except appendectomy)
- Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders
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 |
|---|---|---|
| MidazolamAlso: Dormicum® | Drug | Treatment sequence 1 in female subjects, Treatment sequence 1 in male subjects, Treatment sequence 2, Treatment sequence 3, Treatment sequence 4 |
| BI 44370 low dose | Drug | Treatment sequence 1 in female subjects, Treatment sequence 1 in male subjects |
| BI 44370 medium dose | Drug | Treatment sequence 1 in female subjects |
| BI 44370 high dose | Drug | Treatment sequence 2, Treatment sequence 3, Treatment sequence 4 |
Primary outcome
Cmax (maximum concentration of midazolam in plasma)
Time frame: up to 24 hours after drug administration
AUC0-tz (area under the concentration-time curve of midazolam in plasma over the time interval from 0 to the time of the last quantifiable data point)
Time frame: up to 24 hours after drug administration
AUC0-infinity (area under the concentration-time curve of midazolam in plasma over the time interval from 0 extrapolated to infinity)
Time frame: up to 24 hours after drug administration
17 secondary outcomes
Cmax (maximum measured concentration of the analyte in plasma)
Time frame: Up to 48 hours after drug administration
tmax (time from dosing to maximum measured concentration)
Time frame: up to 48 hours after drug administration
AUC0-∞ (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity)
Time frame: up to 48 hours after drug administration
%AUCtz-∞ (the percentage of the AUC0-∞ that is obtained by extrapolation)
Time frame: up to 48 hours after drug administration
AUC0-tz (area under the concentration-time curve of the analyte in plasma in plasma over the time interval from 0 to the time of the last quantifiable data point)
Time frame: up to 48 hours after drug administration
AUCt1-t2 (Area under the concentration-time curve of the analyte in plasma over the time interval t1 to t2)
Time frame: up to 48 hours after drug administration
λz (terminal rate constant in plasma)
Time frame: up to 48 hours after drug administration
t1/2 (terminal half-life of the analyte in plasma)
Time frame: up to 48 hours after drug administration
MRTp.o. (mean residence time of the analyte in the body after oral administration)
Time frame: up to 48 hours after drug administration
CL/F (total/apparent clearance of the analyte in plasma after extravascular administration)
Time frame: up to 48 hours after drug administration
Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose)
Time frame: up to 48 hours after drug administration
ratio of AUC0-∞ 1-OH-midazolam / AUC0-∞ midazolam
Time frame: up to 48 hours after drug administration
Aet1-t2 (amount of BI 44370 BS eliminated in urine from the time point t1 to time point t2)
Time frame: up to 24 hours after drug administration
fet1-t2 (fraction of BI 44370 BS eliminated in urine from time point t1 to time point t2)
Time frame: up to 24 hours after drug administration
CLR,t1-t2 (renal clearance of BI 44370 BS from the time point t1 until the time point t2)
Time frame: up to 24 hours after drug administration
Number of patients with adverse events
Time frame: up to 8 days after last drug administration
Assessment of tolerability by investigator on a 4-point scale
Time frame: up to 8 days after last drug administration
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 15 Aug 2014.
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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.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Midazolam, BI 44370 low dose and BI 44370 medium dose in people with Healthy, run by Boehringer Ingelheim.
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 28 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 15 Aug 2014. Status can change between updates, so confirm with the study contact before making plans.
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?
Cmax (maximum concentration of midazolam in plasma) (time frame: up to 24 hours after drug 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 15 Aug 2014.