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HealthyPhase 1NCT04107805

A Study in Healthy Men and Women to Test How Well Different Doses of BI 1323495 Are Tolerated

A Phase 1 study testing BI 1323495 and Midazolam in people with Healthy, run by Boehringer Ingelheim at 1 site in Germany.

Completed

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

Official record
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Trial summary

The primary objective of this trial is to investigate the safety and tolerability of BI 1323495 in healthy subjects following bid oral administration of multiple rising doses, each over an 11 day treatment period. Read more about this study

Who is it for?
Ages 18 to 70 yearsHealthy volunteers can take part
Conditions the study is for
Healthy
What is being tested?
BI 1323495 and Midazolam
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
87 participants
Where
1 siteGermany
Study dates
4 Nov 2019to 26 Mar 2021
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 70 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Healthy subjects according to the assessment of the investigator, as based on a complete medical history including a physical examination, vital signs (Blood Pressure (BP), PR), 12-lead Electrocardiogram (ECG), and clinical laboratory tests
  • Age of 18 to 70 years (inclusive)
  • BMI of 18.5 to 29.9 kg/m2 (inclusive)
  • Signed and dated written informed consent prior to admission to the study, in accordance with Good Clinical Practice (GCP) and local legislation
  • For Part I: Subjects genotyped as UGT2B17 extensive metabolizers, i.e., carrying at least one functional allele of the UGT2B17 gene (*1/*1 or *1/*2).
  • For Part II: Subjects genotyped as UGT2B17 poor metabolizers, i.e., carrying no functional allele of the UGT2B17 gene (2/2)
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  • -Male or female subjects:
  • For 'female subjects not of childbearing potential' at least one of the following criteria must be fulfilled:
  • Permanently sterile (permanent sterilisation methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy)
  • Postmenopausal, defined as at least 1 year of spontaneous amenorrhea without an alternative medical cause (in questionable cases a blood sample with FSH above 40 U/L and estradiol below 30 ng/L is confirmatory)
  • Female subjects of childbearing potential must use a highly effective contraception method from at least 30 days before the first administration of trial medication until 14 days after trial completion

Who cannot join

  • Any finding in the medical examination (including Blood Pressure (BP), PR, or Electrocardiogram (ECG)) deviating from normal and assessed as clinically relevant by the investigator. In particular a marked baseline prolongation of QT/QTc interval (such as QTc intervals that are repeatedly greater than 450 ms in males or repeatedly greater than 470 ms in females) at screening
  • Repeated measurement of systolic blood pressure outside the range of 90 to 140 mmHg, diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate outside the range of 50 to 90 bpm
  • Any laboratory value outside the reference range that the investigator considers to be of clinical relevance; safety laboratory screening evaluation can be repeated a maximum of two times
  • Any evidence of a concomitant disease assessed as clinically relevant by the investigator or at risk of requiring concomitant drug therapy, e.g., gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological, or hormonal disorder, diseases of the central nervous system (including, but not limited to any kind of seizures or stroke), and other relevant neurological or psychiatric disorders
  • History of cholecystectomy or other surgery of the gastrointestinal tract that could interfere with the pharmacokinetics of the trial medication (except appendectomy or simple hernia repair)
  • History of relevant orthostatic hypotension, fainting spells, or blackouts
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  • History of relevant allergy or hypersensitivity (including allergy to the trial medication or its excipients); mild seasonal allergy adequately managed by topic administration of drugs to eyes or nose is not excluded
  • Subjects with a documented active malignancy, or malignancy for which the subject has undergone resection, radiation therapy, or drug therapy (e.g., cytostatic, protein kinase inhibitor, or immune checkpoint inhibitor therapy), within the last 5 years.
  • Subjects who have been previously randomised in this study.
  • Use of drugs within 30 days of planned administration of trial medication that might reasonably influence the results of the trial (including drugs that cause QT/QTc interval prolongation)
  • Intake of an investigational drug in another clinical trial within 60 days, or within 5 half-lives of the investigational drug (whichever is longer), of planned administration of investigational drug in the current trial, or concurrent participation in another clinical trial in which investigational drug is administered
  • Major surgery (major according to the investigator's assessment) performed within 6 weeks prior to randomisation or planned within 3 months after screening, e.g. hip replacement.
  • Smoker (more than 10 cigarettes or 3 cigars or 3 pipes per day), also inability to refrain from smoking during in-house confinement
  • Alcohol abuse (consumption of more than 20 g per day for females and 30 g per day for males) or any other drug abuse or positive drug screening
  • Blood donation of more than 100 mL within 30 days of planned administration of trial medication or intended blood donation during the trial
  • Intention to perform excessive physical activities within one week prior to the administration of trial medication or during the trial
  • Inability to comply with the dietary regimen of the trial site
  • A history of additional risk factors for Torsade de Pointes (such as heart failure, hypokalaemia, or family history of Long QT Syndrome)
  • Subjects with veins unsuited for venipuncture (for instance, veins which are difficult to locate, access or puncture, veins with a tendency to rupture during or after puncture) as assessed by the investigator.
  • Subject is assessed as unsuitable for inclusion by the investigator, for instance, because the subject is not considered able to understand and comply with study requirements, or has a condition that would not allow safe participation in the study
  • Male subjects with 'women of childbearing potential' (WOCBP) partner who are unwilling to use male contraception (condom or sexual abstinence) from the first administration of trial medication until 30 days after the last administration of trial medication
  • Known relevant immunodeficiency, as judged by the investigator
  • Chronic or relevant acute infections
  • History and/or presence of tuberculosis; positive result for interferon gamma release assay (IGRA) (i.e., QuantiFERON TB-Gold), or history of pneumococcal infection
  • Positive results for Hepatitis B antigen, Hepatitis C antibodies, and/or human immunodeficiency virus (HIV) 1 antigen or HIV1/2 antibodies, at screening
  • Aural body temperature of more than 37.7°C on Day -3 to -1, or Day -4 to -2 for subjects receiving Midazolam microdosing.
  • Subjects who have received live or live-attenuated vaccine in the 4 weeks prior to dosing
  • C-reactive protein above upper limit of laboratory reference range at screening and/or on Day -3 to -1, or Day -4 to -2 for subjects receiving Midazolam microdosing.
  • Subjects with signs of current gingivitis/periodontitis. Inspection of the oral cavity will be performed by the investigator.
  • Current or history of relevant kidney, urinary tract diseases or abnormalities (e.g. nephrolithiasis, hydronephrosis, acute or chronic nephritis, renal injury, renal failure), according to investigator.
  • Estimated glomerular filtration rate (eGFR) according to CKD-EPI formula < 80 mL/min at screening.
  • Known clinically relevant impairment of liver function or clinically relevant laboratory abnormality at the screening visit (V1) regarding liver aminotransferases, alkaline phosphatase, gamma glutamyl transferase, bilirubin, serum albumin, as judged by the investigator.
  • Subjects with a known coagulopathy or abnormal coagulation laboratory parameters at screening, or subjects who, within 10 days prior to administration of trial medication, used any drug that could reasonably inhibit coagulation
  • Females with a positive pregnancy test or breastfeeding

Trial locations and contacts

1 site in 1 country.

Germany1 site
  • Fraunhofer ITEM

    Hanover, 30625

Other trials in Germany

About this study

Official title: Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Multiple Rising Oral Doses of BI 1323495 Versus Placebo in Healthy Subjects, Including an Investigation of Drug-drug Interaction With Microdose Midazolam (Double-blind, Randomised, Placebo-controlled [Within Dose Groups] Trial)

The primary objective of this trial is to investigate the safety and tolerability of BI 1323495 in healthy subjects following bid oral administration of multiple rising doses, each over an 11 day treatment period.

Secondary objectives are the exploration of the pharmacokinetics (PK) including dose proportionality (only for Part 1) as well as attainment of steady state. This includes exploration of a therapeutic exposure range, a range not adequately achieved in the single-rising dose trial 1405-0001.

Conditions
Healthy
Being tested
BI 1323495, Placebo, Midazolam

What participants receive

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

  • BI 1323495Drug

    Tablet

  • PlaceboDrug

    Tablet

  • MidazolamDrug

    Oral administration

Study groups in NCT04107805
Study groupRoleWhat they receive
10 mg BI 1323495 bid EMExperimentalNot described
Receives: Drug: BI 1323495
10 mg BI 1323495 bid PMExperimentalNot described
Receives: Drug: BI 1323495
30 mg BI 1323495 bid EMExperimentalNot described
Receives: Drug: BI 1323495
30 mg BI 1323495 bid PMExperimentalNot described
Receives: Drug: BI 1323495
70 mg BI 1323495 bid + Midazolam EMExperimentalNot described
Receives: Drug: BI 1323495; Drug: Midazolam
120 mg BI 1323495 bid + Midazolam EMExperimentalNot described
Receives: Drug: BI 1323495; Drug: Midazolam
120 mg BI 1323495 qd EMExperimentalNot described
Receives: Drug: BI 1323495
150 mg BI 1323495 bid + Midazolam EMExperimentalNot described
Receives: Drug: BI 1323495; Drug: Midazolam
Placebo/Placebo+ MidazolamExperimentalNot described
Receives: Drug: Placebo; Drug: Midazolam

What is being measured

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

  1. Percentage of Participants With Treatment-emergent Drug-related Adverse Events (AEs)

    Percentage of participants with treatment-emergent drug-related Adverse Events (AEs) is reported.

    Percentages are calculated using total number of subjects per treatment as the denominator.

    Measured: Midazolam alone: From administration of midazolam on Day -1 until first administration of BI 1323495 on Day 1, up to 24 hours. All others: From first administration until 7 days after the last administration of BI 1323495, up to 18 days.

Secondary outcomes (5)
  1. Area Under the Concentration-time Curve of BI 1323495 in Plasma Over a Time Interval of 12 h After Administration of the First Dose (AUC0-12)

    Area under the concentration-time curve of BI 1323495 in plasma over a time interval of 12 h after administration of the first dose (AUC0-12) is reported.

    Measured: Within 3 hours before and 20 minutes (min), 40 min, 1 hour (h), 1.5h, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, and 12h after the first administration of BI 1323495 on Day 1.

  2. Only for Once Daily (qd) Dosing Group: Area Under the Concentration-time Curve of BI 1323495 in Plasma Over a Uniform Dosing Interval of 24 h After Administration of the First Dose (AUC0-24)

    Area under the concentration-time curve of BI 1323495 in plasma over a uniform dosing interval of 24 h after administration of the first dose (AUC0-24) for the once daily (qd) dosing group is reported.

    Measured: Within 3 hours before and 20 minutes (min), 40 min, 1 hour (h), 1.5h, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, 12h and 24 h after administration of BI 1323495 on Day 1.

  3. Maximum Measured Concentration of BI 1323495 in Plasma After the First Dose (Cmax)

    Maximum measured concentration of BI 1323495 in plasma after the first dose (Cmax) is reported.

    Measured: Within 3 hours before and 20 minutes (min), 40 min, 1 hour (h), 1.5h, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, 12h and 24h* after the first administration of BI 1323495 on Day 1. * Applicable only for the 120 mg BI 1323495 qd EM arm.

  4. Area Under the Concentration-time Curve of BI 1323495 in Plasma at Steady State Over a Uniform Dosing Interval τ (AUCτ,ss)

    Area under the concentration-time curve of BI 1323495 in plasma at steady state over a uniform dosing interval τ (AUCτ,ss) is reported. The dosing interval τ is not the same for all groups. The dosing interval is 12 hours (h) for the dose groups with a twice daily (bid) BI 1323495 administration and 24 h for the dose group with a once daily (qd) BI 1323495 administration.

    Measured: Within 3 hours before and 20 minutes (min), 40 min, 1h, 1.5h, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, 12h and 24h* after the last administration of BI 1323495 on Day 11. * Applicable only for the 120 mg BI 1323495 qd EM arm.

  5. Maximum Measured Concentration of BI 1323495 in Plasma at Steady State Over a Uniform Dosing Interval τ (Cmax,ss)

    Maximum measured concentration of BI 1323495 in plasma at steady state over a uniform dosing interval τ (Cmax,ss) is reported.

    The dosing interval τ is not the same for all groups. The dosing interval is 12 hours (h) for the dose groups with a twice daily (bid) BI 1323495 administration and 24 h for the dose group with a once daily (qd) BI 1323495 administration.

    Measured: Within 3 hours before and 20 min, 40 min, 1h, 1.5h, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, 12h and 24h* after the last drug administration of BI 1323495 on Day 11. * Applicable only for the 120 mg BI 1323495 qd EM arm.

Timeline

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

  1. First posted27 Sep 2019
  2. Study start4 Nov 2019
  3. Primary completion5 Mar 2021
  4. Study completion26 Mar 2021

Resources

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
Sequential
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
87 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04107805
Sponsor's protocol ID
1405-0002
Other IDs
2018-004238-13, 2018
Status last verified
Jul 2023
First submitted
26 Sep 2019
Last updated
22 Feb 2024
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents, except for the following exclusions: 1. studies in products where Boehringer Ingelheim is not the license holder; 2. studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; 3. studies conducted in a single center or targeting rare diseases (because of limitations with anonymization). For more details refer to: https://www.mystudywindow.com/msw/datatransparency

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing BI 1323495 and Midazolam in people with Healthy, run by Boehringer Ingelheim at 1 site in Germany.

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 11 inclusion and 34 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 22 Feb 2024. 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 Germany. 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 22 Feb 2024). 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?

Percentage of Participants With Treatment-emergent Drug-related Adverse Events (AEs) (time frame: Midazolam alone: From administration of midazolam on Day -1 until first administration of BI 1323495 on Day 1, up to 24 hours. All others: From first administration until 7 days after the last administration of BI 1323495, up to 18 days.). 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 22 Feb 2024.

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