CClinicalTrials.gg
CompletedNCT03927209Updated Jun 22, 2021Results posted

A Study in Healthy Men to Test the Effects of Different Doses of BI 1467335 on MAO-B Activity in the Brain.

A Phase 1 interventional study of BI 1467335 in Healthy, sponsored by Boehringer Ingelheim. Completed at 1 site in United Kingdom. Open to male participants aged 21 Years to 55 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2021-06-22.

Sponsored by Boehringer Ingelheim · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
10
Allocation
Non-randomized
Ages
21 Years to 55 Years
Sex
Male
01

Study summary

The main objective of this trial is to investigate the effect of multiple oral dosing of high dose BI 1467335 over 28 days and multiple oral dosing of low dose BI 1467335 over 42 days on MAO-B occupancy in the brain compared to baseline using [11C]-L-deprenyl-D2 PET tracer in healthy male subjects.

02

Conditions studied

  • Healthy
03

In context

Lead sponsor

Boehringer Ingelheim is the lead sponsor of 2,245 studies on the registry; 58 are open to participants now.

Of its 162 completed or terminated interventional studies of FDA-regulated products, 116 (72%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
21 Years to 55 Years
Sexes eligible
Male
Accepts healthy volunteers
Yes

Inclusion criteria

  • Healthy male subjects according to the assessment of the investigator, as based on a complete medical history including a physical examination, vital signs (Blood pressure (BP), Pulse rate (PR)), 12-lead Electrocardiogram (ECG), and clinical laboratory tests
  • Age of 21 to 55 years (inclusive)
  • Body mass index (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
  • Non-smoker with no history of smoking
  • Subjects who are sexually active must use, with their partner, highly effective contraception from the time of administration of trial medication until 4 months after administration of trial medication. Adequate methods are:

    • Condoms plus use of hormonal contraception by the female partner that started at least 2 months prior to administration of trial medication (e.g., implants, injectables, combined oral or vaginal contraceptives, intrauterine device) or
    • Condoms plus surgical sterilization (vasectomy at least 1 year prior to enrolment) or
    • Condoms plus surgically sterilised partner (including hysterectomy) or
    • Condoms plus intrauterine device or
    • Condoms plus partner of non-childbearing potential (including homosexual men) Subjects are required to use condoms to prevent unintended exposure of the partner to the study drug via seminal fluid. Alternatively, true abstinence is acceptable when it is in line with the subject's preferred and usual lifestyle. If a subject is usually not sexually active but becomes active, with their partner, they must comply with the contraceptive requirements detailed above.

Exclusion criteria

Exclusion criteria:

  • Any finding in the medical examination (including Blood pressure (BP), Pulse rate (PR) or Electrocardiogram (ECG)) deviating from normal and assessed as clinically relevant by the investigator
  • 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
  • Any evidence of a concomitant disease assessed as clinically relevant by the investigator
  • Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
  • Cholecystectomy or other surgery of the gastrointestinal tract that could interfere with the pharmacokinetics of the trial medication (except appendectomy or simple hernia repair)
  • 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 relevant orthostatic hypotension, fainting spells, or blackouts
  • Chronic or relevant acute infections
  • History of relevant allergy or hypersensitivity (including allergy to the trial medication or its excipients)
  • 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 90 days or within 5 half-lives, 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
  • Alcohol abuse (consumption of more than 30 g per day for males) within the 24 months prior to dosing
  • Drug abuse within the 24 months prior to dosing 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 marked baseline prolongation of QT/QTc interval (such as QTc intervals that are repeatedly greater than 450 ms) or any other relevant ECG finding at screening
  • A history of additional risk factors for Torsade de Pointes (such as heart failure, hypokalaemia, or family history of Long QT Syndrome)
  • 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
  • Structural brain abnormality has been shown on an Magnetic Resonance Imaging (MRI)
  • Severe anxiety of enclosed spaces
  • Contraindication for arterial cannulation: Allen's test indicating potential risk in placement of the arterial cannula.
  • Contraindication to MRI as determined by screening and safety questionnaire including but not limited to significant tattoos (as determined by the radiographer), cardiac pacemakers, aneurysm clips and cochlear implants.
  • Unable to lie flat on the MRI or Positron emission tomography (PET) scanner for a prolonged period of time.
  • Prior participation in other research protocols in the past year such that the total effective dose including this study would exceed 10 mSv.
05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
10 participants (actual)

Study arms

  • Experimental
    BI 1467335 (low dose)

    Drug: BI 1467335

  • Experimental
    BI 1467335 (high dose)

    Drug: BI 1467335

Interventions

  • DrugBI 1467335

    tablet

06

What researchers measure

Primary outcomes

  1. Percentage Reduction in Whole Brain Monoamine Oxidase (MAO)-B Availability Assessed by Positron Emission Tomography (PET) Imaging

    The primary endpoint of the trial was the percent reduction in whole brain MAO-B availability, as assessed by PET imaging, on the last day of treatment with BI 1467335 (Day 28 for the 10 mg dose group and Day 42 for the 3 mg dose group) compared with baseline. Image analysis was used to generate the outcome parameter for the PET data (proportional to the target availability at each PET scan) using the PET emission and the metabolite corrected arterial plasma input function in an appropriate kinetic model.

    Time frame: Baseline (day -14 to -2) and last day of treatment (Day 28 for the 10 mg dose group and Day 42 for the 3 mg dose group).

Secondary outcomes

  1. Percent Reduction in MAO-B Availability on Day 14 of Treatment With 10 mg BI 1467335 Compared With Baseline

    Percent reduction in MAO-B availability on Day 14 of treatment with 10 mg BI 1467335 compared with baseline. Image analysis was used to generate the outcome parameter for the PET data (proportional to the target availability at each PET scan) using the PET emission and the metabolite corrected arterial plasma input function in an appropriate kinetic model.

    Time frame: Baseline (day -14 to -2) and Day 14 of treatment.

  2. Reduction in MAO-B Availability on Day 28 of Treatment With 3 mg BI 1467335 Compared With Baseline

    Reduction in MAO-B availability on Day 28 of treatment with 3 mg BI 1467335 compared with baseline. Image analysis was used to generate the outcome parameter for the PET data (proportional to the target availability at each PET scan) using the PET emission and the metabolite corrected arterial plasma input function in an appropriate kinetic model.

    Time frame: Baseline (day -14 to -2) and Day 28 of treatment.

  3. MAO-B Inhibition in Platelet Rich Plasma Compared With Baseline

    MAO-B activity in plasma was assessed after 14 days of dosing with BI 1467335 (10 mg dose group only), 28 days of dosing (10 and 3 mg dose groups), and 42 days of dosing (3 mg dose group only).

    Time frame: Baseline (day -14 to -2) and last day of treatment (Day 28 for the 10 mg dose group and Day 42 for the 3 mg dose group).

  4. Maximum Measured Concentration of BI 1467335 in Plasma

    Maximum measured concentration of BI 1467335 in Plasma (Cmax).

    Time frame: Within 3 hours (h) before and 20 minutes (min), 45 min, 1h, 1h 30 min, 3h, 4h, 7h, 11h, 24h (~30 min before next scheduled dosing where applicable) after administration of BI 1467335.

  5. Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to the Time 24 h (AUC 0-24)

    Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time 24 h.

    Time frame: Within 3 hours (h) before and 20 minutes (min), 45 min, 1h, 1h 30 min, 3h, 4h, 7h, 11h, 24h (~30 min before next scheduled dosing where applicable) after administration of BI 1467335.

07

Results

Posted Jun 4, 2021

Participant flow

This phase I trial was conducted using a non-randomised, non-controlled, open-label, parallel-group, multiple-dose design.

Participant flow — Overall Study
MilestoneBI 1467335 10 Milligram (mg)BI 1467335 3 Milligram (mg)
Started55
Completed55
Not completed00

Outcome measures

PrimaryPercentage Reduction in Whole Brain Monoamine Oxidase (MAO)-B Availability Assessed by Positron Emission Tomography (PET) Imaging

The primary endpoint of the trial was the percent reduction in whole brain MAO-B availability, as assessed by PET imaging, on the last day of treatment with BI 1467335 (Day 28 for the 10 mg dose group and Day 42 for the 3 mg dose group) compared with baseline. Image analysis was used to generate the outcome parameter for the PET data (proportional to the target availability at each PET scan) using the PET emission and the metabolite corrected arterial plasma input function in an appropriate kinetic model.

Time frame:
Baseline (day -14 to -2) and last day of treatment (Day 28 for the 10 mg dose group and Day 42 for the 3 mg dose group).
Reported as:
Mean · Percent reduction
Percentage Reduction in Whole Brain Monoamine Oxidase (MAO)-B Availability Assessed by Positron Emission Tomography (PET) Imaging
Percent reductionBI 1467335 10 Milligram (mg)BI 1467335 3 Milligram (mg)
Percentage Reduction in Whole Brain Monoamine Oxidase (MAO)-B Availability Assessed by Positron Emission Tomography (PET) Imaging72.58 ± 11.812.43 ± 6.05
SecondaryPercent Reduction in MAO-B Availability on Day 14 of Treatment With 10 mg BI 1467335 Compared With Baseline

Percent reduction in MAO-B availability on Day 14 of treatment with 10 mg BI 1467335 compared with baseline. Image analysis was used to generate the outcome parameter for the PET data (proportional to the target availability at each PET scan) using the PET emission and the metabolite corrected arterial plasma input function in an appropriate kinetic model.

Time frame:
Baseline (day -14 to -2) and Day 14 of treatment.
Reported as:
Mean · Percent reduction
Percent Reduction in MAO-B Availability on Day 14 of Treatment With 10 mg BI 1467335 Compared With Baseline
Percent reductionBI 1467335 10 Milligram (mg)
Percent Reduction in MAO-B Availability on Day 14 of Treatment With 10 mg BI 1467335 Compared With Baseline44.56 ± 16.20
SecondaryReduction in MAO-B Availability on Day 28 of Treatment With 3 mg BI 1467335 Compared With Baseline

Reduction in MAO-B availability on Day 28 of treatment with 3 mg BI 1467335 compared with baseline. Image analysis was used to generate the outcome parameter for the PET data (proportional to the target availability at each PET scan) using the PET emission and the metabolite corrected arterial plasma input function in an appropriate kinetic model.

Time frame:
Baseline (day -14 to -2) and Day 28 of treatment.
Reported as:
Mean · Percent reduction
Reduction in MAO-B Availability on Day 28 of Treatment With 3 mg BI 1467335 Compared With Baseline
Percent reductionBI 1467335 3 Milligram (mg)
Reduction in MAO-B Availability on Day 28 of Treatment With 3 mg BI 1467335 Compared With Baseline-1.43 ± 6.29
SecondaryMAO-B Inhibition in Platelet Rich Plasma Compared With Baseline

MAO-B activity in plasma was assessed after 14 days of dosing with BI 1467335 (10 mg dose group only), 28 days of dosing (10 and 3 mg dose groups), and 42 days of dosing (3 mg dose group only).

Time frame:
Baseline (day -14 to -2) and last day of treatment (Day 28 for the 10 mg dose group and Day 42 for the 3 mg dose group).

No measurements were reported for this outcome.

SecondaryMaximum Measured Concentration of BI 1467335 in Plasma

Maximum measured concentration of BI 1467335 in Plasma (Cmax).

Time frame:
Within 3 hours (h) before and 20 minutes (min), 45 min, 1h, 1h 30 min, 3h, 4h, 7h, 11h, 24h (~30 min before next scheduled dosing where applicable) after administration of BI 1467335.
Reported as:
Geometric mean · nanomol per liter
Maximum Measured Concentration of BI 1467335 in Plasma
nanomol per literBI 1467335 10 Milligram (mg)BI 1467335 3 Milligram (mg)
Day 1436.4 ± 65.2—
Day 2848.4 ± 85.32.28 ± 76.0
Day 42—3.60 ± 146
SecondaryArea Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to the Time 24 h (AUC 0-24)

Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time 24 h.

Time frame:
Within 3 hours (h) before and 20 minutes (min), 45 min, 1h, 1h 30 min, 3h, 4h, 7h, 11h, 24h (~30 min before next scheduled dosing where applicable) after administration of BI 1467335.
Reported as:
Geometric mean · nanomol * hours per liter
Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to the Time 24 h (AUC 0-24)
nanomol * hours per literBI 1467335 10 Milligram (mg)BI 1467335 3 Milligram (mg)
Day 1485.7 ± 75.5—
Day 28235 ± 148.04.65 ± 54.9
Day 42—4.34 ± 132

Adverse events

Collected over From the date/time of first administration of BI 1467335 until 12 a.m. on the day after subjects end of participation date. (Up to 36 days for 10mg group, up to 50 days for 3mg group). Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
BI 1467335 10 Milligram (mg)0/5 (0%)0/5 (0%)5/5 (100%)
BI 1467335 3 Milligram (mg)0/5 (0%)0/5 (0%)3/5 (60%)
Total on Treatment0/10 (0%)0/10 (0%)8/10 (80%)
Most frequent other events
Showing 10 of 23
Most frequent other events
EventBI 1467335 10 Milligram (mg)BI 1467335 3 Milligram (mg)Total on Treatment
Ear discomfortEar and labyrinth disorders0/51/51/10
Abdominal discomfortGastrointestinal disorders1/50/51/10
Abdominal distensionGastrointestinal disorders0/51/51/10
Abdominal painGastrointestinal disorders0/51/51/10
ConstipationGastrointestinal disorders1/50/51/10
DiarrhoeaGastrointestinal disorders0/51/51/10
Catheter site bruiseGeneral disorders1/51/52/10
Catheter site erythemaGeneral disorders0/51/51/10
Catheter site painGeneral disorders1/50/51/10
FatigueGeneral disorders1/50/51/10

Baseline characteristics

Treated set (TS): The TS included all subjects who were randomized and treated with at least one dose of study drug.

Age, Continuous
Age, Continuous(Years)BI 1467335 10 Milligram (mg)BI 1467335 3 Milligram (mg)Total
Mean43.8 ± 7.739.0 ± 11.441.4 ± 9.5
Sex: Female, Male
Sex: Female, Male(Participants)BI 1467335 10 Milligram (mg)BI 1467335 3 Milligram (mg)Total
Female000
Male5510
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)BI 1467335 10 Milligram (mg)BI 1467335 3 Milligram (mg)Total
Hispanic or Latino000
Not Hispanic or Latino5510
Unknown or Not Reported000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)BI 1467335 10 Milligram (mg)BI 1467335 3 Milligram (mg)Total
American Indian or Alaska Native000
Asian022
Native Hawaiian or Other Pacific Islander000
Black or African American011
White325
More than one race202
Unknown or Not Reported000
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Study locations

1 site
  • Northwick Park Hospital
    Harrow, HA1 3UJ, United Kingdom
09

References and documents

Study documents

  • Study protocol · Jun 24, 2019
  • Statistical analysis plan · Jan 17, 2020

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: 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: http://trials.boehringer-ingelheim.com/

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jun 22, 2021, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT03927209
Lead sponsor
Boehringer Ingelheim
Responsible party
Sponsor
First posted
Apr 25, 2019
Start date
Jun 6, 2019
Primary completion
Nov 22, 2019
Completion
Nov 22, 2019
Results posted
Jun 4, 2021
Last update
Jun 22, 2021

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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