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
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.
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.
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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:
Exclusion criteria:
Drug: BI 1467335
Drug: BI 1467335
tablet
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).
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.
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.
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).
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.
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.
This phase I trial was conducted using a non-randomised, non-controlled, open-label, parallel-group, multiple-dose design.
| Milestone | BI 1467335 10 Milligram (mg) | BI 1467335 3 Milligram (mg) |
|---|---|---|
| Started | 5 | 5 |
| Completed | 5 | 5 |
| Not completed | 0 | 0 |
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.
| Percent reduction | BI 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) Imaging | 72.58 ± 11.81 | 2.43 ± 6.05 |
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.
| Percent reduction | BI 1467335 10 Milligram (mg) |
|---|---|
| Percent Reduction in MAO-B Availability on Day 14 of Treatment With 10 mg BI 1467335 Compared With Baseline | 44.56 ± 16.20 |
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.
| Percent reduction | BI 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 |
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).
No measurements were reported for this outcome.
Maximum measured concentration of BI 1467335 in Plasma (Cmax).
| nanomol per liter | BI 1467335 10 Milligram (mg) | BI 1467335 3 Milligram (mg) |
|---|---|---|
| Day 14 | 36.4 ± 65.2 | — |
| Day 28 | 48.4 ± 85.3 | 2.28 ± 76.0 |
| Day 42 | — | 3.60 ± 146 |
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time 24 h.
| nanomol * hours per liter | BI 1467335 10 Milligram (mg) | BI 1467335 3 Milligram (mg) |
|---|---|---|
| Day 14 | 85.7 ± 75.5 | — |
| Day 28 | 235 ± 148.0 | 4.65 ± 54.9 |
| Day 42 | — | 4.34 ± 132 |
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.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| 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 Treatment | 0/10 (0%) | 0/10 (0%) | 8/10 (80%) |
| Event | BI 1467335 10 Milligram (mg) | BI 1467335 3 Milligram (mg) | Total on Treatment |
|---|---|---|---|
| Ear discomfortEar and labyrinth disorders | 0/5 | 1/5 | 1/10 |
| Abdominal discomfortGastrointestinal disorders | 1/5 | 0/5 | 1/10 |
| Abdominal distensionGastrointestinal disorders | 0/5 | 1/5 | 1/10 |
| Abdominal painGastrointestinal disorders | 0/5 | 1/5 | 1/10 |
| ConstipationGastrointestinal disorders | 1/5 | 0/5 | 1/10 |
| DiarrhoeaGastrointestinal disorders | 0/5 | 1/5 | 1/10 |
| Catheter site bruiseGeneral disorders | 1/5 | 1/5 | 2/10 |
| Catheter site erythemaGeneral disorders | 0/5 | 1/5 | 1/10 |
| Catheter site painGeneral disorders | 1/5 | 0/5 | 1/10 |
| FatigueGeneral disorders | 1/5 | 0/5 | 1/10 |
Treated set (TS): The TS included all subjects who were randomized and treated with at least one dose of study drug.
| Age, Continuous(Years) | BI 1467335 10 Milligram (mg) | BI 1467335 3 Milligram (mg) | Total |
|---|---|---|---|
| Mean | 43.8 ± 7.7 | 39.0 ± 11.4 | 41.4 ± 9.5 |
| Sex: Female, Male(Participants) | BI 1467335 10 Milligram (mg) | BI 1467335 3 Milligram (mg) | Total |
|---|---|---|---|
| Female | 0 | 0 | 0 |
| Male | 5 | 5 | 10 |
| Ethnicity (NIH/OMB)(Participants) | BI 1467335 10 Milligram (mg) | BI 1467335 3 Milligram (mg) | Total |
|---|---|---|---|
| Hispanic or Latino | 0 | 0 | 0 |
| Not Hispanic or Latino | 5 | 5 | 10 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | BI 1467335 10 Milligram (mg) | BI 1467335 3 Milligram (mg) | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 0 | 2 | 2 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 0 | 1 | 1 |
| White | 3 | 2 | 5 |
| More than one race | 2 | 0 | 2 |
| Unknown or Not Reported | 0 | 0 | 0 |
Documents are hosted by the registry — open the source record to download them.
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/
This study is completed, as verified in Jun 2021. You cannot join it, but the record below documents what was studied.
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