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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
10
tablet
Northwick Park Hospital
Harrow, United Kingdom
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).
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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.