Cmax was determined for BN82451B and its metabolites BN2468 and BN7167 on Days 1, 14 and 28. Day 1 data represent the PK after the first dose (Cmax). The data for Days 14 and 28 represent the Cmax at steady state (Cmax,ss) at the initial cohort dose and following dose escalation, respectively. Data is presented for cohorts 1 and 2, as the study terminated prior to dosing of cohort 3.

Tmax is the empirical time of Cmax and was determined for BN82451B and its metabolites BN2468 and BN7167 on Days 1, 14 and 28. Day 1 data represent the PK after the first dose (Tmax). The data for Days 14 and 28 represent the Tmax at steady state (Tmax,ss) at the initial cohort dose and following dose escalation, respectively. Data is presented for cohorts 1 and 2, as the study terminated prior to dosing of cohort 3.

Choreatic (involuntary) movements were assessed using Choreomotography by calculating a position-index and orientation-index. Patients were asked to grasp and lift a device equipped with an electromagnetic sensor, and were asked to hold the device as stable as possible. Three dimensional (3D) changes in position (x, y and z) and orientation (roll, pitch and yaw) were recorded and used to calculate a position-index and an orientation-index. This method provided an objective measure of the involuntary movements. 5 trials of 20 seconds duration were performed with each hand, and the start and end of each trial was signalled by a cueing tone. The mean changes from Baseline to Day 28 in the position-index of the right and left hands are presented as raw data. The statistical analyses present geometric least squares (GLS) mean ratios in the original units.

Choreatic (involuntary) movements were assessed using Choreomotography by calculating a position-index and orientation-index. Patients were asked to grasp and lift a device equipped with an electromagnetic sensor, and were asked to hold the device as stable as possible. 3D changes in position (x, y and z) and orientation (roll, pitch and yaw) were recorded and used to calculate a position-index and an orientation-index. This method provided an objective measure of the involuntary movements. 5 trials of 20 seconds duration were performed with each hand, and the start and end of each trial was signalled by a cueing tone. The mean changes from Baseline to Day 28 in the orientation-index of the right and left hands are presented as raw data. The statistical analyses present GLS mean ratios in the original units.

The coordination of isometric grip forces in the precision grip between the thumb and index finger were assessed by Manumotography. Grip forces were assessed during grip initiation, object transport and in a static holding phase. Subjects were instructed to grasp and lift a device equipped with a force transducer and 3D position sensor in the precision grip between thumb and index finger and hold it stable adjacent to a marker 10 centimetres high. Grip forces and 3D position and orientation of the object were recorded. Mean isometric grip forces and grip force variability in the static phase (expressed as coefficient of variation = standard deviation/mean x 100 [GFV-C]) were calculated during a 15 second period. 5 trials of 20 seconds duration were performed with each hand. The mean changes from Baseline to Day 28 in the grip force variability of each hand are presented as raw data. The statistical analyses present GLS mean ratios in the original units.

The coordination of isometric grip forces in the precision grip between the thumb and index finger were assessed by Manumotography. Grip forces were assessed during grip initiation, object transport and in a static holding phase. Subjects were instructed to grasp and lift a device equipped with a force transducer and 3D position sensor in the precision grip between thumb and index finger and hold it stable adjacent to a marker 10 centimetres high. Grip forces and 3D position and orientation of the object were recorded. Mean isometric grip forces and grip force variability in the static phase (expressed as coefficient of variation = standard deviation/mean x 100 [GFV-C]) were calculated during a 15 second period. 5 trials of 20 seconds duration were performed with each hand. The mean changes from Baseline to Day 28 in the mean isometric grip forces of each hand are presented as raw data. The statistical analyses present GLS mean ratios in the original units.

Digitomotography was used to assess the duration and the variability of tap IOI in an index finger speeded tapping task. The patient placed their hand on a hand rest with their index finger positioned on a force transducer, and recordings were started after practice runs. The patient was then instructed to finger tap as fast as possible between 2 auditory cues. The beginning of a tap was defined as a rise of the force by 0.05 N above maximal baseline level. The tap ended when it dropped to 0.05 N before the maximal baseline level was reached again. 5 trials of 10 seconds duration were performed with each hand. The mean changes from Baseline to Day 28 in the duration and variability of IOI for the left and right hands are presented as raw data. The statistical analyses present GLS mean ratios in the original units.

Digitomotography was used to assess the duration and the variability of TD in an index finger speeded tapping task. The patient placed their hand on a hand rest with their index finger positioned on a force transducer, and recordings were started after practice runs. The patient was then instructed to finger tap as fast as possible between 2 auditory cues. The beginning of a tap was defined as a rise of the force by 0.05 N above maximal baseline level. The tap ended when it dropped to 0.05 N before the maximal baseline level was reached again. 5 trials of 10 seconds duration were performed with each hand. The mean changes from Baseline to Day 28 in the duration and variability of TD for the left and right hands are presented a raw data. The statistical analyses present GLS mean ratios in the original units.

Digitomotography was used to assess the duration and the variability of tap IPI in an index finger speeded tapping task. The patient placed their hand on a hand rest with their index finger positioned on a force transducer, and recordings were started after practice runs. The patient was then instructed to finger tap as fast as possible between 2 auditory cues. The beginning of a tap was defined as a rise of the force by 0.05 N above maximal baseline level. The tap ended when it dropped to 0.05 N before the maximal baseline level was reached again. 5 trials of 10 seconds duration were performed with each hand. The mean changes from Baseline to Day 28 in the duration and variability of IPI for the left and right hands are presented as raw data. The statistical analyses present GLS mean ratios in the original units.

Digitomotography was used to assess the duration and the variability of ITI in an index finger speeded tapping task. The patient placed their hand on a hand rest with their index finger positioned on a force transducer, and recordings were started after practice runs. The patient was then instructed to finger tap as fast as possible between 2 auditory cues. The beginning of a tap was defined as a rise of the force by 0.05 N above maximal baseline level. The tap ended when it dropped to 0.05 N before the maximal baseline level was reached again. 5 trials of 10 seconds duration were performed with each hand. The mean changes from Baseline to Day 28 in the duration and variability of ITI for the left and right hands are presented as raw data. The statistical analyses present GLS mean ratios in the original units.

Digitomotography was used to assess the duration and the variability of TD in an index finger speeded tapping task. The patient placed their hand on a hand rest with their index finger positioned on a force transducer, and recordings were started after practice runs. The patient was then instructed to finger tap as fast as possible between 2 auditory cues. The beginning of a tap was defined as a rise of the force by 0.05 N above maximal baseline level. The tap ended when it dropped to 0.05 N before the maximal baseline level was reached again. 5 trials of 10 seconds duration were performed with each hand. The mean changes from Baseline to Day 28 in the variability of TF for the left and right hands are presented as raw data. The statistical analyses present GLS mean ratios in the original units.

Digitomotography was used to assess the duration and the variability of TD in an index finger speeded tapping task. The patient placed their hand on a hand rest with their index finger positioned on a force transducer, and recordings were started after practice runs. The patient was then instructed to finger tap as fast as possible between 2 auditory cues. The beginning of a tap was defined as a rise of the force by 0.05 N above maximal baseline level. The tap ended when it dropped to 0.05 N before the maximal baseline level was reached again. 5 trials of 10 seconds duration were performed with each hand. The tapping frequency was calculated as the number of taps between the onsets of the first and the last tap divided by the time in between. The mean changes from Baseline to Day 28 in the tapping frequency for the left and right hands are presented as raw data. The statistical analyses present GLS mean ratios in the original units.

Dysdiadochomotography was used to assess the regularity of hand taps performed when alternating between the palm and dorsal surface of the hand performing a repetitive pronation/supination movement. The force and duration of the hand taps were recorded, with their hand positioned on a force transducer, and recordings were started after practice runs. The patient was then instructed to hand tap as fast as possible between 2 auditory cues. The beginning of a tap was defined as a rise of the force by 0.05 N above maximal baseline level. The tap ended when it dropped to 0.05 N before the maximal baseline level was reached again. 5 trials of 10 seconds duration were performed with each hand. The mean changes from Baseline to Day 28 in the duration and variability of IOI for the left and right hands are presented as raw data. The statistical analyses present GLS mean ratios in the original units.

Dysdiadochomotography was used to assess the regularity of hand taps performed when alternating between the palm and dorsal surface of the hand performing a repetitive pronation/supination movement. The force and duration of the hand taps were recorded, with their hand positioned on a force transducer, and recordings were started after practice runs. The patient was then instructed to hand tap as fast as possible between 2 auditory cues. The beginning of a tap was defined as a rise of the force by 0.05 N above maximal baseline level. The tap ended when it dropped to 0.05 N before the maximal baseline level was reached again. 5 trials of 10 seconds duration were performed with each hand. The mean changes from Baseline to Day 28 in the duration and variability of TD for the left and right hands are presented as raw data. The statistical analyses present GLS mean ratios in the original units.

Dysdiadochomotography was used to assess the regularity of hand taps performed when alternating between the palm and dorsal surface of the hand performing a repetitive pronation/supination movement. The force and duration of the hand taps were recorded, with their hand positioned on a force transducer, and recordings were started after practice runs. The patient was then instructed to hand tap as fast as possible between 2 auditory cues. The beginning of a tap was defined as a rise of the force by 0.05 N above maximal baseline level. The tap ended when it dropped to 0.05 N before the maximal baseline level was reached again. 5 trials of 10 seconds duration were performed with each hand. The mean changes from Baseline to Day 28 in the duration and variability of IPI for the left and right hands are presented as raw data. The statistical analyses present GLS mean ratios in the original units.

Dysdiadochomotography was used to assess the regularity of hand taps performed when alternating between the palm and dorsal surface of the hand performing a repetitive pronation/supination movement. The force and duration of the hand taps were recorded, with their hand positioned on a force transducer, and recordings were started after practice runs. The patient was then instructed to hand tap as fast as possible between 2 auditory cues. The beginning of a tap was defined as a rise of the force by 0.05 N above maximal baseline level. The tap ended when it dropped to 0.05 N before the maximal baseline level was reached again. 5 trials of 10 seconds duration were performed with each hand. The mean changes from Baseline to Day 28 in the duration and variability of ITI for the left and right hands are presented as raw data. The statistical analyses present GLS mean ratios in the original units.

Dysdiadochomotography was used to assess the regularity of hand taps performed when alternating between the palm and dorsal surface of the hand performing a repetitive pronation/supination movement. The force and duration of the hand taps were recorded, with their hand positioned on a force transducer, and recordings were started after practice runs. The patient was then instructed to hand tap as fast as possible between 2 auditory cues. The beginning of a tap was defined as a rise of the force by 0.05 N above maximal baseline level. The tap ended when it dropped to 0.05 N before the maximal baseline level was reached again. 5 trials of 10 seconds duration were performed with each hand. The mean changes from Baseline to Day 28 in the variability of TF for the left and right hands are presented as raw data. The statistical analyses present GLS mean ratios in the original units.

Dysdiadochomotography was used to assess the regularity of hand taps performed when alternating between the palm and dorsal surface of the hand performing a repetitive pronation/supination movement. The force and duration of the hand taps were recorded, with their hand positioned on a force transducer, and recordings were started after practice runs. The patient was then instructed to hand tap as fast as possible between 2 auditory cues. The beginning of a tap was defined as a rise of the force by 0.05 N above maximal baseline level. The tap ended when it dropped to 0.05 N before the maximal baseline level was reached again. 5 trials of 10 seconds duration were performed with each hand. The tapping frequency was calculated as the number of taps between the onsets of the first and the last tap divided by the time in between. The mean changes from Baseline to Day 28 in the tapping frequency for the left and right hands are presented as raw data. GLS mean ratios are in original units.

Pedomotography was used to assess the tap duration and variability in a foot speeded tapping task. The patient placed their foot on the foot device such that the ball of the foot was positioned above a force transducer, and recordings were started after practice runs. The patient was then instructed to foot tap as fast as possible between 2 auditory cues. The beginning of a tap was defined as a rise of the force by 0.05 N above maximal baseline level. The tap ended when it dropped to 0.05 N before the maximal baseline level was reached again. 5 trials of 10 seconds duration were performed with each foot. The mean changes from Baseline to Day 28 in the duration and variability of IOI for the left and right feet are presented as raw data. The statistical analyses present GLS mean ratios in the original units.

Pedomotography was used to assess the tap duration and variability in a foot speeded tapping task. The patient placed their foot on the foot device such that the ball of the foot was positioned above a force transducer, and recordings were started after practice runs. The patient was then instructed to foot tap as fast as possible between 2 auditory cues. The patient was then instructed to foot tap as fast as possible between 2 auditory cues. The beginning of a tap was defined as a rise of the force by 0.05 N above maximal baseline level. The tap ended when it dropped to 0.05 N before the maximal baseline level was reached again. 5 trials of 10 seconds duration were performed with each foot. The mean changes from Baseline to Day 28 in the duration and variability of TD for the left and right feet are presented as raw data. The statistical analyses present GLS mean ratios in the original units.

Pedomotography was used to assess the tap duration and variability in a foot speeded tapping task. The patient placed their foot on the foot device such that the ball of the foot was positioned above a force transducer, and recordings were started after practice runs. The patient was then instructed to foot tap as fast as possible between 2 auditory cues. The beginning of a tap was defined as a rise of the force by 0.05 N above maximal baseline level. The tap ended when it dropped to 0.05 N before the maximal baseline level was reached again. 5 trials of 10 seconds duration were performed with each foot. The mean changes from Baseline to Day 28 in the duration and variability of IPI for the left and right feet are presented as raw data. The statistical analyses present GLS mean ratios in the original units.

Pedomotography was used to assess the tap duration and variability in a foot speeded tapping task. The patient placed their foot on the foot device such that the ball of the foot was positioned above a force transducer, and recordings were started after practice runs. The patient was then instructed to foot tap as fast as possible between 2 auditory cues. The beginning of a tap was defined as a rise of the force by 0.05 N above maximal baseline level. The tap ended when it dropped to 0.05 N before the maximal baseline level was reached again. 5 trials of 10 seconds duration were performed with each foot. The mean changes from Baseline to Day 28 in the duration and variability of ITI for the left and right feet are presented as raw data. The statistical analyses present GLS mean ratios in the original units.

Pedomotography was used to assess the tap duration and variability in a foot speeded tapping task. The patient placed their foot on the foot device such that the ball of the foot was positioned above a force transducer, and recordings were started after practice runs. The patient was then instructed to foot tap as fast as possible between 2 auditory cues. The beginning of a tap was defined as a rise of the force by 0.05 N above maximal baseline level. The tap ended when it dropped to 0.05 N before the maximal baseline level was reached again. 5 trials of 10 seconds duration were performed with each foot. The mean changes from Baseline to Day 28 in the variability of TF for the left and right feet are presented as raw data. The statistical analyses present GLS mean ratios in the original units.

Pedomotography was used to assess the tap duration and variability in a foot speeded tapping task. The patient placed their foot on the foot device such that the ball of the foot was positioned above a force transducer, and recordings were started after practice runs. The patient was then instructed to foot tap as fast as possible between 2 auditory cues. The beginning of a tap was defined as a rise of the force by 0.05 N above maximal baseline level. The tap ended when it dropped to 0.05 N before the maximal baseline level was reached again. 5 trials of 10 seconds duration were performed with each foot. The tapping frequency was calculated as the number of taps between the onsets of the first and the last tap divided by the time in between. The mean changes from Baseline to Day 28 in the tapping frequency for the left and right hands are presented as raw data. The statistical analyses present GLS mean ratios in the original units.

Patients were randomised to receive oral placebo b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of placebo was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 mg b.i.d.

For cohort 1, 40 mg placebo b.i.d. was administered during the first 14 days. If this dose was well tolerated then it was increased to 60 mg b.i.d. for 13 days and one morning dose of 60 mg on Day 28.

For cohort 2, 60 mg placebo b.i.d. was administered during the first 14 days. If 60 mg b.i.d was well tolerated then it was increased to 80 mg b.i.d. for 13 days and one morning dose of 80 mg on Day 28.

For cohort 3 it was planned to administer 80 mg placebo b.i.d for 27 days with one morning dose of 80 mg on Day 28. The study was terminated early before completion of cohort 2.

Patients were randomised to receive oral placebo b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of placebo was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 mg b.i.d.

For cohort 1, 40 mg placebo b.i.d. was administered during the first 14 days. If this dose was well tolerated then it was increased to 60 mg b.i.d. for 13 days and one morning dose of 60 mg on Day 28.

For cohort 2, 60 mg placebo b.i.d. was administered during the first 14 days. If 60 mg b.i.d was well tolerated then it was increased to 80 mg b.i.d. for 13 days and one morning dose of 80 mg on Day 28.

For cohort 3 it was planned to administer 80 mg placebo b.i.d for 27 days with one morning dose of 80 mg on Day 28. The study was terminated early before completion of cohort 2.

The AUC was determined for BN82451B and its metabolites BN2468 and BN7167 within a dosage interval (0-12 hours) on Days 1, and 14 and 28. Day 1 data represent the AUC after the first dose (AUC[0-12]). The data for Days 14 and 28 (AUC[τ,ss]) represent the AUC at steady state at the initial cohort dose and following dose escalation, respectively. Data is presented for cohorts 1 and 2, as the study terminated prior to dosing of cohort 3.

The PK population consisted of all subjects from the safety population who had no major protocol deviations affecting the PK variables and who had a sufficient number of plasma BN82451B concentrations to estimate the main PK parameters.

Cmax was determined for BN82451B and its metabolites BN2468 and BN7167 on Days 1, 14 and 28. Day 1 data represent the PK after the first dose (Cmax). The data for Days 14 and 28 represent the Cmax at steady state (Cmax,ss) at the initial cohort dose and following dose escalation, respectively. Data is presented for cohorts 1 and 2, as the study terminated prior to dosing of cohort 3.

The PK population consisted of all subjects from the safety population who had no major protocol deviations affecting the PK variables and who had a sufficient number of plasma BN82451B concentrations to estimate the main PK parameters.

Tmax is the empirical time of Cmax and was determined for BN82451B and its metabolites BN2468 and BN7167 on Days 1, 14 and 28. Day 1 data represent the PK after the first dose (Tmax). The data for Days 14 and 28 represent the Tmax at steady state (Tmax,ss) at the initial cohort dose and following dose escalation, respectively. Data is presented for cohorts 1 and 2, as the study terminated prior to dosing of cohort 3.

The PK population consisted of all subjects from the safety population who had no major protocol deviations affecting the PK variables and who had a sufficient number of plasma BN82451B concentrations to estimate the main PK parameters.

Choreatic (involuntary) movements were assessed using Choreomotography by calculating a position-index and orientation-index. Patients were asked to grasp and lift a device equipped with an electromagnetic sensor, and were asked to hold the device as stable as possible. Three dimensional (3D) changes in position (x, y and z) and orientation (roll, pitch and yaw) were recorded and used to calculate a position-index and an orientation-index. This method provided an objective measure of the involuntary movements. 5 trials of 20 seconds duration were performed with each hand, and the start and end of each trial was signalled by a cueing tone. The mean changes from Baseline to Day 28 in the position-index of the right and left hands are presented as raw data. The statistical analyses present geometric least squares (GLS) mean ratios in the original units.

The Pharmacodynamic (PD) population consisted of all subjects from the safety population who have not reported major protocol violations impacting quantitative measures of motor function (Q-motor) evaluation and who have a Q-motor evaluation assessed both at Baseline (Day -1) and at one post baseline visit.

Choreatic (involuntary) movements were assessed using Choreomotography by calculating a position-index and orientation-index. Patients were asked to grasp and lift a device equipped with an electromagnetic sensor, and were asked to hold the device as stable as possible. 3D changes in position (x, y and z) and orientation (roll, pitch and yaw) were recorded and used to calculate a position-index and an orientation-index. This method provided an objective measure of the involuntary movements. 5 trials of 20 seconds duration were performed with each hand, and the start and end of each trial was signalled by a cueing tone. The mean changes from Baseline to Day 28 in the orientation-index of the right and left hands are presented as raw data. The statistical analyses present GLS mean ratios in the original units.

The PD population consisted of all subjects from the safety population who have not reported major protocol violations impacting Q-motor evaluation and who have a Q-motor evaluation assessed both at Baseline (Day -1) and at one post baseline visit.

The coordination of isometric grip forces in the precision grip between the thumb and index finger were assessed by Manumotography. Grip forces were assessed during grip initiation, object transport and in a static holding phase. Subjects were instructed to grasp and lift a device equipped with a force transducer and 3D position sensor in the precision grip between thumb and index finger and hold it stable adjacent to a marker 10 centimetres high. Grip forces and 3D position and orientation of the object were recorded. Mean isometric grip forces and grip force variability in the static phase (expressed as coefficient of variation = standard deviation/mean x 100 [GFV-C]) were calculated during a 15 second period. 5 trials of 20 seconds duration were performed with each hand. The mean changes from Baseline to Day 28 in the grip force variability of each hand are presented as raw data. The statistical analyses present GLS mean ratios in the original units.

The PD population consisted of all subjects from the safety population who have not reported major protocol violations impacting Q-motor evaluation and who have a Q-motor evaluation assessed both at Baseline (Day -1) and at one post baseline visit.

The coordination of isometric grip forces in the precision grip between the thumb and index finger were assessed by Manumotography. Grip forces were assessed during grip initiation, object transport and in a static holding phase. Subjects were instructed to grasp and lift a device equipped with a force transducer and 3D position sensor in the precision grip between thumb and index finger and hold it stable adjacent to a marker 10 centimetres high. Grip forces and 3D position and orientation of the object were recorded. Mean isometric grip forces and grip force variability in the static phase (expressed as coefficient of variation = standard deviation/mean x 100 [GFV-C]) were calculated during a 15 second period. 5 trials of 20 seconds duration were performed with each hand. The mean changes from Baseline to Day 28 in the mean isometric grip forces of each hand are presented as raw data. The statistical analyses present GLS mean ratios in the original units.

The PD population consisted of all subjects from the safety population who have not reported major protocol violations impacting Q-motor evaluation and who have a Q-motor evaluation assessed both at Baseline (Day -1) and at one post baseline visit.

Digitomotography was used to assess the duration and the variability of tap IOI in an index finger speeded tapping task. The patient placed their hand on a hand rest with their index finger positioned on a force transducer, and recordings were started after practice runs. The patient was then instructed to finger tap as fast as possible between 2 auditory cues. The beginning of a tap was defined as a rise of the force by 0.05 N above maximal baseline level. The tap ended when it dropped to 0.05 N before the maximal baseline level was reached again. 5 trials of 10 seconds duration were performed with each hand. The mean changes from Baseline to Day 28 in the duration and variability of IOI for the left and right hands are presented as raw data. The statistical analyses present GLS mean ratios in the original units.

The PD population consisted of all subjects from the safety population who have not reported major protocol violations impacting Q-motor evaluation and who have a Q-motor evaluation assessed both at Baseline (Day -1) and at one post baseline visit.

Digitomotography was used to assess the duration and the variability of TD in an index finger speeded tapping task. The patient placed their hand on a hand rest with their index finger positioned on a force transducer, and recordings were started after practice runs. The patient was then instructed to finger tap as fast as possible between 2 auditory cues. The beginning of a tap was defined as a rise of the force by 0.05 N above maximal baseline level. The tap ended when it dropped to 0.05 N before the maximal baseline level was reached again. 5 trials of 10 seconds duration were performed with each hand. The mean changes from Baseline to Day 28 in the duration and variability of TD for the left and right hands are presented a raw data. The statistical analyses present GLS mean ratios in the original units.

The PD population consisted of all subjects from the safety population who have not reported major protocol violations impacting Q-motor evaluation and who have a Q-motor evaluation assessed both at Baseline (Day -1) and at one post baseline visit.

Digitomotography was used to assess the duration and the variability of tap IPI in an index finger speeded tapping task. The patient placed their hand on a hand rest with their index finger positioned on a force transducer, and recordings were started after practice runs. The patient was then instructed to finger tap as fast as possible between 2 auditory cues. The beginning of a tap was defined as a rise of the force by 0.05 N above maximal baseline level. The tap ended when it dropped to 0.05 N before the maximal baseline level was reached again. 5 trials of 10 seconds duration were performed with each hand. The mean changes from Baseline to Day 28 in the duration and variability of IPI for the left and right hands are presented as raw data. The statistical analyses present GLS mean ratios in the original units.

The PD population consisted of all subjects from the safety population who have not reported major protocol violations impacting Q-motor evaluation and who have a Q-motor evaluation assessed both at Baseline (Day -1) and at one post baseline visit.

Digitomotography was used to assess the duration and the variability of ITI in an index finger speeded tapping task. The patient placed their hand on a hand rest with their index finger positioned on a force transducer, and recordings were started after practice runs. The patient was then instructed to finger tap as fast as possible between 2 auditory cues. The beginning of a tap was defined as a rise of the force by 0.05 N above maximal baseline level. The tap ended when it dropped to 0.05 N before the maximal baseline level was reached again. 5 trials of 10 seconds duration were performed with each hand. The mean changes from Baseline to Day 28 in the duration and variability of ITI for the left and right hands are presented as raw data. The statistical analyses present GLS mean ratios in the original units.

The PD population consisted of all subjects from the safety population who have not reported major protocol violations impacting Q-motor evaluation and who have a Q-motor evaluation assessed both at Baseline (Day -1) and at one post baseline visit.

Digitomotography was used to assess the duration and the variability of TD in an index finger speeded tapping task. The patient placed their hand on a hand rest with their index finger positioned on a force transducer, and recordings were started after practice runs. The patient was then instructed to finger tap as fast as possible between 2 auditory cues. The beginning of a tap was defined as a rise of the force by 0.05 N above maximal baseline level. The tap ended when it dropped to 0.05 N before the maximal baseline level was reached again. 5 trials of 10 seconds duration were performed with each hand. The mean changes from Baseline to Day 28 in the variability of TF for the left and right hands are presented as raw data. The statistical analyses present GLS mean ratios in the original units.

The PD population consisted of all subjects from the safety population who have not reported major protocol violations impacting Q-motor evaluation and who have a Q-motor evaluation assessed both at Baseline (Day -1) and at one post baseline visit.

Digitomotography was used to assess the duration and the variability of TD in an index finger speeded tapping task. The patient placed their hand on a hand rest with their index finger positioned on a force transducer, and recordings were started after practice runs. The patient was then instructed to finger tap as fast as possible between 2 auditory cues. The beginning of a tap was defined as a rise of the force by 0.05 N above maximal baseline level. The tap ended when it dropped to 0.05 N before the maximal baseline level was reached again. 5 trials of 10 seconds duration were performed with each hand. The tapping frequency was calculated as the number of taps between the onsets of the first and the last tap divided by the time in between. The mean changes from Baseline to Day 28 in the tapping frequency for the left and right hands are presented as raw data. The statistical analyses present GLS mean ratios in the original units.

The PD population consisted of all subjects from the safety population who have not reported major protocol violations impacting Q-motor evaluation and who have a Q-motor evaluation assessed both at Baseline (Day -1) and at one post baseline visit.

Dysdiadochomotography was used to assess the regularity of hand taps performed when alternating between the palm and dorsal surface of the hand performing a repetitive pronation/supination movement. The force and duration of the hand taps were recorded, with their hand positioned on a force transducer, and recordings were started after practice runs. The patient was then instructed to hand tap as fast as possible between 2 auditory cues. The beginning of a tap was defined as a rise of the force by 0.05 N above maximal baseline level. The tap ended when it dropped to 0.05 N before the maximal baseline level was reached again. 5 trials of 10 seconds duration were performed with each hand. The mean changes from Baseline to Day 28 in the duration and variability of IOI for the left and right hands are presented as raw data. The statistical analyses present GLS mean ratios in the original units.

The PD population consisted of all subjects from the safety population who have not reported major protocol violations impacting Q-motor evaluation and who have a Q-motor evaluation assessed both at Baseline (Day -1) and at one post baseline visit.

Dysdiadochomotography was used to assess the regularity of hand taps performed when alternating between the palm and dorsal surface of the hand performing a repetitive pronation/supination movement. The force and duration of the hand taps were recorded, with their hand positioned on a force transducer, and recordings were started after practice runs. The patient was then instructed to hand tap as fast as possible between 2 auditory cues. The beginning of a tap was defined as a rise of the force by 0.05 N above maximal baseline level. The tap ended when it dropped to 0.05 N before the maximal baseline level was reached again. 5 trials of 10 seconds duration were performed with each hand. The mean changes from Baseline to Day 28 in the duration and variability of TD for the left and right hands are presented as raw data. The statistical analyses present GLS mean ratios in the original units.

The PD population consisted of all subjects from the safety population who have not reported major protocol violations impacting Q-motor evaluation and who have a Q-motor evaluation assessed both at Baseline (Day -1) and at one post baseline visit.

Dysdiadochomotography was used to assess the regularity of hand taps performed when alternating between the palm and dorsal surface of the hand performing a repetitive pronation/supination movement. The force and duration of the hand taps were recorded, with their hand positioned on a force transducer, and recordings were started after practice runs. The patient was then instructed to hand tap as fast as possible between 2 auditory cues. The beginning of a tap was defined as a rise of the force by 0.05 N above maximal baseline level. The tap ended when it dropped to 0.05 N before the maximal baseline level was reached again. 5 trials of 10 seconds duration were performed with each hand. The mean changes from Baseline to Day 28 in the duration and variability of IPI for the left and right hands are presented as raw data. The statistical analyses present GLS mean ratios in the original units.

The PD population consisted of all subjects from the safety population who have not reported major protocol violations impacting Q-motor evaluation and who have a Q-motor evaluation assessed both at Baseline (Day -1) and at one post baseline visit.

Dysdiadochomotography was used to assess the regularity of hand taps performed when alternating between the palm and dorsal surface of the hand performing a repetitive pronation/supination movement. The force and duration of the hand taps were recorded, with their hand positioned on a force transducer, and recordings were started after practice runs. The patient was then instructed to hand tap as fast as possible between 2 auditory cues. The beginning of a tap was defined as a rise of the force by 0.05 N above maximal baseline level. The tap ended when it dropped to 0.05 N before the maximal baseline level was reached again. 5 trials of 10 seconds duration were performed with each hand. The mean changes from Baseline to Day 28 in the duration and variability of ITI for the left and right hands are presented as raw data. The statistical analyses present GLS mean ratios in the original units.

The PD population consisted of all subjects from the safety population who have not reported major protocol violations impacting Q-motor evaluation and who have a Q-motor evaluation assessed both at Baseline (Day -1) and at one post baseline visit.

Dysdiadochomotography was used to assess the regularity of hand taps performed when alternating between the palm and dorsal surface of the hand performing a repetitive pronation/supination movement. The force and duration of the hand taps were recorded, with their hand positioned on a force transducer, and recordings were started after practice runs. The patient was then instructed to hand tap as fast as possible between 2 auditory cues. The beginning of a tap was defined as a rise of the force by 0.05 N above maximal baseline level. The tap ended when it dropped to 0.05 N before the maximal baseline level was reached again. 5 trials of 10 seconds duration were performed with each hand. The mean changes from Baseline to Day 28 in the variability of TF for the left and right hands are presented as raw data. The statistical analyses present GLS mean ratios in the original units.

The PD population consisted of all subjects from the safety population who have not reported major protocol violations impacting Q-motor evaluation and who have a Q-motor evaluation assessed both at Baseline (Day -1) and at one post baseline visit.

Dysdiadochomotography was used to assess the regularity of hand taps performed when alternating between the palm and dorsal surface of the hand performing a repetitive pronation/supination movement. The force and duration of the hand taps were recorded, with their hand positioned on a force transducer, and recordings were started after practice runs. The patient was then instructed to hand tap as fast as possible between 2 auditory cues. The beginning of a tap was defined as a rise of the force by 0.05 N above maximal baseline level. The tap ended when it dropped to 0.05 N before the maximal baseline level was reached again. 5 trials of 10 seconds duration were performed with each hand. The tapping frequency was calculated as the number of taps between the onsets of the first and the last tap divided by the time in between. The mean changes from Baseline to Day 28 in the tapping frequency for the left and right hands are presented as raw data. GLS mean ratios are in original units.

The PD population consisted of all subjects from the safety population who have not reported major protocol violations impacting Q-motor evaluation and who have a Q-motor evaluation assessed both at Baseline (Day -1) and at one post baseline visit.

Pedomotography was used to assess the tap duration and variability in a foot speeded tapping task. The patient placed their foot on the foot device such that the ball of the foot was positioned above a force transducer, and recordings were started after practice runs. The patient was then instructed to foot tap as fast as possible between 2 auditory cues. The beginning of a tap was defined as a rise of the force by 0.05 N above maximal baseline level. The tap ended when it dropped to 0.05 N before the maximal baseline level was reached again. 5 trials of 10 seconds duration were performed with each foot. The mean changes from Baseline to Day 28 in the duration and variability of IOI for the left and right feet are presented as raw data. The statistical analyses present GLS mean ratios in the original units.

The PD population consisted of all subjects from the safety population who have not reported major protocol violations impacting Q-motor evaluation and who have a Q-motor evaluation assessed both at Baseline (Day -1) and at one post baseline visit.

Pedomotography was used to assess the tap duration and variability in a foot speeded tapping task. The patient placed their foot on the foot device such that the ball of the foot was positioned above a force transducer, and recordings were started after practice runs. The patient was then instructed to foot tap as fast as possible between 2 auditory cues. The patient was then instructed to foot tap as fast as possible between 2 auditory cues. The beginning of a tap was defined as a rise of the force by 0.05 N above maximal baseline level. The tap ended when it dropped to 0.05 N before the maximal baseline level was reached again. 5 trials of 10 seconds duration were performed with each foot. The mean changes from Baseline to Day 28 in the duration and variability of TD for the left and right feet are presented as raw data. The statistical analyses present GLS mean ratios in the original units.

The PD population consisted of all subjects from the safety population who have not reported major protocol violations impacting Q-motor evaluation and who have a Q-motor evaluation assessed both at Baseline (Day -1) and at one post baseline visit.

Pedomotography was used to assess the tap duration and variability in a foot speeded tapping task. The patient placed their foot on the foot device such that the ball of the foot was positioned above a force transducer, and recordings were started after practice runs. The patient was then instructed to foot tap as fast as possible between 2 auditory cues. The beginning of a tap was defined as a rise of the force by 0.05 N above maximal baseline level. The tap ended when it dropped to 0.05 N before the maximal baseline level was reached again. 5 trials of 10 seconds duration were performed with each foot. The mean changes from Baseline to Day 28 in the duration and variability of IPI for the left and right feet are presented as raw data. The statistical analyses present GLS mean ratios in the original units.

The PD population consisted of all subjects from the safety population who have not reported major protocol violations impacting Q-motor evaluation and who have a Q-motor evaluation assessed both at Baseline (Day -1) and at one post baseline visit.

Pedomotography was used to assess the tap duration and variability in a foot speeded tapping task. The patient placed their foot on the foot device such that the ball of the foot was positioned above a force transducer, and recordings were started after practice runs. The patient was then instructed to foot tap as fast as possible between 2 auditory cues. The beginning of a tap was defined as a rise of the force by 0.05 N above maximal baseline level. The tap ended when it dropped to 0.05 N before the maximal baseline level was reached again. 5 trials of 10 seconds duration were performed with each foot. The mean changes from Baseline to Day 28 in the duration and variability of ITI for the left and right feet are presented as raw data. The statistical analyses present GLS mean ratios in the original units.

The PD population consisted of all subjects from the safety population who have not reported major protocol violations impacting Q-motor evaluation and who have a Q-motor evaluation assessed both at Baseline (Day -1) and at one post baseline visit.

Pedomotography was used to assess the tap duration and variability in a foot speeded tapping task. The patient placed their foot on the foot device such that the ball of the foot was positioned above a force transducer, and recordings were started after practice runs. The patient was then instructed to foot tap as fast as possible between 2 auditory cues. The beginning of a tap was defined as a rise of the force by 0.05 N above maximal baseline level. The tap ended when it dropped to 0.05 N before the maximal baseline level was reached again. 5 trials of 10 seconds duration were performed with each foot. The mean changes from Baseline to Day 28 in the variability of TF for the left and right feet are presented as raw data. The statistical analyses present GLS mean ratios in the original units.

The PD population consisted of all subjects from the safety population who have not reported major protocol violations impacting Q-motor evaluation and who have a Q-motor evaluation assessed both at Baseline (Day -1) and at one post baseline visit.

Pedomotography was used to assess the tap duration and variability in a foot speeded tapping task. The patient placed their foot on the foot device such that the ball of the foot was positioned above a force transducer, and recordings were started after practice runs. The patient was then instructed to foot tap as fast as possible between 2 auditory cues. The beginning of a tap was defined as a rise of the force by 0.05 N above maximal baseline level. The tap ended when it dropped to 0.05 N before the maximal baseline level was reached again. 5 trials of 10 seconds duration were performed with each foot. The tapping frequency was calculated as the number of taps between the onsets of the first and the last tap divided by the time in between. The mean changes from Baseline to Day 28 in the tapping frequency for the left and right hands are presented as raw data. The statistical analyses present GLS mean ratios in the original units.

The PD population consisted of all subjects from the safety population who have not reported major protocol violations impacting Q-motor evaluation and who have a Q-motor evaluation assessed both at Baseline (Day -1) and at one post baseline visit.

Patients were randomised to receive oral placebo b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of placebo was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 mg b.i.d.

For cohort 1, 40 mg placebo b.i.d. was administered during the first 14 days. If this dose was well tolerated then it was increased to 60 mg b.i.d. for 13 days and one morning dose of 60 mg on Day 28.

For cohort 2, 60 mg placebo b.i.d. was administered during the first 14 days. If 60 mg b.i.d was well tolerated then it was increased to 80 mg b.i.d. for 13 days and one morning dose of 80 mg on Day 28.

For cohort 3 it was planned to administer 80 mg placebo b.i.d for 27 days with one morning dose of 80 mg on Day 28. The study was terminated early before completion of cohort 2.