Trial Outcomes & Findings for Study Exploring Safety, Pharmacokinetic and Pharmacodynamic of BN82451 in Male Huntington's Disease Patients (NCT NCT02231580)

NCT ID: NCT02231580

Last Updated: 2019-01-15

Results Overview

The safety and tolerability of BN82451B versus placebo was determined after oral administration b.i.d. for 28 days in patients with HD. Numbers of patients experiencing TEAEs, including information on seriousness, intensity, drug relationship and those leading to withdrawal are presented for all doses of BN82451B and placebo.

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 17 participants
• Primary outcome timeframe: From Day 1 to end of study (a period of up to 7 weeks).
• Results posted on: 2019-01-15

Participant Flow

The study was a double blind, placebo controlled, randomised, sequential dose ranging repeated dose trial where patients were recruited to a single study centre in Germany. It was planned to enrol 30 patients (10 in each of 3 cohorts). Patients were enrolled to the study from 1 September 2014 until early termination of the study on 31 March 2016.

Male patients 20-70 years with a documented diagnosis of Huntington's Disease (HD) with at least 36 cytosine adenine guanine repeats in the Huntington gene were screened. Eligibile patients needed to meet defined criteria during quantitative motor function assessments. 25 patients were screened, 17 were enrolled and randomised to treatment.

Participant milestones

Measure	BN82451B Patients were randomised to receive oral study medication, BN82451B, b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of BN82451B was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 milligrams (mg) b.i.d. For cohort 1, 40 mg BN82451B 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 BN82451B 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 BN82451B 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.	Placebo 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.
Overall Study STARTED	14	3
Overall Study Cohort 1	8	2
Overall Study Cohort 2	6	1
Overall Study COMPLETED	9	3
Overall Study NOT COMPLETED	5	0

Reasons for withdrawal

Measure	BN82451B Patients were randomised to receive oral study medication, BN82451B, b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of BN82451B was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 milligrams (mg) b.i.d. For cohort 1, 40 mg BN82451B 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 BN82451B 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 BN82451B 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.	Placebo 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.
Overall Study Adverse Event	5	0

Baseline Characteristics

Study Exploring Safety, Pharmacokinetic and Pharmacodynamic of BN82451 in Male Huntington's Disease Patients

Baseline characteristics by cohort

Measure	BN82451B n=14 Participants Patients were randomised to receive oral study medication, BN82451B, b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of BN82451B was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 milligrams (mg) b.i.d. For cohort 1, 40 mg BN82451B 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 BN82451B 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 BN82451B 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.	Placebo n=3 Participants 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.	Total Title n=17 Participants
Age, Continuous	46.6 years STANDARD_DEVIATION 14.4 • n=5 Participants	50.0 years STANDARD_DEVIATION 8.7 • n=7 Participants	46.6 years STANDARD_DEVIATION 14.4 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	14 Participants n=5 Participants	3 Participants n=7 Participants	17 Participants n=5 Participants

PRIMARY outcome

Timeframe: From Day 1 to end of study (a period of up to 7 weeks).

Population: The Safety Population consisted of all randomised patients who received at least one dose of study medication.

The safety and tolerability of BN82451B versus placebo was determined after oral administration b.i.d. for 28 days in patients with HD. Numbers of patients experiencing TEAEs, including information on seriousness, intensity, drug relationship and those leading to withdrawal are presented for all doses of BN82451B and placebo.

Outcome measures

Measure	BN82451B n=14 Participants Patients were randomised to receive oral study medication, BN82451B, b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of BN82451B was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 milligrams (mg) b.i.d. For cohort 1, 40 mg BN82451B 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 BN82451B 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 BN82451B 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.	Placebo n=3 Participants 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.
Numbers of Patients Experiencing Treatment Emergent Adverse Events (TEAEs). Patients with at least 1 moderate TEAE	8 Participants	1 Participants
Numbers of Patients Experiencing Treatment Emergent Adverse Events (TEAEs). Patients with at least 1 mild TEAE	11 Participants	1 Participants
Numbers of Patients Experiencing Treatment Emergent Adverse Events (TEAEs). Patients with TEAEs related to study medication	9 Participants	0 Participants
Numbers of Patients Experiencing Treatment Emergent Adverse Events (TEAEs). Patients with TEAEs leading to withdrawal	5 Participants	0 Participants
Numbers of Patients Experiencing Treatment Emergent Adverse Events (TEAEs). Patients with any TEAEs leading to death	0 Participants	0 Participants
Numbers of Patients Experiencing Treatment Emergent Adverse Events (TEAEs). Patients with any TEAEs	11 Participants	2 Participants
Numbers of Patients Experiencing Treatment Emergent Adverse Events (TEAEs). Patients with any serious TEAE	0 Participants	0 Participants
Numbers of Patients Experiencing Treatment Emergent Adverse Events (TEAEs). Patients with at least 1 severe TEAE	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 0-12 hours on Days 1, 14 and 28

Population: 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.

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.

Outcome measures

Measure	BN82451B n=8 Participants Patients were randomised to receive oral study medication, BN82451B, b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of BN82451B was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 milligrams (mg) b.i.d. For cohort 1, 40 mg BN82451B 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 BN82451B 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 BN82451B 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.	Placebo n=6 Participants 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.
Area Under the Plasma Concentration Time Curve (AUC) Day 1 BN82451B AUC(0-12)	512.93 hours*nanograms per millilitre (h*ng/mL) Standard Deviation 112.53	783.78 hours*nanograms per millilitre (h*ng/mL) Standard Deviation 144.45
Area Under the Plasma Concentration Time Curve (AUC) Day 1 BN2468 AUC(0-12)	90.66 hours*nanograms per millilitre (h*ng/mL) Standard Deviation 40.68	—
Area Under the Plasma Concentration Time Curve (AUC) Day 1 BN7167 AUC(0-12)	16.82 hours*nanograms per millilitre (h*ng/mL) Standard Deviation 9.01	31.67 hours*nanograms per millilitre (h*ng/mL) Standard Deviation 24.63
Area Under the Plasma Concentration Time Curve (AUC) Day 14 BN82451B AUCτ,ss	1521.11 hours*nanograms per millilitre (h*ng/mL) Standard Deviation 593.22	2594.05 hours*nanograms per millilitre (h*ng/mL) Standard Deviation 1077.08
Area Under the Plasma Concentration Time Curve (AUC) Day 14 BN2468 AUC(τ,ss)	735.51 hours*nanograms per millilitre (h*ng/mL) Standard Deviation 203.91	1531.00 hours*nanograms per millilitre (h*ng/mL) Standard Deviation 412.43
Area Under the Plasma Concentration Time Curve (AUC) Day 14 BN7167 AUC(τ,ss)	33.39 hours*nanograms per millilitre (h*ng/mL) Standard Deviation 20.08	46.73 hours*nanograms per millilitre (h*ng/mL) Standard Deviation 36.76
Area Under the Plasma Concentration Time Curve (AUC) Day 28 BN82451B AUC(τ,ss)	2357.95 hours*nanograms per millilitre (h*ng/mL) Standard Deviation 977.74	3313.45 hours*nanograms per millilitre (h*ng/mL) Standard Deviation 1517.6
Area Under the Plasma Concentration Time Curve (AUC) Day 28 BN2468 AUC(τ,ss)	1509.67 hours*nanograms per millilitre (h*ng/mL) Standard Deviation 105.94	1936.35 hours*nanograms per millilitre (h*ng/mL) Standard Deviation 569.97
Area Under the Plasma Concentration Time Curve (AUC) Day 28 BN7167 AUC(τ,ss)	34.64 hours*nanograms per millilitre (h*ng/mL) Standard Deviation 16.05	63.81 hours*nanograms per millilitre (h*ng/mL) Standard Deviation 57.70

SECONDARY outcome

Timeframe: Days 1, 14 and 28

Population: 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.

Outcome measures

Measure	BN82451B n=8 Participants Patients were randomised to receive oral study medication, BN82451B, b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of BN82451B was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 milligrams (mg) b.i.d. For cohort 1, 40 mg BN82451B 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 BN82451B 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 BN82451B 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.	Placebo n=6 Participants 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.
Peak Plasma Concentration (Cmax) Day 1 BN82451B Cmax	71.61 ng/mL Standard Deviation 14.81	101.45 ng/mL Standard Deviation 16.25
Peak Plasma Concentration (Cmax) Day 1 BN2468 Cmax	9.03 ng/mL Standard Deviation 4.14	18.87 ng/mL Standard Deviation 13.00
Peak Plasma Concentration (Cmax) Day 1 BN7167 Cmax	3.62 ng/mL Standard Deviation 1.62	5.61 ng/mL Standard Deviation 3.62
Peak Plasma Concentration (Cmax) Day 14 BN82451B Cmax,ss	162.88 ng/mL Standard Deviation 56.31	271.64 ng/mL Standard Deviation 99.90
Peak Plasma Concentration (Cmax) Day 14 BN2468 Cmax,ss	75.34 ng/mL Standard Deviation 15.16	125.34 ng/mL Standard Deviation 38.13
Peak Plasma Concentration (Cmax) Day 14 BN7167 Cmax,ss	4.90 ng/mL Standard Deviation 2.35	6.28 ng/mL Standard Deviation 3.55
Peak Plasma Concentration (Cmax) Day 28 BN82451B Cmax,ss	251.77 ng/mL Standard Deviation 105.64	340.41 ng/mL Standard Deviation 156.61
Peak Plasma Concentration (Cmax) Day 28 BN2468 Cmax,ss	135.19 ng/mL Standard Deviation 5.06	171.64 ng/mL Standard Deviation 47.64
Peak Plasma Concentration (Cmax) Day 28 BN 7167 Cmax,ss	5.51 ng/mL Standard Deviation 1.82	9.54 ng/mL Standard Deviation 6.92

SECONDARY outcome

Timeframe: Days 1, 14 and 28

Population: 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.

Outcome measures

Measure	BN82451B n=8 Participants Patients were randomised to receive oral study medication, BN82451B, b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of BN82451B was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 milligrams (mg) b.i.d. For cohort 1, 40 mg BN82451B 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 BN82451B 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 BN82451B 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.	Placebo n=6 Participants 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.
Time to Peak Plasma Concentration (Tmax) Day 1 BN82451B Tmax	3.0 hours Interval 2.0 to 3.0	2.51 hours Interval 2.0 to 3.0
Time to Peak Plasma Concentration (Tmax) Day 1 BN2468 Tmax	9.98 hours Interval 1.0 to 12.02	11.92 hours Interval 11.92 to 11.92
Time to Peak Plasma Concentration (Tmax) Day 1 BN7167 Tmax	1.00 hours Interval 1.0 to 2.0	1.00 hours Interval 1.0 to 2.0
Time to Peak Plasma Concentration (Tmax) Day 14 BN82451B Tmax,ss	3.0 hours Interval 2.0 to 4.0	3.0 hours Interval 2.0 to 3.5
Time to Peak Plasma Concentration (Tmax) Day 14 BN2468 Tmax,ss	4 hours Interval 1.05 to 8.0	2.51 hours Interval 1.0 to 8.0
Time to Peak Plasma Concentration (Tmax) Day 14 BN7167 Tmax,ss	1 hours Interval 1.0 to 2.13	1 hours Interval 1.0 to 2.0
Time to Peak Plasma Concentration (Tmax) Day 28 BN82451B Tmax,ss	3 hours Interval 2.02 to 4.0	2.56 hours Interval 2.0 to 3.02
Time to Peak Plasma Concentration (Tmax) Day 28 BN2468 Tmax,ss	4.06 hours Interval 2.0 to 6.0	2.06 hours Interval 1.0 to 12.0
Time to Peak Plasma Concentration (Tmax) Day 28 BN7167 Tmax,ss	1 hours Interval 0.55 to 2.0	1.52 hours Interval 1.0 to 2.0

SECONDARY outcome

Timeframe: Baseline (Day-1) to Day 28

Population: 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. 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.

Outcome measures

Measure	BN82451B n=11 Participants Patients were randomised to receive oral study medication, BN82451B, b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of BN82451B was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 milligrams (mg) b.i.d. For cohort 1, 40 mg BN82451B 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 BN82451B 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 BN82451B 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.	Placebo n=3 Participants 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.
Change From Baseline to Day 28 in the Position-index as Determined by Choreomotography Left hand position-index	0.021 metres per second (m/s) Standard Deviation 0.024	0.009 metres per second (m/s) Standard Deviation 0.007
Change From Baseline to Day 28 in the Position-index as Determined by Choreomotography Right hand position-index	0.018 metres per second (m/s) Standard Deviation 0.014	0.009 metres per second (m/s) Standard Deviation 0.006

SECONDARY outcome

Timeframe: Baseline (Day -1) to Day 28

Population: 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.

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.

Outcome measures

Measure	BN82451B n=11 Participants Patients were randomised to receive oral study medication, BN82451B, b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of BN82451B was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 milligrams (mg) b.i.d. For cohort 1, 40 mg BN82451B 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 BN82451B 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 BN82451B 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.	Placebo n=3 Participants 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.
Change From Baseline to Day 28 in the Orientation-index as Determined by Choreomotography Left hand orientation-index	0.131 radians per second (radians/s) Standard Deviation 0.125	0.082 radians per second (radians/s) Standard Deviation 0.100
Change From Baseline to Day 28 in the Orientation-index as Determined by Choreomotography Right hand orientation-index	0.098 radians per second (radians/s) Standard Deviation 0.087	0.054 radians per second (radians/s) Standard Deviation 0.045

SECONDARY outcome

Timeframe: Baseline (Day -1) to Day 28

Population: 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.

Outcome measures

Measure	BN82451B n=11 Participants Patients were randomised to receive oral study medication, BN82451B, b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of BN82451B was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 milligrams (mg) b.i.d. For cohort 1, 40 mg BN82451B 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 BN82451B 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 BN82451B 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.	Placebo n=3 Participants 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.
Change From Baseline to Day 28 in the Mean Grip Force Variability as Determined by Manumotography Left hand grip force variability	5.74 percentage of variation Standard Deviation 4.38	2.61 percentage of variation Standard Deviation 4.57
Change From Baseline to Day 28 in the Mean Grip Force Variability as Determined by Manumotography Right hand grip force variability	5.82 percentage of variation Standard Deviation 7.94	2.35 percentage of variation Standard Deviation 1.17

SECONDARY outcome

Timeframe: Baseline (Day -1) to Day 28

Population: 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.

Outcome measures

Measure	BN82451B n=11 Participants Patients were randomised to receive oral study medication, BN82451B, b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of BN82451B was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 milligrams (mg) b.i.d. For cohort 1, 40 mg BN82451B 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 BN82451B 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 BN82451B 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.	Placebo n=3 Participants 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.
Change From Baseline to Day 28 in the Mean Isometric Grip Forces as Determined by Manumotography Left hand isometric grip forces	-0.75 Newton Standard Deviation 2.86	1.55 Newton Standard Deviation 1.99
Change From Baseline to Day 28 in the Mean Isometric Grip Forces as Determined by Manumotography Right hand isometric grip forces	-2.06 Newton Standard Deviation 6.00	0.91 Newton Standard Deviation 1.67

SECONDARY outcome

Timeframe: Baseline (Day-1) to Day 28

Population: 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.

Outcome measures

Measure	BN82451B n=11 Participants Patients were randomised to receive oral study medication, BN82451B, b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of BN82451B was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 milligrams (mg) b.i.d. For cohort 1, 40 mg BN82451B 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 BN82451B 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 BN82451B 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.	Placebo n=3 Participants 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.
Change From Baseline to Day 28 in the Mean Duration and Variability of Inter Onset Intervals (IOI) as Assessed by Digitomotography Left finger IOI variability	0.039 seconds Standard Deviation 0.048	-0.009 seconds Standard Deviation 0.002
Change From Baseline to Day 28 in the Mean Duration and Variability of Inter Onset Intervals (IOI) as Assessed by Digitomotography Right finger IOI variability	0.057 seconds Standard Deviation 0.062	0.038 seconds Standard Deviation 0.049
Change From Baseline to Day 28 in the Mean Duration and Variability of Inter Onset Intervals (IOI) as Assessed by Digitomotography Left finger IOI duration	0.088 seconds Standard Deviation 0.075	-0.015 seconds Standard Deviation 0.041
Change From Baseline to Day 28 in the Mean Duration and Variability of Inter Onset Intervals (IOI) as Assessed by Digitomotography Right finger IOI duration	0.069 seconds Standard Deviation 0.059	0.032 seconds Standard Deviation 0.031

SECONDARY outcome

Timeframe: Baseline (Day -1) to Day 28

Population: 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.

Outcome measures

Measure	BN82451B n=11 Participants Patients were randomised to receive oral study medication, BN82451B, b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of BN82451B was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 milligrams (mg) b.i.d. For cohort 1, 40 mg BN82451B 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 BN82451B 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 BN82451B 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.	Placebo n=3 Participants 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.
Change From Baseline to Day 28 in the Mean Duration and Variability of Tap Durations (TD) as Assessed by Digitomotography Left finger Variability of TD	0.007 seconds Standard Deviation 0.024	-0.007 seconds Standard Deviation 0.015
Change From Baseline to Day 28 in the Mean Duration and Variability of Tap Durations (TD) as Assessed by Digitomotography Right finger Variability of TD	0.017 seconds Standard Deviation 0.016	0.012 seconds Standard Deviation 0.017
Change From Baseline to Day 28 in the Mean Duration and Variability of Tap Durations (TD) as Assessed by Digitomotography Left finger Duration of TD	0.010 seconds Standard Deviation 0.021	-0.011 seconds Standard Deviation 0.039
Change From Baseline to Day 28 in the Mean Duration and Variability of Tap Durations (TD) as Assessed by Digitomotography Right finger Duration of TD	0.012 seconds Standard Deviation 0.021	0.001 seconds Standard Deviation 0.025

SECONDARY outcome

Timeframe: Baseline (Day -1) to Day 28

Population: 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.

Outcome measures

Measure	BN82451B n=11 Participants Patients were randomised to receive oral study medication, BN82451B, b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of BN82451B was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 milligrams (mg) b.i.d. For cohort 1, 40 mg BN82451B 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 BN82451B 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 BN82451B 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.	Placebo n=3 Participants 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.
Change From Baseline to Day 28 in the Mean Duration and Variability of Inter Peak Intervals (IPI) as Assessed by Digitomotography Left finger IPI variability	0.040 seconds Standard Deviation 0.049	-0.009 seconds Standard Deviation 0.007
Change From Baseline to Day 28 in the Mean Duration and Variability of Inter Peak Intervals (IPI) as Assessed by Digitomotography Right finger IPI variability	0.057 seconds Standard Deviation 0.067	0.038 seconds Standard Deviation 0.044
Change From Baseline to Day 28 in the Mean Duration and Variability of Inter Peak Intervals (IPI) as Assessed by Digitomotography Left finger IPI duration	0.088 seconds Standard Deviation 0.076	-0.017 seconds Standard Deviation 0.042
Change From Baseline to Day 28 in the Mean Duration and Variability of Inter Peak Intervals (IPI) as Assessed by Digitomotography Right finger IPI duration	0.069 seconds Standard Deviation 0.059	0.031 seconds Standard Deviation 0.030

SECONDARY outcome

Timeframe: Baseline (Day-1) to Day 28

Population: 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.

Outcome measures

Measure	BN82451B n=11 Participants Patients were randomised to receive oral study medication, BN82451B, b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of BN82451B was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 milligrams (mg) b.i.d. For cohort 1, 40 mg BN82451B 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 BN82451B 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 BN82451B 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.	Placebo n=3 Participants 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.
Change From Baseline to Day 28 in the Mean Duration and Variability of Inter Tap Intervals (ITI) as Assessed by Digitomotography Left finger ITI Variability	0.041 seconds Standard Deviation 0.05	-0.007 seconds Standard Deviation 0.01
Change From Baseline to Day 28 in the Mean Duration and Variability of Inter Tap Intervals (ITI) as Assessed by Digitomotography Right finger ITI Variability	0.053 seconds Standard Deviation 0.068	0.03 seconds Standard Deviation 0.034
Change From Baseline to Day 28 in the Mean Duration and Variability of Inter Tap Intervals (ITI) as Assessed by Digitomotography Left finger ITI Duration	0.078 seconds Standard Deviation 0.076	-0.005 seconds Standard Deviation 0.006
Change From Baseline to Day 28 in the Mean Duration and Variability of Inter Tap Intervals (ITI) as Assessed by Digitomotography Right finger ITI Duration	0.056 seconds Standard Deviation 0.048	0.03 seconds Standard Deviation 0.046

SECONDARY outcome

Timeframe: Baseline (Day-1) to Day 28

Population: 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.

Outcome measures

Measure	BN82451B n=11 Participants Patients were randomised to receive oral study medication, BN82451B, b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of BN82451B was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 milligrams (mg) b.i.d. For cohort 1, 40 mg BN82451B 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 BN82451B 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 BN82451B 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.	Placebo n=3 Participants 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.
Change From Baseline to Day 28 in the Mean Variability of Peak Tapping Forces (TF) as Assessed by Digitomotography Left finger TF	0.65 percentage of variation Standard Deviation 6.97	-6.43 percentage of variation Standard Deviation 6.26
Change From Baseline to Day 28 in the Mean Variability of Peak Tapping Forces (TF) as Assessed by Digitomotography Right finger TF	3.75 percentage of variation Standard Deviation 12.86	-0.11 percentage of variation Standard Deviation 8.26

SECONDARY outcome

Timeframe: Baseline (Day-1) to Day 28

Population: 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.

Outcome measures

Measure	BN82451B n=11 Participants Patients were randomised to receive oral study medication, BN82451B, b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of BN82451B was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 milligrams (mg) b.i.d. For cohort 1, 40 mg BN82451B 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 BN82451B 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 BN82451B 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.	Placebo n=3 Participants 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.
Change From Baseline to Day 28 in the Mean Tapping Frequency (Freq) as Assessed by Digitomotography Left finger freq	-0.492 Hertz Standard Deviation 0.382	-0.001 Hertz Standard Deviation 0.315
Change From Baseline to Day 28 in the Mean Tapping Frequency (Freq) as Assessed by Digitomotography Right finger freq	-0.466 Hertz Standard Deviation 0.389	-0.365 Hertz Standard Deviation 0.231

SECONDARY outcome

Timeframe: Baseline (Day -1) to Day 28

Population: 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.

Outcome measures

Measure	BN82451B n=11 Participants Patients were randomised to receive oral study medication, BN82451B, b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of BN82451B was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 milligrams (mg) b.i.d. For cohort 1, 40 mg BN82451B 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 BN82451B 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 BN82451B 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.	Placebo n=3 Participants 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.
Change From Baseline to Day 28 in the Mean Duration and Variability of IOI as Assessed by Dysdiadochomotography Left hand IOI variability	0.032 seconds Standard Deviation 0.135	0.036 seconds Standard Deviation 0.023
Change From Baseline to Day 28 in the Mean Duration and Variability of IOI as Assessed by Dysdiadochomotography Right hand IOI variability	0.031 seconds Standard Deviation 0.094	0.163 seconds Standard Deviation 0.276
Change From Baseline to Day 28 in the Mean Duration and Variability of IOI as Assessed by Dysdiadochomotography Left hand IOI duration	0.054 seconds Standard Deviation 0.114	0.028 seconds Standard Deviation 0.043
Change From Baseline to Day 28 in the Mean Duration and Variability of IOI as Assessed by Dysdiadochomotography Right hand IOI duration	0.074 seconds Standard Deviation 0.101	0.074 seconds Standard Deviation 0.132

SECONDARY outcome

Timeframe: Baseline (Day -1) to Day 28

Population: 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.

Outcome measures

Measure	BN82451B n=11 Participants Patients were randomised to receive oral study medication, BN82451B, b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of BN82451B was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 milligrams (mg) b.i.d. For cohort 1, 40 mg BN82451B 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 BN82451B 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 BN82451B 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.	Placebo n=3 Participants 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.
Change From Baseline to Day 28 in the Mean Duration and Variability of TD as Assessed by Dysdiadochomotography Left hand variability of TD	0.001 seconds Standard Deviation 0.138	0.023 seconds Standard Deviation 0.026
Change From Baseline to Day 28 in the Mean Duration and Variability of TD as Assessed by Dysdiadochomotography Right hand variability of TD	-0.012 seconds Standard Deviation 0.073	0.078 seconds Standard Deviation 0.128
Change From Baseline to Day 28 in the Mean Duration and Variability of TD as Assessed by Dysdiadochomotography Left hand duration of TD	-0.006 seconds Standard Deviation 0.088	0.017 seconds Standard Deviation 0.027
Change From Baseline to Day 28 in the Mean Duration and Variability of TD as Assessed by Dysdiadochomotography Right hand duration of TD	-0.019 seconds Standard Deviation 0.089	0.022 seconds Standard Deviation 0.069

SECONDARY outcome

Timeframe: Baseline (Day-1) to Day 28

Population: 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.

Outcome measures

Measure	BN82451B n=11 Participants Patients were randomised to receive oral study medication, BN82451B, b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of BN82451B was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 milligrams (mg) b.i.d. For cohort 1, 40 mg BN82451B 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 BN82451B 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 BN82451B 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.	Placebo n=3 Participants 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.
Change From Baseline to Day 28 in the Mean Duration and Variability of IPI as Assessed by Dysdiadochomotography Left hand IPI variability	0.045 seconds Standard Deviation 0.124	0.049 seconds Standard Deviation 0.046
Change From Baseline to Day 28 in the Mean Duration and Variability of IPI as Assessed by Dysdiadochomotography Right hand IPI variability	0.027 seconds Standard Deviation 0.07	0.131 seconds Standard Deviation 0.219
Change From Baseline to Day 28 in the Mean Duration and Variability of IPI as Assessed by Dysdiadochomotography Left hand IPI duration	0.057 seconds Standard Deviation 0.109	0.029 seconds Standard Deviation 0.04
Change From Baseline to Day 28 in the Mean Duration and Variability of IPI as Assessed by Dysdiadochomotography Right hand IPI duration	0.079 seconds Standard Deviation 0.105	0.066 seconds Standard Deviation 0.118

SECONDARY outcome

Timeframe: Baseline (Day -1) to Day 28

Population: 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.

Outcome measures

Measure	BN82451B n=11 Participants Patients were randomised to receive oral study medication, BN82451B, b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of BN82451B was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 milligrams (mg) b.i.d. For cohort 1, 40 mg BN82451B 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 BN82451B 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 BN82451B 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.	Placebo n=3 Participants 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.
Change From Baseline to Day 28 in the Mean Duration and Variability of ITI as Assessed by Dysdiadochomotography Left hand ITI variability	0.036 seconds Standard Deviation 0.061	0.015 seconds Standard Deviation 0.017
Change From Baseline to Day 28 in the Mean Duration and Variability of ITI as Assessed by Dysdiadochomotography Right hand ITI variability	0.053 seconds Standard Deviation 0.082	0.017 seconds Standard Deviation 0.018
Change From Baseline to Day 28 in the Mean Duration and Variability of ITI as Assessed by Dysdiadochomotography Left hand ITI duration	0.064 seconds Standard Deviation 0.070	0.006 seconds Standard Deviation 0.029
Change From Baseline to Day 28 in the Mean Duration and Variability of ITI as Assessed by Dysdiadochomotography Right hand ITI duration	0.094 seconds Standard Deviation 0.097	0.022 seconds Standard Deviation 0.014

SECONDARY outcome

Timeframe: Baseline (Day-1) to Day 28

Population: 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.

Outcome measures

Measure	BN82451B n=11 Participants Patients were randomised to receive oral study medication, BN82451B, b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of BN82451B was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 milligrams (mg) b.i.d. For cohort 1, 40 mg BN82451B 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 BN82451B 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 BN82451B 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.	Placebo n=3 Participants 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.
Change From Baseline to Day 28 in the Mean Variability of Peak TF as Assessed by Dysdiadochomotography Left hand TF variability	3.50 percentage of variation Standard Deviation 7.44	9.98 percentage of variation Standard Deviation 2.22
Change From Baseline to Day 28 in the Mean Variability of Peak TF as Assessed by Dysdiadochomotography Right hand TF variability	2.5 percentage of variation Standard Deviation 10.87	3.61 percentage of variation Standard Deviation 2.42

SECONDARY outcome

Timeframe: Baseline (Day -1) to Day 28

Population: 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.

Outcome measures

Measure	BN82451B n=11 Participants Patients were randomised to receive oral study medication, BN82451B, b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of BN82451B was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 milligrams (mg) b.i.d. For cohort 1, 40 mg BN82451B 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 BN82451B 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 BN82451B 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.	Placebo n=3 Participants 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.
Change From Baseline to Day 28 in the Mean Tapping Frequency as Assessed by Dysdiadochomotography Left hand freq	-0.185 Hertz Standard Deviation 0.402	-0.073 Hertz Standard Deviation 0.088
Change From Baseline to Day 28 in the Mean Tapping Frequency as Assessed by Dysdiadochomotography Right hand freq	-0.236 Hertz Standard Deviation 0.349	-0.121 Hertz Standard Deviation 0.189

SECONDARY outcome

Timeframe: Baseline (Day-1) to Day 28

Population: 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.

Outcome measures

Measure	BN82451B n=10 Participants Patients were randomised to receive oral study medication, BN82451B, b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of BN82451B was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 milligrams (mg) b.i.d. For cohort 1, 40 mg BN82451B 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 BN82451B 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 BN82451B 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.	Placebo n=3 Participants 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.
Change From Baseline to Day 28 in the Mean Duration and Variability of IOI as Assessed by Pedomotography Left foot IOI duration	0.109 seconds Standard Deviation 0.354	-0.123 seconds Standard Deviation 0.199
Change From Baseline to Day 28 in the Mean Duration and Variability of IOI as Assessed by Pedomotography Left foot IOI variability	0.146 seconds Standard Deviation 0.353	-0.1 seconds Standard Deviation 0.122
Change From Baseline to Day 28 in the Mean Duration and Variability of IOI as Assessed by Pedomotography Right foot IOI variability	0.120 seconds Standard Deviation 0.177	0.090 seconds Standard Deviation 0.15
Change From Baseline to Day 28 in the Mean Duration and Variability of IOI as Assessed by Pedomotography Right foot IOI duration	0.267 seconds Standard Deviation 0.461	0.075 seconds Standard Deviation 0.164

SECONDARY outcome

Timeframe: Baseline (Day-1) to Day 28

Population: 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.

Outcome measures

Measure	BN82451B n=10 Participants Patients were randomised to receive oral study medication, BN82451B, b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of BN82451B was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 milligrams (mg) b.i.d. For cohort 1, 40 mg BN82451B 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 BN82451B 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 BN82451B 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.	Placebo n=3 Participants 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.
Change From Baseline to Day 28 in the Mean Duration and Variability of TD as Assessed by Pedomotography Left foot TD variability	0.225 seconds Standard Deviation 0.332	-0.056 seconds Standard Deviation 0.058
Change From Baseline to Day 28 in the Mean Duration and Variability of TD as Assessed by Pedomotography Right foot TD variability	0.306 seconds Standard Deviation 0.566	0.105 seconds Standard Deviation 0.140
Change From Baseline to Day 28 in the Mean Duration and Variability of TD as Assessed by Pedomotography Left foot TD duration	0.179 seconds Standard Deviation 0.28	-0.040 seconds Standard Deviation 0.106
Change From Baseline to Day 28 in the Mean Duration and Variability of TD as Assessed by Pedomotography Right foot TD duration	0.358 seconds Standard Deviation 0.609	0.083 seconds Standard Deviation 0.133

SECONDARY outcome

Timeframe: Baseline (Day-1) to Day 28

Population: 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.

Outcome measures

Measure	BN82451B n=10 Participants Patients were randomised to receive oral study medication, BN82451B, b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of BN82451B was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 milligrams (mg) b.i.d. For cohort 1, 40 mg BN82451B 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 BN82451B 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 BN82451B 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.	Placebo n=3 Participants 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.
Change From Baseline to Day 28 in the Mean Duration and Variability of IPI as Assessed by Pedomotography Right foot IPI variability	0.117 seconds Standard Deviation 0.150	0.098 seconds Standard Deviation 0.164
Change From Baseline to Day 28 in the Mean Duration and Variability of IPI as Assessed by Pedomotography Right foot IPI duration	0.295 seconds Standard Deviation 0.469	0.073 seconds Standard Deviation 0.158
Change From Baseline to Day 28 in the Mean Duration and Variability of IPI as Assessed by Pedomotography Left foot IPI variability	0.115 seconds Standard Deviation 0.248	-0.108 seconds Standard Deviation 0.131
Change From Baseline to Day 28 in the Mean Duration and Variability of IPI as Assessed by Pedomotography Left foot IPI duration	0.117 seconds Standard Deviation 0.383	-0.123 seconds Standard Deviation 0.206

SECONDARY outcome

Timeframe: Baseline (Day-1) to Day 28

Population: 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.

Outcome measures

Measure	BN82451B n=10 Participants Patients were randomised to receive oral study medication, BN82451B, b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of BN82451B was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 milligrams (mg) b.i.d. For cohort 1, 40 mg BN82451B 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 BN82451B 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 BN82451B 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.	Placebo n=3 Participants 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.
Change From Baseline to Day 28 in the Mean Duration and Variability of ITI as Assessed by Pedomotography Left foot ITI variability	0.003 seconds Standard Deviation 0.203	-0.047 seconds Standard Deviation 0.108
Change From Baseline to Day 28 in the Mean Duration and Variability of ITI as Assessed by Pedomotography Right foot ITI variability	0.023 seconds Standard Deviation 0.118	-0.016 seconds Standard Deviation 0.089
Change From Baseline to Day 28 in the Mean Duration and Variability of ITI as Assessed by Pedomotography Left foot ITI duration	-0.049 seconds Standard Deviation 0.232	-0.076 seconds Standard Deviation 0.092
Change From Baseline to Day 28 in the Mean Duration and Variability of ITI as Assessed by Pedomotography Right foot ITI duration	-0.016 seconds Standard Deviation 0.121	-0.012 seconds Standard Deviation 0.056

SECONDARY outcome

Timeframe: Baseline (Day -1) to Day 28

Population: 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.

Outcome measures

Measure	BN82451B n=10 Participants Patients were randomised to receive oral study medication, BN82451B, b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of BN82451B was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 milligrams (mg) b.i.d. For cohort 1, 40 mg BN82451B 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 BN82451B 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 BN82451B 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.	Placebo n=3 Participants 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.
Change From Baseline to Day 28 in the Mean Variability of Peak TF as Assessed by Pedomotography Left foot TF variability	11.63 percentage of variation Standard Deviation 16.38	-20.19 percentage of variation Standard Deviation 34.30
Change From Baseline to Day 28 in the Mean Variability of Peak TF as Assessed by Pedomotography Right foot TF variability	-2.52 percentage of variation Standard Deviation 22.35	-18.31 percentage of variation Standard Deviation 6.52

SECONDARY outcome

Timeframe: Baseline (Day -1) to Day 28

Population: 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.

Outcome measures

Measure	BN82451B n=10 Participants Patients were randomised to receive oral study medication, BN82451B, b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of BN82451B was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 milligrams (mg) b.i.d. For cohort 1, 40 mg BN82451B 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 BN82451B 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 BN82451B 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.	Placebo n=3 Participants 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.
Change From Baseline to Day 28 in the Mean Tapping Frequency as Assessed by Pedomotography Right foot freq	-0.383 Hertz Standard Deviation 0.481	-0.18 Hertz Standard Deviation 0.550
Change From Baseline to Day 28 in the Mean Tapping Frequency as Assessed by Pedomotography Left foot freq	-0.259 Hertz Standard Deviation 0.513	0.556 Hertz Standard Deviation 0.678

Adverse Events

BN82451B

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	BN82451B n=14 participants at risk Patients were randomised to receive oral study medication, BN82451B, b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of BN82451B was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 milligrams (mg) b.i.d. For cohort 1, 40 mg BN82451B 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 BN82451B 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 BN82451B 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.	Placebo n=3 participants at risk 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.
Skin and subcutaneous tissue disorders Rash	35.7% 5/14 • Number of events 5 • From Day 1 to the end of study visit (a period of up to 7 weeks, consisting of up to 28 days of treatment and up to 3 weeks follow up). AE data is reported as TEAEs.	0.00% 0/3 • From Day 1 to the end of study visit (a period of up to 7 weeks, consisting of up to 28 days of treatment and up to 3 weeks follow up). AE data is reported as TEAEs.
Skin and subcutaneous tissue disorders Acne	7.1% 1/14 • Number of events 1 • From Day 1 to the end of study visit (a period of up to 7 weeks, consisting of up to 28 days of treatment and up to 3 weeks follow up). AE data is reported as TEAEs.	0.00% 0/3 • From Day 1 to the end of study visit (a period of up to 7 weeks, consisting of up to 28 days of treatment and up to 3 weeks follow up). AE data is reported as TEAEs.
Skin and subcutaneous tissue disorders Rash generalised	7.1% 1/14 • Number of events 1 • From Day 1 to the end of study visit (a period of up to 7 weeks, consisting of up to 28 days of treatment and up to 3 weeks follow up). AE data is reported as TEAEs.	0.00% 0/3 • From Day 1 to the end of study visit (a period of up to 7 weeks, consisting of up to 28 days of treatment and up to 3 weeks follow up). AE data is reported as TEAEs.
Skin and subcutaneous tissue disorders Dry skin	7.1% 1/14 • Number of events 1 • From Day 1 to the end of study visit (a period of up to 7 weeks, consisting of up to 28 days of treatment and up to 3 weeks follow up). AE data is reported as TEAEs.	0.00% 0/3 • From Day 1 to the end of study visit (a period of up to 7 weeks, consisting of up to 28 days of treatment and up to 3 weeks follow up). AE data is reported as TEAEs.
Skin and subcutaneous tissue disorders Hyperhidrosis	7.1% 1/14 • Number of events 1 • From Day 1 to the end of study visit (a period of up to 7 weeks, consisting of up to 28 days of treatment and up to 3 weeks follow up). AE data is reported as TEAEs.	0.00% 0/3 • From Day 1 to the end of study visit (a period of up to 7 weeks, consisting of up to 28 days of treatment and up to 3 weeks follow up). AE data is reported as TEAEs.
General disorders Fatigue	21.4% 3/14 • Number of events 3 • From Day 1 to the end of study visit (a period of up to 7 weeks, consisting of up to 28 days of treatment and up to 3 weeks follow up). AE data is reported as TEAEs.	0.00% 0/3 • From Day 1 to the end of study visit (a period of up to 7 weeks, consisting of up to 28 days of treatment and up to 3 weeks follow up). AE data is reported as TEAEs.
General disorders Face oedema	14.3% 2/14 • Number of events 3 • From Day 1 to the end of study visit (a period of up to 7 weeks, consisting of up to 28 days of treatment and up to 3 weeks follow up). AE data is reported as TEAEs.	0.00% 0/3 • From Day 1 to the end of study visit (a period of up to 7 weeks, consisting of up to 28 days of treatment and up to 3 weeks follow up). AE data is reported as TEAEs.
General disorders Inflammation	7.1% 1/14 • Number of events 1 • From Day 1 to the end of study visit (a period of up to 7 weeks, consisting of up to 28 days of treatment and up to 3 weeks follow up). AE data is reported as TEAEs.	0.00% 0/3 • From Day 1 to the end of study visit (a period of up to 7 weeks, consisting of up to 28 days of treatment and up to 3 weeks follow up). AE data is reported as TEAEs.
Nervous system disorders Headache	21.4% 3/14 • Number of events 4 • From Day 1 to the end of study visit (a period of up to 7 weeks, consisting of up to 28 days of treatment and up to 3 weeks follow up). AE data is reported as TEAEs.	0.00% 0/3 • From Day 1 to the end of study visit (a period of up to 7 weeks, consisting of up to 28 days of treatment and up to 3 weeks follow up). AE data is reported as TEAEs.
Nervous system disorders Dizziness	7.1% 1/14 • Number of events 1 • From Day 1 to the end of study visit (a period of up to 7 weeks, consisting of up to 28 days of treatment and up to 3 weeks follow up). AE data is reported as TEAEs.	0.00% 0/3 • From Day 1 to the end of study visit (a period of up to 7 weeks, consisting of up to 28 days of treatment and up to 3 weeks follow up). AE data is reported as TEAEs.
Nervous system disorders Hypoaesthesia	7.1% 1/14 • Number of events 1 • From Day 1 to the end of study visit (a period of up to 7 weeks, consisting of up to 28 days of treatment and up to 3 weeks follow up). AE data is reported as TEAEs.	0.00% 0/3 • From Day 1 to the end of study visit (a period of up to 7 weeks, consisting of up to 28 days of treatment and up to 3 weeks follow up). AE data is reported as TEAEs.
Nervous system disorders Depressed level of consciousness	7.1% 1/14 • Number of events 1 • From Day 1 to the end of study visit (a period of up to 7 weeks, consisting of up to 28 days of treatment and up to 3 weeks follow up). AE data is reported as TEAEs.	0.00% 0/3 • From Day 1 to the end of study visit (a period of up to 7 weeks, consisting of up to 28 days of treatment and up to 3 weeks follow up). AE data is reported as TEAEs.
Nervous system disorders Presyncope	14.3% 2/14 • Number of events 2 • From Day 1 to the end of study visit (a period of up to 7 weeks, consisting of up to 28 days of treatment and up to 3 weeks follow up). AE data is reported as TEAEs.	0.00% 0/3 • From Day 1 to the end of study visit (a period of up to 7 weeks, consisting of up to 28 days of treatment and up to 3 weeks follow up). AE data is reported as TEAEs.
Nervous system disorders Dyskinesia	7.1% 1/14 • Number of events 1 • From Day 1 to the end of study visit (a period of up to 7 weeks, consisting of up to 28 days of treatment and up to 3 weeks follow up). AE data is reported as TEAEs.	0.00% 0/3 • From Day 1 to the end of study visit (a period of up to 7 weeks, consisting of up to 28 days of treatment and up to 3 weeks follow up). AE data is reported as TEAEs.
Gastrointestinal disorders Vomiting	21.4% 3/14 • Number of events 4 • From Day 1 to the end of study visit (a period of up to 7 weeks, consisting of up to 28 days of treatment and up to 3 weeks follow up). AE data is reported as TEAEs.	0.00% 0/3 • From Day 1 to the end of study visit (a period of up to 7 weeks, consisting of up to 28 days of treatment and up to 3 weeks follow up). AE data is reported as TEAEs.
Gastrointestinal disorders Diarrhoea	14.3% 2/14 • Number of events 2 • From Day 1 to the end of study visit (a period of up to 7 weeks, consisting of up to 28 days of treatment and up to 3 weeks follow up). AE data is reported as TEAEs.	0.00% 0/3 • From Day 1 to the end of study visit (a period of up to 7 weeks, consisting of up to 28 days of treatment and up to 3 weeks follow up). AE data is reported as TEAEs.
Gastrointestinal disorders Nausea	14.3% 2/14 • Number of events 3 • From Day 1 to the end of study visit (a period of up to 7 weeks, consisting of up to 28 days of treatment and up to 3 weeks follow up). AE data is reported as TEAEs.	0.00% 0/3 • From Day 1 to the end of study visit (a period of up to 7 weeks, consisting of up to 28 days of treatment and up to 3 weeks follow up). AE data is reported as TEAEs.
Ear and labyrinth disorders Ear swelling	7.1% 1/14 • Number of events 1 • From Day 1 to the end of study visit (a period of up to 7 weeks, consisting of up to 28 days of treatment and up to 3 weeks follow up). AE data is reported as TEAEs.	0.00% 0/3 • From Day 1 to the end of study visit (a period of up to 7 weeks, consisting of up to 28 days of treatment and up to 3 weeks follow up). AE data is reported as TEAEs.
Injury, poisoning and procedural complications Laceration	7.1% 1/14 • Number of events 1 • From Day 1 to the end of study visit (a period of up to 7 weeks, consisting of up to 28 days of treatment and up to 3 weeks follow up). AE data is reported as TEAEs.	0.00% 0/3 • From Day 1 to the end of study visit (a period of up to 7 weeks, consisting of up to 28 days of treatment and up to 3 weeks follow up). AE data is reported as TEAEs.
Injury, poisoning and procedural complications Excoriation	7.1% 1/14 • Number of events 1 • From Day 1 to the end of study visit (a period of up to 7 weeks, consisting of up to 28 days of treatment and up to 3 weeks follow up). AE data is reported as TEAEs.	0.00% 0/3 • From Day 1 to the end of study visit (a period of up to 7 weeks, consisting of up to 28 days of treatment and up to 3 weeks follow up). AE data is reported as TEAEs.
Infections and infestations Impetigo	7.1% 1/14 • Number of events 1 • From Day 1 to the end of study visit (a period of up to 7 weeks, consisting of up to 28 days of treatment and up to 3 weeks follow up). AE data is reported as TEAEs.	0.00% 0/3 • From Day 1 to the end of study visit (a period of up to 7 weeks, consisting of up to 28 days of treatment and up to 3 weeks follow up). AE data is reported as TEAEs.
Infections and infestations Nasopharyngitis	0.00% 0/14 • From Day 1 to the end of study visit (a period of up to 7 weeks, consisting of up to 28 days of treatment and up to 3 weeks follow up). AE data is reported as TEAEs.	33.3% 1/3 • Number of events 1 • From Day 1 to the end of study visit (a period of up to 7 weeks, consisting of up to 28 days of treatment and up to 3 weeks follow up). AE data is reported as TEAEs.
Musculoskeletal and connective tissue disorders Back pain	14.3% 2/14 • Number of events 2 • From Day 1 to the end of study visit (a period of up to 7 weeks, consisting of up to 28 days of treatment and up to 3 weeks follow up). AE data is reported as TEAEs.	0.00% 0/3 • From Day 1 to the end of study visit (a period of up to 7 weeks, consisting of up to 28 days of treatment and up to 3 weeks follow up). AE data is reported as TEAEs.
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/14 • From Day 1 to the end of study visit (a period of up to 7 weeks, consisting of up to 28 days of treatment and up to 3 weeks follow up). AE data is reported as TEAEs.	33.3% 1/3 • Number of events 1 • From Day 1 to the end of study visit (a period of up to 7 weeks, consisting of up to 28 days of treatment and up to 3 weeks follow up). AE data is reported as TEAEs.
Investigations Gamma-glutamyltransferase increased	7.1% 1/14 • Number of events 1 • From Day 1 to the end of study visit (a period of up to 7 weeks, consisting of up to 28 days of treatment and up to 3 weeks follow up). AE data is reported as TEAEs.	0.00% 0/3 • From Day 1 to the end of study visit (a period of up to 7 weeks, consisting of up to 28 days of treatment and up to 3 weeks follow up). AE data is reported as TEAEs.

Additional Information

Vice President Early Development & Clinical Pharmacology

Ipsen

Email: clinical.trials@ipsen.com

Results disclosure agreements

• Principal investigator is a sponsor employee PI shall not proceed to publication or communication in connection with the subject matter of this Agreement or Results, without the prior written consent of Ipsen.
• Publication restrictions are in place

Restriction type: OTHER