Preliminary Study of Piclozotan in Patients With Motor Complications Associated With Parkinson's Disease

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to obtain preliminary information on the effect of piclozotan on motor complications associated with Parkinson's Disease.

Official Title
-----------------
A Double-Blind, Placebo-Controlled, Preliminary Study of the Efficacy, Safety, and Tolerability of Intravenous SUN N4057 in Patients With Motor Complications Associated With Parkinson's Disease

Conditions
-----------------
Parkinson's Disease

Intervention / Treatment
-----------------
* Drug: piclozotan
* Drug: 0.9% sodium chloride (normal saline)


Participation Criteria
=================
Eligibility Criteria
-----------------
Main Inclusion Criteria: Idiopathic Parkinson's disease for at least 5 years Presence of motor fluctuations and dyskinesia Stable regimen of levodopa/carbidopa for 30 days At least 25% response/improvement in Unified Parkinson's Disease Rating Scale (UPDRS) part III scores after dosing with regular Parkinson's disease (PD) medications Mini-Mental State Examination (MMSE) score of 25 or higher Main Exclusion Criteria: Atypical or secondary parkinsonism. Prior use of neuroleptic agents. History of intracranial procedures for PD. Active psychosis. History of drug or alcohol abuse in past 12 months. Cardiac conduction system abnormality. Predisposing medical condition that causes nausea or vomiting or routine use of an anti-emetic.

Ages Eligible for Study
-----------------
Minimum Age: 40 Years
Maximum Age: 85 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: piclozotan<br>Participants will be randomized to receive two 12-hour intravenous (IV) infusions of piclozotan administered at a plasma level of 30 ng/mL over 2 inpatient days. | Drug: piclozotan<br>* piclozotan, intravenous (IV) infusion<br>* Other names: SUN N4057;|
| Placebo Comparator: 0.9 % sodium chloride (normal saline)<br>Participants will be randomized to receive two 12-hour intravenous (IV) infusions of 0.9 % sodium chloride (normal saline) administered at a plasma level of 30 ng/mL over 2 inpatient days. | Drug: 0.9% sodium chloride (normal saline)<br>* 0.9% sodium chloride (normal saline) intravenous (IV) infusion<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Percentage of On Time Without Dyskinesia Averaged Over Days 1 and 2 in Participants Treated With SUN N4057 and Those Treated With a Placebo | Improvement in motor complications associated with Parkinson's disease are measured as on (good medication response); OR on with dyskinesia (good medication response, but with superimposed involuntary movements that interfere with activities), OR off (poor medication response). | Baseline (Day-7) up to 2 days post-dose. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline up to Day 2 in the Percentage of on Time Without Dyskinesia, as Assessed Over Hours 1 to 8 for Each Time Point in Participants Treated With SUN N4057 and Those Treated With a Placebo | Improvement in motor complications associated with Parkinson's disease are measured as on (good medication response); OR on with dyskinesia (good medication response, but with superimposed involuntary movements that interfere with activities), OR off (poor medication response). | Baseline (Day -7), Day 1, and Day 2 post-dose. | 
| Percentage of on Time With Dyskinesia at Baseline up to Day 2, and the Change From Baseline in Participants Treated With SUN N4057 and Those Treated With a Placebo | Improvement in motor complications associated with Parkinson's disease are measured as on (good medication response); OR on with dyskinesia (good medication response, but with superimposed involuntary movements that interfere with activities), OR off (poor medication response). Negative values indicate a decrease in on time from baseline to measured time point. | Baseline (Day -7), Day 1, and Day 2 post-dose. | 
| Percentage of on Time With Dyskinesia for the Average of Days 1 and 2, and the Change From Baseline in Participants Treated With SUN N4057 and Those Treated With a Placebo | Improvement in motor complications associated with Parkinson's disease are measured as on (good medication response); OR on with dyskinesia (good medication response, but with superimposed involuntary movements that interfere with activities), OR off (poor medication response). Negative values indicate a decrease in on time from baseline to measured time point. | Baseline (Day -7), Day 1, and Day 2 post-dose. | 
| Percentage of on Time With or Without Dyskinesia at Baseline up to Day 2, and the Change From Baseline in Participants Treated With SUN N4057 and Those Treated With a Placebo | Improvement in motor complications associated with Parkinson's disease are measured as on (good medication response); OR on with dyskinesia (good medication response, but with superimposed involuntary movements that interfere with activities), OR off (poor medication response). Negative values indicate a decrease in on time from baseline to measured time point. | Baseline (Day -7), Day 1 and Day 2 post-dose. | 
| Percentage of on Time With or Without Dyskinesia for the Average of Days 1 and 2, and the Change From Baseline in Participants Treated With SUN N4057 and Those Treated With a Placebo | Improvement in motor complications associated with Parkinson's disease are measured as on (good medication response); OR on with dyskinesia (good medication response, but with superimposed involuntary movements that interfere with activities), OR off (poor medication response). Negative values indicate a decrease in on time from baseline to measured time point. | Baseline (Day -7), Day 1 and Day 2 post-dose. | 
| Percentage of Off Time at Baseline up to Day 2, and the Change From Baseline in Participants Treated With SUN N4057 and Those Treated With a Placebo | Improvement in motor complications associated with Parkinson's disease are measured as on (good medication response); OR on with dyskinesia (good medication response, but with superimposed involuntary movements that interfere with activities), OR off (poor medication response). Negative values indicate a decrease in off time from baseline to measured time point. | Baseline (Day -7), Day 1, and Day 2 post-dose. | 
| Percentage of Off Time for the Average of Days 1 and 2, and the Change From Baseline in Participants Treated With SUN N4057 and Those Treated With a Placebo | Improvement in motor complications associated with Parkinson's disease are measured as on (good medication response); OR on with dyskinesia (good medication response, but with superimposed involuntary movements that interfere with activities), OR off (poor medication response). Negative values indicate a decrease in off time from baseline to measured time point. | Baseline (Day -7), Day 1, and Day 2 post-dose. | 
| Change From Baseline up to Day 2 in the Average Abnormal Involuntary Movement Scale (AIMS) Total Score in Participants Treated With SUN N4057 and Those Treated With a Placebo | The Abnormal Involuntary Movement Scale (AIMS) is an assessment of dyskinesia in patients with movement disorders. The AIMS was originally developed to assess neuroleptic-induced extrapyramidal symptoms but has also been applied to the assessment of dyskinesia in patients with Parkinson's disease. AIMS questions 1 to 7 rate the degree of dyskinesia on a 0 to 4 scale in the extremities, trunk, and face, where 0 is no dyskinesia (better outcome) and 4 is severe dyskinesia (worse outcome). The total score range is 0 (better outcome) to 28 (worse outcome). Higher scores indicate a worse outcome. | Baseline (Day -7), Day 1, and Day 2 post-dose. | 
| Average of Days 1 and 2 in the Average Abnormal Involuntary Movement Scale (AIMS) Total Score in Participants Treated With SUN N4057 and Those Treated With a Placebo | The Abnormal Involuntary Movement Scale (AIMS) is an assessment of dyskinesia in patients with movement disorders. The AIMS was originally developed to assess neuroleptic-induced extrapyramidal symptoms but has also been applied to the assessment of dyskinesia in patients with Parkinson's disease. AIMS questions 1 to 7 rate the degree of dyskinesia on a 0 to 4 scale in the extremities, trunk, and face, where 0 is no dyskinesia (better outcome) and 4 is severe dyskinesia (worse outcome). The total score range is 0 (better outcome) to 28 (worse outcome). Higher scores indicate a worse outcome. | Day 1 and Day 2 post-dose. | 
| Mean SUN N4057 Plasma Concentrations Over Time Following Treatment With SUN N4057 | The mean concentration of study drug, SUN N4057, in participant blood plasma samples drawn during infusions. | Day 1 pre-dose (Hour 0), 1 hour, 6 hours, 12 hours; Day 2 pre-dose (Hour 24), 1 hour (Hour 25), 6 hours (Hour 30), 12 hours (Hour 36), and Day 3 Hour 0 (Hour 48) post-dose. | 
| Mean SUN N4057 Plasma Pharmacokinetic Parameter of Observed Maximum Concentration (Cmax) Following Treatment With SUN N4057 | Cmax is the observed maximum concentration of SUN N4057 in the participant blood plasma sample after drug administration. | Baseline (Day 1 pre-dose) up to Hour 24, and Hour 48 post-dose. | 
| Mean SUN N4057 Plasma Pharmacokinetic Parameter of Observed Minimum Concentration (Cmin) Following Treatment With SUN N4057 | Cmin is the observed minimum concentration of SUN N4057 in the participant blood plasma sample after drug administration. Average of C24 and C48 [ie, 24 hours after the initiation of infusion on Days 1 and 2. Cmin = average of (C24 and C48) | Day 1 pre-dose (Hour 0) up to Hour 24, and Hour 48 post-dose. | 
| Mean SUN N4057 Plasma Pharmacokinetic Parameter of Observed Mean Concentration (Caverage) Following Treatment With SUN N4057 | Caverage is the mean concentration of SUN N4057 in the participant blood plasma sample obtained from the observed concentrations during the 2-day drug infusions (average of C1, C6, C12, C25, C30, and C36 [ie, Hours 1, 6, 12, 25, 30, and 36 after the initiation of infusion on Day 1]). Caverage = average of (C1, C6, C12, C25, C30, and C36) | Day 1 at 1 hour, 6 hours, and12 hours; Day 2 at 25 hours, 30 hours, and 36 hours post-dose. | 
| Mean SUN N4057 Pharmacokinetic Parameter of Area Under the Drug Concentration vs Time Curve (AUCt) Following Treatment With SUN N4057 | AUCt is defined as the area under the drug concentration vs time curve from zero up to the last sampling point with a quantifiable drug concentration which is above the lower limit of quantification. | Baseline (Day 1 pre-dose) up to Hour 0, Hour 1, Hour 6, Hour 12, Hour 24, Hour 25, Hour 30, Hour 36, and Hour 48 post-dose. | 
| Treatment-Related Treatment-Emergent Adverse Events Reported Following Treatment With SUN N4057 or Placebo | A treatment-emergent adverse event (TEAE) was defined as an Adverse Event (AE) that was new in onset or aggravated in severity or frequency following administration of the investigational agent. This included any change from the screening physical examination findings or results of diagnostic procedures (eg, laboratory test, ECG) that were clinically significant, eg, required diagnostic or therapeutic intervention beyond confirmation alone. | Baseline up to Day 16 post-dose, up to approximately a total 12 months. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Parkinson's Disease, motor complications, dyskinesia, Motor complications associated with Parkinson's