A Study of KW-6356 in Patients With Parkinson's Disease on Treatment With Levodopa-containing Preparations

Study Overview
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Brief Summary
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The primary objective of this study is to determine the recommended dose and evaluate the effect of KW-6356 on motor symptoms in Parkinson's disease and the primary endpoint is the change from baseline in Movement disorder society-unified Parkinson's disease rating scale(MDS-UPDRS) partIII score between KW-6356 and placebo in patients with Parkinson's disease on treatment with Levodopa-containing preparations as an adjunctive therapy.

Official Title
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A Phase 2b Study of KW-6356 in Subjects With Parkinson's Disease on Treatment With Levodopa-containing Preparations

Conditions
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Parkinson's Disease

Intervention / Treatment
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* Drug: KW-6356
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject fulfills the UK Parkinson's Disease Society brain bank clinical diagnostic criteria. Parkinson's disease patients in Stages 2 to 4 on the Modified Hoehn and Yahr Scale. (mH&Y, Evaluation at ON state for patients who experience Wearing-off phenomenon) MDS-UPDRS partIII score of >= 15. (Evaluation at ON state) Subject who are responsive to levodopa/DCI (carbidopa or benserazide) combination therapy and who have been on the therapy for 6 months or longer without interruption at enrollment. Subject who have not started any new antiparkinsonian drugs and have been on a stable regimen of antiparkinsonian drugs in the 3 months before enrollment. Exclusion Criteria: Use of any CYP3A4/5-related drugs within 2 weeks prior to enrollment. Use of any of the following drugs within 3 months (or 6 month in case of depot preparations) prior to enrollment; Antipsychotics, tiapride, metoclopramide, amoxapine, reserpine, tetrabenazine, methyldopa, papaverine, Levodopa/carbidopa intestinal gel and apomorphine hydrochloride injection Treatment by transcranial magnetic stimulation (TMS) within 6 months prior to enrollment. Neurosurgical operation for Parkinson's disease. (stereotactic surgery, deep brain stimulation or gamma knife) Subject who have received administration of adenosine A2A receptor antagonist. Either of the following criteria consecutively at screening and enrollment; Resting Pulse > 100 bpm Resting systolic blood pressure > 140 mmHg, or diastolic blood pressure > 90 mmHg Significant dementia or a Mini-Mental State Examination (MMSE) score of =< 23. Subject has a history or evidence of suicidal ideation (severity of 4 or 5) or any suicidal behavior based on an assessment with the Columbia-Suicide Severity Rating Scale (C-SSRS) at baseline. Anyone otherwise considered unsuitable for the study by the investigator or subinvestigator including those who are unable to communicate or to cooperate with the investigator or subinvestigator.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: An interventional, multicenter, randomized, double-blind, placebo-controlled, parallel-group trial
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: KW-6356 Low Dose<br>Oral administration | Drug: KW-6356<br>* Oral administration<br>|
| Experimental: KW-6356 High Dose<br>Oral administration | Drug: KW-6356<br>* Oral administration<br>|
| Placebo Comparator: placebo<br>Oral administration | Drug: Placebo<br>* Oral administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in the Movement disorder society-unified Parkinson's disease rating scale(MDS-UPDRS) part III score | MDS-UPDRS retains the four-scale structure with a reorganization of the various subscales. The scales are now titled; (Part I) nonmotor experiences of daily living (13 items), (Part II) motor experiences of daily living (13 items), (Part III) motor examination (18 items), and (Part IV) motor complications (six items). Each subscale now has 0-4 ratings, where 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. The total score is the sum of the subscale scores for Parts III and ranges from 0 (no disability) to 136 (total dependence). | Up to 26 weeks after dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in the total hours of awake time per day spent in the OFF state. (total hours per day spent in the OFF state) |  | Up to 26 weeks after dosing |