A 12-week Randomized Study to Evaluate Oral Istradefylline in Subjects With Moderate to Severe Parkinson's Disease

Phase 3

Completed

Conditions: Idiopathic Parkinson's Disease

Interventions: Drug: Istradefylline 20 mg
Drug: Istradefylline 40 mg
Drug: Placebo

Registration Number: NCT01968031

Lead Sponsor: Kyowa Kirin Co., Ltd.

Brief Summary: This is a study to assess the efficacy and safety of oral Istradefylline (KW-6002) in patients with moderate to severe Parkinson's Disease. While on this study, participants will continue to take their usual, prescribed, stable regimen of Levodopa/Carbidopa or Levodopa/Benserazide therapy plus adjunct Parkinson's medications. Patients will be randomized 1:1:1 to receive either Istradefylline 20 mg per day, or Istradefylline 40 mg per day or an equivalent placebo. Patients will be treated for a 12 week period to demonstrate the effectiveness of Istradefylline in improving Parkinson's disease symptoms (referred to as improvement in patient OFF time) and that Istradefylline has an acceptable safety profile in this group.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 613

Inclusion Criteria

30 years of age or older.
UK Parkinson's Disease Society (UKPDS) brain bank criteria (Step 1 and 2) for PD
PD Stages 2-4 in the ON state for Modified Hoehn and Yahr Scale.
On levodopa therapy for at least 1 year with beneficial clinical response at the baseline visit
Taking at least 400mg levodopa combination daily and on stable regimen of any other anti-Parkinsonian drugs (MAO-B, COMT, DA) for at least 2 weeks prior to randomization
Stable dopaminergic regimen for at least 4 weeks immediately prior to randomization
Documented end-of-dose wearing-off and levodopa-induced dyskinesia
Have an average of two hours of OFF time per day

Exclusion Criteria

Subjects on apomorphine and/or dopamine receptor antagonists or direct gastrointestinal levodopa infusion.
Subject who have had neurosurgical operation for PD
Subjects taking A2a antagonist, potent CYP3A4 inhibitors, potent CYP34A inducers
Subjects who smoke > 5 cigarettes/day

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Istradefylline 20 mg/day	Istradefylline 20 mg	Istradefylline 20 mg and placebo to match istradefylline 40 mg: A daily, oral, double-blind treatment dose of both tablets will be taken in the morning for 12 weeks.
Istradefylline 20 mg/day	Placebo	Istradefylline 20 mg and placebo to match istradefylline 40 mg: A daily, oral, double-blind treatment dose of both tablets will be taken in the morning for 12 weeks.
Istradefylline 40 mg/day	Istradefylline 40 mg	Istradefylline 40 mg and placebo to match istradefylline 20 mg: A daily, oral, double-blind treatment dose of both tablets will be taken in the morning for 12 weeks.
Istradefylline 40 mg/day	Placebo	Istradefylline 40 mg and placebo to match istradefylline 20 mg: A daily, oral, double-blind treatment dose of both tablets will be taken in the morning for 12 weeks.
Placebo	Placebo	Placebo to match istradefylline 20 mg and placebo to match istradefylline 40 mg: A daily, oral, double-blind treatment dose of both tablets will be taken in the morning for 12 weeks.

Primary Outcome Measures

Name	Time	Method
Change From Baseline in the Total Hours of Awake Time/Day Spent in the OFF State at Week 12	Baseline, Week 2, Week 6, Week 10 and Week 12.	Based on the 24-hour ON/OFF patient diary data.

Secondary Outcome Measures

Name	Time	Method
Total Hours of ON Time Per Day Without Troublesome Dyskinesia	Baseline, Week 2, Week 6, Week 10 and Week 12.	Based on Patient's ON/OFF Diary
Unified Parkinson's Disease Rating Scale (UPDRS) Motor Examination Score (Part III);	Baseline, Week 2, Week 6, Week 10 and Week 12.	The Unified Parkinson's Disease Rating Scale (UPDRS) evaluates various aspects of Parkinson's disease including non-motor and motor experiences of daily living and motor complications. Part III assesses the motor signs of Parkinson's Disease with a rating from 0 to 4, where 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. The possible score range of Part III is 0 to 68. The lower the score, the more favorable the response.
Unified Parkinson's Disease Rating Scale (UPDRS) Activities of Daily Living (ADL) Score (Part II)	Baseline, Week 2, Week 6, Week 10 and Week 12.	The Unified Parkinson's Disease Rating Scale (UPDRS) evaluates various aspects of Parkinson's disease including non-motor and motor experiences of daily living and motor complications. Part II is a self-evaluation of the activities of daily life (ADL) including speech, swallowing, handwriting, dressing, hygiene, falling, salivating, turning in bed, walking, and cutting food with a rating from 0 to 4, where 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. The possible score range of Part II is 0 to 52. The lower the score, the more favorable the response.
Unified Parkinson's Disease Rating Scale (UPDRS Mentation, Behaviour) and Mood (Part I)	Baseline, Week 2, Week 6, Week 10 and Week 12.	The Unified Parkinson's Disease Rating Scale (UPDRS) evaluates various aspects of Parkinson's disease including non-motor and motor experiences of daily living and motor complications. Part I is the evaluation of mentation, behavior, and mood with a rating from 0 to 4, where 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. The possible score range of Part I is 0 to 16. The lower the score, the more favorable the response.
Total UPDRS (Parts I + II + III);	Baseline, Week 2, Week 6, Week 10 and Week 12.	The Unified Parkinson's Disease Rating Scale (UPDRS) evaluates various aspects of Parkinson's disease including non-motor and motor experiences of daily living and motor complications with a rating from 0 to 4, where 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. The total possible score range for all parts combined is 0 to 136. The lower the score, the more favorable the response.
Patient Global Impression - Improvement (PGI-I) Scale	Baseline, Week 2, Week 6, Week 10, Week 12 and 30-day FU visit	The "key symptom" on the PGI-I was evaluated at baseline and subsequent post-baseline visits for the subject's overall condition and the symptoms of fatigue, sleep, motivation to get things done, and each subject's key symptom. Subjects rated each on a scale of 1 to 5 for change from baseline utilizing the following scale: * 1 = Moderate improvement (or greater) * 2 = Mild improvement * 3 = No change from baseline * 4 = Mild deterioration * 5 = Moderate deterioration (or greater) A lower number is a better outcome. Overall condition is presented below.
Sleep Time in Hours Per Day Based Upon 24-hour Diaries.	Baseline, Week 2, Week 6, Week 10 and Week 12.
Percentage of Awake Time Per Day Spent in the OFF State	Baseline, Week 2, Week 6, Week 10 and Week 12.
Percentage of ON Time Per Day Without Troublesome Dyskinesia.	Baseline, Week 2, Week 6, Week 10 and Week 12.
Montreal Cognitive Assessment (MoCA)	Baseline and Week 12.	The Montreal Cognitive Assessment (MoCA) assesses different cognitive domains, broken down as follows: Visuospatial and executive functioning: 5 points Animal Naming: 3 points Attention: 6 points Language: 3 points Abstraction: 2 points Delayed recall (short-term memory): 5 points Orientation: 6 points Scores can range from 0 to 30. A score of 26 or above is considered normal.
Beck Depression Inventory (BDI)	Baseline and Week 12.	The Beck Depression Inventory is a 21-question test that measures the severity of depression. Subjects rated each on a scale of 0 to 3 for change from baseline utilizing the following scale: * 0 = I do not feel sad * 1 = I feel sad * 2 = I am sad all the time and I can't snap out of it * 3 = I am so sad or unhappy that I can't stand it The test is scored for each question using the above scale to determine the severity of depression. Scoring is as shown below: * 0 to 9: minimal depression * 10 to 18: mild depression * 19 to 29: moderate depression * 30 to 63: severe depression

Trial Locations

Locations (4): Kyowa PD Site 2
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Belgrade, Serbia
Kyowa PD Site
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Novi Sad, Serbia
Kyowa PD Site 1
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Belgrade, Serbia
Kyowa PD Site 4
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Belgrade, Serbia