A 12-week Randomized Study to Evaluate Oral Istradefylline in Subjects With Moderate to Severe Parkinson's Disease (KW-6002)

A Phase 3, 12-week, Double-Blind, Placebo-Controlled, Randomized, Multicenter Study to Evaluate the Efficacy of Oral Istradefylline 20 and 40 mg/Day as Treatment for Subjects With Moderate to Severe Parkinson's Disease

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.

Study Overview

• Status: Completed
• Conditions: Idiopathic Parkinson's Disease
• Intervention / Treatment: Drug: Placebo; Drug: Istradefylline 20 mg; Drug: Istradefylline 40 mg

• Study Type: Interventional
• Enrollment (Actual): 613
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, AB T2N
      • Kyowa PD Site
  • Ontario
    • Kingston, Ontario, Canada, K7L 2V7
      • Kyowa PD Site
    • Toronto, Ontario, Canada, M5T 2S8
      • Kyowa PD Site
  • Quebec
    • Gatineau, Quebec, Canada, J9J 0A5
      • Kyowa PD Site
    • Quebec City, Quebec, Canada, G1S 2L6
      • Kyowa PD Site
• Czechia
  • Brno, Czechia, 656 91
    • Kyowa PD Site
  • Litomysl, Czechia, 570 01
    • Kyowa PD Site
  • Olomouc, Czechia, 775 20
    • Kyowa PD Site
  • Prague, Czechia, 12 000
    • Kyowa PD Site
  • Prague, Czechia, 140 00
    • Kyowa PD Site
  • Prague, Czechia, 150 06
    • Kyowa PD Site
• Germany
  • Beelitz-Heilstätten, Germany, 14547
    • Kyowa PD Site
  • Berlin, Germany, 12203
    • Kyowa PD Site
  • Berlin, Germany, 13088
    • Kyowa PD Site
  • Bremerhaven, Germany, 27574
    • Kyowa PD Site
  • Dresden, Germany, 01307
    • Kyowa PD Site
  • Gottingen, Germany, 37075
    • Kyowa PD Site
  • Haag, Germany, 83527
    • Kyowa PD Site
  • Kassel, Germany, 34128
    • Kyowa PD Site
  • Marburg, Germany, 35043
    • Kyowa PD Site
  • Munich, Germany, 80804
    • Kyowa PD Site
  • Tubingen, Germany, 72076
    • Kyowa PD Site
  • Ulm, Germany, 89081
    • Kyowa PD Site
• Israel
  • Haifa, Israel, 39106
    • Kyowa PD Site
  • Jerusalem, Israel, 91120
    • Kyowa PD Site
  • Petach Tiqva, Israel, 49372
    • Kyowa PD Site
  • Ramat Gan, Israel, 52621
    • Kyowa PD Site
  • Tel Aviv, Israel, 64239
    • Kyowa PD Site
• Italy
  • Cassino, Italy, 03043
    • Kyowa PD Site
  • Chieti, Italy, 66013
    • Kyowa PD Site
  • Grosseto, Italy, 58100
    • Kyowa PD Site
  • Pavia, Italy, 27100
    • Kyowa PD Site
  • Pisa, Italy, 56126
    • Kyowa PD Site
  • Rome, Italy, 00163
    • Kyowa PD Site
  • Rome, Italy, 00133
    • Kyowa PD Site
  • Venezia, Italy, 30126
    • Kyowa PD Site
  • Vicenza, Italy, 36057
    • Kyowa PD Site
• Poland
  • Bydgoszcz, Poland, 85-796
    • Kyowa PD Site
  • Kielce, Poland, 25-103
    • Kyowa PD Site
  • Krakow, Poland, 31-505
    • Kyowa PD Site
  • Lublin, Poland, 20-093
    • Kyowa PD Site
  • Poznan, Poland, 61-853
    • Kyowa PD Site
  • Warsaw, Poland, 01-697
    • Kyowa PD Site
  • Warsaw, Poland, 04-364
    • Kyowa PD Site
• Serbia
  • Belgrade, Serbia, 11000
    • Kyowa PD Site 1
  • Belgrade, Serbia, 11000
    • Kyowa PD Site 4
  • Belgrade, Serbia, 11000
    • Kyowa PD Site 2
  • Novi Sad, Serbia, 21000
    • Kyowa PD Site
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85004
      • Kyowa PD Site
    • Sun City, Arizona, United States, 85351
      • Kyowa PD Site
    • Tucson, Arizona, United States, 85724
      • Kyowa PD Site
  • California
    • Fountain Valley, California, United States, 92708
      • Kyowa PD Site
    • Irvine, California, United States, 92697
      • Kyowa PD Site
    • Los Angeles, California, United States, 90048
      • Kyowa PD Site
    • Oxnard, California, United States, 93030
      • Kyowa PD Site
    • Pasadena, California, United States, 91105
      • Kyowa PD Site
    • Reseda, California, United States, 91335
      • Kyowa PD Site
    • Sunnyvale, California, United States, 94085
      • Kyowa PD Site
    • Torrance, California, United States, 90505
      • Kyowa PD Site
  • Colorado
    • Englewood, Colorado, United States, 80113
      • Kyowa PD Site
  • Connecticut
    • Danbury, Connecticut, United States, 06810
      • Kyowa PD Site
  • Florida
    • Boca Raton, Florida, United States, 33486
      • Kyowa PD Site
    • Jacksonville, Florida, United States, 32209
      • Kyowa PD Site
    • Panama City, Florida, United States, 32405
      • Kyowa PD Site
    • Port Charlotte, Florida, United States, 33980
      • Kyowa PD Site
    • Tampa, Florida, United States, 33647
      • Kyowa PD Site
  • Georgia
    • Atlanta, Georgia, United States, 30329
      • Kyowa PD Site
    • Augusta, Georgia, United States, 29841
      • Kyowa PD Site
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Kyowa PD Site
    • Chicago, Illinois, United States, 60612
      • Kyowa PD Site
  • Iowa
    • Des Moines, Iowa, United States, 50309
      • Kyowa PD Site
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Kyowa PD Site
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Kyowa PD Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Kyowa PD Site
  • Michigan
    • West Bloomfield, Michigan, United States, 48322
      • Kyowa PD Site
  • Minnesota
    • Minneapolis, Minnesota, United States, 55414
      • Kyowa PD Site
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Kyowa PD Site
  • New York
    • Albany, New York, United States, 12208
      • Kyowa PD Site
    • New York, New York, United States, 10016
      • Kyowa PD Site
    • New York, New York, United States, 10032
      • Kyowa PD Site
  • North Carolina
    • Asheville, North Carolina, United States, 28806
      • Kyowa PD Site
    • Durham, North Carolina, United States, 27705
      • Kyowa PD Site
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Kyowa PD Site
    • Cleveland, Ohio, United States, 44195
      • Kyowa PD Site
    • Toledo, Ohio, United States, 43614
      • Kyowa PD Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Kyowa PD Site
  • South Carolina
    • Charleston, South Carolina, United States, 29401
      • Kyowa PD Site
  • Texas
    • Dallas, Texas, United States, 75390-9036
      • Kyowa PD Site
    • Houston, Texas, United States, 77030
      • Kyowa PD Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Istradefylline 20 mg/day; 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.	Drug: Placebo; Placebo; Drug: Istradefylline 20 mg; Istradefylline 20 mg and placebo; Other Names: KW-6002
Experimental: Istradefylline 40 mg/day; 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.	Drug: Placebo; Placebo; Drug: Istradefylline 40 mg; Istradefylline 40 mg and placebo; Other Names: KW-6002
Placebo Comparator: 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.	Drug: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Hours of ON Time Per Day Without Troublesome Dyskinesia	Based on Patient's ON/OFF Diary	Baseline, Week 2, Week 6, Week 10 and Week 12.
Unified Parkinson's Disease Rating Scale (UPDRS) Motor Examination Score (Part III);	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.	Baseline, Week 2, Week 6, Week 10 and Week 12.
Unified Parkinson's Disease Rating Scale (UPDRS) Activities of Daily Living (ADL) Score (Part II)	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.	Baseline, Week 2, Week 6, Week 10 and Week 12.
Unified Parkinson's Disease Rating Scale (UPDRS Mentation, Behaviour) and Mood (Part I)	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.	Baseline, Week 2, Week 6, Week 10 and Week 12.
Total UPDRS (Parts I + II + III);	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.	Baseline, Week 2, Week 6, Week 10 and Week 12.
Patient Global Impression - Improvement (PGI-I) Scale	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.	Baseline, Week 2, Week 6, Week 10, Week 12 and 30-day FU visit
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)	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.	Baseline and Week 12.
Beck Depression Inventory (BDI)	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	Baseline and Week 12.

Collaborators and Investigators

• Sponsor: Kyowa Kirin Co., Ltd.
• Collaborators: Kyowa Hakko Kirin Pharma, Inc.
• Investigators: Study Chair: Kyowa Hakko Kirin Pharma, Inc., Kyowa Hakko Kirin Pharma, Inc.

Publications and helpful links

Helpful Links

• Fox Trial Finder is a clinical trial matching tool that helps a Parkinson's patient connect with research sites. Volunteers who sign up will receive a list of trials in their area.

Study record dates

Study Major Dates

• Study Start: October 1, 2013
• Primary Completion (Actual): October 1, 2016
• Study Completion (Actual): October 1, 2016

Study Registration Dates

• First Submitted: October 18, 2013
• First Submitted That Met QC Criteria: October 18, 2013
• First Posted (Estimated): October 23, 2013

Study Record Updates

• Last Update Posted (Actual): April 25, 2024
• Last Update Submitted That Met QC Criteria: April 23, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Parkinson's disease; Moderate to Severe Parkinson's Disease
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Purinergic Antagonists; Purinergic Agents; Purinergic P1 Receptor Antagonists; Adenosine A2 Receptor Antagonists; Istradefylline
• Other Study ID Numbers: 6002-014; 2013-002254-70 (EudraCT Number)