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

Recruitment Status
COMPLETED - HAS RESULTS
(See Contacts and Locations)Verified March 2024 by Kyowa Kirin Co., Ltd.
Sponsor
Kyowa Kirin Co., Ltd.
Information Provided by (Responsible Party)
Kyowa Kirin Co., Ltd.
Clinicaltrials.gov Identifier
NCT01968031
Other Study ID Numbers:
6002-014
First Submitted
October 17, 2013
First Posted
October 22, 2013
Results First Posted
September 15, 2020
Last Update Posted
April 24, 2024
Last Verified
March 2024

ClinicalTrials.gov processed this data on April 2024. Link to the current ClinicalTrials.gov record .

History of Changes

Study Details

Study Description

Condition or DiseaseIntervention/Treatment
Idiopathic Parkinson's Disease
Drug: Istradefylline 20 mgDrug: Istradefylline 40 mgDrug: Placebo

Study Design

Study TypeInterventional
Actual Enrollment613 participants
Design AllocationRandomized
Interventional ModelParallel Assignment
MaskingQuadruple
Primary PurposeTreatment
Official TitleA 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
Study Start DateSeptember 30, 2013
Actual Primary Completion DateSeptember 30, 2016
Actual Study Completion DateSeptember 30, 2016

Groups and Cohorts

Group/CohortIntervention/Treatment
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: Istradefylline 20 mg
Istradefylline 20 mg and placebo
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: Istradefylline 40 mg
Istradefylline 40 mg and 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.
Drug: Placebo
Placebo

Outcome Measures

Primary Outcome Measures
  1. 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.
Secondary Outcome Measures
  1. Total Hours of ON Time Per Day Without Troublesome Dyskinesia
    Based on Patient's ON/OFF Diary
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. Sleep Time in Hours Per Day Based Upon 24-hour Diaries.
  8. Percentage of Awake Time Per Day Spent in the OFF State
  9. Percentage of ON Time Per Day Without Troublesome Dyskinesia.
  10. 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.
  11. 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

Eligibility Criteria

Ages Eligible for Study(Adult, Older Adult)
Sexes Eligible for StudyAll
Accepts Healthy VolunteersNo
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

Contacts and Locations

Sponsors and CollaboratorsKyowa Kirin Co., Ltd.
Locations
Kyowa PD Site | Phoenix Arizona, United States, 85004Kyowa PD Site | Sun City Arizona, United States, 85351Kyowa PD Site | Tucson Arizona, United States, 85724Kyowa PD Site | Fountain Valley California, United States, 92708Kyowa PD Site | Irvine California, United States, 92697Kyowa PD Site | Los Angeles California, United States, 90048Kyowa PD Site | Oxnard California, United States, 93030Kyowa PD Site | Pasadena California, United States, 91105Kyowa PD Site | Reseda California, United States, 91335Kyowa PD Site | Sunnyvale California, United States, 94085Kyowa PD Site | Torrance California, United States, 90505Kyowa PD Site | Englewood Colorado, United States, 80113Kyowa PD Site | Danbury Connecticut, United States, 06810Kyowa PD Site | Boca Raton Florida, United States, 33486Kyowa PD Site | Jacksonville Florida, United States, 32209Kyowa PD Site | Panama City Florida, United States, 32405Kyowa PD Site | Port Charlotte Florida, United States, 33980Kyowa PD Site | Tampa Florida, United States, 33647Kyowa PD Site | Atlanta Georgia, United States, 30329Kyowa PD Site | Augusta Georgia, United States, 29841Kyowa PD Site | Chicago Illinois, United States, 60611Kyowa PD Site | Chicago Illinois, United States, 60612Kyowa PD Site | Des Moines Iowa, United States, 50309Kyowa PD Site | Kansas City Kansas, United States, 66160Kyowa PD Site | Baltimore Maryland, United States, 21201Kyowa PD Site | Boston Massachusetts, United States, 02215Kyowa PD Site | West Bloomfield Michigan, United States, 48322Kyowa PD Site | Minneapolis Minnesota, United States, 55414Kyowa PD Site | St Louis Missouri, United States, 63110Kyowa PD Site | Albany New York, United States, 12208Kyowa PD Site | New York New York, United States, 10016Kyowa PD Site | New York New York, United States, 10032Kyowa PD Site | Asheville North Carolina, United States, 28806Kyowa PD Site | Durham North Carolina, United States, 27705Kyowa PD Site | Cincinnati Ohio, United States, 45219Kyowa PD Site | Cleveland Ohio, United States, 44195Kyowa PD Site | Toledo Ohio, United States, 43614Kyowa PD Site | Philadelphia Pennsylvania, United States, 19107Kyowa PD Site | Charleston South Carolina, United States, 29401Kyowa PD Site | Dallas Texas, United States, 75390-9036Kyowa PD Site | Houston Texas, United States, 77030Kyowa PD Site | Calgary Alberta, Canada, AB T2NKyowa PD Site | Kingston Ontario, Canada, K7L 2V7Kyowa PD Site | Toronto Ontario, Canada, M5T 2S8Kyowa PD Site | Gatineau Quebec, Canada, J9J 0A5Kyowa PD Site | Québec Quebec, Canada, G1S 2L6Kyowa PD Site | Brno , Czechia, 656 91Kyowa PD Site | Litomyšl , Czechia, 570 01Kyowa PD Site | Olomouc , Czechia, 775 20Kyowa PD Site | Prague , Czechia, 12 000Kyowa PD Site | Prague , Czechia, 140 00Kyowa PD Site | Prague , Czechia, 150 06Kyowa PD Site | Beelitz-Heilstätten , Germany, 14547Kyowa PD Site | Berlin , Germany, 12203Kyowa PD Site | Berlin , Germany, 13088Kyowa PD Site | Bremerhaven , Germany, 27574Kyowa PD Site | Dresden , Germany, 01307Kyowa PD Site | Göttingen , Germany, 37075Kyowa PD Site | Haag , Germany, 83527Kyowa PD Site | Kassel , Germany, 34128Kyowa PD Site | Marburg , Germany, 35043Kyowa PD Site | Munich , Germany, 80804Kyowa PD Site | Tübingen , Germany, 72076Kyowa PD Site | Ulm , Germany, 89081Kyowa PD Site | Haifa , Israel, 39106Kyowa PD Site | Jerusalem , Israel, 91120Kyowa PD Site | Petach Tiqva , Israel, 49372Kyowa PD Site | Ramat Gan , Israel, 52621Kyowa PD Site | Tel Aviv , Israel, 64239Kyowa PD Site | Cassino , Italy, 03043Kyowa PD Site | Chieti , Italy, 66013Kyowa PD Site | Grosseto , Italy, 58100Kyowa PD Site | Pavia , Italy, 27100Kyowa PD Site | Pisa , Italy, 56126Kyowa PD Site | Rome , Italy, 00133Kyowa PD Site | Rome , Italy, 00163Kyowa PD Site | Venezia , Italy, 30126Kyowa PD Site | Vicenza , Italy, 36057Kyowa PD Site | Bydgoszcz , Poland, 85-796Kyowa PD Site | Kielce , Poland, 25-103Kyowa PD Site | Krakow , Poland, 31-505Kyowa PD Site | Lublin , Poland, 20-093Kyowa PD Site | Poznan , Poland, 61-853Kyowa PD Site | Warsaw , Poland, 01-697Kyowa PD Site | Warsaw , Poland, 04-364Kyowa PD Site 1 | Belgrade , Serbia, 11000Kyowa PD Site 2 | Belgrade , Serbia, 11000Kyowa PD Site 4 | Belgrade , Serbia, 11000Kyowa PD Site | Novi Sad , Serbia, 21000
Investigators
Study Chair: Kyowa Hakko Kirin Pharma, Inc., Kyowa Hakko Kirin Pharma, Inc.