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

Idiopathic Parkinson's Disease Clinical Trial

— KW-6002  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01968031
• Other study ID #: 6002-014
• Secondary ID: 2013-002254-70
• Status: Completed
• Phase: Phase 3
• Start date: October 2013
• Est. completion date: October 2016

Study information

• Verified date: April 2024
• Source: Kyowa Kirin Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 613
• Est. completion date: October 2016
• Est. primary completion date: October 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Idiopathic Parkinson's Disease
• Parkinson Disease

Intervention

Drug:
• Istradefylline 40 mg
Istradefylline 40 mg and placebo
• Istradefylline 20 mg
Istradefylline 20 mg and placebo
• Placebo
Placebo

Locations

Country	Name	City	State
Canada	Kyowa PD Site	Calgary	Alberta
Canada	Kyowa PD Site	Gatineau	Quebec
Canada	Kyowa PD Site	Kingston	Ontario
Canada	Kyowa PD Site	Quebec City	Quebec
Canada	Kyowa PD Site	Toronto	Ontario
Czechia	Kyowa PD Site	Brno
Czechia	Kyowa PD Site	Litomysl
Czechia	Kyowa PD Site	Olomouc
Czechia	Kyowa PD Site	Prague
Czechia	Kyowa PD Site	Prague
Czechia	Kyowa PD Site	Prague
Germany	Kyowa PD Site	Beelitz-Heilstätten
Germany	Kyowa PD Site	Berlin
Germany	Kyowa PD Site	Berlin
Germany	Kyowa PD Site	Bremerhaven
Germany	Kyowa PD Site	Dresden
Germany	Kyowa PD Site	Gottingen
Germany	Kyowa PD Site	Haag
Germany	Kyowa PD Site	Kassel
Germany	Kyowa PD Site	Marburg
Germany	Kyowa PD Site	Munich
Germany	Kyowa PD Site	Tubingen
Germany	Kyowa PD Site	Ulm
Israel	Kyowa PD Site	Haifa
Israel	Kyowa PD Site	Jerusalem
Israel	Kyowa PD Site	Petach Tiqva
Israel	Kyowa PD Site	Ramat Gan
Israel	Kyowa PD Site	Tel Aviv
Italy	Kyowa PD Site	Cassino
Italy	Kyowa PD Site	Chieti
Italy	Kyowa PD Site	Grosseto
Italy	Kyowa PD Site	Pavia
Italy	Kyowa PD Site	Pisa
Italy	Kyowa PD Site	Rome
Italy	Kyowa PD Site	Rome
Italy	Kyowa PD Site	Venezia
Italy	Kyowa PD Site	Vicenza
Poland	Kyowa PD Site	Bydgoszcz
Poland	Kyowa PD Site	Kielce
Poland	Kyowa PD Site	Krakow
Poland	Kyowa PD Site	Lublin
Poland	Kyowa PD Site	Poznan
Poland	Kyowa PD Site	Warsaw
Poland	Kyowa PD Site	Warsaw
Serbia	Kyowa PD Site 1	Belgrade
Serbia	Kyowa PD Site 2	Belgrade
Serbia	Kyowa PD Site 4	Belgrade
Serbia	Kyowa PD Site	Novi Sad
United States	Kyowa PD Site	Albany	New York
United States	Kyowa PD Site	Asheville	North Carolina
United States	Kyowa PD Site	Atlanta	Georgia
United States	Kyowa PD Site	Augusta	Georgia
United States	Kyowa PD Site	Baltimore	Maryland
United States	Kyowa PD Site	Boca Raton	Florida
United States	Kyowa PD Site	Boston	Massachusetts
United States	Kyowa PD Site	Charleston	South Carolina
United States	Kyowa PD Site	Chicago	Illinois
United States	Kyowa PD Site	Chicago	Illinois
United States	Kyowa PD Site	Cincinnati	Ohio
United States	Kyowa PD Site	Cleveland	Ohio
United States	Kyowa PD Site	Dallas	Texas
United States	Kyowa PD Site	Danbury	Connecticut
United States	Kyowa PD Site	Des Moines	Iowa
United States	Kyowa PD Site	Durham	North Carolina
United States	Kyowa PD Site	Englewood	Colorado
United States	Kyowa PD Site	Fountain Valley	California
United States	Kyowa PD Site	Houston	Texas
United States	Kyowa PD Site	Irvine	California
United States	Kyowa PD Site	Jacksonville	Florida
United States	Kyowa PD Site	Kansas City	Kansas
United States	Kyowa PD Site	Los Angeles	California
United States	Kyowa PD Site	Minneapolis	Minnesota
United States	Kyowa PD Site	New York	New York
United States	Kyowa PD Site	New York	New York
United States	Kyowa PD Site	Oxnard	California
United States	Kyowa PD Site	Panama City	Florida
United States	Kyowa PD Site	Pasadena	California
United States	Kyowa PD Site	Philadelphia	Pennsylvania
United States	Kyowa PD Site	Phoenix	Arizona
United States	Kyowa PD Site	Port Charlotte	Florida
United States	Kyowa PD Site	Reseda	California
United States	Kyowa PD Site	Saint Louis	Missouri
United States	Kyowa PD Site	Sun City	Arizona
United States	Kyowa PD Site	Sunnyvale	California
United States	Kyowa PD Site	Tampa	Florida
United States	Kyowa PD Site	Toledo	Ohio
United States	Kyowa PD Site	Torrance	California
United States	Kyowa PD Site	Tucson	Arizona
United States	Kyowa PD Site	West Bloomfield	Michigan

Sponsors (2)

Lead Sponsor	Collaborator
Kyowa Kirin Co., Ltd.	Kyowa Hakko Kirin Pharma, Inc.

Countries where clinical trial is conducted

United States,  Canada,  Czechia,  Germany,  Israel,  Italy,  Poland,  Serbia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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
Secondary	Sleep Time in Hours Per Day Based Upon 24-hour Diaries.		Baseline, Week 2, Week 6, Week 10 and Week 12.
Secondary	Percentage of Awake Time Per Day Spent in the OFF State		Baseline, Week 2, Week 6, Week 10 and Week 12.
Secondary	Percentage of ON Time Per Day Without Troublesome Dyskinesia.		Baseline, Week 2, Week 6, Week 10 and Week 12.
Secondary	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.
Secondary	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.

External 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.