Clinical trial NCT01968031: A 12-week Randomized Study to Evaluate Oral Istradefylline in Subjects With Moderate to Severe Parkinson's Disease
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Idiopathic Parkinson's Disease
Keywords: Parkinson's disease
Moderate to Severe Parkinson's Disease
Lead sponsor: Kyowa Kirin Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Kyowa Hakko Kirin Pharma, Inc.
First posted: 2013-10-23
Enrollment: 613
Sex: ALL
Minimum age (years): 30
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Change From Baseline in the Total Hours of Awake Time/Day Spent in the OFF State at Week 12
timeFrame: Baseline, Week 2, Week 6, Week 10 and Week 12.
Secondary outcomes:
measure: Total Hours of ON Time Per Day Without Troublesome Dyskinesia
timeFrame: Baseline, Week 2, Week 6, Week 10 and Week 12.
measure: Unified Parkinson's Disease Rating Scale (UPDRS) Motor Examination Score (Part III);
timeFrame: Baseline, Week 2, Week 6, Week 10 and Week 12.
measure: Unified Parkinson's Disease Rating Scale (UPDRS) Activities of Daily Living (ADL) Score (Part II)
timeFrame: Baseline, Week 2, Week 6, Week 10 and Week 12.
measure: Unified Parkinson's Disease Rating Scale (UPDRS Mentation, Behaviour) and Mood (Part I)
timeFrame: Baseline, Week 2, Week 6, Week 10 and Week 12.
measure: Total UPDRS (Parts I + II + III);
timeFrame: Baseline, Week 2, Week 6, Week 10 and Week 12.
measure: Patient Global Impression - Improvement (PGI-I) Scale
timeFrame: Baseline, Week 2, Week 6, Week 10, Week 12 and 30-day FU visit
measure: Sleep Time in Hours Per Day Based Upon 24-hour Diaries.
timeFrame: Baseline, Week 2, Week 6, Week 10 and Week 12.
measure: Percentage of Awake Time Per Day Spent in the OFF State
timeFrame: Baseline, Week 2, Week 6, Week 10 and Week 12.
measure: Percentage of ON Time Per Day Without Troublesome Dyskinesia.
timeFrame: Baseline, Week 2, Week 6, Week 10 and Week 12.
measure: Montreal Cognitive Assessment (MoCA)
timeFrame: Baseline and Week 12.
measure: Beck Depression Inventory (BDI)
timeFrame: Baseline and Week 12.
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Kyowa PD Site
state: Arizona
city: Sun City
country: United States
facility: Kyowa PD Site
state: Arizona
city: Tucson
country: United States
facility: Kyowa PD Site
state: Arizona
city: Fountain Valley
country: United States
facility: Kyowa PD Site
state: California
city: Irvine
country: United States
facility: Kyowa PD Site
state: California
city: Los Angeles
country: United States
facility: Kyowa PD Site
state: California
city: Oxnard
country: United States
facility: Kyowa PD Site
state: California
city: Pasadena
country: United States
facility: Kyowa PD Site
state: California
city: Reseda
country: United States
facility: Kyowa PD Site
state: California
city: Sunnyvale
country: United States
facility: Kyowa PD Site
state: California
city: Torrance
country: United States
facility: Kyowa PD Site
state: California
city: Englewood
country: United States
facility: Kyowa PD Site
state: Colorado
city: Danbury
country: United States
facility: Kyowa PD Site
state: Connecticut
city: Boca Raton
country: United States
facility: Kyowa PD Site
state: Florida
city: Jacksonville
country: United States
facility: Kyowa PD Site
state: Florida
city: Panama City
country: United States
facility: Kyowa PD Site
state: Florida
city: Port Charlotte
country: United States
facility: Kyowa PD Site
state: Florida
city: Tampa
country: United States
facility: Kyowa PD Site
state: Florida
city: Atlanta
country: United States
facility: Kyowa PD Site
state: Georgia
city: Augusta
country: United States
facility: Kyowa PD Site
state: Georgia
city: Chicago
country: United States
facility: Kyowa PD Site
state: Illinois
city: Chicago
country: United States
facility: Kyowa PD Site
state: Illinois
city: Des Moines
country: United States
facility: Kyowa PD Site
state: Iowa
city: Kansas City
country: United States
facility: Kyowa PD Site
state: Kansas
city: Baltimore
country: United States
facility: Kyowa PD Site
state: Maryland
city: Boston
country: United States
facility: Kyowa PD Site
state: Massachusetts
city: West Bloomfield
country: United States
facility: Kyowa PD Site
state: Michigan
city: Minneapolis
country: United States
facility: Kyowa PD Site
state: Minnesota
city: Saint Louis
country: United States
facility: Kyowa PD Site
state: Missouri
city: Albany
country: United States
facility: Kyowa PD Site
state: New York
city: New York
country: United States
facility: Kyowa PD Site
state: New York
city: New York
country: United States
facility: Kyowa PD Site
state: New York
city: Asheville
country: United States
facility: Kyowa PD Site
state: North Carolina
city: Durham
country: United States
facility: Kyowa PD Site
state: North Carolina
city: Cincinnati
country: United States
facility: Kyowa PD Site
state: Ohio
city: Cleveland
country: United States
facility: Kyowa PD Site
state: Ohio
city: Toledo
country: United States
facility: Kyowa PD Site
state: Ohio
city: Philadelphia
country: United States
facility: Kyowa PD Site
state: Pennsylvania
city: Charleston
country: United States
facility: Kyowa PD Site
state: South Carolina
city: Dallas
country: United States
facility: Kyowa PD Site
state: Texas
city: Houston
country: United States
facility: Kyowa PD Site
state: Texas
city: Calgary
country: Canada
facility: Kyowa PD Site
state: Alberta
city: Kingston
country: Canada
facility: Kyowa PD Site
state: Ontario
city: Toronto
country: Canada
facility: Kyowa PD Site
state: Ontario
city: Gatineau
country: Canada
facility: Kyowa PD Site
state: Quebec
city: Quebec City
country: Canada
facility: Kyowa PD Site
state: Quebec
city: Brno
country: Czechia
facility: Kyowa PD Site
city: Litomysl
country: Czechia
facility: Kyowa PD Site
city: Olomouc
country: Czechia
facility: Kyowa PD Site
city: Prague
country: Czechia
facility: Kyowa PD Site
city: Prague
country: Czechia
facility: Kyowa PD Site
city: Prague
country: Czechia
facility: Kyowa PD Site
city: Beelitz-Heilstätten
country: Germany
facility: Kyowa PD Site
city: Berlin
country: Germany
facility: Kyowa PD Site
city: Berlin
country: Germany
facility: Kyowa PD Site
city: Bremerhaven
country: Germany
facility: Kyowa PD Site
city: Dresden
country: Germany
facility: Kyowa PD Site
city: Gottingen
country: Germany
facility: Kyowa PD Site
city: Haag
country: Germany
facility: Kyowa PD Site
city: Kassel
country: Germany
facility: Kyowa PD Site
city: Marburg
country: Germany
facility: Kyowa PD Site
city: Munich
country: Germany
facility: Kyowa PD Site
city: Tubingen
country: Germany
facility: Kyowa PD Site
city: Ulm
country: Germany
facility: Kyowa PD Site
city: Haifa
country: Israel
facility: Kyowa PD Site
city: Jerusalem
country: Israel
facility: Kyowa PD Site
city: Petach Tiqva
country: Israel
facility: Kyowa PD Site
city: Ramat Gan
country: Israel
facility: Kyowa PD Site
city: Tel Aviv
country: Israel
facility: Kyowa PD Site
city: Cassino
country: Italy
facility: Kyowa PD Site
city: Chieti
country: Italy
facility: Kyowa PD Site
city: Grosseto
country: Italy
facility: Kyowa PD Site
city: Pavia
country: Italy
facility: Kyowa PD Site
city: Pisa
country: Italy
facility: Kyowa PD Site
city: Rome
country: Italy
facility: Kyowa PD Site
city: Rome
country: Italy
facility: Kyowa PD Site
city: Venezia
country: Italy
facility: Kyowa PD Site
city: Vicenza
country: Italy
facility: Kyowa PD Site
city: Bydgoszcz
country: Poland
facility: Kyowa PD Site
city: Kielce
country: Poland
facility: Kyowa PD Site
city: Krakow
country: Poland
facility: Kyowa PD Site
city: Lublin
country: Poland
facility: Kyowa PD Site
city: Poznan
country: Poland
facility: Kyowa PD Site
city: Warsaw
country: Poland
facility: Kyowa PD Site
city: Warsaw
country: Poland
facility: Kyowa PD Site
city: Belgrade
country: Serbia
facility: Kyowa PD Site 1
city: Belgrade
country: Serbia
facility: Kyowa PD Site 2
city: Belgrade
country: Serbia
facility: Kyowa PD Site 4
city: Novi Sad
country: Serbia
facility: Kyowa PD Site
Study officials:
affiliation: Kyowa Hakko Kirin Pharma, Inc.
name: Kyowa Hakko Kirin Pharma, Inc.
role: STUDY_CHAIR
References: