A Phase 2b Study of Istradefylline (KW-6002) for the Treatment of Parkinson's Disease in Patients Taking Levodopa

Placebo-controlled, Double-blind, Parallel Group, Fixed Dose Study of KW-6002 (Istradefylline) in the Treatment of Parkinson's Disease (Phase 2 Study)

The purpose of this study is to establish the efficacy of 20 mg/day and 40 mg/day doses of istradefylline for reducing the mean total hours of awake time per day spent in the OFF state in patients with advanced Parkinson's disease (PD) treated with levodopa.

Study Overview

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

Detailed Description

To establish the efficacy of 20 mg/day and 40 mg/day doses of istradefylline for reducing the mean total hours of awake time per day spent in the OFF state in patients with advanced Parkinson's disease (PD) treated with levodopa. Patients who meet entry criteria will be randomized in a 1:1:1 ratio to double blind treatment with oral doses of 20 or 40mg/day istradefylline or matching placebo. Patients will be treated for 12 weeks and will have interim visits and end of treatment visit to assess the efficacy and safety of istradefylline.

• Study Type: Interventional
• Enrollment (Actual): 363
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Tokyo, Japan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. UK Parkinson's Disease Society (UKPDS) brain bank criteria (Step 1 and 2) for PD.
2. PD stages 2-4 in the OFF state for Modified Hoehn and Yahr Scale.
3. On levodopa/dopa-decarboxylase inhibitor for at least one year.
4. Taking at least three doses and >=300mg of levodopa per day for at least four weeks before randomization.
5. Predictable end of dose wearing off.
6. Able to satisfactorily complete Hauser based 24-hour patient Parkinson's diary.
7. Have an average of two hours of OFF time on 24-hour diaries.
8. On a stable regimen of any other anti-Parkinson's drugs for at least four weeks before randomization.
9. Be at least 20 years of age.
10. Be willing and able to give written informed consent.

Exclusion Criteria:

1. Taking any excluded medications.
2. Neurosurgical treatment or Transcranial Magnetic Stimulation for PD.
3. Diagnosis of cancer within 5 years.
4. Diagnosis of clinically significant illness of any organ system.
5. Diagnosis of dementia or mini-mental status examination score of 25 or less.
6. History of drug or alcohol abuse or dependence within the past two years.
7. History of psychosis.
8. Significant drug allergies.
9. Taking anticonvulsants for seizures.
10. History of neurological malignant syndrome.
11. Pregnant or lactating females.

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: 1; 20 mg KW-6002 per day (two 10 mg tablets orally once daily for 12 weeks)	Drug: Istradefylline; Two 10 mg KW-6002 tablets orally once daily for 12 weeks; Other Names: KW-6002; Drug: Istradefylline; Two 20 mg tablets orally once a day for 12 weeks; Other Names: KW-6002
Experimental: 2; 40mg KW-6002 per day (two 20 mg KW-6002 tablets orally once daily for 12 weeks)	Drug: Istradefylline; Two 10 mg KW-6002 tablets orally once daily for 12 weeks; Other Names: KW-6002; Drug: Istradefylline; Two 20 mg tablets orally once a day for 12 weeks; Other Names: KW-6002
Placebo Comparator: 3; Two placebo tablets once daily for 12 weeks	Drug: Placebo; Two placebo tablets orally once daily for 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To establish the efficacy of 20 mg/day and 40 mg/day doses of istradefylline for reducing the mean total hours of awake time per day spent in the OFF state in patients with Parkinson's disease (PD) treated with levodopa/dopa-decarboxylase inhibitor.	Last Visit

Secondary Outcome Measures

Outcome Measure	Time Frame
To evaluate the efficacy of 20 mg/day and 40 mg/day doses of istradefylline for reducing the mean percentage of awake time per day spent in the OFF state.	Every Visit
To evaluate mean change in the total hours and the percentage of awake time per day spent in the ON state (without dyskinesia, with dyskinesia, with non-troublesome dyskinesia, and with troublesome dyskinesia).	Every Visit
To evaluate the change in Unified Parkinson's Disease Rating Scale (UPDRS).	Every Visit
To evaluate change in the Clinical Global Impression - Improvement scale (CGI-I).	Visit 4 and Last Visit
To evaluate the safety of 20 mg/day and 40mg/day doses of istradefylline	Every Visit

Collaborators and Investigators

• Sponsor: Kyowa Kirin Co., Ltd.

Study record dates

Study Major Dates

• Study Start: March 1, 2007
• Primary Completion (Actual): August 1, 2008
• Study Completion (Actual): August 1, 2008

Study Registration Dates

• First Submitted: April 2, 2007
• First Submitted That Met QC Criteria: April 2, 2007
• First Posted (Estimate): April 3, 2007

Study Record Updates

• Last Update Posted (Estimate): August 29, 2012
• Last Update Submitted That Met QC Criteria: August 28, 2012
• Last Verified: August 1, 2012

More Information

Terms related to this study

• Keywords: levodopa; Parkinson's disease; end of dose wearing off; OFF time
• 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: 6002-0608