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

• ClinicalTrials.gov Identifier: NCT00455507
• Recruitment Status: Completed
• First Posted: April 3, 2007
• Last Update Posted: August 29, 2012
• Sponsor: Kyowa Kirin Co., Ltd.
• Information provided by (Responsible Party): Kyowa Kirin Co., Ltd.

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Parkinson's Disease	Drug: Istradefylline; Drug: Placebo	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 363 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Placebo-controlled, Double-blind, Parallel Group, Fixed Dose Study of KW-6002 (Istradefylline) in the Treatment of Parkinson's Disease (Phase 2 Study)
• Study Start Date: March 2007
• Actual Primary Completion Date: August 2008
• Actual Study Completion Date: August 2008

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. 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. [ Time Frame: Last Visit ]

Secondary Outcome Measures :

1. 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. [ Time Frame: Every Visit ]
2. 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). [ Time Frame: Every Visit ]
3. To evaluate the change in Unified Parkinson's Disease Rating Scale (UPDRS). [ Time Frame: Every Visit ]
4. To evaluate change in the Clinical Global Impression - Improvement scale (CGI-I). [ Time Frame: Visit 4 and Last Visit ]
5. To evaluate the safety of 20 mg/day and 40mg/day doses of istradefylline [ Time Frame: Every Visit ]

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

Japan

Tokyo, Japan

Sponsors and Collaborators

Kyowa Kirin Co., Ltd.

Investigators

• Study Director: Study Director; Kyowa Kirin Co., Ltd.

More Information

• Responsible Party: Kyowa Kirin Co., Ltd.
• ClinicalTrials.gov Identifier: NCT00455507
• Other Study ID Numbers: 6002-0608
• First Posted: April 3, 2007
• Last Update Posted: August 29, 2012
• Last Verified: August 2012

Keywords provided by Kyowa Kirin Co., Ltd.:

Parkinson's disease; levodopa; end of dose wearing off; OFF time

Additional relevant MeSH terms:

Parkinson Disease; Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Istradefylline; Adenosine A2 Receptor Antagonists; Purinergic P1 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs