A 16-week, Double-Blind, Placebo-Controlled, Randomised, Parallel-Group, Multicentre, International Study to Evaluate the Efficacy and Safety of 40 mg/day KW-6002 (istradefylline) and that of Entacapone versus Placebo as Treatment for Parkinson's Disease in Patients with Motor Response Complications on Levodopa Therapy.

Conditions: Parkinson's Disease

Registration Number: EUCTR2004-000817-20-LT

Lead Sponsor: Kyowa Hakko U.K. Limited

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 405

Inclusion Criteria

Each patient must meet all inclusion criteria to qualify for entrance into the study:

1. Patients who meet the UK Parkinson's Disease Society (UKPDS) brain bank diagnostic criteria (Step 1 and 2) for Parkinson's disease (refer to Appendix 14.3 of protocol).
2. Patients who have PD in Stages 2-4 while in the OFF state on the Modified Hoehn and Yahr Scale (refer to Appendix 14.4 of protocol).
3. Patients who have been on standard preparations of levodopa (with either carbidopa or benserazide) for at least one year, and who have been on a stable PD regimen within normal therapeutic limits including levodopa for at least four weeks before baseline.
4. Patients who currently take at least three doses of levodopa per day.
5. Patients who have predictable end-of-dose wearing off.
6. Patients and site staff must each complete a practice diary and achieve concordance of 80% with respect to both ON and OFF periods at the Week -1 visit.
7. Patients who successfully complete two ‘valid’ diaries on any two consecutive days during the week (7-day period) before the visit at baseline (refer to Section 9.4.1 Screening of protocol).
8. Patients who have an average of at least 3 hours of OFF time on the two diaries prior to the baseline visit, and not more than four invalid entries per diary.
9. Patients who are male or female and at least 30 years of age.
10. Patients who are female must be non-pregnant and non-nursing. Women of Child-Bearing Potential (WOCBP) must use a reliable method of contraception (e.g., oral contraceptive or long-term injectable or implantable hormonal contraceptive, double-barrier methods, such as condom and diaphragm, condom and foam, condom and sponge or intra-uterine devices) and have a negative urine pregnancy test at screening and at baseline. Women are considered to not be of child-bearing potential if they have been surgically sterilized (physician-documented hysterectomy or tubal ligation) or if they are post-menopausal [complete absence of menses for two consecutive years and a serum FSH level of > 30 IU/L in the absence of hormone replacement therapy (HRT)].
11. Patients who are able to give written informed consent.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

A patient who meets any of the following criteria will NOT qualify for the study:

1. Patients who are currently being treated with any restricted medications listed (refer to Concomitant Treatment section 7.5 of protocol).
2. Patients who are treated within 30 days before baseline (or five half-lives of the compound, if longer) with any investigational agent.
3. Patients who have a history of a psychotic illness.
4. Patients who are treated within three months (six months if patient was treated with depot) before baseline with an anti-psychotic agent, apart from patients experiencing levodopa or Parkinson’s disease-induced hallucinations with insight retained where atypical anti-psychotic agents may be allowed at the discretion of the designated Medical Officer.
5. Patients who are treated with any centrally acting drug that has known dopamine antagonist properties at therapeutic doses (e.g., buspirone, amoxapine).
6. Patients who have had a neurosurgical operation for Parkinson's disease (e.g., pallidotomy, thalamotomy, deep brain stimulation).
7. Patients who have previously received istradefylline.
8. Patients who have atypical parkinsonism.
9. Patients who have secondary parkinsonism variants.
10. Patients who have a diagnosis of cancer or evidence of continued disease within five years of study enrolment (except for patients that have had basal cell carcinoma or carcinoma in situ of the cervix surgically excised).
11. Patients who have a clinically significant illness of any organ system which may compromise the safety of the patient during the trial or affect the ability of the patient to complete the trial.
12. Patients who, for any reason, are judged by the Investigator to be inappropriate for this study, including a patient who is unable to communicate or to cooperate with the Investigator.
13. Patients who have an ALT and/or AST level greater than 1.5 ULN at screening.
14. Patients with a Mini-Mental Status Examination (MMSE) score of 25 or less (refer to Appendix 14.5 of protocol).
15. Patients who have a history of drug or alcohol abuse or dependence within the last year (DSM-IVR).
16. Patients with significant drug allergies.
17. Patients who, in the opinion of the Investigator, currently have a clinically relevant depression (whether or not under active treatment).
18. Patients who have a history of seizure or seizure disorders.
19. Patients who have a history of neuroleptic malignant syndrome.
20. Patients taking, or with a history of taking, any COMT inhibitor.