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.

• Register: EUCTR
• Last refreshed on: 3 September 2012
• Main ID: EUCTR2004-000817-20-LT
• Date of registration: 07/01/2005
• Prospective Registration: No
• Primary sponsor: Kyowa Hakko U.K. Limited
• Public title: 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.
• Scientific title: 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.
• Date of first enrolment: 16/09/2004
• Target sample size: 405
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2004-000817-20
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: no

Countries of recruitment

Italy, Latvia, Lithuania, Spain

Key inclusion & exclusion criteria

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.




Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Parkinson's Disease

Intervention(s)

Product Name: Istradefylline
Product Code: KW-6002
Pharmaceutical Form: Tablet
INN or Proposed INN: Istradefylline
Current Sponsor code: KW-6002
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Trade Name: Comtess
Product Name: Comtess
Pharmaceutical Form: Tablet
INN or Proposed INN: Entacapone
CAS Number: 130929-57-6
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-
Pharmaceutical form of the placebo: Capsule*
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: • To evaluate the efficacy of a 40 mg/day dose of istradefylline for reducing the total hours of OFF time.
• To evaluate the change in total hours of ON time and percentage of ON time (without dyskinesia, with dyskinesia, with non-troublesome dyskinesia and with troublesome dyskinesia).
• To evaluate the change, in Unified Parkinson’s Disease Rating Scale (UPDRS) Mentation, Behaviour and Mood score (part I), Activities of Daily Living score (ADL) (part II), Motor Examination score (part III) or Dyskinesia score (part IVA)
• To evaluate the change, in Parkinson’s Disease Questionnaire (PDQ-39) and Medical Outcomes Study 36-item Short Form (SF-36)
• To evaluate the Patient Global Impression - Improvement scale (PGI-I)
• To evaluate change in the Clinical Global Impression - Severity of Illness scale (CGI-S)
• To evaluate the safety of a 40 mg/day dose of istradefylline by evaluation of changes in safety parameters as noted in Section 10.1.1 of the protocol.

Primary end point(s): The Primary efficacy variable will be the change from baseline in percentage of awake time per day spent in the OFF state at Endpoint. Supportive efficacy variables will be all other OFF state variables including total hours per day spent in the OFF state, change from baseline in total hours OFF, and percentage of awake time per day spent in the OFF state.

Main Objective: To establish the efficacy of 40 mg/day of istradefylline in reducing the percentage of OFF time in patients with advanced Parkinson’s disease treated with levodopa.

Secondary ID(s)

2004-000817-20-LV

6002-EU-007