| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated | | Moderate to severe Parkinson s disease with motor fluctuation and dyskinesias. | |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 8.1 | | E.1.2 | Level | LLT | | E.1.2 | Classification code | 10061536 | | E.1.2 | Term | Parkinson's disease | |
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial | | To assess the efficacy of a range of SCH 420814 doses 1 mg BID, 2 mg BID, 5 mg BID, and possibly 10 mg BID in subjects with moderate to severe Parkinson s disease who are on a stable dose regimen of L-dopa/dopa decarboxylase inhibitor and other adjunctive treatments ie, dopamine agonists, entacapone, or others and are still experiencing on/off motor fluctuations and dyskinesias. | |
| E.2.2 | Secondary objectives of the trial | | To assess the safety and tolerability of a range of SCH 420814 doses 1 mg BID, 2 mg BID, 5 mg BID, and possibly 10 mg BID . | |
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria | | 1. Subjects must be 30 years of age, of either sex, and of any race, with a diagnosis of moderate to severe idiopathic Parkinson s disease for at least 5 years. 2. Subjects must have been on L-dopa for at least 2 years. 3. Subjects must have been judged to be in Hoehn and Yahr stages ranging from 3 to 4 in the off state. 4. Subjects must have been on a stable regimen of L-dopa and a dopamine agonist for at least 4 weeks before screening, and are still experiencing on/off motor fluctuations and dyskinesias. 5. During the baseline period, subjects must demonstrate a minimum of 2 hours of off time during awake time per day on 3 consecutive days excluding the morning predose period and the postdose period of 1 hour . 6. Women of childbearing potential must have a negative serum pregnancy test at Screening. If subject is postmenopausal not surgically induced , she must be postmenopausal by history for at least 2 years before study entry. If not, proper birth control must be used. Note Acceptable methods of birth control include oral or injectable hormonal contraceptive, medically prescribed IUD, and double-barrier method eg, condom in combination with spermicide . Bilateral tubal ligation is an acceptable method of birth control for this study. 7. Subjects clinical laboratory tests CBC, blood chemistries, and urinalysis must be within normal limits or clinically acceptable to the investigator/sponsor. | |
| E.4 | Principal exclusion criteria | | 1. Subjects with any form of drug-induced or atypical parkinsonism, cognitive impairment Mini-Mental State Examination MMSE score 23 , a history of DSM IV diagnosed major depression, unstable mild depression or psychosis, or subjects taking tolcapone will be excluded. Subjects with mild depression who are well controlled on a stable dose of an antidepressant medication for at least 4 weeks before screening will be eligible. 2. Subjects with values of greater than the ULN at Screening for any of the following LFTs ALT, AST, GGT, ALK-P, or T-BIL. 3. All subjects with a severe or ongoing unstable medical condition will be excluded including those with a history of uncontrolled hypertension, cerebrovascular disease, or any form of clinically significant cardiac disease, symptomatic orthostatic hypotension, renal failure, history of abnormal renal function, seizures, alcohol/drug dependence, or previous surgery for Parkinson s disease. 4. Subjects with a serologically confirmed hepatic dysfunction defined as viral infection hepatitis A, B, or C; HIV; EB; CMV ; drug-induced diagnoses of hepatic toxicity or frank hepatitis; or abnormal ALT 3 x ULN on more than one occasion . 5. Elevated BP systolic BP 180 mm Hg; OR diastolic BP 105 mm Hg . 6. Subjects who have received any prohibited treatment including potentially hepatotoxic drugs more recently than the indicated washout period prior to Baseline or those who must continue to receive treatment listed in Table 3. 7. Because it is not known whether SCH 420814 passes into breast milk and because the effects, if any, of SCH 420814 on the developing human are unknown, women who are breastfeeding or who are considering breastfeeding are excluded from this trial. 8. Subjects with allergy/sensitivity to study drug or its excipients. 9. Subjects with any clinically significant condition or situation, other than the condition being studied that, in the opinion of the investigator, would interfere with the study evaluations or optimal participation in the study. 10. Subjects who have used any other investigational drugs within 4 weeks of Screening. 11. Subjects who are participating in any other clinical study. | |
| E.5 End points |
| E.5.1 | Primary end point(s) | | The primary efficacy endpoint is the mean change from Baseline to endpoint of 12 weeks of treatment in the 3-day average based on subject diaries of time in hours spent in the off state, excluding the morning predose and postdose period of 1 hour. | |
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | Yes |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | Information not present in EudraCT |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Information not present in EudraCT |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.3 | The trial involves single site in the Member State concerned | No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned | |
| E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
| E.8.8 | Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial | |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
