A Placebo- and Active-Controlled Study of Preladenant in Early Parkinson's Disease (Study P05664)

• Register: EUCTR
• Last refreshed on: 3 February 2014
• Main ID: EUCTR2009-013552-72-SE
• Date of registration: 06/10/2010
• Prospective Registration: Yes
• Primary sponsor: Schering-Plough Research Institute, a division of Schering Corporation
• Public title: A Placebo- and Active-Controlled Study of Preladenant in Early Parkinson's Disease (Study P05664)
• Scientific title: A Phase 3, Double-Blind, Double-Dummy, Placebo- and Active-Controlled Dose-Range-Finding Efficacy and Safety Study of Preladenant in Subjects With Early Parkinson’s Disease (Phase 3 Protocol No. P05664) - PARADYSE - Monotherapy
• Date of first enrolment: 02/12/2010
• Target sample size: 1000
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-013552-72
• 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 Number of treatment arms in the trial: 5

Countries of recruitment

Argentina, Austria, Brazil, Bulgaria, Canada, Chile, Colombia, Czech Republic, Finland, France, Germany, Hungary, India, Israel, Italy, Mexico, Netherlands, Peru, Poland, Portugal, Russian Federation, Spain, Sweden, Turkey, United Kingdom, United States

Contacts

• Name: Kenneth Wolski, MD
• Affiliation: Schering-Plough Research Institute, a division of Schering Corporation

• Name: Kenneth Wolski, MD
• Affiliation: Schering-Plough Research Institute, a division of Schering Corporation

Key inclusion & exclusion criteria

Inclusion criteria:
• Subjects with a diagnosis of idiopathic PD for less than 5 years based on the United Kingdom Parkinson’s Disease Society Brain Bank Criteria (see Appendix 1) and the inclusion/exclusion criteria for this protocol.
a. Subject should have bradykinesia and at least one of the following symptoms:
i. Muscular rigidity
ii. Resting tremor (4 to 6 Hz; Please note that for the purposes of this study, a diagnosis based solely on bradykinesia and postural instability is insufficient for diagnosis of idiopathic Parkinson's Disease, and subjects diagnosed in this manner cannot be enrolled in the study)
b. If resting tremor is not present at screening, the rigidity and/or bradykinesia must be asymmetric.
• Subject who is receiving amantadine and/or anticholinergics must have been on a stable regimen of treatment for at least the 5 weeks before Screening.
• Each subject must have a UPDRS Part 3 score of >= 10.
• Each subject's Hoehn and Yahr Stage must be <= 3.
• Each subject must be willing and able to provide written informed consent for the trial. For a subject who is unable to provide independent consent, a legal representative may provide written informed consent. Subjects who are unwilling to provide written informed consent for exploratory pharmacogenetic testing may be included in the trial; however, exploratory pharmacogenetic samples must not be obtained.
• Each subject must be 30 to 85 years of age. A subject may be of either gender and any race/ethnicity.
• Each subject must have results of Screening clinical laboratory tests (hematology, blood chemistries, and urinalysis) drawn within 5 weeks (which can be extended by no more than 7 days, if the Sponsor's
approval is obtained for the extension) prior to Randomization, clinically acceptable to the investigator, and not within the parameters specified for exclusion (below).
• All subjects that are sexually active or plan to be sexually active agree to use a highly effective method of birth control while the subject is in the study and for 2 weeks after the last dose of study drug. A male subject must also not donate sperm during the trial and within 2 weeks after the last dose of study drug. Complete details regarding contraceptive requirements are specified in protocol Section 7.7.2.7.
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 400
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 600

Exclusion criteria:
Subjects must not have/be:
• A form of drug induced or atypical parkinsonism, cognitive impairment (MoCA score<22), bipolar disorder, schizophrenia or other psychotic disorder.
• A history of repeated strokes; with stepwise progression of Parkinsonian features; repeated head injury; definitive encephalitis; oculogyric crises; neuroleptic treatment at onset of symptoms; more than one first degree relative affected; sustained remission; strictly unilateral features after 3 years; supranuclear gaze palsy; cerebellar signs; early severe autonomic involvement; severe symptomatic autonomic involvement unrelated to medications; early severe dementia with disturbances of memory, language, and; praxis; Babinski sign with clear, clinically significant pyramidal tract involvement; negative response to large doses of L-dopa (if malabsorption excluded) or failure to respond to an adequate previous treatment with dopaminergic therapy; MPTP or known neurotoxin exposure; hallucinations unrelated to medications; surgery for PD.
• Treated with L-dopa or dopamine agonists for 30 days or more. A subject who has been treated with L-dopa or dopamine agonists for <30 days at any time will be allowed to enrol. Subjects who are still taking dopaminergic medication at Screening or who stopped taking dopaminergic medication within 30 days of Randomization must still wash out from dopaminergic medication for a total of 30 days prior Randomization. Motor scores (UPDRS Pt3) should be evaluated at wash out Day 15, at an unscheduled Visit during the mandatory 30 day washout period for those subjects who stop taking their dopaminergic medications at Screening.
• At imminent risk of self-harm or to others (in the investigator's opinion based on CSSRS).
• A systolic BP >=150mm Hg OR diastolic BP >=95mm Hg at Screening and at a BP recheck prior Randomization. Measures to control/adjust BP can be taken to meet the BP entry criterion up to Randomization (Day 1), but if the subject's BP is not within range on Day 1 then s/he cannot enrol. Repeated BP measurements intended to obtain acceptable BP entry criteria are not allowed, ie if the subject's BP is not within the range as per BP exclusion criterion on Day 1 then s/he cannot be randomized. If BP is elevated at the Screening Visit, initiation or alteration of the dose of antihypertensive medicine can be done to obtain 2 BP measurements meeting this criterion at consecutive separate visits (scheduled or unscheduled) between the Screening Visit and the Randomization Visit (which is 5 weeks and may be extended by no more than 7days if the Sponsor's approval is obtained for the extension).
• An untreated major depressive disorder meeting Diagnostic and Statistical Manual of Mental Disorders IV Text Revision criteria or BDI II score =19. A subject is eligible to enrol if successfully treated with stable doses of allowed antidepressant medications for at least 5 weeks immediately before Screening.
• Any clinically significant cardiovascular event/procedure for 6 months prior Randomization, including but not limited to, myocardial infarction, prolonged QTc interval (a subject must not have a QTcF result >500msec), angioplasty, unstable angina or heart failure (staged NYHA
Class III or IV).
• An ALT or AST >=3 x ULN or total bilirubin (T-BIL) >=1.5 x ULN. Should an LFT be abnormal (ALT/AST >ULN but <3 x ULN, T-BIL >ULN but <1.5 x ULN) at Screening, the investigator should attempt to characterize at entry the reason(s) for elevati

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

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Parkinson's disease
MedDRA version: 16.0 Level: PT Classification code 10061536 Term: Parkinson's disease System Organ Class: 10029205 - Nervous system disorders

Intervention(s)

Product Name: Preladenant
Product Code: SCH 420814
Pharmaceutical Form: Coated tablet
INN or Proposed INN: Preladenant
CAS Number: 377727-87-2
Current Sponsor code: SCH 420814
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 2-10
Pharmaceutical form of the placebo: Coated tablet
Route of administration of the placebo: Oral use

Trade Name: Azilect
Product Name: Azilect
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Rasagiline mesylate
CAS Number: 161735-79-1
Other descriptive name: RASAGILINE MESYLATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Trade Name: Azilect
Product Name: Azilect
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Rasagiline mesylate
CAS Number: 161735-79-1
Other descriptive name: RASAGILINE MESYLATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: The primary efficacy objective of this trial is to evaluate the efficacy of a range of preladenant doses compared with placebo in subjects with early Parkinson's disease as measured by the sum of UPDRS Parts 2 and 3 scores. The primary safety objective of this trial is to evaluate the safety and tolerability of preladenant compared to placebo in subjects with early PD.

Timepoint(s) of evaluation of this end point: 2,4,8,16,20,26,

Secondary Objective: The Key Secondary Objective of this trial is to evaluate the efficacy of a range of preladenant doses compared with placebo in subjects with early PD as measured by the proportion of Responders and by the the UPDRS Part 2 score.

Primary end point(s): Change from Baseline to Week 26 (End of Part 1 treatment) in the sum of the UPDRS Parts 2 and 3 scores.

Secondary Outcome(s)

Secondary end point(s): The Key Secondary Efficacy Endpoints are:
• The proportion of Responders, where a Responder is defined as a subject with at least a 20% improvement in UPDRS2+3 from Baseline to Week 26 (End of Part 1 Treatment).
• The change from Baseline in the UPDRS Part 2 score (Activities of Daily Living [ADL]) at Week 26.

Timepoint(s) of evaluation of this end point: 2,4,8,16,20,26,

Secondary ID(s)

2009-013552-72-FI

NCT01155479

P05664

Source(s) of Monetary Support

Schering-Plough Research Institute, a division of Schering Corporation