| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10061536 |
|
| 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 |
Primary Efficacy 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 moderate to severe Parkinson’s disease (PD)
experiencing motor fluctuations and receiving a stable dose of levodopa (L-dopa), as measured by “off” time.
Primary Safety Objective: The Primary Safety Objective of this trial is to assess the safety and tolerability of
preladenant compared with placebo in subjects with moderate to severe PD experiencing motor fluctuations
and receiving a stable dose of L-dopa. |
|
| E.2.2 | Secondary objectives of the trial |
Key Secondary Trial Objectives: The Key Secondary Efficacy Objectives for this trial are to evaluate the
efficacy of a range of preladenant doses compared with placebo in subjects with moderate to severe PD
experiencing motor fluctuations and receiving a stable dose of L-dopa as measured by “on” time without
troublesome dyskinesia and by the proportion of Responders. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Each subject must have a diagnosis of idiopathic PD based on the following criteria:
Each subject should have bradykinesia and at least one of the following symptoms:
i) Muscular rigidity
ii) Resting tremor (4 to 6 Hz)
iii) Postural instability (impairment of postural reflexes, eg, as assessed by the pull test) unrelated to
primary visual, cerebellar, vestibular, or proprioceptive dysfunction
• Each subject must have received prior therapy with L-dopa for approximately 2 or more years immediately
before Screening and must continue to have a beneficial clinical response to L-dopa at Screening.
• Each subject must have been on a stable, optimal dopaminergic treatment regimen, defined as maximum
therapeutic effect achieved with available anti-parkinsonian treatment, for at least the 4 weeks immediately
before Randomization.
• Subjects receiving the adjunct PD medications listed in the table below are permitted to enroll in this trial.
Each subject who is receiving one or more of the adjunct PD medications listed below must have been on a
stable regimen of treatment for at least the 4 weeks immediately before Randomization.Amantadine
Anticholinergics
Dopa decarboxylase inhibitors
Dopamine agonists
Entacapone
L-dopa
• Each subject’s Hoehn and Yahr stage must be ≥2.5 and ≤4 when in the “off” state following optimum titration
of treatment medications at Screening.
• Each subject must be experiencing motor fluctuations AND dyskinesias following optimum titration of
treatment medications and within the 4 weeks immediately before Screening.
• Each subject must be experiencing a minimum of 2 hours/day of “off” time as estimated by the investigator
and supported by the 3-day symptom diary (Daily Diary) at the Diary Training Visit.
• Each subject, with or without the help of a caregiver, must be capable of maintaining an accurate and
complete symptom diary (Daily Diary) as assessed at the Diary Training Visit.
• Each subject (or subject’s legal representative) 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 sex, any race/ethnicity.
• Each subject must have results of Screening clinical laboratory tests (hematology, blood chemistries, and
urinalysis) drawn within 3 weeks prior to Randomization, clinically acceptable to the investigator, and not
within the parameters specified for exclusion (below).
• Each subject must have results of a physical examination within normal limits or clinically acceptable limits
to the investigator.
• Each subject must be able to adhere to dose and visit schedules.
• Each subject is either a male or:
a) A sexually-active female of reproductive potential and agrees to use (or have their partner use) one of
the highly effective methods of birth control within the projected duration of the study OR b) A female not of reproductive potential. |
|
| E.4 | Principal exclusion criteria |
A subject must not have a form of drug-induced or atypical parkinsonism, cognitive impairment (ie, Montreal
Cognitive Assessment [MoCA] score <26), bipolar disorder, schizophrenia, or other psychotic disorder.
(Subjects with non-troublesome hallucinations, stable on low dose quetiapine or clozapine are allowed to
enroll.)
• A subject must not have a history of repeated strokes with stepwise progression, repeated head injury,
encephalitis and/or oculogyric crises on no drug treatment.
• A subject must not have experienced a stroke within 6 months of Screening or have a persistent
neurological deficit that may interfere with study assessments.
• A subject must not have definite encephalitis, strictly unilateral features 3 years after being diagnosed with
PD, other neurological features such as supranuclear gaze palsy, cerebellar signs, a Babinski sign with
clear, clinically significant pyramidal tract involvement, frequent falls, hallucinations unrelated to
medications, or presence of cerebral tumor or communicating hydrocephalus on neuroimaging (by history).
• A subject must not have severe, symptomatic autonomic involvement unrelated to medications.
• A subject must not have exposure to a known neurotoxin.
• A subject must not have a history of sustained remission of their Parkinson’s symptoms.
• A subject must not have had surgery for PD.
• A subject must not have an untreated major depressive disorder meeting Diagnostic and Statistical Manual
of Mental Disorders IV Text Revision (DSM-IV-TR) criteria. (A subject who is successfully treated [Beck
Depression Inventory-II {BDI-II} score <19] with stable doses of allowed antidepressant medications for at
least the 4 weeks immediately before Screening is eligible to enroll in the trial.)
• A subject must not be at imminent risk of self-harm or harm to others, in the investigator’s opinion based on
clinical interview and responses provided on the Columbia Suicide Severity Rating Scale (CSSRS).
Subjects must be excluded if they report suicidal ideation of Type 4 or 5 in the past 2 months or suicidal
behavior in the past 6 months as measured by the CSSRS during Screening or at Baseline.
• Blood Pressure: A subject must not have a systolic blood pressure (BP) ≥150 mm Hg OR diastolic BP
≥100 mm Hg at Screening and at a BP recheck prior to Randomization. Should the BP remain elevated, the
subject may not enter the trial until the BP has been adequately controlled as demonstrated by
2 BP measurements meeting this criterion at consecutive separate visits within 3 weeks prior to
Randomization. Subjects may be on stable antihypertensive medication.
• Cardiovascular Disease: A subject must not have had any clinically significant cardiovascular event or
procedure for 6 months prior to Randomization, including, but not limited to, myocardial infarction,
angioplasty, unstable angina, or heart failure; and a subject must not have heart failure staged New York
Heart Association Class III or IV. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The change from Baseline to End of Treatment (Week 12) in mean “off” time in hours per day. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| 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) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| 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 | Yes |
| 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) | Yes |
| 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.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 73 |
| 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 | Yes |
| 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
|
| ultima visita dell`ultimo soggetto |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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