advanced stage of idiopathic PD with dose-dependent motor fluctuations. MedDRA version: 8.1 Level: LLT Classification code 10013113 Term: Disease Parkinson's
Conditions
Sponsors
Solvay Pharmaceuticals
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects with advanced stage of idiopathic PD and dose-dependent motor fluctuations. – The clinical diagnosis of subjects must meet the criteria for "Diagnosis of idiopathic Parkinson’s Disease" according to the United Kingdom Parkinson's Disease Society (UKPDS) Brain Bank criteria. – A PD disease stage corresponding to 2-4 in the OFF state according to the modified Hoehn and Yahr classification of disease severity. – Stable treatment with L-dopa for at least 28 days prior to randomization, requiring at least three but not more than seven dose periods of L-dopa per day. – Presence of a recognizable ON and OFF state (motor fluctuations). – Minimum hours of OFF-time per day of 2.5 hours (during waking hours including early morning akinesia) as recorded per baseline diaries. – Subjects = 30 years. – Ability to keep home diary (with or without assistance of caregivers/partners) for recording ON/OFF symptoms and dyskinesia as verified by screening concordance testing and compliance rate of baseline home diary recordings. – For anti-PD medication other than pardoprunox (SLV308) and pramipexole, the following criteria apply: – Previous treatment with dopamine agonists should have been terminated at least 28 days prior to baseline. – Efficacious previous treatment with dopamine agonists is not allowed to be stopped for the sole purpose of enrolling the subject into this study. – Concurrent anti-PD treatment other than L-dopa (i.e., monoamine oxidase-B inhibitors, anti cholinergics, amantadine) is allowed if the doses have been kept stable for at least 28 days prior to baseline and during the study. The use of catechol-O-methyltransferase (COMT) inhibitors needs to be stable at least 28 days prior to baseline, with the exception of tolcapone which needs to be stabilized at least six months prior to baseline. Modification of the dose of COMT inhibitors during the study is allowed only if required in conjunction to modification of L-dopa dose. – Out-patients. – Male and female. Females must be of non-childbearing potential or: – have a negative serum b-human chorionic gonadotropin, and – use an accepted form of contraception (a stable dose of contraceptive drug for at least three months or barrier methods: intra uterine device, diaphragm, combination of a condom and spermicide). Non-childbearing potential is defined as being post-menopausal for at least 24 months prior to the screening visit or surgically sterilized (i.e., tubal ligation or hysterectomy). 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
Exclusion criteria: Related to Parkinson’s Disease 1. Presence of complex ON/OFF phenomena or ‘yo-yoing’ and/or an abrupt unpredictable loss of efficacy unrelated to the timing of L-dopa administration. 2. Prevalent expression of severely disabling dyskinesias during the waking day, i.e. dyskinesias are present at least 50% of the waking hours (UPDRS Part 4 item 32 = 3) in combination with a degree of disability which is moderate or higher (UPDRS Part 4 item 33 = 3). 3. Diagnosis is unclear or a suspicion of other parkinsonian syndromes exists, such as secondary parkinsonism (caused by drugs, toxins, infectious agents, vascular disease, trauma, brain neoplasm), Parkinson-plus syndromes (e.g., multiple system atrophy, progressive supranuclear palsy) or heredodegenerative diseases. 4. Subjects who have undergone surgery for the treatment of PD (e.g., pallidotomy, deep brain stimulation, fetal tissue transplantation) or have undergone any other brain surgery. 5. Subjects for whom previous treatment with dopamine agonists needed to be terminated within the last year because of the induction of hallucinations, psychosis, intolerable somnolence, impulse control disorder and/or any other side effect that has led to discontinuation. Related to Psychiatric and Neurological Disorders 6. Current diagnosis or history of drug or alcohol abuse (Diagnostic and Statistical Manual of Mental Disorders [DSM]-IV criteria), within 12 months prior to screening visit. 7. Current primary psychiatric diagnosis of acute psychotic disorder or other primary psychiatric diagnoses, such as bipolar disorder or major depressive disorder (DSM-IV criteria). 8. Subjects who, based on history and mental status examination, are considered to be violent (likely to harm themselves or others), or subjects considered at suicidal risk by the Investigator. 9. Other psychiatric, neurological or behavioral disorders that may interfere with the conduct or interpretation of the study. Cognitive impairment defined as Mini Mental State Examination (MMSE) =24, dementia or significant concomitant neurological disease would also be included under this category. 10. A history of hallucinations, psychosis and/or treatment with antipsychotics for any indication within a year from baseline. 11. A history of, or current, seizure disorders (other than febrile seizures in childhood) and subjects requiring treatment with anti-convulsants for any indication. 12. Subjects known with serious symptomatic cerebral disease, cerebrovascular disease, focal neurological lesions (previous brain surgery), or any acute brain trauma requiring treatment with anticonvulsant therapy at the time of study entry.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the efficacy of pardoprunox (SLV308) compared to placebo in reducing OFF-time in Parkinson’s disease (PD) patients on L-dopa therapy characterized by motor fluctuations, as based on patient home diaries.;Secondary Objective: Key secondary objectives: - To investigate the effects of pardoprunox (SLV308) compared to placebo with respect to increasing ON-time without troublesome dyskinesia based on patient home diaries. - To determine that the efficacy of pardoprunox (SLV308) is at least as good as that of pramipexole in reducing OFF-time in PD patients on L-dopa treatment characterized by motor fluctuations, as based on patient home diaries. - To investigate whether pardoprunox (SLV308) is superior to placebo in improving core PD motor symptoms and activities of daily living (ADL) as measured by the Unified Parkinson’s Disease Rating Scale (UPDRS; sum of Parts 2 and 3 in the ON phase). - To evaluate the effects of pardoprunox (SLV308) compared to pramipexole with respect to increasing ON-time without troublesome dyskinesia based on patient home diaries. - To investigate the effects of pardoprunox (SLV308) compared to placebo on health-related quality of life (PDQ-39).;Primary end point(s): Efficacy: ON/OFF/dyskinesia symptom recording in patient home diary, UPDRS, CGI Severity (CGI-S), CGI Improvement (CGI-I), Parkinson’s Disease Questionnaire (PDQ-39), EuroQol 5-item questionnaire (EQ-5D), Caregiver Burden Inventory (CBI), Caregiver’s Assistance in Activities of Daily Living. Pharmacokinetics: Data obtained on population pharmacokinetics of pardoprunox (SLV308). Safety: Adverse events, concomitant medications, vital signs, physical examination, electrocardiogram (ECG), laboratory assessments, Parkinson’s Disease Sleeping Scale (PDSS), Epworth Sleepiness Scale (ESS). | — |
Countries
Hungary
Outcome results
None listed