Advanced Parkinson's Disease MedDRA version: 9.1 Level: LLT Classification code 10013113 Term: Disease Parkinson's
Conditions
Interventions
Product Name: Pardoprunox
Product Code: SLV308
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Pardoprunox hydrochloride
CAS Number: 269718-83-4
Current Sponsor code: Pardoprunox hydrochloride
Sponsors
Solvay Pharmaceuticals BV
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. The clinical diagnosis of subjects must meet the criteria for "Diagnosis of idiopathic Parkinson’s Disease" according to the UKPDS Brain Bank criteria (see Appendix 16.3). 2. Stable treatment with L dopa and one dopamine agonist (only permitted are pramipexole or ropinirole) for at least 28 days prior to randomization. 3. Presence of a recognizable ON and OFF state (motor fluctuations). 4. Minimum hours of OFF time per day of 1.5 hours (during waking hours including early morning akinesia) as recorded per baseline diaries. 5. Minimum hours of ON time with troublesome dyskinesia of two hours (during waking hours) as recorded per baseline diaries. 6. Prevalent expression of severely disabling dyskinesias during the waking day, i.e., dyskinesias are present more than 25% of the waking hours (UPDRS Part 4 item 32 = 2) in combination with a degree of disability which is moderate or higher (UPDRS Part 4 item 33 = 2). 7. Subjects of = 30 years old. 8. 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. 9. For anti-PD medication other than L dopa and dopamine agonists the following criteria apply: - Concurrent treatment with anti-PD treatment with monoamine oxidase-B inhibitors, anti cholinergics and/or 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 for at least 28 days prior to baseline, with the exception of tolcapone which needs to be stabilized for at least six months prior to baseline. - Apomorphine is not allowed during the study and should not have been taken 28 days prior to baseline with the exception of rescue dose during the first two weeks after the switch at baseline and M6 (see Section 4.1). 10. Subject complying with the following contraception requirements - Females must be of non-childbearing potential or: - have a negative serum ß-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., bilateral tubal ligation or hysterectomy). - Males -Unless have undergone a vasectomy, they must use a combination of a condom and spermicide as a contraception measure for the duration of the trial, or their female partners must use an accepted form of contraception, i.e., oral contraceptive, or barrier methods as described above, for the duration of their partner’s participation in the study. 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: 1. Diagnosis is unclear or a suspicion of other parkinsonian syndromes exists, such as secondary parkinsonism, Parkinson-plus syndromes 2. Subjects who have undergone surgery for the treatment of PD or have planned such a surgery taking place during the blinded part of the study, or have undergone any other brain surgery. 3. Treatment within 60 days prior to baseline with monoamine oxidase inhibitors , alpha methyldopa or metoclopramide; treatment within last 30 days before baseline with parenteral ergots, methylphenidate, amphetamine, beta blockers for treating tremor, isoprenaline, adrenaline, dopamine, dobutamide, reserpine, flunarizine or cinnarizine. 4. History of non-effectiveness or non-tolerability of pramipexole. 5. Current diagnosis or history of drug or alcohol abuse, within 12 months prior to screening visit. 6. Lifetime history of primary psychiatric diagnosis of acute psychotic disorder or other primary psychiatric diagnoses, such as schizophrenia or bipolar disorder. 7. A history of hallucinations, illusions, vivid dreams, psychosis and/or treatment with antipsychotics for any indication within a year from baseline. 8. Subjects who, based on history and mental status examination, are considered to be violent, 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 = 25 (see Appendix 16.12), dementia or significant concomitant neurological disease would also be included under this category. 10. A history of, or current, seizure disorders and subjects requiring treatment with anti-convulsants for seizure disorders. 11. Subjects known with serious symptomatic cerebral disease, cerebrovascular disease, focal neurological lesions or any acute brain trauma currently requiring treatment. Related to Other Medical Conditions 12. Clinically significant abnormal laboratory data at the screening visit or any abnormal laboratory value that could interfere with the assessment of safety or efficacy. 13. Hypokalemia and/or hypomagnesemia. 14. Current evidence of clinically significant pulmonary, hematological, autoimmune, endocrine, cardiovascular, renal or gastrointestinal disorder that would possibly interfere with the subject’s participation in the study. 15. Subjects whose current regimen of medication or condition suggests that it will not remain constant for the duration of study participation. 16. Known uncontrolled insulin dependent diabetes mellitus or on oral anti-hyperglycemics for less than 28 days prior to baseline. 17. Any malignant disease or a history of neoplasms, other than carcinoma in situ of the cervix or basal cell carcinoma of the skin. 18. A history of, or a known current gastrointestinal, liver, kidney or other known condition, which may interfere with the absorption, distribution, metabolism or excretion of the study medication and/or assessments 19. Clinically relevant ischemic heart symptoms or history of myocardial infarction, coronary artery bypass surgery or percutaneous transluminal coronary angioplasty. 20. Subjects with unstable hypertension or symptomatic hypotension, or orthostatic hypotension which is defined as a decrease of 30 mmHg in systolic blood pressure (SBP) and/or 20 mmHg in diastolic blood pressure (DBP) after at least two minutes standing compared to the previous sitting SBP at two se
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to investigate whether treatment with pardoprunox adjunctive to L dopa can reduce the severity and/or duration of dyskinesia from baseline to week 12/endpoint while maintaining or improving motor symptoms as measured by change of ON time without dyskinesia recorded on home diary cards in subjects with advanced stage PD experiencing motor fluctuations and dyskinesia.;Secondary Objective: -To investigate whether pardoprunox treatment changes the dyskinetic profile under individually optimized treatment compared to baseline as measured by parts 3 and 4 of the Unified Dyskinesia Rating Scale (UDysRS). -To investigate the extent of improvement in motor functioning as assessed by investigator by UPDRS during ON and OFF stages. -To investigate whether pardoprunox treatment changes the dyskinetic characteristics in the response to a single challenge with L dopa in terms of severity of dyskinesia compared to baseline as measured by parts 3 and 4 of the UDysRS. -To investigate the effects of pardoprunox treatment on health-related quality of life (Parkinson’s Disease Questionnaire [PDQ-39] and Hospital Anxiety and Depression Scale [HADS]). ;Primary end point(s): Change from baseline to maintenance Week 12/endpoint in ON time without dyskinesia based on the diary cards. | — |
Countries
Germany, Italy, Portugal
Outcome results
None listed