Parkinsons disease is complicated by dyskinesias and dystonia. Due stabilizing properties, we believe (-)-OSU6162 may alleviate dyskinesias, without causing parkinsonism. Aim: To evaluate in a double-blind cross over pilot study whether OSU6162 attenuates dyskinesias without worsening parkinsonism in PD patients with motor complications using clinical examination and patient diaries.
Conditions
Interventions
Product Name: not available
Product Code: OSU 6162 similar to (-)-OSU 6162
Pharmaceutical Form: Coated tablet
INN or Proposed INN: not available
CAS Number: 146798-66-5
Current Sponsor code: OSU 6162
Sponsors
Björn Holmberg
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subjects who fulfill the British Brain Bank diagnostic criteria for definite PD; 2. Long standing disease duration (more than 5 years); 3. Moderately disabling dyskinesias during at least 25% of the waking day, despite best medical treatment (UPDRS IV items no. 32 and 33 each =2). 4. Patient can rate on/off time and dyskinesias with at least a 66% concordance between patient and investigator/coordinator in a day in which patient experienced on with and without dyskinesias and off time. In order to be able to complete the home diaries, patients will be instructed in rating themselves in regard to on/off time and dyskinesias. This will be done at screening, before inclusion in the study, in a day in which the patient experiences on with and without dyskinesias and off time. Patients will spend in the clinic at least 4 hours or as long as needed, as judged by the investigator, during which time they will fill in the home diary form every hour, with the investigator performing the same evaluation concomitantly. Only patients eventually attaining at least a 66% concordance between their own and the assessment of the investigator/coordinator will be included in the study. 5. Subjects have signed the informed consent form. 6. Stable antiparkinsonian and antidepressant medication during the last 4 weeks prior to inclusion 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. Significant co-morbidity including alcohol or drug abuse. Medical problems such as unstable or/and untreated ischemic cardiac disease, diabetes, hypertension, vitamin deficiencies, thyroid diseases. 2. Pregnant women. 3. Women of childbearing age not on contraceptives. 4. Sick sinus syndrome; resting heart rate below 50 beats per minute; congestive heart failure classified as functional Class III or IV by the New York Heart Association; myocardial infarction within six months of randomization; a prolonged QTc interval at screen or pretreatment (defined as a QTc interval of> 450 msec for males or> 470 msec for females); atrio-ventricular conduction block; other clinically significant heart conditions which would negatively impact on the patient completing the study. 5. Clinically significant liver disease and/or an elevation in either total bilirubin, alkaline phosphatase, LDH, SGOT above the laboratory reference. Clinically significant renal disease which may prevent the patient from completing the study and/or an elevation in serum creatinine above the laboratory reference. 6. Presence of active neoplastic disease. 7. Patients who have had electroconvulsive therapy within 90 days. 8. Patients with any surgical or medical condition which, in the judgment of the clinical investigator, might interfere with the absorption, distribution, metabolism or excretion of the drug. 9. Patients who are using drugs capable of inducing hepatic enzyme metabolism (e.g., barbiturates, rifampicin, carbamazepine, phenytoin, primidone) within the previous 4 weeks (or 5 half lives of inducing agent, whichever is longer) of enrollment in this study. 10. Patients with a medical history of seizures. 11. Other medications as exclusion criteria: · Changes in patients’ antiparkinsonian or psychopharmaceutical treatment within 4 weeks before inclusion in the study or during the study is an exclusion criterion. Stable therapies implying that they are started at least 4 weeks before the inclusion in the study and continued unchanged during the study period are permitted. The following stable therapies are permitted: atypical neuroleptics such clozapine and quetiapine; antidepressant therapy; antiparkinsonian drugs; hypnotics and anxiolytics. · Tetrabenazine and amantadine treatment are not permitted during the study and the wash out period before the study must be at least 4 weeks, for a patient to be included. · Use of acute or chronic medications for other medical conditions is allowed based on clinical judgment . Occasional use of over-the-counter (OTC) medications is allowed at the investigator's discretion. Analgetics such as NSAIDs, acetyl salicylic acid and paracetamol are permitted. · All concomitant medications, whether OTC or prescription, are required to be noted on the Concomitant Medication Form. 12. Untreated severe depression with a Beck Depression Inventory (BDI) score of 21 or more (Beck et al., 1961, 1996). 13. Abnormal laboratory parameters such as: Hemoglobine, white blood cells count, electrolytes, TSH, T4, B12, folic acid. All levels above the laboratory references levels are considered abnormal. 14. Suspicion of an atypical parkinsonian disorder. 15. Dementia defined as a score of 27 or less on the Mini Mental Test Score (MMTS) (Folstein et al., 1975). 16. Unsatisfactory communication with the patient due to language difficulties or unsatisfactory compliance with study protocol. 17. Suicidal patients according to the clinical est
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: I. Primary Effects of treatement with OSU 6162 in advanced PD, measured as the difference between baseline and treatment week 4/8 on motor function, motor complications, and quality of life. The following tests will be performed: a. On-time without dyskinesia (patient diaries). b. Unified Parkinson's Disease Rating Scale (UPDRS) part IV (complications of treatment). c. Parkinson's Disease Quality of Life (PDQ 39). ;Secondary Objective: II. Secondary The difference between baseline and treatment week 4/8 on mental function, motor function, activities of daily living, and depressivity. The following tests will be performed: a. On-time with dyskinesia (patient diaries). b. Unified Parkinson's Disease Rating Scale (UPDRS) part I-III (mentation, activities of daily living and motor function, respectively), .including videorecordings of the UPDRS part III test. c. Beck Depression Inventory. ;Primary end point(s): Effects of treatement with OSU 6162 in advanced PD, measured as the difference between baseline and treatment on motor function, motor complications, and quality of life. | — |
Countries
Sweden
Outcome results
None listed