Parkinson's Disease Subjects with Levodopa-Induced Dyskinesias MedDRA version: 17.0 Level: PT Classification code 10061536 Term: Parkinson's disease System Organ Class: 10029205 - Nervous system disorders
Conditions
Sponsors
Osmotica Pharmaceutical Corp.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: For a subject to be eligible for participation in this study, all of the following criteria must be met at screening. Subject must: - Sign an informed consent form (ICF) indicating that they have been informed of the procedures to be followed, the experimental nature of the therapy, alternatives, potential benefits, side-effects, risks, and discomforts. - Have been diagnosed with idiopathic Parkinson's disease as defined by the UK Parkinson's Disease Society Brain Bank criteria. - Be male or female 30 to 85 years old. - Have levodopa induced, predictable peak-effect dyskinesia that are considered by the subject to be problematic and/or disabling. - Have screening serum creatinine level within the normal range for the testing laboratory. - Have been on stable doses of all oral anti-Parkinson's medication, including any levodopa preparation, for 30 days and be willing to remain on the same doses throughout the course of the subject's participation in the trial. - The subject/caregiver must demonstrate the ability to complete an accurate home diary based on training and evaluation during the screening period. 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 46 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 116
Exclusion criteria
Exclusion criteria: A subject will not be eligible for participation in this study if any of the following criteria apply. The subject: 1. Is diagnosed with secondary parkinsonian syndrome, such as vascular, post-inflammatory, drug-induced, neoplastic and post-traumatic parkinsonism or any atypical parkinsonian syndrome (e.g., Progressive Supranuclear Palsy, Multi-System Atrophy, etc.) 2. Has used amantadine in any dosage or pharmaceutical form within the past 14 days, or has previously interrupted the use of amantadine due to an adverse event 3. Is currently using medications that would potentially interfere with the actions of the study medication or outcome variables, including neuroleptics and atypical antipsychotic agents, acetylcholinesterase inhibitors, apomorphine, rimantadine, memantine and dextromethorphan and quinidine if used in combination for treating dyskinesia. 4. Has a history of pallidotomy or other ablative surgery for the treatment of PD, or is implanted with a uni- or bilateral deep brain stimulator 5. Has any medical condition or past medical history that, in the Investigator's judgment, would increase the risk of exposure to Amantadine HCl Extended Release Tablets or interfere with safety and efficacy evaluations. These include: o seizure disorders or history of seizures other than childhood febrile convulsions o history of glaucoma o current hallucinations o urinary retention o abuse of legal or illegal drugs within the past 12 months 6. Has a history of cancer within 5 years of screening that may compromise the life-expectancy of the subject; exceptions are adequately treated non-melanomatous skin cancers, localized bladder cancer, non-metastatic prostate cancer or in situ cervical cancer. 7. Has a history or current diagnosis of schizophrenia or bipolar disorder 8. Has current diagnosis of inadequately treated Major Depressive Disorder. Subjects who are on stable doses of selective serotonin reuptake inhibitors (SSRIs) or serotonin -norepinephrine reuptake inhibitors (SNRIs) for depression are eligible for the study 9. Is at imminent risk of suicide (score of 4 or 5 on the C-SSRS) or had a suicide attempt within 6 months of the screening visit. 10. Has a history of, or current diagnosis of Impulse Control Disorder or is judged to be at risk according to the QUIP-RS 11. Has an estimated plasma creatinine clearance of <60 mL/min at screening using the Cockroft-Gault equation 12. Has a history of or currently has any of the following clinically significant conditions, that in the investigator's opinion may interfere with the study procedures or compromise the subject's safety: o Cardiovascular disease o Respiratory disease o Renal disease o Hepatic disease o Gastrointestinal disease 13. Upon evaluation at the screening visit, the subject has: o Any clinically significant vital sign, ECG, or laboratory abnormalities o A positive test for human immunodeficiency virus (HIV) antibody of a history of HIV o A positive test for hepatitis B surface antigen unless the positive test followed a recent (<28 days) vaccination for hepatitis B and the vaccination record is available o A positive test for hepatitis C antibody o A positive urine drug test 14. The subject is female, and is pregnant or lactating (breastfeeding) at the time of screening or has a positive pregnancy test result pre-dose 15. If a sexually active female, is not surgically sterile or at least 2 years post-menopausal, or does not agree to utilize an effective method of contr
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Demonstrate the efficacy of Amantadine Extended Release (ER) Tablets versus placebo on the Unified Dyskinesia Rating Scale (UDysRS) in patients with Levodopa-Induced Dyskinesia after 12 weeks of treatment at a fixed dose.;Secondary Objective: - To compare the change in the percent of waking hours that subjects report being "OFF" during 12 weeks of treatment with Amantadine HCl ER Tablets versus placebo using the Mobility State Self-Assessment (Subject Diary Cards) - To compare the change in the percent of waking hours that subjects report having no dyskinesias during "ON" time during 12 weeks of treatment with Amantadine HCl Extended Release Tablets versus placebo using the Mobility State Self-Assessment (Subject Diary Cards) - To compare the change in the MDS-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) score in Parts II and III, in Parkinson's Disease subjects with LID during 12 weeks of treatment with Amantadine HCl Extended Release Tablets versus placebo - To evaluate the relationship between amantadine plasma concentrations and clinical efficacy, safety and renal function during 12 weeks of treatment with Amantadine HCl Extended Release Tablets.;Primary end point(s): The change from baseline to Day 98 (Visit 7) of treatment in the sum of the items comprising the Unified Dyskinesia Rating Scale (UDysRS).;Timepoint(s) of evaluation of this end point: Day 98 (Visit 7) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Endpoints - Efficacy - The change from baseline to Day 14 (Visit 4), Day 42 (Visit 5), Day 70 (Visit 6), Day 98 (Visit 7) of treatment in the sum of the items comprising the Unified Dyskinesia Rating Scale (UDysRS). - The change from baseline to Day 14 (Visit 4), Day 42 (Visit 5), Day 70 (Visit 6), Day 98 (Visit 7) of treatment in the percent of waking hours that subjects report being "OFF" in the Mobility State Self-Assessment (Subject Diaries). - The change from baseline to Day 14 (Visit 4), Day 42 (Visit 5), Day 70 (Visit 6), Day 98 (Visit 7) of treatment in the percent of waking hours that subjects report being "ON" having no dyskinesias, non-troublesome dyskinesias, and troublesome dyskinesias in the Mobility State Self-Assessment (Subject Diaries). - The change from baseline to Day 14 (Visit 4), Day 42 (Visit 5), Day 70 (Visit 6), Day 98 (Visit 7) of treatment in the sum of Parts II, and III of the MDS-UPDRS. - The change from baseline to Day 14 (Visit 4), Day 42 (Visit 5), Day 70 (Visit 6), Day 98 (Visit 7) in the Fatigue Severity Scale (FSS); Secondary Endpoints - Safety - Safety and tolerability of Amantadine HCl Extended Release Tablets as assessed by frequency and nature of adverse events (AEs), laboratory results, vital sign measurements, physical examinations, and 12-lead electrocardiograms (ECGs); - Assessment of the potential occurrence of psychiatric side effects (SCOPA-PC), sleep disorders, Livedo Reticularis and orthostatic hypotension; - Assessment of suicidality using the Columbia-Suicide Severity Rating Scale (C-SSRS) (Baseline/Screening), (Since Last Visit); - Assessment of potential occurrence of Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease ? Rating Scale (QUIP-RS) - Relationship of plasma amantadine concentrations to clinical efficacy, safety, and renal function.;Timepoint(s) of evaluation of this end point: Secondary Endpoints - Efficacy: - Day 14 (Visit 4), Day 42 (Visit 5), Day | — |
Countries
Canada, France, Germany, Spain, United States
Contacts
Public ContactGene Wright
Osmotica Pharmaceutical Corp.
Outcome results
None listed