ADS-5102 for the Treatment of Levodopa Induced Dyskinesia (EASE LID Study)

Study Overview
=================
Brief Summary
-----------------
This is a multi-center, randomized, double-blind, placebo-controlled, 2-arm, parallel group study to evaluate the efficacy and safety of ADS-5102 extended release (ER) capsules, an investigational formulation of amantadine, dosed once nightly at bedtime for the treatment of levodopa induced dyskinesia (LID) in subjects with Parkinson's disease (PD). The novel pharmacokinetic profile of ADS-5102 is expected to achieve i) maximal concentrations in the early morning through mid-day, when LID can be troublesome, and ii) lower concentrations in the evening, potentially reducing the negative impact of amantadine on sleep. This pharmacokinetic profile could enable higher doses to be tolerated with a once-nightly ER formulation than can be tolerated with an immediate-release formulation. The once-nightly dosing regimen may also provide enhanced convenience and compliance. In a previous clinical study, ADS-5102 met its primary endpoint; LID was significantly reduced as measured by the change in UDysRS score over 8 weeks vs. placebo.

Official Title
-----------------
Efficacy and Safety of ADS-5102 (Amantadine HCl) Extended Release Capsules for the Treatment of Levodopa Induced Dyskinesia in Parkinson's Disease Patients (EASE LID Study)

Conditions
-----------------
Dyskinesia, Levodopa Induced Dyskinesia (LID), Parkinson's Disease

Intervention / Treatment
-----------------
* Drug: ADS-5102
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Signed a current IRB/REB/IEC-approved informed consent form Parkinson's disease, per UK Parkinson's Disease Society (UKPDS) Brain Bank Clinical Diagnostic Criteria On a stable regimen of antiparkinson's medications for at least 30 days prior to screening, including a levodopa preparation administered not less than three times daily, and willing to continue the same doses and regimens during study participation Following diary training, the subject is willing and able to understand and complete the 24-hour PD home diary (caregiver/study partner assistance allowed) Any other current and allowed prescription/non-prescription medications and/or nutritional supplements taken regularly must have been at a stable dose and regimen for at least 30 days prior to screening, and subject must be willing to continue the same doses and regimens during study participation (this criterion does not apply to medications that are being taken pre-study only on an as-needed basis) Exclusion Criteria: History of neurosurgical intervention related to Parkinson's disease (e.g. deep brain stimulation) History of seizures within 2 years prior to screening History of stroke or transient ischemic attack (TIA) within 2 years prior to screening History of cancer within 5 years prior to screening, with the following exceptions: adequately treated non-melanomatous skin cancers, localized bladder cancer, non-metastatic prostate cancer or in situ cervical cancer Presence of cognitive impairment, as evidenced by a Mini-Mental Status Examination (MMSE) score of less than 24 during screening If female, is pregnant or lactating 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 contraception from screening through at least 4 weeks after the completion of study treatment. Treatment with an investigational drug or device within 30 days prior to screening Treatment with an investigational biologic within 6 months prior to screening Current participation in another clinical trial

Ages Eligible for Study
-----------------
Minimum Age: 30 Years
Maximum Age: 85 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ADS-5102<br>ADS-5102 (amantadine HCl extended release) | Drug: ADS-5102<br>* Oral capsules to be administered once nightly at bedtime, for 25 weeks<br>* Other names: amantadine HCl extended release;|
| Placebo Comparator: Placebo<br>Placebo | Other: Placebo<br>* Oral capsules to be administered once nightly at bedtime, for 25 weeks<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Unified Dyskinesia Rating Scale (UDysRS) Score at Week 12 | The UDysRS is a dyskinesia rating scale from 0-104; it evaluates involuntary movements associated with PD. A higher score indicates more severe PD. The UDysRS was measured at Baseline and Weeks 2, 8, 12, 18, and 24. | Baseline to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Unified Dyskinesia Rating Scale (UDysRS) Score at Week 24 | The UDysRS is a dyskinesia rating scale from 0-104; it evaluates involuntary movements associated with PD. A higher score indicates more severe PD. The UDysRS was measured at Baseline and Weeks 2, 8, 12, 18, and 24. | Baseline to Week 24 | 
| Change in the Standardized PD Home Diary (ON Time Without Troublesome Dyskinesia, ON Time With Troublesome Dyskinesia, OFF Time) | A PD home diary was used to score 5 different conditions in 30-minute intervals: ASLEEP, OFF, ON (ie, had adequate control of PD symptoms) without dyskinesia, ON with non-troublesome dyskinesia, and ON with troublesome dyskinesia. The results were based on 2 consecutive 24-hour diaries taken prior to the day of randomization and prior to the Week 2, 8, 12, 18, and 24 visits. | Baseline (BL) to Week 12 (W12) and Week 24 (W24) | 
| Change in the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Combined Score (Parts I, II, and III) | The MDS-UPDRS Parts I, II, and III examined non-motor experiences of daily living, motor experiences of daily living, and motor examination, respectively. Each Part contains items or questions that were each rated on a scale from 0 (normal) to 4 (severe). The Combined Parts I, II, and III (representing the sum of the individual scores from Parts I, II, and III) has a scale range of 0-236. Higher scores, whether for individual Parts or the sum of the combined Parts, indicate more severe PD. | Baseline (BL) to Week 12 (W12) and Week 24 (W24) | 
| Clinician's Global Impression of Change (CGI-C) in Overall PD Symptoms | The CGI-C consisted of a single question that assessed the investigator's global impression of the subject's change from Baseline in overall PD symptoms, including but not limited to LID. The CGI-C required that the investigator rate the extent to which the subject's PD had improved or worsened (from marked worsening to marked improvement). The CGI-C was assessed at Baseline and Weeks 2, 8, 12, 18, and 24. | Baseline to Week 12 and Week 24 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
LID, Levodopa Induced Dyskinesia, Parkinsonism