Efficacy and Safety Study of ADS-5102 in PD Patients With Levodopa-Induced Dyskinesia

Study Overview
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Brief Summary
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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
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ADS-5102 (Amantadine HCl) Extended Release Efficacy and Safety Study in Parkinson's Disease Patients With Levodopa-Induced Dyskinesia (EASE LID 3 Study)

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

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


Participation Criteria
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Eligibility Criteria
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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 (trained 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 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, in situ cervical cancer, or other definitively treated cancer that is considered cured; 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, using one of the following: barrier methods (diaphragm or partner using condoms plus use of spermicidal jelly or foam, preferably double-barrier methods); oral or implanted hormonal contraceptive; intrauterine device (IUD); or vasectomized male partner; 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
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Minimum Age: 30 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ADS-5102 (amantadine HCl extended release)<br>ADS-5102 (amantadine HCl extended release) | Drug: ADS-5102<br>* Oral capsules to be administered once nightly at bedtime, for 13 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 13 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the Unified Dyskinesia Rating Scale (UDysRS) Total Score | 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, 4, 8, and 12. | Baseline to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the Standardized PD Home Diary (ON Time Without 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, 4, 8, and 12 visits. | Baseline to Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Levodopa-Induced Dyskinesia, LID, Parkinsonism, Parkinson's Disease