Safety and Efficacy of ADS-5102 in Patients With Multiple Sclerosis and Walking Impairment

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 of ADS-5102 extended release (ER) capsules, an investigational formulation of amantadine, dosed once daily at bedtime for the treatment of walking impairment in MS. ADS-5102 is designed to be administered once daily at bed time, ADS-5102 achieves higher plasma amantadine concentrations in the early morning, sustained throughout the afternoon, and lower concentrations in the evening when patients are sleeping. ADS-5102 is designed to deliver its primary treatment effect during the day, and potentially reduce the adverse events of immediate-release amantadine when the patient is asleep.

Official Title
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Safety and Efficacy of ADS-5102 (Amantadine HCl) Extended Release Capsules in Patients With Multiple Sclerosis and Walking Impairment

Conditions
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Walking Impairment, Multiple Sclerosis

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-approved informed consent form; Male or female subjects between 18 and 70 years of age, inclusive; Confirmed diagnosis of Multiple Sclerosis according to the 2010 Revised McDonald criteria; On a stable regimen of medications taken specifically to treat MS for at least 30 days prior to screening, and willing to continue the same doses and regimens for the duration of study participation; Stable physical activity level for at least 30 days prior to screening and willing to continue without change for the duration of study participation; Maximum EDSS score during screening of 6.5; Sufficient ambulatory ability to complete two trials of the Timed 25 Foot Walk (T25FW) at the screening visit; A score on each completed screening T25FW test between 8 and 45 seconds, inclusive; 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; If taking an antidepressant, must be on a stable dose for at least 60 days prior to screening. Exclusion Criteria: History of seizures within 2 years prior to screening; Clinically significant MS relapse with onset less than 30 days prior to screening; Presence of vertigo or other vestibular dysfunction that might compromise ability to safely perform the T25FW; Received physical therapy within 30 days prior to screening; Received systemic steroids within 30 days prior to screening; Received dalfampridine, methylphenidate, modafinil, armodafinil, amantadine, and/or any product containing amphetamines, or any treatment specifically for fatigue or to improve walking within 30 days prior to screening; Received any botulinum toxin containing product used as antispasmodic agent within 3 months prior to screening; History of clinically significant hallucinations due to an MS medication or other/unknown cause, within 2 years prior to screening; History of Bipolar Disorder or Psychosis, regardless of treatment; Presence of cognitive impairment sufficient, in the opinion of the investigator, to affect the subject's ability to complete study assessments, or which would not be in the subject's best interest to participate in the study; History of stroke or TIA within 2 years prior to screening; History of cancer within 5 years; Presence of untreated angle closure glaucoma; 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 a highly effective hormonal method of contraception (an IUD, or vasectomized male partner is also acceptable), in combination with a barrier method, 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; Planned elective surgery during study participation.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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> | Drug: ADS-5102<br>* Oral capsules to be administered once daily at bedtime for 4 weeks<br>* Other names: amantadine HCl extended release;|
| Placebo Comparator: Placebo<br> | Other: Placebo<br>* Oral capsules to be administered once daily at bedtime for 4 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of ADS-5102 assessed by adverse events, safety-related study drug discontinuations, vital signs, and safety laboratory test |  | Up to 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Timed 25 Foot Walk |  | Up to 4 weeks | 
| Timed Up and go |  | Up to 4 weeks | 
| 2 Minute Walk Test |  | Up to 4 weeks | 
| MS Walking Scale-12 |  | Up to 4 weeks |