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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03436199
Recruitment Status : Completed
First Posted : February 19, 2018
Results First Posted : December 21, 2021
Last Update Posted : December 21, 2021
Sponsor:
Information provided by (Responsible Party):
Adamas Pharmaceuticals, Inc.

Brief Summary:
This study assessed the efficacy and safety of ADS-5102 (at daily doses of 137 mg or 274 mg) compared with placebo in MS patients with walking impairment.

Condition or disease Intervention/treatment Phase
Walking Impairment Multiple Sclerosis Drug: ADS-5102, 137 mg Drug: ADS-5102, 274 mg Other: Placebo Phase 3

Detailed Description:

This was a multicenter, 3-arm, randomized, placebo-controlled, double-blind, parallel-group study of ADS-5102 (amantadine) extended release capsules in MS subjects with walking impairment. The study consisted of a screening period (up to 3 weeks), a single-blind placebo run-in period (4 weeks; during which subjects were blinded to treatment), and a double-blind treatment period (12 weeks).

For at least 30 days prior to screening, all subjects were to have received a stable regimen of MS medications, both disease-modifying and symptomatic; these medications were to continue at the same doses and regimens for the duration of the subjects' participation in the study, to the extent compatible with good neurological care. Subjects were not to have used amantadine, dalfampridine, or any 4 aminopyridine or 2,4 diaminopyridine preparation within 30 days prior to screening.

Consented subjects who completed the screening period were to undergo a 4-week single-blind placebo run-in period during which they received placebo as 2 capsules once daily at bedtime.

Subjects who completed the single-blind placebo run-in period and continued to meet study eligibility criteria were randomized with equal probability to 1 of 3 treatment groups: placebo or ADS-5102 at a final dose of 137 mg/day or 274 mg/day. Study drugs were administered as 2 capsules once daily at bedtime.

Subjects were to return to the clinic for safety and efficacy assessments at Week 0 and Week 2 prior to randomization and at Weeks 4 (randomization and baseline visit), 6 (only safety), 8, 12, and 16 after randomization. In addition, telephone visits for safety assessments were conducted at Weeks 5 and 7. Subjects who withdrew from the study before Week 16 were to have an early termination visit that included safety follow-up and efficacy assessments, as appropriate.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 558 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A 3-arm, Multicenter, Double-blind, Placebo-controlled, Randomized Study to Assess the Efficacy and Safety of ADS-5102 Amantadine Extended Release Capsules in Multiple Sclerosis Patients With Walking Impairment
Actual Study Start Date : March 29, 2018
Actual Primary Completion Date : December 10, 2019
Actual Study Completion Date : December 10, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: ADS-5102, 137 mg
ADS-5102, administered once daily at bedtime from Week 4 through Week 16
Drug: ADS-5102, 137 mg
Oral capsules
Other Names:
  • ADS-5102
  • amantadine extended release

Experimental: ADS-5102, 274 mg
ADS-5102, administered once daily at bedtime from Week 4 through Week 16
Drug: ADS-5102, 274 mg
Oral capsules
Other Names:
  • ADS-5102
  • amantadine extended release

Placebo
placebo, administered once daily at bedtime from Week 4 through Week 16
Other: Placebo
Oral capsules




Primary Outcome Measures :
  1. Timed 25 Foot Walk (T25FW, Feet/Second): the Proportion of Subjects With a ≥ 20% Increase in Walking Speed (Measured by T25FW) From Baseline at Week 16 (Responder Analysis) [ Time Frame: 16 weeks ]
    The T25FW is a measure of lower extremity function. The subject is directed to a clearly marked 25-foot course and is instructed to walk 25 feet as quickly as possible, but safely. The task is immediately administered again by having the subject walk back the same distance. For this outcome measure, the result is reported as speed (feet per second). Improvement is indicated by an increase in speed.


Secondary Outcome Measures :
  1. Timed 25 Foot Walk: Change From Baseline at Week 16 [ Time Frame: 16 weeks ]
    The T25FW is a measure of lower extremity function. The subject is directed to a clearly marked 25-foot course and is instructed to walk 25 feet as quickly as possible, but safely. The task is immediately administered again by having the subject walk back the same distance. For this outcome measure, the result is reported as or speed (feet per second). Improvement is indicated by an increase in speed.

  2. Timed Up and Go (TUG): Change From Baseline at Week 16 [ Time Frame: 16 weeks ]
    The TUG is a measure of lower extremity strength, balance, and coordination. The subject stands up from a chair, walks 3 meters then turns around and walks back to the chair to sit down. The result is reported in seconds. Improvement is indicated by negative change scores.

  3. 2-Minute Walk Test (2MWT): Change From Baseline at Week 16 [ Time Frame: 16 weeks ]
    The 2MWT is a measure of lower extremity function. The subject is instructed to walk as far as possible in 2 minutes, and the distance is measured in meters. Improvement is indicated by positive change scores.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Signed a current IRB-approved informed consent form
  • Male or female subjects between 18 and 70 years of age, inclusive, at the time of Screening
  • Confirmed diagnosis of MS according to the 2017 McDonald criteria
  • Current medication regimen must be stable for at least 30 days prior to screening, and subject must be willing to continue the same dosing regimen for the duration of study participation
  • Maximum Expanded Disability Status Scale (EDSS) score during screening of 6.5
  • Stable physical activity level (inclusive of prescribed physical therapy) for at least 30 days prior to screening and willing to continue without change for the duration of study participation
  • A score on each of two completed screening T25FW tests between 8 and 45 seconds, inclusive

Exclusion Criteria:

  • Documented inability to tolerate amantadine
  • Clinically significant MS relapse with onset less than 30 days prior to screening
  • Receipt of dalfampridine (or any 4-aminopyridine or 2,4-diaminopyridine preparation) or amantadine within 30 days prior to screening
  • History of seizures within 3 years prior to screening
  • History of hallucinations (visual, auditory, or any other type) within 3 years prior to screening
  • History of bipolar disorder, schizophrenia, or psychosis, regardless of treatment
  • For subjects with a history of major depressive disorder, the presence of active depressive symptoms that, in the opinion of the investigator, would 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
  • Presence of orthostatic hypotension at screening: a decrease in systolic blood pressure (at least 20 mm Hg) or diastolic blood pressure (at least 10 mm Hg) within 3 minutes of the subject standing up, compared to pressures obtained while sitting
  • 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. If a sexually active male, does not agree to utilize condoms 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 or 5 half-lives, whichever is longer, prior to screening

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03436199


Locations
Show Show 84 study locations
Sponsors and Collaborators
Adamas Pharmaceuticals, Inc.
Investigators
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Study Director: Clinical Trials Director Adamas Pharmaceuticals
  Study Documents (Full-Text)

Documents provided by Adamas Pharmaceuticals, Inc.:
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Responsible Party: Adamas Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT03436199    
Other Study ID Numbers: ADS-AMT-MS301
First Posted: February 19, 2018    Key Record Dates
Results First Posted: December 21, 2021
Last Update Posted: December 21, 2021
Last Verified: December 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Multiple Sclerosis
Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Amantadine
Antiparkinson Agents
Anti-Dyskinesia Agents
Antiviral Agents
Anti-Infective Agents
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents