Safety and Efficacy of ADS-5102 in Multiple Sclerosis Patients With Walking Impairment
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| ClinicalTrials.gov Identifier: NCT03436199 |
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Recruitment Status :
Completed
First Posted : February 19, 2018
Results First Posted : December 21, 2021
Last Update Posted : December 21, 2021
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Walking Impairment Multiple Sclerosis | Drug: ADS-5102, 137 mg Drug: ADS-5102, 274 mg Other: Placebo | Phase 3 |
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.
| 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 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: ADS-5102, 137 mg
ADS-5102, administered once daily at bedtime from Week 4 through Week 16
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Drug: ADS-5102, 137 mg
Oral capsules
Other Names:
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Experimental: ADS-5102, 274 mg
ADS-5102, administered once daily at bedtime from Week 4 through Week 16
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Drug: ADS-5102, 274 mg
Oral capsules
Other Names:
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Placebo
placebo, administered once daily at bedtime from Week 4 through Week 16
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Other: Placebo
Oral capsules |
- 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.
- 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.
- 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.
- 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.
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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 |
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
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
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| Study Director: | Clinical Trials Director | Adamas Pharmaceuticals |
Documents provided by Adamas Pharmaceuticals, Inc.:
| 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 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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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 |