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
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 558
- 试验地点
- 2
- 主要终点
- 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)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
ADS-5102, 137 mg
ADS-5102, administered once daily at bedtime from Week 4 through Week 16
干预措施: ADS-5102, 137 mg (Drug)
ADS-5102, 274 mg
ADS-5102, administered once daily at bedtime from Week 4 through Week 16
干预措施: ADS-5102, 274 mg (Drug)
Placebo
placebo, administered once daily at bedtime from Week 4 through Week 16
干预措施: Placebo (Other)
结局指标
主要结局
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)
时间窗: 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.
次要结局
- Timed Up and Go (TUG): Change From Baseline at Week 16(16 weeks)
- 2-Minute Walk Test (2MWT): Change From Baseline at Week 16(16 weeks)
- Timed 25 Foot Walk: Change From Baseline at Week 16(16 weeks)