A Multicenter, Double- Blind, Placebo- Controlled Study of Montelukast on Gastrointestinal Tolerability in Patients With Relapsing Forms of Multiple Sclerosis Receiving Tecfidera® (Dimethyl Fumarate) Delayed Release Capsules
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- Biogen
- 入组人数
- 102
- 试验地点
- 1
- 主要终点
- Percentage of Participants With a Worsening in Severity of Gastrointestinal (GI) Adverse Events (AEs) on the GSRS From Day 0 to Day 10
研究概览
简要总结
The primary objective of this study is to evaluate whether montelukast can reduce the severity of gastrointestinal (GI) events, measured by the Gastrointestinal Symptom Rating Scale (GSRS), after oral administration of dimethyl fumarate (DMF) in participants with relapsing forms of Multiple Sclerosis (MS). The secondary objectives of this study are as follows: To evaluate whether montelukast after oral administration of DMF in participants with relapsing forms of MS decreases discontinuations due to GI events and reduces the number of participants taking symptomatic therapies for GI events; To investigate the effect of montelukast on the incidence of flushing events after oral administration of 240 mg DMF in participants with relapsing forms of MS.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Reside in the United States and have a confirmed diagnosis of a relapsing form of MS and satisfy the therapeutic indication as described in the local label
- •As perceived by the Investigator, have the ability to comply with all requirements of the study protocol and to operate the eDiary required to record GI-related events
- •Female participants of childbearing potential who are not surgically sterile must practice effective contraception during their participation in the study and be willing and able to continue contraception for 30 days after they complete or withdraw from the study. All men must practice effective contraception, and they should not donate sperm throughout the study and for at least 90 days after their last dose of study treatment.
排除标准
- •History of significant GI disease (for example, irritable bowel disease, peptic ulcer disease, history of major GI surgery, eosinophilic GI disease, or food allergies)
- •Chronic use (≥7 consecutive days) of bismuth subsalicylate, simethicone, calcium carbonate, loperamide, proton-pump inhibitors, or ondansetron within 1 month prior to the Screening Visit
- •Use of the following medications: montelukast, immunotherapy, mast cell stabilizers, or parenteral, inhaled, or oral steroids up to 1 month prior to the Screening Visit. Use of these medications is also not permitted for the duration of the study (except for the use of montelukast as per study protocol) and will lead to discontinuation
- •Have one or more major comorbidities that, in the opinion of the Investigator, may affect the outcome of the study
- •History of malignancy (except for basal cell carcinoma that had been completely excised prior to study entry), severe allergic or anaphylactic reactions or known drug hypersensitivity, abnormal laboratory results indicative of any significant disease, and/or a major disease that would preclude participation in a clinical study
- •NOTE: Other protocol defined Inclusion/Exclusion criteria may apply
研究组 & 干预措施
DMF plus montelukast
DMF as described in the United States Prescribing Information (USPI) plus 10mg montelukast tablet once daily according to the prevailing product label (Singulair)
干预措施: dimethyl fumarate (Drug)
DMF plus montelukast
DMF as described in the United States Prescribing Information (USPI) plus 10mg montelukast tablet once daily according to the prevailing product label (Singulair)
干预措施: montelukast (Drug)
DMF plus placebo
DMF as described in the USPI plus matched placebo
干预措施: dimethyl fumarate (Drug)
DMF plus placebo
DMF as described in the USPI plus matched placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Percentage of Participants With a Worsening in Severity of Gastrointestinal (GI) Adverse Events (AEs) on the GSRS From Day 0 to Day 10
时间窗: Baseline (Day 0), Day 10 (10 days after Day 0)
The GSRS is a weekly recall scale that was modified for daily recall. The 15-question GSRS is summarized with a 7-point Likert scale: no discomfort at all=0; minor discomfort=1; mild discomfort=2; moderate discomfort=3; moderately severe discomfort=4; severe discomfort=5 and very severe discomfort=6. The overall GSRS score is a mean score that ranges from 0 (no symptoms) to 6 (the worst possible symptoms). Worsening in severity was defined as a positive average change from baseline (Day 0) to Day 10 in the GSRS score. Day 0: the day before a participant started randomized treatment (if the GI threshold was reached 1 day previously) or the first day of randomized treatment if the threshold was reached that day. If the threshold was reached \>1 day previously, then Day 0 was the last day when the threshold was reached, prior to the first dose. Average change is the sum of changes from baseline in GSRS score over the first 10 days divided by the total of days with a GSRS score.
次要结局
- Average Change From Baseline in GSRS Overall Score at Day 1 to Day 10(Baseline (Day 0), Day 1 (1 day after Day 0), Day 10 (10 days after Day 0))
- Average Change From Baseline in GSRS Overall Score at Day 1 to Week 10(Baseline (Day 0), Day 1 (1 day after Day 0), Week 10 (10 weeks after Day 0))
- Time to First Worsening From Baseline in GSRS Overall Score at Day 1 to Day 10(Baseline (Day 0), Day 1 (1 day after Day 0) to Day 10 (10 days after Day 0))
- Time to Recovery to Baseline GSRS Score From Last Occurrence of Worst GSRS Score at Day 1 to Week 8(Baseline (Day 0), Day 1 (1 Day after Day 0) to Week 8 (8 weeks after Day 0))
- Average Change From Baseline in GSRS Overall Score at Day 1 to Weeks 1 to 8(Baseline (Day 0), Day 1 (1 Day after Day 0), Weeks 1 to 8 (1-8 weeks after Day 0))
- Average Change From Baseline in GSRS Overall Score at Day 0 to 72 Hours From the Initiation of Randomized Study Treatment(Baseline (Day 0), Day 3 (72 hours after Day 0))
- Percentage of Participants Who Required GI Symptomatic Therapy During the Study(Day 10 to Week 10)
- Percentage of Participants Who Discontinued DMF Therapy Due to GI-Related Adverse Events (AEs) From Day 0 to Week 10(Day 0 to Week 10)
- Percentage of Participants Who Experienced AEs Related to Flushing(Day of first DMF dose (up to 27 days before Day 0) to Week 10)