A Phase 3 Multicenter 24-Week Open-Label Study to Evaluate the Safety, Tolerability, and Efficacy of Atogepant When Added to OnabotulinumtoxinA (BOTOX) for the Preventive Treatment of Chronic Migraine
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 75
- 试验地点
- 58
- 主要终点
- Number of Participants With Adverse Events (AEs)
研究概览
简要总结
Migraine is characterized by attacks of throbbing, moderate or severe headache, often associated with nausea, vomiting, and/or sensitivity to light and/or sound. The study will assess safety and tolerability of atogepant when added to BOTOX, as well as prospectively evaluate the efficacy of add-on atogepant for migraine prevention. Adverse events and change in disease activity will be monitored.
Atogepant is an investigational drug being developed to prevent chronic migraine. Approximately 75 adult participants will be enrolled at approximately 30 sites in the United States.
All participants will receive atogepant oral tablet once a day (QD) during the 24-week treatment period, in addition to their standard of care Botox.
There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •At least a 1-year history of chronic migraine (CM), with or without aura, consistent with a diagnosis according to International Classification of Headache Disorders 3rd edition (ICHD-3 2018) and with or without acute medication overuse as defined in the protocol.
- •Must be currently treated with BOTOX for CM: treated with >= 2 treatment cycles in the 8 months prior to Visit 2 (Day 1) with documentation of payer authorization or written attestation of self-pay to support continued use of BOTOX.
- •Must have 8 to 23 (inclusive) migraine days in the electronic diary [eDiary] screening/baseline period (eDiary data must have been collected for at least 20 days).
排除标准
- •Use of opioid-containing products for more than 4 days per month for acute treatment of headache in the 3 months prior to Screening or during the screening/baseline period.
- •Treatment of study target muscles using acupuncture, transcutaneous electrical nerve stimulation (TENS), cranial traction, dental splints for headache, or head and/or neck injections of anesthetics/steroids within 4 weeks prior to Screening and throughout the study.
- •Concurrent use of any migraine prevention treatment other than BOTOX (required concomitant medication; or topiramate <=100mg daily) including use of oral gepants in the 4 weeks prior to screening nor during the screening/baseline period.
- •Current use or use within the 6 months (24 weeks) prior to Screening, of mAbs blocking the CGRP pathway.
- •Concurrent use of oral gepants for acute migraine treatment in the 4 weeks prior to screening nor during the screening/baseline period.
研究组 & 干预措施
Atogepant
Participants received atogepant 60 mg once a day (QD) during the 24-week treatment period.
干预措施: Atogepant (Drug)
结局指标
主要结局
Number of Participants With Adverse Events (AEs)
时间窗: Up to approximately 28 Weeks
An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above.
Change From Baseline in Monthly Migraine Days
时间窗: Baseline (Week 0) through 24 Weeks
Change from Baseline in monthly migraine days, defined by International Headache Society (IHS) Guidelines 2018 will be assessed.
Change from Baseline in Monthly Headache Days, Moderate or Severe Headache Days, Cumulative Hours of Headache, Acute Treatment Medication Use Days, Headache Free Days, and Migraine Symptom-Free Days
时间窗: Baseline (Week 0) through 24 Weeks
Change from baseline in monthly headache days, moderate or severe headache days, cumulative hours of headache, acute treatment medication use days, headache free days, and migraine symptom-free days, defined by IHS Guidelines 2018 will be assessed.
Responder Status of at least 25% Reduction in the Frequency of Monthly Migraine Days Collected via Daily Electronic Diary (eDiary)
时间窗: Baseline (Week 0) through 24 Weeks
Percentage of participants achieving at least 25% reduction from baseline in the frequency of monthly migraine days will be assessed.
Change from Baseline in Monthly Activity Impairment in Migraine - Diary (AIM-D)
时间窗: Baseline (Week 0) through 24 Weeks
The AIM-D is an 11-item daily diary measure that assesses the impact of migraine and is comprised of two domains that evaluate performance of daily activities (7 items) and physical impairment (4 items).
Responder Status of at least 30% Reduction in the Frequency of Monthly Migraine Days Collected via eDiary
时间窗: Baseline (Week 0) through 24 Weeks
Percentage of participants achieving at least 30% reduction from baseline in the frequency of monthly migraine days will be assessed.
Responder Status of at least 75% Reduction in the Frequency of Monthly Migraine Days Collected via eDiary
时间窗: Baseline (Week 0) through 24 Weeks
Percentage of participants achieving at least 75% reduction from baseline in the frequency of monthly migraine days will be assessed.
Responder Status of at least 50% Reduction in the Frequency of Monthly Migraine Days Collected via eDiary
时间窗: Baseline (Week 0) through 24 Weeks
Percentage of participants achieving at least 50% reduction from baseline in the frequency of monthly migraine days will be assessed.
Responder Status of at least 100% Reduction in the Frequency of Monthly Migraine Days Collected via eDiary
时间窗: Baseline (Week 0) through 24 Weeks
Percentage of participants achieving at least 100% reduction from baseline in the frequency of monthly migraine days will be assessed.
Change from Baseline in Monthly days with Non-Headache Migraine Symptoms
时间窗: Baseline (Week 0) through 24 Weeks
Change from baseline in monthly days with non-headache migraine symptoms such as photophobia, phonophobia, nausea and/or vomiting, dizziness, neck pain, tiredness, mood change, yawning, thirst, cravings, urinary frequency, cranial autonomic symptoms
Number of Participants With Adverse Events (AEs)
时间窗: From first dose of study drug until 4 weeks following last dose of study drug (up to 28 weeks)
An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study drug. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent adverse events/treatment-emergent serious adverse events (TEAEs/TESAEs) are defined as any event that began or worsened in severity on or after the first dose of study drug.
Percentage of Participants With Potentially Clinically Significant (PCS) Laboratory Values (Chemistry, Hematology, Urinalysis) as Assessed by the Investigator
时间窗: From first dose of study drug until last dose of study drug (24 weeks)
Clinical laboratory test values are considered PCS if they meet either the lower-limit or higher-limit PCS criteria defined in the categories below. The percentage of participants with PCS laboratory values are summarized for hematology, chemistry, and urinalysis. Glomerular Filtration Rate (GFR) is a clinical measurement that calculates how many milliliters of blood the kidneys filter every second. Glucose, Urinalysis: At least 1+ indicates that the urine contains an increased concentration of sugar. Protein, Urinalysis: At least 1+ indicates that the urine contains an increased concentration of protein.
Percentage of Participants With Potentially Clinically Significant (PCS) Vital Sign Measurements as Assessed by the Investigator
时间窗: From first dose of study drug until last dose of study drug (24 weeks)
Potentially Clinically Significant post-Baseline vital sign values are summarized for categories: systolic and diastolic blood pressures \[sitting\], pulse rate \[sitting\], and weight. Number of participants with non-PCS baseline values who met the PCS criterion at least once post-baseline are reported.
Percentage of Participants With Most Severe Suicidal Ideation and Suicidal Behavior as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) During the Open-Label Treatment Period
时间窗: From first dose of study drug until last dose of study drug (24 weeks)
The C-SSRS is a clinician-rated instrument that reports the severity of both suicidal ideation and behavior. Suicidal ideation is classified on a 5-item scale: 1 (wish to be dead), 2 (nonspecific active suicidal thoughts), 3 (active suicidal ideation with any methods \[not plan\] without intent to act), 4 (active suicidal ideation with some intent to act, without specific plan), and 5 (active suicidal ideation with specific plan and intent). Suicidal behavior is classified on a 5-item scale: 0 (no suicidal behavior), 1 (preparatory acts or behavior), 2 (aborted attempt), 3 (interrupted attempt), and 4 (actual attempt). More than 1 classification can be selected provided they represent separate episodes. (Minimum total score 0, maximum total score 5; higher total scores indicate more suicidal ideation and/or suicidal behavior).
Percentage of Participants With Potentially Clinically Significant (PCS) Electrocardiograms (ECGs) Findings as Assessed by the Investigator
时间窗: From first dose of study drug until last dose of study drug (24 weeks)
12-lead ECGs were performed at select study visits.
次要结局
未报告次要终点