A Phase 2/3, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Rimegepant in Migraine Prevention
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 1,590
- 试验地点
- 87
- 主要终点
- Change From Baseline in the Mean Number of Total Migraine Days Per Month in the Last 4 Weeks of the DBT Phase
研究概览
简要总结
The purpose of this is study is to compare the efficacy of BHV-3000 (rimegepant) to placebo as a preventive treatment for migraine, as measured by the reduction in the number of migraine days per month.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 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
- •Subject has at least 1 year history of migraine (with or without aura) consistent with a diagnosis according to the International Classification of Headache Disorders, 3rd Edition, including the following:
- •Age of onset of migraines prior to 50 years of age
- •Migraine attacks, on average, lasting 4 - 72 hours if untreated
- •Per subject report, 4 - 18 migraine attacks of moderate to severe intensity per month within the last 3 months prior to the Screening Visit
- •6 or more migraine days during the Observation Period
- •Not more than 18 headache days during the Observation Period
- •Ability to distinguish migraine attacks from tension/cluster headaches
- •Subjects on prophylactic migraine medication are permitted to remain on 1 medication with possible migraine-prophylactic effects if the dose has been stable for at least 3 months prior to the Screening Visit, and the dose is not expected to change during the course of the study.
排除标准
- •Subject with a history of HIV disease
- •Subject history with current evidence of uncontrolled, unstable or recently diagnosed cardiovascular disease, such as ischemic heart disease, coronary artery vasospasm, and cerebral ischemia. Subjects with Myocardial Infarction (MI), Acute Coronary Syndrome (ACS), Percutaneous Coronary Intervention (PCI), cardiac surgery, stroke or transient ischemic attack (TIA) during the 6 months prior to screening
- •Uncontrolled hypertension (high blood pressure), or uncontrolled diabetes (however subjects can be included who have stable hypertension and/or diabetes for at least 3 months prior to screening).
- •Subjects with major depressive episode within the last 12 months, major depressive disorder or any anxiety disorder requiring more than 1 medication for each disorder. Medications to treat major depressive disorder or an anxiety disorder must have been at a stable dose for at least 3 months prior to the Screening visit.
- •Subjects with other pain syndromes, psychiatric conditions, dementia, or significant neurological disorders (other than migraine) that, in the Investigator's opinion, might interfere with study assessments
- •Subject has a history of gastric, or small intestinal surgery (including Gastric Bypass, Gastric Banding, Gastric Sleeve, Gastric Balloon, etc.), or has disease that causes malabsorption
- •Body mass index ≥ 33 kg/m2
- •Subject has current diagnosis of major depressive disorder requiring treatment with atypical antipsychotics, schizophrenia, bipolar disorder, or borderline personality disorder
- •History of gallstones or cholecystectomy.
- •The subject has a history or current evidence of any unstable medical conditions (e.g., history of congenital heart disease or arrhythmia, known or suspected infection, hepatitis B or C, or cancer) that, in the investigator's opinion, would expose them to undue risk of a significant adverse event (AE) or interfere with assessments of safety or efficacy during the course of the trial.
研究组 & 干预措施
DBT Rimegepant/OL Rimegepant
DBT Phase (Weeks 1 through 12): Participants received a single oral dose of rimegepant 75 mg tablet every other day (EOD) for 12 weeks.
OLE Phase (Weeks 13 through 64): Participants who continued to meet study entry criteria and had acceptable laboratory test results per protocol, entered the OLE phase and received a single oral dose of rimegepant 75 mg tablet EOD for 52 weeks. If participants had a migraine on a day that they were not scheduled to dose with rimegepant, they could take one tablet of rimegepant 75 mg on that calendar day to treat a migraine (as needed [PRN] dosing).
After completing the OLE phase, participants had follow-up safety visits 2 and 8 weeks after the End-of-Treatment (EOT) visit. Participants who did not complete the DBT phase and/or did not enter or complete the OLE phase were to complete the EOT visit, the 2-week follow-up safety visit, and the 8-week follow-up safety visit after their early discontinuation.
干预措施: Rimegepant (Drug)
DBT Placebo/OL Rimegepant
DBT Phase (Weeks 1 through 12): Participants received a single oral dose of placebo matching to rimegepant tablet EOD for 12 weeks.
OLE Phase (Weeks 13 through 64): Participants who continued to meet study entry criteria and had acceptable laboratory test results per protocol, entered the OLE phase and received a single oral dose of rimegepant 75 mg tablet EOD for 52 weeks. If participants had a migraine on a day that they were not scheduled to dose with rimegepant, they could take one tablet of rimegepant 75 mg on that calendar day to treat a migraine (PRN dosing).
After completing the OLE phase, participants had follow-up safety visits 2 and 8 weeks after the End-of-Treatment (EOT) visit. Participants who did not complete the DBT phase and/or did not enter or complete the OLE phase were to complete the EOT visit, the 2-week follow-up safety visit, and the 8-week follow-up safety visit after their early discontinuation.
干预措施: Rimegepant (Drug)
DBT Placebo/OL Rimegepant
DBT Phase (Weeks 1 through 12): Participants received a single oral dose of placebo matching to rimegepant tablet EOD for 12 weeks.
OLE Phase (Weeks 13 through 64): Participants who continued to meet study entry criteria and had acceptable laboratory test results per protocol, entered the OLE phase and received a single oral dose of rimegepant 75 mg tablet EOD for 52 weeks. If participants had a migraine on a day that they were not scheduled to dose with rimegepant, they could take one tablet of rimegepant 75 mg on that calendar day to treat a migraine (PRN dosing).
After completing the OLE phase, participants had follow-up safety visits 2 and 8 weeks after the End-of-Treatment (EOT) visit. Participants who did not complete the DBT phase and/or did not enter or complete the OLE phase were to complete the EOT visit, the 2-week follow-up safety visit, and the 8-week follow-up safety visit after their early discontinuation.
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Baseline in the Mean Number of Total Migraine Days Per Month in the Last 4 Weeks of the DBT Phase
时间窗: OP and Weeks 9 to 12 of the DBT phase
A migraine day: any calendar day in which the participant experienced a qualified migraine headache (onset, continuation, or recurrence of the migraine headache). A qualified migraine headache: a migraine with or without aura, lasting for ≥30 minutes, and meeting at least 1 of the following criteria (a and/or b): a) ≥2 of the following: unilateral location, pulsating quality, moderate to severe pain intensity, aggravation by or causing avoidance of routine physical activity; b) ≥1 of the following: nausea and/or vomiting, photophobia, and phonophobia. If the participant took a migraine-specific medication during aura or to treat headache on a calendar day, it was counted as a migraine day regardless of the duration and pain features/associated symptoms. Months were defined as 28-day intervals. The change from baseline was calculated as the number of monthly migraine days during the last 4 weeks of the DBT phase (Weeks 9 to 12) minus number of monthly migraine days during the OP.
次要结局
- Number of Participants Who Had ≥ 50% Reduction in Moderate or Severe Migraine Days Per Month in the Last 4 Weeks of the DBT Phase(OP and Weeks 9 to 12 of the DBT phase)
- Change From Baseline in the Mean Number of Migraine Days Per Month Over the Entire Course of the DBT Phase(OP and Weeks 1 to 12 of the DBT phase)
- Number of Participants With AEs, SAEs, AEs Leading to Study Drug Discontinuation in the OLE Phase(OLE Phase (Weeks 13 through 64))
- Number of Participants With Clinically Significant Laboratory Abnormalities in the DBT Phase(Weeks 1 to 12 of the DBT phase)
- Number of Participants With Hepatic-related AEs and Hepatic-related AEs Leading to Discontinuation During the OLE Phase(OLE Phase (Weeks 13 through 64))
- Frequency of Use of Rescue Medication Days Per Month in the Last Month of the DBT Phase(Weeks 9 to 12 of the DBT phase)
- Number of Participants With Clinically Significant Laboratory Abnormalities in the OLE Phase(OLE Phase (Weeks 13 through 64))
- Number of Participants With Elevations of AST or ALT > 3 x Upper Limit of Normal (ULN) Concurrent With Total Bilirubin (TBL) > 2 x ULN During the DBT Phase(Weeks 1 to 12 of the DBT phase)
- Change From Baseline in the Mean Number of Total Migraine Days Per Month in the First Month of the DBT Phase(OP and Weeks 1 to 4 of the DBT phase)
- Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), AEs Leading to Study Drug Discontinuation in the DBT Phase(Weeks 1 to 12 of the DBT phase)
- Percentage of Participants With Elevations of AST or ALT > 3 x ULN Concurrent With TBL > 2 x ULN During the OLE Phase(OLE Phase (Weeks 13 through 64))
- Mean Change From Baseline in the Migraine Disability Assessment (MIDAS) Total Score at Week 12 of the DBT Phase(Baseline, Week 12 of the DBT Phase)
- Number of Participants With Hepatic-related AEs and Hepatic-related AEs Leading to Discontinuation During the DBT Phase(Weeks 1 to 12 of the DBT phase)
- Mean Change From Baseline in the Migraine Specific Quality of Life (MSQoL) Role Function-Restrictive Domain Score at Week 12 of the DBT Phase(Baseline, Week 12 of the DBT Phase)