A Phase IIb, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Pharmacokinetic Study of MK-1602 in the Treatment of Acute Migraine
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Allergan
- 入组人数
- 195
- 主要终点
- Percentage of Participants With Pain Relief (PR) at 2 Hours Post-Dose on Migraine Treatment Day
研究概览
简要总结
The purpose of this study is to characterize the pharmacokinetics of MK-1602 in the treatment of acute migraine, including the influence of demographic and other variables on MK-1602 pharmacokinetics, and to evaluate the relationship between MK-1602 concentrations and efficacy of the drug.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •> 1 year history of migraine with or without aura as defined by International Headache Society (IHS) criteria 1.1 and/or 1.2
- •Migraines typically last between 4 to 72 hours, if untreated
- •≥ 2 and ≤ 8 moderate or severe migraine attacks per month in each of
- •the two months prior to screening
- •Male, female who is not of reproductive potential, or female of
- •reproductive potential with a screening serum β-human chorionic gonadotropin (β-hCG) level consistent with a not-pregnant state, and who agrees to use acceptable contraception
排除标准
- •Pregnant or breast-feeding, or is a female expecting to conceive within the projected duration of study participation
- •Participant has difficulty distinguishing his/her migraine attacks from tension-type headaches
- •History of predominantly mild migraine attacks or migraines that usually
- •resolve spontaneously in less than two hours
- •More than 15 headache-days per month or has taken medication for acute headache on more than 10 days per month in any of the three months prior to screening
- •Basilar-type or hemiplegic migraine headache
- •> 50 years old at age of migraine onset
- •Taking migraine prophylactic medication where the prescribed daily dose
- •has changed during the 3 months prior to screening and during the study
- •Taking a proton pump inhibitor (PPI) or a histamine receptor 2 (H2) blocker on a daily or near daily basis (> 3 days per week)
- •Taking the following medications from 1 month prior to screening through study period: potent cytochrome P450 (CYP) 3A4 inhibitors (e.g., cyclosporine, itraconazole, ketoconazole, fluconazole, erythromycin, clarithromycin, nefazodone, telithromycin, cimetidine, quinine, diltiazem, verapamil, modafinil and human immunodeficiency virus [HIV] protease inhibitors), moderate or marked CYP3A4 inducers (e.g., rifampicin, rifabutin, barbiturates [e.g., phenobarbital and primidone], systemic glucocorticoids, nevirapine, efavirenz, pioglitazone, carbamazepine, phenytoin, and St. Johns wort), or drugs with narrow therapeutic margins and potential for drug interactions in the CYP2C family (e.g., warfarin)
- •Participant is unable to refrain from consumption of grapefruit or grapefruit juice during study
- •History of hypersensitivity to, or has experienced a serious adverse event
- •in response to 3 or more classes of drugs (prescription and over-the-counter)
- •Clinical or laboratory evidence of uncontrolled diabetes, HIV disease, or significant pulmonary, renal, hepatic, endocrine, or other systemic disease
- •Other confounding pain syndromes, psychiatric conditions such as uncontrolled major depression, dementia or significant neurological disorders other than migraine. Patients who are currently being treated with non-prohibited medication for depression and symptoms are well controlled are eligible to participate
- •Participant is at imminent risk of self-harm
- •History of malignancy ≤ 5 years prior to study, except for adequately treated basal cell or squamous cell skin cancer, or in situ cervical cancer
- •History of gastric or small intestinal surgery (including gastric bypass
- •surgery or banding), or presence of a disease that causes malabsorption
- •History or current evidence of any condition, therapy, lab abnormality or
- •other circumstance that might confound the results of the study, or interfere with subject's participation for the full duration of the study
- •Participant has recent history (within the last year) of drug or alcohol abuse or dependence or is a user of recreational or illicit drugs
- •Participant is legally or mentally incapacitated
- •Donation of blood products or phlebotomy of > 300 ml within 8
- •weeks of study, or intent to donate blood products or receive
- •blood products within 30 days of screening and throughout study
- •Intent to donate eggs or sperm within the projected duration of the
- •Current participation in or participation within 30 days of screening
- •in a study with an investigational compound or device, with the exception of MK-1602 Protocol 006
- •Previous exposure to MK-0974 and/or MK-3207
- •Use within the past 2 months of an opioid- or barbiturate-containing
- •analgesic for migraine relief
- •Inpatient or emergency department treatment of an acute migraine
- •attack within the past 2 months
研究组 & 干预措施
Placebo
MK-1602 placebo-matching tablet orally for 3 doses: Dose 1 at the onset of a moderate or severe migraine (Day 1), Dose 2 in the evening of Day 3 and Dose 3 on Day 4. After 2 hours participants were able to take rescue medication if necessary.
干预措施: Placebo (Drug)
Placebo
MK-1602 placebo-matching tablet orally for 3 doses: Dose 1 at the onset of a moderate or severe migraine (Day 1), Dose 2 in the evening of Day 3 and Dose 3 on Day 4. After 2 hours participants were able to take rescue medication if necessary.
干预措施: Rescue medication (Drug)
MK-1602 1 mg
MK-1602 1 mg tablet orally for 3 doses: Dose 1 at the onset of a moderate or severe migraine (Day 1), Dose 2 in the evening of Day 3 and Dose 3 on Day 4. After 2 hours participants were able to take rescue medication if necessary.
干预措施: MK-1602 (Drug)
MK-1602 1 mg
MK-1602 1 mg tablet orally for 3 doses: Dose 1 at the onset of a moderate or severe migraine (Day 1), Dose 2 in the evening of Day 3 and Dose 3 on Day 4. After 2 hours participants were able to take rescue medication if necessary.
干预措施: Rescue medication (Drug)
MK-1602 10 mg
MK-1602 10 mg tablet orally for 3 doses: Dose 1 at the onset of a moderate or severe migraine (Day 1), Dose 2 in the evening of Day 3 and Dose 3 on Day 4. After 2 hours participants were able to take rescue medication if necessary.
干预措施: MK-1602 (Drug)
MK-1602 10 mg
MK-1602 10 mg tablet orally for 3 doses: Dose 1 at the onset of a moderate or severe migraine (Day 1), Dose 2 in the evening of Day 3 and Dose 3 on Day 4. After 2 hours participants were able to take rescue medication if necessary.
干预措施: Rescue medication (Drug)
MK-1602 25 mg
MK-1602 25 mg tablet orally for 3 doses: Dose 1 at the onset of a moderate or severe migraine (Day 1), Dose 2 in the evening of Day 3 and Dose 3 on Day 4. After 2 hours participants were able to take rescue medication if necessary.
干预措施: MK-1602 (Drug)
MK-1602 25 mg
MK-1602 25 mg tablet orally for 3 doses: Dose 1 at the onset of a moderate or severe migraine (Day 1), Dose 2 in the evening of Day 3 and Dose 3 on Day 4. After 2 hours participants were able to take rescue medication if necessary.
干预措施: Rescue medication (Drug)
MK-1602 50 mg
MK-1602 50 mg tablet orally for 3 doses: Dose 1 at the onset of a moderate or severe migraine (Day 1), Dose 2 in the evening of Day 3 and Dose 3 on Day 4. After 2 hours participants were able to take rescue medication if necessary.
干预措施: MK-1602 (Drug)
MK-1602 50 mg
MK-1602 50 mg tablet orally for 3 doses: Dose 1 at the onset of a moderate or severe migraine (Day 1), Dose 2 in the evening of Day 3 and Dose 3 on Day 4. After 2 hours participants were able to take rescue medication if necessary.
干预措施: Rescue medication (Drug)
MK-1602 100 mg
MK-1602 100 mg tablet orally for 3 doses: Dose 1 at the onset of a moderate or severe migraine (Day 1), Dose 2 in the evening of Day 3 and Dose 3 on Day 4. After 2 hours participants were able to take rescue medication if necessary.
干预措施: MK-1602 (Drug)
MK-1602 100 mg
MK-1602 100 mg tablet orally for 3 doses: Dose 1 at the onset of a moderate or severe migraine (Day 1), Dose 2 in the evening of Day 3 and Dose 3 on Day 4. After 2 hours participants were able to take rescue medication if necessary.
干预措施: Rescue medication (Drug)
结局指标
主要结局
Percentage of Participants With Pain Relief (PR) at 2 Hours Post-Dose on Migraine Treatment Day
时间窗: 2 hours post dose 1
PR was defined as a decrease from a moderate or severe migraine headache (Grade 2 or 3) at Baseline to a mild headache or no headache (Grade 1 or 0) 2 hours post dose. Headache severity was reported by the participant using a 4-point scale where: 0=no pain, 1=mild pain, 2=moderate pain and 3=severe pain.
Dry Blood Spot (DBS) MK-1602 Concentration at 2 Hours Post-Dose on Migraine Treatment Day
时间窗: 2 hours post dose 1
The participant collected blood by fingerstick on a card. The card was sent to a laboratory and the concentration of MK-1602 determined using the dried blood spot (DBS) assay.
Percentage of Participants Reporting Pain Freedom (PF) at 2 Hours Post-Dose on Migraine Treatment Day
时间窗: 2 hours post dose 1
PF was defined as a decrease from a moderate or severe migraine headache (Grade 2 or 3) at Baseline to no pain (Grade 0) 2 hours post-dose. Headache severity was reported by the participant using a 4-point scale where: 0=no pain, 1=mild pain, 2=moderate pain and 3=severe pain.
次要结局
- Percentage of Participants With TMF From 2-24 Hours Post-Dose on Migraine Treatment Day(2-24 hours post dose 1)
- Percentage of Participants Reporting Absence of Photophobia at 2 Hours Post-Dose on Migraine Treatment Day(2 hours post dose 1)
- Percentage of Participants Reporting Absence of Nausea at 2 Hours Post-Dose on Migraine Treatment Day(2 hours post dose 1)
- Percentage of Participants With Sustained Pain Freedom (SPF) From 2-24 Hours Post-Dose on Migraine Treatment Day(2-24 hours post dose 1)
- Percentage of Participants With Total Migraine Freedom (TMF) at 2 Hours Post-Dose on Migraine Treatment Day(2 hours post dose 1)
- Percentage of Participants Reporting Absence of Phonophobia at 2 Hours Post-Dose on Migraine Treatment Day(2 hours post dose 1)
- Percentage of Participants With Sustained Pain Relief (SPR) From 2-24 Hours Post-Dose on Migraine Treatment Day(2-24 hours post dose 1)