Phase I, Randomized, Parallel-group, Double-Blind, Placebo-Controlled, Single Dose Study to Evaluate the Blockade of CGRP Receptor by AMG 334 in Preventing PACAP-38 Induced Migraine-like Attacks in Migraine Patients
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Amgen
- 入组人数
- 35
- 试验地点
- 1
- 主要终点
- Number of Participants With a MLA Within 24 Hours of Challenge Agent Infusion
研究概览
简要总结
Phase I, Randomized, Parallel-group, Double-Blind, Placebo-Controlled, Single Dose Study to Evaluate the Blockade of CGRP Receptor by AMG 334 in Preventing PACAP-38 Induced Migraine-like Attacks in Migraine Patients.
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 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults ≥ 18 to ≤ 45 years of age upon entry into screening
- •History of migraine headaches without aura for ≥ 6 months prior to screening according to the International Headache Society (IHS) International Classification of Headache Disorders (ICHD-II) (Headache Classification Committee of the International Headache Society, 2004) based on medical records and/or patient self-report
- •Migraine frequency: ≥ 1 and ≤ 5 migraine days per month in each of the 3 months prior to screening
排除标准
- •History of migraine with aura, cluster headache or hemiplegic migraine headache according to the IHS Classification ICHD-II (Headache Classification Committee of the International Headache Society, 2004) based on medical records and/or patient self-report
- •≥ 6 migraine days per month in the last 3 months prior to study enrollment and during screening period
- •Other headache disorders (except for episodic tension-type headache <5 days/month)
研究组 & 干预措施
PACAP-38 Challenge Agent
In Part A, 4 cohorts of 2 to 5 participants sequentially received an intravenous infusion of 10 picomol/kilogram/minute (pmol/kg/minute) PACAP-38 for 2.5, 5, 7.5 and 10 minutes each in order to determine the dose for Part B.
干预措施: PACAP-38 Challenge Agent (Drug)
Placebo
Participants were randomized to receive matching erenumab placebo by intravenous administration over 30 minutes on day 1. On day 8 participants were administered the dose of PACAP-38 determined from Part A of the study (100 pmol/kg) and were followed up for 11 weeks.
干预措施: Placebo (Drug)
Placebo
Participants were randomized to receive matching erenumab placebo by intravenous administration over 30 minutes on day 1. On day 8 participants were administered the dose of PACAP-38 determined from Part A of the study (100 pmol/kg) and were followed up for 11 weeks.
干预措施: PACAP-38 Challenge Agent (Drug)
Erenumab
Participants were randomized to receive 140 milligrams (mg) erenumab by intravenous administration over 30 minutes on day 1 in Part B. On day 8 participants were administered the dose of PACAP-38 determined from Part A of the study (100 pmol/kg) and were followed up for 11 weeks.
干预措施: Erenumab (Drug)
Erenumab
Participants were randomized to receive 140 milligrams (mg) erenumab by intravenous administration over 30 minutes on day 1 in Part B. On day 8 participants were administered the dose of PACAP-38 determined from Part A of the study (100 pmol/kg) and were followed up for 11 weeks.
干预措施: PACAP-38 Challenge Agent (Drug)
结局指标
主要结局
Number of Participants With a MLA Within 24 Hours of Challenge Agent Infusion
时间窗: Part B randomization phase day 8 plus 24 hours.
On day 1 of the double-blind randomization phase participants received 140 mg intravenous erenumab over 30 minutes or matching placebo. On day 8, participants received 10 mol/kg/minute PACAP-38 over 10 minutes and were observed for 24 hours after PACAP-38 infusion. A MLA was defined as fulfilling 1 of the 2 criteria: 1. Headache with at least 2 of the following characteristics: unilateral location, pulsating quality, moderate or severe pain intensity, aggravated by/causing avoidance of routine physical activity. Additionally, during the headache at least 1 of the following: nausea and/or vomiting, photophobia or phonophobia. 2. Headache described as mimicking usual migraine attack treated with triptan.
次要结局
- Mean Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at Day 1, Day 8 and EOS(Part B randomization phase baseline and day 1, day 8 and EOS (week 12).)
- Mean Change From Baseline in Respiratory Rate at Day 1, Day 8 and EOS(Part B randomization phase baseline and day 1, day 8 and EOS (week 12).)
- Mean Change From Baseline in Blood Urea at Day 8, Day 9 and EOS(Part B randomization baseline and day 8, day 9 and EOS (week 12).)
- Mean Change From Baseline in Creatine Kinase at Day 8, Day 9 and EOS(Part B randomization baseline and day 8, day 9 and EOS (week 12).)
- Mean Change From Baseline in Direct Bilirubin at Day 8, Day 9 and EOS(Part B randomization baseline and day 8, day 9 and EOS (week 12).)
- PK: Mean Area Under the Concentration-time Curve From Time 0 to 84 Days Post-dose (AUC84d)(Part B randomization phase baseline and 84 days post-dose.)
- Number of Participants With Treatment Emergent Adverse Events (TEAEs)(Part B randomization phase day 1 until EOS (up to 12 weeks).)
- Number of Participants With a Headache Within 24 Hours of Challenge Agent Infusion(Part B randomization phase day 8 plus 24 hours.)
- Mean Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) at Day 8, Day 9 and EOS(Part B randomization phase baseline and day 8, day 9 and EOS (week 12).)
- Mean Change From Baseline in Total Bilirubin at Day 8, Day 9 and EOS(Part B randomization baseline and day 8, day 9 and EOS (week 12).)
- Mean Change From Baseline in Heart Rate at Day 1, Day 8 and EOS(Part B randomization phase baseline and day 1, day 8 and EOS (week 12).)
- Mean Change From Baseline in Temperature at Day 1, Day 8 and EOS(Part B randomization phase baseline and day 1, day 8 and EOS (week 12).)
- Mean Change From Baseline in Creatinine at Day 8, Day 9 and EOS(Part B randomization baseline and day 8, day 9 and EOS (week 12).)
- Mean Change From Baseline in Eosinophil Count at Day 8, Day 9 and EOS(Part B randomization baseline and day 8, day 9 and EOS (week 12).)
- Mean Change From Baseline in Blood Glucose at Day 8, Day 9 and EOS(Part B randomization baseline and day 8, day 9 and EOS (week 12).)
- Pharmacokinetics (PK): Mean Erenumab Serum Concentration at 1 Hour (C1h)(Part B randomization phase 1 hour post-dose day 1.)
- Number of Participants With Anti-Erenumab Antibodies(Part B randomization phase baseline and EOS.)
- Mean Change From Baseline in Hemoglobin A1C (Fraction of 1) at Day 8, Day 9 and EOS(Part B randomization baseline and day 8, day 9 and EOS (week 12).)
- Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Parameters(Part B randomization phase baseline and EOS.)
- Number of Participants With Clinically Significant Changes in Physical Parameters(Part B randomization phase baseline and EOS.)
- Number of Participants With Clinically Significant Changes in Neurological Assessments(Part B randomization phase baseline and EOS.)