A Phase I, Randomized, Double-Blind, Placebo-Controlled, Ascending Single Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AMG 334 in Healthy Subjects and Migraine Patients
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Amgen
- 入组人数
- 61
- 试验地点
- 1
- 主要终点
- Number of Participants With Adverse Events
研究概览
简要总结
The primary purpose of this study is to determine whether erenumab is safe and well tolerated in healthy adults and migraine patients. As part of the secondary objectives, this study will be conducted to characterize the pharmacokinetic (PK) profile of erenumab after single subcutaneous (SC) or intravenous (IV) doses in healthy participants and migraine patients as well as to characterize the effect of erenumab on the capsaicin-induced increase in dermal blood flow after single SC or IV doses in healthy participants and migraine patients.
详细描述
This study was a single-dose, double-blind, placebo-controlled, sequential dose escalation study in which participants were to be enrolled into 8 cohorts.
In Part 1 healthy participants were randomized in a 3:1 ratio (erenumab:placebo) into 6 cohorts: 5 cohorts received the investigational product (IP) as an SC administration and 1 cohort received it as an IV administration. In Part 2 a total of 12 migraine patients were randomized in a 1:1 ratio (erenumab:placebo) in cohort 7. An additional 8 migraine patients could have been enrolled and randomized in a 3:1 ratio in the optional cohort 8, however this cohort was not enrolled.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy male and female subjects between 18 and 45 years of age, or male or female subjects with migraines between 18 and 55 years of age, inclusive, with no history or evidence of clinically relevant medical disorders as determined by the investigator in consultation with the Amgen physician;
排除标准
- •History or evidence of clinically significant disorder (including psychiatric), condition or disease that, in the opinion of the Investigator or Amgen physician would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion;
研究组 & 干预措施
Erenumab
Participants received a single dose of erenumab by subcutaneous injection at doses of 1 mg, 7 mg, 21 mg, 70 mg, 140 mg, and 210 mg or by IV injection at a dose of 140 mg.
干预措施: Erenumab (Drug)
Placebo
Participants received a single dose of matching placebo administered by SC or IV injection.
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Participants With Adverse Events
时间窗: From the initial dose of study drug up to 155 days.
An adverse event (AE) is defined as any untoward medical occurrence in a clinical trial participant. The event does not necessarily have a causal relationship with study treatment. The definition of adverse events includes worsening of a pre-existing medical condition. Laboratory value changes that require treatment or adjustment in current therapy are considered adverse events. Teatment-related adverse events (TRAEs) are those assessed by the investigator as being possibly related to study drug. A serious adverse event is defined as an adverse event that meets at least 1 of the following serious criteria: * fatal * life-threatening (places the subject at immediate risk of death) * requires in-patient hospitalization or prolongation of existing hospitalization * results in persistent or significant disability/incapacity * congenital anomaly/birth defect * other medically important serious event.
Number of Participants Who Developed Anti-erenumab Antibodies
时间窗: Baseline and up to 155 days postdose
Participants who had a negative or no result at baseline and were antibody positive postbaseline. Blood samples were first tested for anti-erenumab binding antibodies, samples testing positive for binding antibodies were also tested for neutralizing antibodies.
次要结局
- Maximum Observed Concentration (Cmax) of Erenumab(Predose to 155 days postdose)
- Time to Maximum Observed Concentration (Tmax) of Erenumab(Predose to 155 days postdose)
- Area Under the Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) of Erenumab(Predose to 155 days postdose)
- Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) of Erenumab(Predose to 155 days postdose)
- Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow(Days 4, 15, 29, 43, 64, 85, 99, 127, and end of study (defined as day 43 for the 1 mg, 7 mg and 21 mg erenumab cohorts, day 99 for the 70 mg erenumab cohort, day 127 for the 140 mg erenumab cohorts and day 155 for the 210 mg erenumab cohort).)