Multiple-Ascending Dose, Safety, Tolerability, Pharmacokinetic, and Drug-Drug Interaction Study of Lasmiditan
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 70
- 试验地点
- 1
- 主要终点
- Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration
研究概览
简要总结
The purpose of this study is to look at how much lasmiditan, study drug, gets into the blood stream and how long it takes the body to get rid of it.
When drugs are taken together, one or all of the drugs used in combination may be affected. This study will also evaluate the concentrations in the blood of a probe drug cocktail taken alone and in combination with lasmiditan. Information about any side effects that may occur will also be collected.
The study has two parts. Participants will only enroll in one part. This study will last about 25 days for group 1 and 22 days for group 2, not including screening. Screening is required within 28 days prior to the start of the study.
This study is for research purposes only and is not intended to treat any medical condition.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Basic Science
- 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
- 是
入选标准
- •Healthy males or females, as determined by medical history and physical examination
- •Have a body mass index (BMI) of 19.0 to 35.0 kilograms per meter squared (kg/m²) inclusive, at the time of screening
排除标准
- •Have participated, within the last 30 days, in a clinical study involving an Investigational Product (IP)
- •Have previously completed or withdrawn from this study or any other study investigating Lasmiditan, and have previously received Lasmiditan
- •Have clinically significant abnormality in the 12-lead ECG, including corrected QT interval (QTc) with Fridericia's correction (QTcF) greater than (>) 450 milliseconds (ms) for men or >470 ms for women or any abnormality that in the opinion of the investigator increases the risk of participating in the study (not limited to significant bradycardia or heart block)
- •History of, show evidence of, or are undergoing treatment for significant active neuropsychiatric disease (for example, manic depressive illness, schizophrenia, depression), have a recent history of a suicide attempt (30 days within screening visit and any time between screening visit and baseline); or are clinically judged by the investigator to be at risk for suicide
- •History of hypoglycemia
- •Known history of glucose-6-phosphate dehydrogenase deficiency
- •Are taking a concomitant medication or a dietary substance that affects cytochrome P450 (CYP)1A2, CYP2C9, and/or CYP3A isotypes within 14 days of screening
研究组 & 干预措施
Probe Drug Cocktail (Cohort 1a)
Probe Drug Cocktail administered orally on Day -3.
干预措施: Probe Drug Cocktail (Drug)
200 milligrams (mg) Lasmiditan+Probe Drug Cocktail (Cohort 1)
200 mg lasmiditan administered alone, orally, on Days 1-6 and concurrently with probe drug cocktail on Day 7.
干预措施: Probe Drug Cocktail (Drug)
200 milligrams (mg) Lasmiditan+Probe Drug Cocktail (Cohort 1)
200 mg lasmiditan administered alone, orally, on Days 1-6 and concurrently with probe drug cocktail on Day 7.
干预措施: Lasmiditan (Drug)
Placebo+Probe Drug Cocktail (Cohort 1b)
Placebo administered alone, orally, on Days 1-6 and concurrently with probe drug cocktail on Day 7.
干预措施: Probe Drug Cocktail (Drug)
Placebo+Probe Drug Cocktail (Cohort 1b)
Placebo administered alone, orally, on Days 1-6 and concurrently with probe drug cocktail on Day 7.
干预措施: Placebo (Drug)
400 mg Lasmiditan (Cohort 2a)
400 mg lasmiditan administered orally for 7 days.
干预措施: Lasmiditan (Drug)
Placebo (Cohort 2b)
Placebo administered orally for 7 days.
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration
时间窗: Baseline through 14 days after last administration of study drug
A summary of SAEs and other non-serious adverse events (AEs), regardless of causality, will be reported in the Reported Adverse Events module. Adverse events for this outcome measure are reported by arm. SAEs are reported by study drug in the Adverse Events module.
次要结局
- Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Lasmiditan on Day 1(Lasmiditan PK: Day 1:0.5 hour (hr), 1hr , 1.5hr, 2hr, 2.5hr, 3hr, 4hr, 6hr, 8hr, 12hr, 24hr and 48 hr postdose)
- Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Lasmiditan on Day 7(Lasmiditan PK: Day 7: 0.5hour(hr), 1hr, 1.5hr, 2hr, 2.5hr, 3hr, 4hr, 6hr, 8hr, 12hr, 24hr postdose)
- Pharmacokinetics (PK): Area Under the Concentration Curve to the End of the Dosing Period (AUC[Tau]) Lasmiditan on Day 1(Day 1:0.5 hour (hr), 1hr , 1.5hr, 2hr, 2.5hr, 3hr, 4hr, 6hr, 8hr, 12hr, and 24hr postdose)
- Pharmacokinetics (PK): Area Under the Concentration Curve to the End of the Dosing Period (AUC[Tau]) Lasmiditan on Day 7(Lasmiditan PK: Day 7: 0.5hour(hr), 1hr, 1.5hr, 2hr, 2.5hr, 3hr, 4hr, 6hr, 8hr, 12hr,and 24hr postdose)
- Physician Withdrawal Checklist (PWC)Total Score(Day 7 and Day 21 at anytime)
- Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Metabolite M8 on Day 1(Day 1: 0.5 hr, 1hr, 1.5hr, 2 hr, 2.5hr, 3hr, 4hr, 6hr, 8hr, 12hr, 24 hr adn 48 hr postdose)
- Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Metabolite M8 on Day 7(Day 7: Predose, 0.5hr, 1hr, 1.5hr, 2hr, 2.5hr, 3hr, 4hr, 6hr, 8hr, 12hr, 24 hr and 48 hr postdose)
- Benzodiazepine Withdrawal Symptom Questionnaire (BWSQ) Total Score(PreDose Day 7 and Day 21)
- Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Midazolam on Day 7(Day 7:Predose, 0,5hr,1hr, 1.5hr. 2hr, 2.5hr, 3hr, 4hr, 6hr, 8hr, and 12 hr postdose)
- Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Midazolam(Day -3: Predose, 0.5 hour(hr), 1hr, 1.5hr. 2hr, 2.5hr, 3hr, 4hr, 6hr, 8hr, and 12 hr postdose,)