An Open Label, Single Dose, Randomized, Active Comparator, Quantitative Electroencephalogram Crossover Study to Assess the Time to Onset of Action of Staccato Alprazolam Versus Intravenous Midazolam and of Staccato Alprazolam Versus Nasal Diazepam in Healthy Study Participants
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 55
- 试验地点
- 1
- 主要终点
- Time to reach a z-score of absolute power >2 and maintained for at least 60 seconds in the combined spindle and β1 frequency bands within the first 60 minutes of study intervention administration of Staccato alprazolam in Group 1
研究概览
简要总结
The purpose of this study is to estimate the difference in the time to onset of action between Staccato alprazolam and intravenous (iv) midazolam using changes in power in the combined spindle and β1 frequency bands in the qEEG (quantitative electroencephalogram).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Participant must be 20 years to 55 years of age, inclusive, at the time of signing the ICF.
- •Participant is overtly healthy as determined by medical evaluation, including medical history, physical examination, laboratory tests, and cardiac monitoring, at the Screening Visit and on Day -1 of the single Intervention Period for the Pilot Part or on Day -1 of the first Intervention Period for the Main Part of the study.
- •Participant has a bodyweight of at least 45 kilograms (kg) (female) and 50 kg (male) and a body mass index within the range of 18 Kilograms per meter square (Kg/m2) to 30 kg/m2 (inclusive)
- •Participant has given informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in protocol.
排除标准
- •Participant has any medical or psychiatric condition that, in the opinion of the investigator, could jeopardize or would compromise the participant's ability to participate in this study.
- •Participant has a history of chronic alcohol or drug abuse, as defined in the most recent version of the Diagnostic and Statistical Manual of Mental Disorders, within 6 months prior to the Screening Visit.
- •Participant has a history of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrinological, hematological, neurological, cerebrovascular, or other major disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention; or interfering with the interpretation of data.
- •Participant has a history of or has been diagnosed with epilepsy or epileptic seizures.
- •Participant has abnormal EEG findings at Screening including background slowing (<8Hz), focal slowing (focal δ-activity), or epileptiform discharges.
研究组 & 干预措施
Pilot Part
Study participants who successfully completed the Screening Period will receive single dose of Intravenous (IV) midazolam on Day 1 of the Intervention Period.
干预措施: Midazolam (Drug)
Main Part-Group 1: Treatment Sequence AB
Study participants randomized in Group 1 will receive Treatment A: Staccato Alprazolam on Day 1 of the Intervention Period 1 followed by Treatment B: IV Midazolam on Day 1 of the Intervention Period 2.
干预措施: Staccato Alprazolam (Drug)
Main Part-Group 1: Treatment Sequence AB
Study participants randomized in Group 1 will receive Treatment A: Staccato Alprazolam on Day 1 of the Intervention Period 1 followed by Treatment B: IV Midazolam on Day 1 of the Intervention Period 2.
干预措施: Midazolam (Drug)
Main Part-Group 1: Treatment Sequence BA
Study participants randomized in Group 1 will receive Treatment B: IV Midazolam on Day 1 of the Intervention Period 1 followed by Treatment A: Staccato Alprazolam on Day 1 of the Intervention Period 2.
干预措施: Staccato Alprazolam (Drug)
Main Part-Group 1: Treatment Sequence BA
Study participants randomized in Group 1 will receive Treatment B: IV Midazolam on Day 1 of the Intervention Period 1 followed by Treatment A: Staccato Alprazolam on Day 1 of the Intervention Period 2.
干预措施: Midazolam (Drug)
Main Part-Group 2: Treatment Sequence AC
Study participants randomized in Group 2 will receive Treatment A: Staccato Alprazolam on Day 1 of the Intervention Period 1 followed by Treatment C: Nasal Diazepam on Day 1 of the Intervention Period 2.
干预措施: Staccato Alprazolam (Drug)
Main Part-Group 2: Treatment Sequence AC
Study participants randomized in Group 2 will receive Treatment A: Staccato Alprazolam on Day 1 of the Intervention Period 1 followed by Treatment C: Nasal Diazepam on Day 1 of the Intervention Period 2.
干预措施: Diazepam (Drug)
Main Part-Group 2: Treatment Sequence CA
Study participants randomized in Group 2 will receive Treatment C: Nasal Diazepam on Day 1 of the Intervention Period 1 followed by Treatment A: Staccato Alprazolam on Day 1 of the Intervention Period 2.
干预措施: Staccato Alprazolam (Drug)
Main Part-Group 2: Treatment Sequence CA
Study participants randomized in Group 2 will receive Treatment C: Nasal Diazepam on Day 1 of the Intervention Period 1 followed by Treatment A: Staccato Alprazolam on Day 1 of the Intervention Period 2.
干预措施: Diazepam (Drug)
结局指标
主要结局
Time to reach a z-score of absolute power >2 and maintained for at least 60 seconds in the combined spindle and β1 frequency bands within the first 60 minutes of study intervention administration of Staccato alprazolam in Group 1
时间窗: Within the first 60 minutes of the study intervention administration on Day 1 of the Intervention Period in Group 1
Time to reach a z-score of absolute power \>2 is derived from the z-scores over time for the combined spindle and β1 frequency bands. The z-scores are calculated using an algorithm applied to the quantitative electroencephalogram (qEEG) data recorded for each study participant.
Time to reach a z-score of absolute power >2 and maintained for at least 60 seconds in the combined spindle and β1 frequency bands within the first 60 minutes of study intervention administration of iv midazolam in Group 1
时间窗: Within the first 60 minutes of the study intervention administration on Day 1 of the Intervention Period in Group 1
Time to reach a z-score of absolute power \>2 is derived from the z-scores over time for the combined spindle and β1 frequency bands. The z-scores are calculated using an algorithm applied to the quantitative electroencephalogram (qEEG) data recorded for each study participant.
次要结局
- Occurrence of Treatment Emergent Adverse Events (TEAEs) from the first study intervention administration to the Safety Follow-Up (SFU) Visit/ Early Termination Visit (ETV)(From the first study intervention administration to the Safety Follow-Up (SFU) Visit/ Early Termination Visit (ETV) (up to 55 Days))
- Occurrence of Serious TEAEs from the first study intervention administration to the Safety Follow-Up (SFU) Visit/ Early Termination Visit (ETV)(From the first study intervention administration to the Safety Follow-Up (SFU) Visit/ Early Termination Visit (ETV) (up to 55 Days))
- Time to reach a z-score of absolute power >2 and maintained for at least 60 seconds in the combined spindle and β1 frequency bands within the first 60 Minutes of study intervention administration of Staccato alprazolam in Group 2(Within the first 60 minutes of the study intervention administration on Day 1 of the Intervention Period in Group 2)
- Time to reach a z-score of absolute power >2 and maintained for at least 60 seconds in the combined spindle and β1 frequency bands within the first 60 Minutes of study intervention administration of nasal diazepam in Group 2(Within the first 60 minutes of the study intervention administration on Day 1 of the Intervention Period in Group 2)
- Maximum concentration (Cmax) of alprazolam(Plasma samples will be collected at predose (Day 1) and at pre-defined time points upto 24 hours postdose)
- Area under the concentration-time curve from time 0 to the last quantifiable concentration (AUC[0-t]) of alprazolam(Plasma samples will be collected at predose (Day 1) and at pre-defined time points upto 24 hours postdose)
- Area Under the Concentration Time Curve From Time 0 to Infinity (AUC) of alprazolam(Plasma samples will be collected at predose (Day 1) and at pre-defined time points upto 24 hours postdose)
- Maximum concentration (Cmax) of midazolam(Plasma samples will be collected at predose (Day 1) and at pre-defined time points upto 24 hours postdose)
- Area under the concentration-time curve from time 0 to the last quantifiable concentration (AUC[0-t]) of midazolam(Plasma samples will be collected at predose (Day 1) and at pre-defined time points upto 24 hours postdose)
- Area Under the Concentration Time Curve From Time 0 to Infinity (AUC) of midazolam(Plasma samples will be collected at predose (Day 1) and at pre-defined time points upto 24 hours postdose)
- Maximum concentration (Cmax) of diazepam(Plasma samples will be collected at predose (Day 1) and at pre-defined time points upto 24 hours postdose)
- Area under the concentration-time curve from time 0 to the last quantifiable concentration (AUC[0-t]) of diazepam(Plasma samples will be collected at predose (Day 1) and at pre-defined time points upto 24 hours postdose)
- Area Under the Concentration Time Curve From Time 0 to Infinity (AUC) of diazepam(Plasma samples will be collected at predose (Day 1) and at pre-defined time points upto 24 hours postdose)