Assessment of Staccato® Alprazolam on the EEG Photoparoxysmal Response in Patients With Epilepsy
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 5
- 试验地点
- 3
- 主要终点
- Maximum Observed Change From Pretreatment Baseline in the Standardized Photosensitivity Range (SPR)
研究概览
简要总结
The purpose of this study is to determine whether people who usually have photosensitive epilepsy will show a reduction in epileptic activity when they take a single dose of Staccato Alprazolam as compared to placebo.
详细描述
The purpose of this study is to determine whether people who usually have photosensitive epilepsy will show a reduction in epileptic activity when they take a single dose of Staccato Alprazolam as compared to placebo. People with photosensitive epilepsy have changes on their electroencephalogram (EEG) when shown flashing lights. Three dose levels of Staccato Alprazolam will be compared to placebo.
This study will also assess the level of sedation of Staccato Alprazolam compared to placebo.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female subjects between the ages of 18 to 60 years, inclusive
- •Body mass index (BMI) ≥18 and ≤35 kg/m2
- •Able to speak, read, and understand English and willing and able to provide written informed consent on an IRB-approved form before the initiation of any study procedures
- •A diagnosis and history of a photoparoxysmal response on EEG with or without a diagnosis of epilepsy for which patients are on 0-2 concomitant antiepileptic drugs
- •At least 3 of the EEGs performed during the screen visit must have a reproducible IPS-induced photoparoxysmal response (PPR) on EEG of at least 3 points on a frequency assessment scale in at least one eye condition
- •In otherwise good general health as determined by a complete medical history, physical examination, 12-lead ECG, blood chemistry profile, hematology, and urinalysis
- •Female participants (if of child-bearing potential and sexually active) and male participants (if sexually active with a partner of child-bearing potential) who agree to use a medically acceptable and effective birth control method throughout the study and for 1 week following the end of the study. Medically acceptable methods of contraception that may be used by the participant and/or his/her partner include abstinence, birth control pills or patches, diaphragm with spermicide, intrauterine device (IUD), surgical sterilization, and progestin implant or injection. Prohibited methods include: the rhythm method, withdrawal, condoms alone, or diaphragm alone
排除标准
- •History of non-epileptic seizures (e.g. metabolic, structural, or pseudo-seizures)
- •History of seizure worsening in response to narrow spectrum drugs
- •An active CNS infection, demyelinating disease, degenerative neurological disease or any CNS disease deemed to be progressive during the course of the study that may confound the interpretation of the study results
- •Use of more than 2 concomitant AEDs for epilepsy treatment
- •Subjects taking known inhibitors or inducers of CYP3A , including carbamazepine
- •Subjects with a history of allergic reactions to alprazolam or other benzodiazepines
- •Treatment with an investigational drug within 30 days (or within 5 half-lives of the investigational drug, if >30 days) before Visit 2
- •A history within the past 1 year of drug or alcohol dependence or abuse
- •Positive urine screen for drugs of abuse at Visit 1 - Screening
- •A history of HIV-positivity
- •Female subjects who have a positive pregnancy test at screening or prior to test sessions or are breastfeeding
- •History of acute narrow angle glaucoma, Parkinson's disease, hydrocephalus, or history of significant head trauma
- •Subjects who have a current history of asthma, chronic obstructive lung disease (COPD), or any lung disease associated with bronchospasm
- •Subjects who use medications to treat airways disease, such as asthma or COPD
- •Subjects who have any acute respiratory signs/symptoms (e.g., wheezing)
- •Clinically significant ECG abnormality including (but not limited to) any of the following conduction abnormalities or dysrhythmias: atrial fibrillation, mean QTcF (QT interval corrected for heart rate using Fridericia's method) interval >450 msec, ventricular rate <45 beats/min, second or third degree AV block, left bundle branch block, or evidence of prior myocardial infarction (MI) or acute ischemia
- •Hypotension (systolic blood pressure ≤90 mm Hg, diastolic blood pressure ≤50 mm Hg), or hypertension (systolic blood pressure ≥140 mm Hg, diastolic blood pressure ≥100 mm Hg) measured while seated at screening or baseline
- •Significant hepatic, renal, gastroenterologic, cardiovascular (including ischemic heart disease and congestive heart failure), endocrine, neurologic (including history of seizures or stroke), or hematologic disease
- •Any other disease or condition, by history, physical examination, or laboratory abnormalities that in the investigator's opinion, would present undue risk to the subject, or may confound the interpretation of study results
研究组 & 干预措施
Sequence CDAEB
A=Placebo, B=Inhaled Alprazolam 0.5 mg, C=Inhaled Alprazolam 1 mg, D= Inhaled Alprazolam 2 mg, E=Placebo
干预措施: B=Inhaled Alprazolam 0.5 mg (Drug)
Sequence CDAEB
A=Placebo, B=Inhaled Alprazolam 0.5 mg, C=Inhaled Alprazolam 1 mg, D= Inhaled Alprazolam 2 mg, E=Placebo
干预措施: C=Inhaled Alprazolam 1 m (Drug)
Sequence CABED
A=Placebo, B=Inhaled Alprazolam 0.5 mg, C=Inhaled Alprazolam 1 mg, D= Inhaled Alprazolam 2 mg, E=Placebo
干预措施: D= Inhaled Alprazolam 2 mg (Drug)
Sequence CDAEB
A=Placebo, B=Inhaled Alprazolam 0.5 mg, C=Inhaled Alprazolam 1 mg, D= Inhaled Alprazolam 2 mg, E=Placebo
干预措施: A=Placebo (Drug)
Sequence CDAEB
A=Placebo, B=Inhaled Alprazolam 0.5 mg, C=Inhaled Alprazolam 1 mg, D= Inhaled Alprazolam 2 mg, E=Placebo
干预措施: E=Placebo (Drug)
Sequence DEBAC
A=Placebo, B=Inhaled Alprazolam 0.5 mg, C=Inhaled Alprazolam 1 mg, D= Inhaled Alprazolam 2 mg, E=Placebo
干预措施: A=Placebo (Drug)
Sequence DEBAC
A=Placebo, B=Inhaled Alprazolam 0.5 mg, C=Inhaled Alprazolam 1 mg, D= Inhaled Alprazolam 2 mg, E=Placebo
干预措施: B=Inhaled Alprazolam 0.5 mg (Drug)
Sequence CABED
A=Placebo, B=Inhaled Alprazolam 0.5 mg, C=Inhaled Alprazolam 1 mg, D= Inhaled Alprazolam 2 mg, E=Placebo
干预措施: A=Placebo (Drug)
Sequence CABED
A=Placebo, B=Inhaled Alprazolam 0.5 mg, C=Inhaled Alprazolam 1 mg, D= Inhaled Alprazolam 2 mg, E=Placebo
干预措施: E=Placebo (Drug)
Sequence EDBAC
A=Placebo, B=Inhaled Alprazolam 0.5 mg, C=Inhaled Alprazolam 1 mg, D= Inhaled Alprazolam 2 mg, E=Placebo
干预措施: D= Inhaled Alprazolam 2 mg (Drug)
Sequence EDBAC
A=Placebo, B=Inhaled Alprazolam 0.5 mg, C=Inhaled Alprazolam 1 mg, D= Inhaled Alprazolam 2 mg, E=Placebo
干预措施: E=Placebo (Drug)
Sequence BEADC
A=Placebo, B=Inhaled Alprazolam 0.5 mg, C=Inhaled Alprazolam 1 mg, D= Inhaled Alprazolam 2 mg, E=Placebo
干预措施: A=Placebo (Drug)
Sequence BEADC
A=Placebo, B=Inhaled Alprazolam 0.5 mg, C=Inhaled Alprazolam 1 mg, D= Inhaled Alprazolam 2 mg, E=Placebo
干预措施: B=Inhaled Alprazolam 0.5 mg (Drug)
Sequence BEADC
A=Placebo, B=Inhaled Alprazolam 0.5 mg, C=Inhaled Alprazolam 1 mg, D= Inhaled Alprazolam 2 mg, E=Placebo
干预措施: C=Inhaled Alprazolam 1 m (Drug)
Sequence BEADC
A=Placebo, B=Inhaled Alprazolam 0.5 mg, C=Inhaled Alprazolam 1 mg, D= Inhaled Alprazolam 2 mg, E=Placebo
干预措施: D= Inhaled Alprazolam 2 mg (Drug)
Sequence BEADC
A=Placebo, B=Inhaled Alprazolam 0.5 mg, C=Inhaled Alprazolam 1 mg, D= Inhaled Alprazolam 2 mg, E=Placebo
干预措施: E=Placebo (Drug)
Sequence CDAEB
A=Placebo, B=Inhaled Alprazolam 0.5 mg, C=Inhaled Alprazolam 1 mg, D= Inhaled Alprazolam 2 mg, E=Placebo
干预措施: D= Inhaled Alprazolam 2 mg (Drug)
Sequence DEBAC
A=Placebo, B=Inhaled Alprazolam 0.5 mg, C=Inhaled Alprazolam 1 mg, D= Inhaled Alprazolam 2 mg, E=Placebo
干预措施: C=Inhaled Alprazolam 1 m (Drug)
Sequence DEBAC
A=Placebo, B=Inhaled Alprazolam 0.5 mg, C=Inhaled Alprazolam 1 mg, D= Inhaled Alprazolam 2 mg, E=Placebo
干预措施: D= Inhaled Alprazolam 2 mg (Drug)
Sequence DEBAC
A=Placebo, B=Inhaled Alprazolam 0.5 mg, C=Inhaled Alprazolam 1 mg, D= Inhaled Alprazolam 2 mg, E=Placebo
干预措施: E=Placebo (Drug)
Sequence EDBAC
A=Placebo, B=Inhaled Alprazolam 0.5 mg, C=Inhaled Alprazolam 1 mg, D= Inhaled Alprazolam 2 mg, E=Placebo
干预措施: A=Placebo (Drug)
Sequence EDBAC
A=Placebo, B=Inhaled Alprazolam 0.5 mg, C=Inhaled Alprazolam 1 mg, D= Inhaled Alprazolam 2 mg, E=Placebo
干预措施: B=Inhaled Alprazolam 0.5 mg (Drug)
Sequence EDBAC
A=Placebo, B=Inhaled Alprazolam 0.5 mg, C=Inhaled Alprazolam 1 mg, D= Inhaled Alprazolam 2 mg, E=Placebo
干预措施: C=Inhaled Alprazolam 1 m (Drug)
Sequence CABED
A=Placebo, B=Inhaled Alprazolam 0.5 mg, C=Inhaled Alprazolam 1 mg, D= Inhaled Alprazolam 2 mg, E=Placebo
干预措施: B=Inhaled Alprazolam 0.5 mg (Drug)
Sequence CABED
A=Placebo, B=Inhaled Alprazolam 0.5 mg, C=Inhaled Alprazolam 1 mg, D= Inhaled Alprazolam 2 mg, E=Placebo
干预措施: C=Inhaled Alprazolam 1 m (Drug)
结局指标
主要结局
Maximum Observed Change From Pretreatment Baseline in the Standardized Photosensitivity Range (SPR)
时间窗: SPR was recorded pretreatment, 2, 10, 30 min, 1, 2, 4, and 6 hr post each study drug administration The maximum change from baseline occurred at: 10 min for alprazolam 2 mg, 1 hour for alprazolam 0.5 and 1 mg and placebo
Photosensitivity describes the presentation of an epileptiform EEG response (photoparoxysmal response) from exposure to intermittent photic stimulation (IPS). SPR is the number of frequency steps (2, 5, 8, 10, 13, 15, 18, 20, 23, 25, 30, 40, 50 and 60 Hz). between the upper and lower limits of sensitivity to IPS for that patient at that time, in order not to evoke seizures. Thus a reduction (-change) means the intervention is working (desired effect on sensitivity)
次要结局
- Maximum Sedation Using Visual Analog Scale (Sedated-Alert)(Sedation was recorded pretreatment, 2, 10, 30 min, 1, 2, 4, and 6 hr post each study drug administration The maximum change from baseline occurred at:: 30 min for alprazolam 1 mg, 1 hour for alprazolam 0.5 and 2 mg, and 4 hours for placebo)
- Correlation of Plasma Concentrations of Alprazolam With Pharmacodynamic Effects on Standardized Photosensitivity Range (SPR)(Pretreatment, 2, 10, 30 min, 1, 2, 4, and 6 hr post each study drug administration)
- Correlation of Plasma Concentrations of Alprazolam With Pharmacodynamic Effects on Visual Analog Scale (Sedated-Alert)(Pretreatment, 2, 10, 30 min, 1, 2, 4, and 6 hr post each study drug administration)
- Correlation of Plasma Concentrations of Alprazolam With Pharmacodynamic Effects on Visual Analog Scale (Sleepy-Awake)(Pretreatment, 2, 10, 30 min, 1, 2, 4, and 6 hr post each study drug administration)
- Maximum Sedation Using Visual Analog Scale (Sleepy-Awake)(Sleepiness was recorded pretreatment, 2, 10, 30 min, 1, 2, 4, and 6 hr post each study drug administration The maximum change from baseline occurred: at: 30 min for alprazolam 1 mg, 1 hour for alprazolam 0.5 and 2 mg and placebo)