NCT04592536已完成1 期
A Randomized, Double-blind, Placebo- and Active Comparator-controlled, Crossover Trial to Examine the Effect of Multiple Doses of CVL-865 on Panic Symptoms Induced by Carbon Dioxide Inhalation in Healthy Subject
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 56
- 试验地点
- 1
- 主要终点
- PSL-IV score
研究概览
简要总结
The purpose of this study is to determine anxiolytic effect of multiple doses of CVL-865 using an experimental medicine model of carbon dioxide (CO2) inhalation in healthy volunteers.
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 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy male and female subjects, ages 18 to 55 years, inclusive, at the time of signing the ICF. Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure and heart rate measurement, 12-lead ECG, and clinical laboratory tests, as evaluated by the investigator.
- •Body mass index of 18.5 to 30.0 kg/m2, inclusive, and a total body weight >50 kg (110 lbs)
- •A female subject of childbearing potential who is sexually active with a nonsterilized male partner must agree to use a highly effective method of contraception from signing of informed consent and for 30 days post last dose. A male subject with a pregnant or a nonpregnant partner of childbearing potential must agree to use condom during treatment and until the end of relevant systemic exposure in the male subject for 94 days following the last dose with IMP.
- •Capable of giving signed informed consent
- •Ability, in the opinion of the investigator, to understand the nature of the trial and comply with protocol requirements, including the prescribed dosage regimens, scheduled visits, laboratory tests, and other trial procedures.
- •Defined as sensitive to the anxiogenic effects of double-breath CO2 inhalation
排除标准
- •Subjects with a current history of clinically significant cardiovascular pulmonary, gastrointestinal, renal, hepatic, metabolic, hematological, immunological, or neurological disease.
- •Subjects with a current or past history of clinically significant respiratory conditions
- •Subject with a personal or family history of sickle cell anemia
- •Subject with a personal or family history of cerebral aneurysm
- •Subjects with a clinically significant current or past personal or family history of any psychiatric disorder as classified by DSM-4 or DSM-5 criteria
- •Subjects with epilepsy or a history of seizures except for a single seizure episode
- •Subjects with a history of substance or alcohol-use disorder (DSM-5 criteria)
- •Subjects who answer "Yes" on the C-SSRS Suicidal Ideation Item 4, 5 and whose most recent episode meeting criteria for this C-SSRS Item 4, 5 occurred within the last 6 months
- •Subjects who, in the opinion of the investigator, present a serious risk of suicide
- •Subjects with human immunodeficiency virus seropositive status or acquired immunodeficiency syndrome, chronic hepatitis B or C (defined as positive serology and aspartate aminotransferase or alanine aminotransferase elevated to >2 × ULN)
- •Subject with a positive drug screen for illicit drugs
- •Subjects with a 12-lead ECG demonstrating either of the following:
- •QT interval corrected for heart rate using Fridericia's formula >450 msec (average of 3 ECGs obtained at the Screening Visit)
- •QRS interval >120 msec at the Screening Visit
- •Subjects with any of the following abnormalities in clinical laboratory tests at the Screening Visit, as assessed by the local laboratory and confirmed by a single repeat measurement, if deemed necessary:
- •AST or ALT ≥2 × ULN
- •Total bilirubin ≥1.5 × ULN. Subjects with a history of Gilbert's syndrome may be eligible provided the direct bilirubin is <ULN
- •Females: Hemoglobin <11 g/dL; Males: hemoglobin <12 g/dL
- •White blood cell count <3.0 × 109/L
- •Neutrophil count <2.0 × 109/L
- •Platelet count <150 × 109/L
- •Subjects with other abnormal laboratory test results, vital sign results, or ECG findings unless, based on the investigator's judgment, the findings are not medically significant
- •Systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg at Screening or Day -1
- •Subjects taking prohibited medication or who would be likely to require prohibited concomitant therapy
- •Subject has a current or past history of BZD abuse and/or dependence
- •Female subjects who are breastfeeding and/or who have a positive pregnancy test result prior to receiving IMP
- •Subjects who currently use or have used tobacco or nicotine-containing products within 30 days prior to signing the ICF. Subjects who test positive for urine cotinine
- •Subjects who has a history of consuming foods or beverages containing >8 units of methylxanthines per day and refuses to abstain from consumption of methylxanthine containing food and beverages while in the clinic.
- •Subjects with any condition possibly affecting drug absorption
- •Subjects with difficulty swallowing
- •Subjects who are known to be allergic or hypersensitive to the IMP or any of its components
- •Subjects with a known sensitivity or contraindication to alprazolam
- •Subjects who have participated in any clinical trial within 90 days prior to signing the ICF.
- •Subjects who have demonstrated a non-response to 35% CO2 double inhalation challenge in a previous trial.
- •Any subject who, in the opinion of the sponsor, investigator, or medical monitor, should not participate in the trial
- •Subjects with a positive SARS-CoV-2 quantitative PCR test result at Day -1, Period 1 are excluded. Results from subjects reporting a positive SARS-CoV-2 quantitative PCR test result prior to Day -1, Period need to be discussed with the sponsor/medical monitor prior to enrolment of the subject into the trial
研究组 & 干预措施
CVL-865
Experimental
High dose CVL-865 (25mg) Low dose CVL-865 (7.5mg)
干预措施: CVL-865 High dose (Drug)
CVL-865
Experimental
High dose CVL-865 (25mg) Low dose CVL-865 (7.5mg)
干预措施: CVL-865 low dose (Drug)
Alprazolam
Active Comparator
Active Comparator Alprazolam with extended release oral tablets; 1 tablet BID
干预措施: Alprazolam 1mg XR (Drug)
Placebo
Placebo Comparator
Placebo Comparator matching oral tablets for CVL-865, capsule for Alprazolam
干预措施: Placebo (Drug)
结局指标
主要结局
PSL-IV score
时间窗: up to Day 8
Change in Panic Symptom List -IV (PSL-IV), a questionnaire including 13 symptoms, each with intensity rating from 0 (not at all) to 4 (very intense), from pre-CO2 to Post CO2 challenge value
次要结局
- VAS Fear score(up to Day 8)
- Treatment-emergent AEs(From screening to Follow-up Visit)
- CVL-865 (and alprazolam, if appropriate) concentrations(Day 8)
- CO2 challenge(Screening, Day 1, Day 8)
- Change From Baseline in NeuroCart test battery Score(Screening, Day 1, Day 8)
- Suicidality assessed using Columbia - Suicide Severity Rating Scale (C-SSRS)(Screening, Day -1, Day 8)
- Change from Baseline in Bond & Lader Visual Analogue Scale (VAS)(Day 1, Day 8)
研究者
研究点 (1)
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