A Randomized, Double-Blind, Placebo-Controlled, Cross-over Evaluation of Evoked Responses as Pharmacodynamic Biomarkers in Healthy Adults and Schizophrenic Patients
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 38
- 试验地点
- 2
- 主要终点
- Mean Inter-trial Coherence (ITC) Magnitude of 40 Hz-derived Auditory Steady-state Response (ASSR) in HC and SZ Participants at Baseline
研究概览
简要总结
The primary purpose of this randomized, double-blind, placebo-controlled cross-over study was to record and measure 40 Hz-auditory steady-state response (ASSR) in healthy controls (HC) and participants with mild-to-moderate schizophrenia (SZ) to determine if the mean inter-trial coherence (ITC) magnitude derived from the 40 Hz-ASSR is lower in SZ than in HC at baseline.
详细描述
This is a 2-part study. Part 1 was a 2-period study in which participants received either 21 mg nicotine patches and then placebo patches or vice versa, with each patch co-administered with placebo capsules, in a counterbalanced order. In Part 2, participants were randomized to receive either MK-4334 250 mg capsule or placebo capsule, each with placebo patches.
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
- Triple (Participant, 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
- •HC Participants:
- •Is in generally good health
- •Has no history of clinically relevant neuropsychiatric illness
- •Is a mild-to-moderate tobacco user of ≥1-year duration, smoking the equivalent of ~10-15 cigarettes/day
- •Participants with Mild-to-Moderate SZ:
- •Has a current diagnosis of SZ with a duration ≥1 year
- •Is clinically stable and in the residual (non-acute) phase of illness for ≥12 weeks prior to the study
- •Is stably maintained on a regimen of up to 2 first- or second-generation antipsychotics with no dose changes >50% in combination with concomitant medication commonly prescribed to this population for ≥8 weeks prior to screening and during the study
- •Is a mild-to-moderate tobacco user of ≥1-year duration, smoking the equivalent of ~10-15 cigarettes/day
- •All Participants:
- •For males, agrees to be abstinent from heterosexual intercourse, or use an approved contraception method, during the study and for 90 days after the last dose of study drug
- •For females, is not of childbearing potential
- •Is willing to comply with restrictions on the use of nicotine or nicotine-containing products during the study
排除标准
- •HC Participants:
- •Has known biological family history of psychotic disorder in a first or second degree relative
- •Participants with Mild-to-Moderate SZ:
- •May be excluded from participation by the investigator based on treatment history and/or performance on various screening tests
- •All Participants:
- •Is positive for hepatitis B surface antigen, hepatitis C antibodies, or human immunodeficiency virus (HIV)
- •Is at imminent risk of self-harm
- •Has had major surgery or donated blood within 4 weeks prior to screening
- •Has evidence of cognitive impairment or significant mental disability
- •Has a history of clinically significant abnormality or disease
- •Has a history of cancer (malignancy)
- •Is unable to refrain, or anticipates use, of any non-prescription drugs or herbal remedies
- •Has participated in another clinical study within 6 weeks or 5 half-lives (whichever is greater) prior to screening
研究组 & 干预措施
Panel A: Healthy Control Participants
In Part 1, HC participants receive nicotine patch + capsule placebo, and patch placebo + capsule placebo, under a cross-over design in Periods 1 and 2. In Part 2 (Period 3), HC participants are randomly assigned to receive either MK-4334 250 mg capsule + patch placebo or capsule placebo + patch placebo.
干预措施: Nicotine patch (Drug)
Panel A: Healthy Control Participants
In Part 1, HC participants receive nicotine patch + capsule placebo, and patch placebo + capsule placebo, under a cross-over design in Periods 1 and 2. In Part 2 (Period 3), HC participants are randomly assigned to receive either MK-4334 250 mg capsule + patch placebo or capsule placebo + patch placebo.
干预措施: MK-4334 (Drug)
Panel A: Healthy Control Participants
In Part 1, HC participants receive nicotine patch + capsule placebo, and patch placebo + capsule placebo, under a cross-over design in Periods 1 and 2. In Part 2 (Period 3), HC participants are randomly assigned to receive either MK-4334 250 mg capsule + patch placebo or capsule placebo + patch placebo.
干预措施: Placebo patch (Drug)
Panel A: Healthy Control Participants
In Part 1, HC participants receive nicotine patch + capsule placebo, and patch placebo + capsule placebo, under a cross-over design in Periods 1 and 2. In Part 2 (Period 3), HC participants are randomly assigned to receive either MK-4334 250 mg capsule + patch placebo or capsule placebo + patch placebo.
干预措施: Placebo capsule (Drug)
Panel B: Participants with Mild-to-Moderate SZ
In Part 1, participants with mild-to-moderate SZ receive nicotine patch + capsule placebo, and patch placebo + capsule placebo, under a cross-over design in Periods 1 and 2. In Part 2 (Period 3), SZ participants are randomly assigned to receive either MK-4334 250 mg capsule + patch placebo or capsule placebo + patch placebo.
干预措施: Nicotine patch (Drug)
Panel B: Participants with Mild-to-Moderate SZ
In Part 1, participants with mild-to-moderate SZ receive nicotine patch + capsule placebo, and patch placebo + capsule placebo, under a cross-over design in Periods 1 and 2. In Part 2 (Period 3), SZ participants are randomly assigned to receive either MK-4334 250 mg capsule + patch placebo or capsule placebo + patch placebo.
干预措施: MK-4334 (Drug)
Panel B: Participants with Mild-to-Moderate SZ
In Part 1, participants with mild-to-moderate SZ receive nicotine patch + capsule placebo, and patch placebo + capsule placebo, under a cross-over design in Periods 1 and 2. In Part 2 (Period 3), SZ participants are randomly assigned to receive either MK-4334 250 mg capsule + patch placebo or capsule placebo + patch placebo.
干预措施: Placebo patch (Drug)
Panel B: Participants with Mild-to-Moderate SZ
In Part 1, participants with mild-to-moderate SZ receive nicotine patch + capsule placebo, and patch placebo + capsule placebo, under a cross-over design in Periods 1 and 2. In Part 2 (Period 3), SZ participants are randomly assigned to receive either MK-4334 250 mg capsule + patch placebo or capsule placebo + patch placebo.
干预措施: Placebo capsule (Drug)
结局指标
主要结局
Mean Inter-trial Coherence (ITC) Magnitude of 40 Hz-derived Auditory Steady-state Response (ASSR) in HC and SZ Participants at Baseline
时间窗: Day -1 (Baseline)
The ITC magnitude derived from the 40Hz ASSR is presented. ASSR is measured following a short stream of click trains with a 500 msec inter-train interval (duration), at standard tone and at 40Hz tone. The magnitude of ITC represents the phase consistency of oscillatory activities, in response to EEG coherence at 40Hz stimulation. ITC as a unit of measure is expressed as frequency (40Hz) vs time (msec).
次要结局
- Duration Deviant Mismatch Negativity (DD-MMN) in HC and SZ Participants: MMN-A, N100-A, and P3A-A Tests(Day -1 (Baseline))
- Duration Deviant Mismatch Negativity (DD-MMN) in HC and SZ Participants: MMN-L, N100-L, and P3A-L Tests(Day -1 (Baseline))
- Effect of Nicotine on Mean ITC Magnitude of 40 Hz-derived ASSR in HC and SZ Participants Compared to Baseline(Day -1 (baseline), Day 1, and Day 8)
- Plasma Nicotine Concentration 2 Hours After Patch Application (C2h) Assessed During Event Related Potential (ERP) Recording Sessions(2 hours after patch application on Day 1 or Day 8)