A Double-Blind, Cross-Over Placebo-Controlled and Active-Controlled Trial To Evaluate The Effect Of A Supratherapeutic Dose Of MK-8189 On The QTc Interval In Participants With Schizophrenia
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 107
- 试验地点
- 4
- 主要终点
- Change From Baseline in QT Interval Corrected for Heart Rate (QTc) Following MK-8189 Treatment
研究概览
简要总结
The primary purpose of this study to evaluate the effect of a supratherapeutic dose of 80 mg MK-8189 on the QT interval corrected for heart rate (QTc interval) and to assess the safety and tolerability of multiple once-daily doses of MK-8189 in participants with schizophrenia. The effects of 3 treatment sequences 1) MK-8189 (48 mg [Day 1] and 80 mg [Day2]); 2) standard image placebo (Day 1) and moxifloxacin 400 mg (Day 2); and 3) MK-8189 placebo (Day 1 and Day 2) were assessed with 5-day washout intervening sequence. Participants received all treatments in a counter-balanced order according to 1 of 6 possible treatment sequences.
The primary hypothesis is that the administration of an 80 mg MK-8189 dose on Day 2 does not prolong the QTc interval to a clinically significant degree. Specifically, the true mean difference (MK-8189 - placebo) in QTc change from baseline is less than 10 milliseconds (msec).
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
- Double (Participant, Investigator)
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
- •Meets diagnostic criteria for schizophrenia or schizoaffective disorder according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria.
- •Is in the non-acute phase of their illness.
- •Has a history of receiving and tolerating antipsychotics medication within the usual dose range employed for schizophrenia.
- •Participants with hypothyroidism, diabetes, high blood pressure, chronic respiratory conditions or other medical conditions could be considered if their condition is stable.
排除标准
- •History of a primary DSM-5 axis I psychiatric diagnosis other than schizophrenia or schizoaffective disorder per the allowed DSM-5 criteria.
- •History of intellectual disability, borderline personality disorder, anxiety disorder, or organic brain syndrome.
- •History of neuroleptic malignant syndrome or moderate to severe tardive dyskinesia (TD).
- •History of seizure disorder beyond childhood or is receiving treatment with any anticonvulsant to prevent seizures.
- •History of cancer.
- •History or presence of sick sinus syndrome, atrioventricular (AV) block, myocardial infarction, pulmonary congestion, cardiac arrhythmia, prolonged QTc interval, or conduction abnormalities.
- •History of risk factors for Torsades de Pointes (e.g., heart failure/cardiomyopathy or family history of long QT syndrome).
- •History of frequent syncope, vasovagal episodes, or epileptic seizures.
- •Family history of sudden cardiac death.
- •Has a positive test(s) for hepatitis B surface antigen (HBsAg), hepatitis C antibodies or human immunodeficiency virus (HIV).
- •Had major surgery, donated, or lost 1 unit of blood within 4 weeks prior to the pre-study visit.
研究组 & 干预措施
Sequence 1: MK-8189 (Treatment A)→Moxifloxacin (Treatment B)→Placebo (Treatment C)
Participants receive a sequence of Treatment A in Period 1 followed by Treatment B in Period 2 followed by Treatment C in Period 3; there will be a 5-day washout between periods. Treatment A consists of MK-8189 administered orally at 48 mg on Day 1 and 80 mg on day 2. Treatment B consists of placebo administered orally on Day 1 and moxifloxacin administered orally at 400 mg on Day 2. Treatment C consists of placebo administered orally on Day 1 and Day 2.
干预措施: MK-8189 (Drug)
Sequence 1: MK-8189 (Treatment A)→Moxifloxacin (Treatment B)→Placebo (Treatment C)
Participants receive a sequence of Treatment A in Period 1 followed by Treatment B in Period 2 followed by Treatment C in Period 3; there will be a 5-day washout between periods. Treatment A consists of MK-8189 administered orally at 48 mg on Day 1 and 80 mg on day 2. Treatment B consists of placebo administered orally on Day 1 and moxifloxacin administered orally at 400 mg on Day 2. Treatment C consists of placebo administered orally on Day 1 and Day 2.
干预措施: Moxifloxacin (Drug)
Sequence 1: MK-8189 (Treatment A)→Moxifloxacin (Treatment B)→Placebo (Treatment C)
Participants receive a sequence of Treatment A in Period 1 followed by Treatment B in Period 2 followed by Treatment C in Period 3; there will be a 5-day washout between periods. Treatment A consists of MK-8189 administered orally at 48 mg on Day 1 and 80 mg on day 2. Treatment B consists of placebo administered orally on Day 1 and moxifloxacin administered orally at 400 mg on Day 2. Treatment C consists of placebo administered orally on Day 1 and Day 2.
干预措施: Placebo (Drug)
Sequence 2: Moxifloxacin (Treatment B) →Placebo (Treatment C) →MK-8189 (Treatment A)
Participants receive a sequence of Treatment B in Period 1 followed by Treatment C in Period 2 followed by Treatment A in Period 3; there will be a 5-day washout between periods. Treatment B consists of placebo administered orally on Day 1 and moxifloxacin administered orally at 400 mg on Day 2. Treatment C consists of placebo administered orally on Day 1 and Day 2. Treatment A consists of MK-8189 administered orally at 48 mg on Day 1 and 80 mg on Day 2.
干预措施: MK-8189 (Drug)
Sequence 2: Moxifloxacin (Treatment B) →Placebo (Treatment C) →MK-8189 (Treatment A)
Participants receive a sequence of Treatment B in Period 1 followed by Treatment C in Period 2 followed by Treatment A in Period 3; there will be a 5-day washout between periods. Treatment B consists of placebo administered orally on Day 1 and moxifloxacin administered orally at 400 mg on Day 2. Treatment C consists of placebo administered orally on Day 1 and Day 2. Treatment A consists of MK-8189 administered orally at 48 mg on Day 1 and 80 mg on Day 2.
干预措施: Moxifloxacin (Drug)
Sequence 2: Moxifloxacin (Treatment B) →Placebo (Treatment C) →MK-8189 (Treatment A)
Participants receive a sequence of Treatment B in Period 1 followed by Treatment C in Period 2 followed by Treatment A in Period 3; there will be a 5-day washout between periods. Treatment B consists of placebo administered orally on Day 1 and moxifloxacin administered orally at 400 mg on Day 2. Treatment C consists of placebo administered orally on Day 1 and Day 2. Treatment A consists of MK-8189 administered orally at 48 mg on Day 1 and 80 mg on Day 2.
干预措施: Placebo (Drug)
Sequence 3: Placebo (Treatment C) →MK-8189 (Treatment A) →Moxifloxacin (Treatment B)
Participants receive a sequence of Treatment C in Period 1 followed by Treatment A in in Period 2 followed by Treatment B in Period 3; there will be a 5-day washout between periods. Treatment C consists of placebo administered orally on Day 1 and Day 2. Treatment A consists of MK-8189 administered orally at 48 mg on Day 1 and 80 mg on Day 2. Treatment B consists of placebo administered orally on Day 1 and moxifloxacin administered orally at 400 mg on Day 2.
干预措施: MK-8189 (Drug)
Sequence 3: Placebo (Treatment C) →MK-8189 (Treatment A) →Moxifloxacin (Treatment B)
Participants receive a sequence of Treatment C in Period 1 followed by Treatment A in in Period 2 followed by Treatment B in Period 3; there will be a 5-day washout between periods. Treatment C consists of placebo administered orally on Day 1 and Day 2. Treatment A consists of MK-8189 administered orally at 48 mg on Day 1 and 80 mg on Day 2. Treatment B consists of placebo administered orally on Day 1 and moxifloxacin administered orally at 400 mg on Day 2.
干预措施: Moxifloxacin (Drug)
Sequence 3: Placebo (Treatment C) →MK-8189 (Treatment A) →Moxifloxacin (Treatment B)
Participants receive a sequence of Treatment C in Period 1 followed by Treatment A in in Period 2 followed by Treatment B in Period 3; there will be a 5-day washout between periods. Treatment C consists of placebo administered orally on Day 1 and Day 2. Treatment A consists of MK-8189 administered orally at 48 mg on Day 1 and 80 mg on Day 2. Treatment B consists of placebo administered orally on Day 1 and moxifloxacin administered orally at 400 mg on Day 2.
干预措施: Placebo (Drug)
Sequence 4: Moxifloxacin (Treatment B) → MK-8189 (Treatment A) → Placebo (Treatment C)
Participants receive a sequence of Treatment B in Period 1 followed by Treatment A in Period 2 followed by Treatment C in Period 3; there will be a 5-day washout between periods. Treatment B consists of placebo administered orally on Day 1 and moxifloxacin administered orally at 400 mg on Day 2. Treatment A consists of MK-8189 administered orally at 48 mg on Day 1 and 80 mg on Day 2. Treatment C consists of placebo administered orally on Day 1 and Day 2.
干预措施: MK-8189 (Drug)
Sequence 4: Moxifloxacin (Treatment B) → MK-8189 (Treatment A) → Placebo (Treatment C)
Participants receive a sequence of Treatment B in Period 1 followed by Treatment A in Period 2 followed by Treatment C in Period 3; there will be a 5-day washout between periods. Treatment B consists of placebo administered orally on Day 1 and moxifloxacin administered orally at 400 mg on Day 2. Treatment A consists of MK-8189 administered orally at 48 mg on Day 1 and 80 mg on Day 2. Treatment C consists of placebo administered orally on Day 1 and Day 2.
干预措施: Moxifloxacin (Drug)
Sequence 4: Moxifloxacin (Treatment B) → MK-8189 (Treatment A) → Placebo (Treatment C)
Participants receive a sequence of Treatment B in Period 1 followed by Treatment A in Period 2 followed by Treatment C in Period 3; there will be a 5-day washout between periods. Treatment B consists of placebo administered orally on Day 1 and moxifloxacin administered orally at 400 mg on Day 2. Treatment A consists of MK-8189 administered orally at 48 mg on Day 1 and 80 mg on Day 2. Treatment C consists of placebo administered orally on Day 1 and Day 2.
干预措施: Placebo (Drug)
Sequence 5: MK-8189 (Treatment A) →Placebo (Treatment C) →Moxifloxacin (Treatment B)
Participants receive a sequence of Treatment A in Period 1 followed by Treatment C in Period 2 followed by Treatment B in Period 3; there will be a 5-day washout between periods. Treatment A consists of MK-8189 administered orally at 48 mg on Day 1 and 80 mg on Day 2. Treatment C consists of placebo administered orally on Day 1 and Day 2. Treatment B consists of placebo administered orally on Day 1 and moxifloxacin administered orally at 400 mg on Day 2.
干预措施: MK-8189 (Drug)
Sequence 5: MK-8189 (Treatment A) →Placebo (Treatment C) →Moxifloxacin (Treatment B)
Participants receive a sequence of Treatment A in Period 1 followed by Treatment C in Period 2 followed by Treatment B in Period 3; there will be a 5-day washout between periods. Treatment A consists of MK-8189 administered orally at 48 mg on Day 1 and 80 mg on Day 2. Treatment C consists of placebo administered orally on Day 1 and Day 2. Treatment B consists of placebo administered orally on Day 1 and moxifloxacin administered orally at 400 mg on Day 2.
干预措施: Moxifloxacin (Drug)
Sequence 5: MK-8189 (Treatment A) →Placebo (Treatment C) →Moxifloxacin (Treatment B)
Participants receive a sequence of Treatment A in Period 1 followed by Treatment C in Period 2 followed by Treatment B in Period 3; there will be a 5-day washout between periods. Treatment A consists of MK-8189 administered orally at 48 mg on Day 1 and 80 mg on Day 2. Treatment C consists of placebo administered orally on Day 1 and Day 2. Treatment B consists of placebo administered orally on Day 1 and moxifloxacin administered orally at 400 mg on Day 2.
干预措施: Placebo (Drug)
Sequence 6: Placebo (Treatment C) →Moxifloxacin (Treatment B) → MK-8189 (Treatment A)
Participants receive a sequence of Treatment C in Period 1 followed by Treatment B in Period 2 followed by Treatment A in Period 3; there will be a 5-day washout between periods. Treatment C consists of placebo administered orally on Day 1 and Day 2. Treatment B consists of placebo administered orally on Day 1 and moxifloxacin administered orally at 400 mg on Day 2. Treatment A consists of MK-8189 administered orally at 48 mg on Day 1 and 80 mg on Day 2.
干预措施: MK-8189 (Drug)
Sequence 6: Placebo (Treatment C) →Moxifloxacin (Treatment B) → MK-8189 (Treatment A)
Participants receive a sequence of Treatment C in Period 1 followed by Treatment B in Period 2 followed by Treatment A in Period 3; there will be a 5-day washout between periods. Treatment C consists of placebo administered orally on Day 1 and Day 2. Treatment B consists of placebo administered orally on Day 1 and moxifloxacin administered orally at 400 mg on Day 2. Treatment A consists of MK-8189 administered orally at 48 mg on Day 1 and 80 mg on Day 2.
干预措施: Moxifloxacin (Drug)
Sequence 6: Placebo (Treatment C) →Moxifloxacin (Treatment B) → MK-8189 (Treatment A)
Participants receive a sequence of Treatment C in Period 1 followed by Treatment B in Period 2 followed by Treatment A in Period 3; there will be a 5-day washout between periods. Treatment C consists of placebo administered orally on Day 1 and Day 2. Treatment B consists of placebo administered orally on Day 1 and moxifloxacin administered orally at 400 mg on Day 2. Treatment A consists of MK-8189 administered orally at 48 mg on Day 1 and 80 mg on Day 2.
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Baseline in QT Interval Corrected for Heart Rate (QTc) Following MK-8189 Treatment
时间窗: Day 1 (MK-8189 48 mg and placebo) and Day 2 (MK-8189 80 mg and placebo)
Electrocardiogram data was obtained using a digital Holter device and the Fridericia correction of the QT interval (QTcF) was determined. The change from baseline in QTcF (ΔQTcF \[msec\]) was calculated by subtracting the QTcF value at the timepoint from the QTcF baseline value. Negative values represent a decrease from baseline and vice versa. An average of up to 9 predose ECGs on Day 1 served as baseline to compare postdose effects. Per protocol, the primary endpoint compares MK-8189 to placebo.
Number of Participants With Adverse Events (AEs)
时间窗: Up to ~30 days after each dose
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
Number of Participants Discontinuing Study Therapy Due to AE
时间窗: Up to ~30 days after each dose
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
次要结局
- Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours (AUC0-24) of MK-8189(Day 1: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 14, 24 hours postdose; Day 2: 0.5, 1, 2, 3, 4, 8, 11, 14, 16, 24 hours postdose)
- Apparent Terminal Half-life (t½) of MK-8189(Day 2: 0.5, 1, 2, 3, 4, 8, 11, 14, 16, 24, 36, 48, 72 hours postdose)
- Change From Baseline in QT Interval Corrected for Heart Rate (QTc) Following Moxifloxacin Treatment(Day 2)
- Area Under the Plasma Concentration-Time Curve From Time 0 to Last Measurable Concentration (AUC0-last) of MK-8189(Day 1: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 14, 24 hours postdose; Day 2: 0.5, 1, 2, 3, 4, 8, 11, 14, 16, 24, 36, 48, and 72 hours postdose)
- Maximum Concentration (Cmax) of MK-8189(Day 1: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 14, 24 hours postdose; Day 2: 0.5, 1, 2, 3, 4, 8, 11, 14, 16, 24, 36, 48, 72 hours postdose)
- Concentration of MK-8189 at 24 Hours (C24) Post-dose(Day 1 and Day 2: 24 hours postdose)
- Time to Maximum Concentration (Tmax) of MK-8189(Day 1: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 14, and 24 hours postdose; Day 2: 0.5, 1, 2, 3, 4, 8, 11, 14, 16, 24, 36, 48, and 72 hours postdose)