Thorough QT/QTc Study of 2 Doses of ADASUVE® in Healthy Volunteers
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Maximum Effect of ADASUVE on Cardiac Repolarization (QTc Interval Duration) at the Maximum Clinical Dose Compared to Placebo
研究概览
简要总结
Assess the potential effects on the QT interval of 2 consecutive doses of ADASUVE administered 2 hours apart, in relation to placebo and an active control in healthy volunteers.
详细描述
It has been shown in a pre-marketing clinical study that clinically relevant QT prolongation does not appear to be associated with a single dose of ADASUVE. The potential risk of QTc prolongation following repeat dosing is unknown. Therefore the current study will assess the potential effects on the QT interval of 2 consecutive doses of ADASUVE administered 2 hours apart, in relation to placebo and an active control in healthy volunteers.
The study hypothesis H0: Placebo-subtracted max mean dQTc > 10 msec
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Other
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Male and female subjects between the ages of 18 to 65 years, inclusive.
- •Body mass index (BMI) ≥18 and ≤
- •Subjects who are willing and able to comply with the study schedule and requirements, and stay at the CRU for a 4-day period and 2 consecutive 3-day periods.
- •Subjects who speak, read, and understand English and/or Dutch and are willing and able to provide written informed consent on an IEC approved form prior to the initiation of any study procedures.
- •Subjects who are in good general health prior to study participation
- •Female or male participants who agree to use a medically acceptable and effective birth control method
排除标准
- •Subjects who regularly consume large amounts of xanthine-containing substances (≥ 5 cups of coffee/day).
- •Subjects who have taken prescription or nonprescription medication within 5 days of Visit
- •Subjects who have had an acute illness within the last 5 days of Visit
- •Subjects who have smoked tobacco within the last 30 days or who have a positive cotinine test.
- •Subjects who have a history of HIV, anti-HCV or HbsAg positivity.
- •Subjects who have a history within the past 2 years of drug or alcohol dependence or abuse as defined by DSM-IV.
- •Subjects who test positive for alcohol or have a positive urine drug screen.
- •Subjects who have a history of allergy or intolerance to loxapine or amoxapine or history of bronchospasm following inhaled loxapine treatment.
- •Subjects who have an ECG abnormality.
- •Subjects who have hypotension, or hypertension.
- •Subjects who have a history of unstable angina, syncope, coronary artery disease, myocardial infarction, congestive heart failure, transient ischemic attack, history of convulsions or other neurological disorder.
- •Subjects who have a current history of asthma, chronic obstructive lung disease, or any other 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).
- •Female subjects who have a positive pregnancy test at screening or at admission to any of the treatment visits, or are breastfeeding.
- •Subjects who have received an investigational drug within 60 days prior to the Screening Visit.
研究组 & 干预措施
Treatment sequence ABC
Treatment: A = Inhaled loxapine (2 doses of 10 mg 2 hours apart) + oral placebo, B = Inhaled placebo + oral placebo, C = Oral moxifloxacin 400 mg + Inhaled placebo
干预措施: Inhaled Placebo (Drug)
Treatment sequence ABC
Treatment: A = Inhaled loxapine (2 doses of 10 mg 2 hours apart) + oral placebo, B = Inhaled placebo + oral placebo, C = Oral moxifloxacin 400 mg + Inhaled placebo
干预措施: ADASUVE 10 mg 2 doses 2 hours apart (Drug)
Treatment sequence ABC
Treatment: A = Inhaled loxapine (2 doses of 10 mg 2 hours apart) + oral placebo, B = Inhaled placebo + oral placebo, C = Oral moxifloxacin 400 mg + Inhaled placebo
干预措施: Oral moxifloxacin 400 mg (Drug)
Treatment sequence ABC
Treatment: A = Inhaled loxapine (2 doses of 10 mg 2 hours apart) + oral placebo, B = Inhaled placebo + oral placebo, C = Oral moxifloxacin 400 mg + Inhaled placebo
干预措施: Oral placebo (Drug)
Treatment sequence ACB
Treatment: A = Inhaled loxapine (2 doses of 10 mg 2 hours apart) + oral placebo, B = Inhaled placebo + oral placebo, C = Oral moxifloxacin 400 mg + Inhaled placebo
干预措施: ADASUVE 10 mg 2 doses 2 hours apart (Drug)
Treatment sequence ACB
Treatment: A = Inhaled loxapine (2 doses of 10 mg 2 hours apart) + oral placebo, B = Inhaled placebo + oral placebo, C = Oral moxifloxacin 400 mg + Inhaled placebo
干预措施: Inhaled Placebo (Drug)
Treatment sequence ACB
Treatment: A = Inhaled loxapine (2 doses of 10 mg 2 hours apart) + oral placebo, B = Inhaled placebo + oral placebo, C = Oral moxifloxacin 400 mg + Inhaled placebo
干预措施: Oral moxifloxacin 400 mg (Drug)
Treatment sequence ACB
Treatment: A = Inhaled loxapine (2 doses of 10 mg 2 hours apart) + oral placebo, B = Inhaled placebo + oral placebo, C = Oral moxifloxacin 400 mg + Inhaled placebo
干预措施: Oral placebo (Drug)
Treatment sequence BCA
Treatment: A = Inhaled loxapine (2 doses of 10 mg 2 hours apart) + oral placebo, B = Inhaled placebo + oral placebo, C = Oral moxifloxacin 400 mg + Inhaled placebo
干预措施: ADASUVE 10 mg 2 doses 2 hours apart (Drug)
Treatment sequence BCA
Treatment: A = Inhaled loxapine (2 doses of 10 mg 2 hours apart) + oral placebo, B = Inhaled placebo + oral placebo, C = Oral moxifloxacin 400 mg + Inhaled placebo
干预措施: Inhaled Placebo (Drug)
Treatment sequence BCA
Treatment: A = Inhaled loxapine (2 doses of 10 mg 2 hours apart) + oral placebo, B = Inhaled placebo + oral placebo, C = Oral moxifloxacin 400 mg + Inhaled placebo
干预措施: Oral moxifloxacin 400 mg (Drug)
Treatment sequence BCA
Treatment: A = Inhaled loxapine (2 doses of 10 mg 2 hours apart) + oral placebo, B = Inhaled placebo + oral placebo, C = Oral moxifloxacin 400 mg + Inhaled placebo
干预措施: Oral placebo (Drug)
Treatment sequence BAC
Treatment: A = Inhaled loxapine (2 doses of 10 mg 2 hours apart) + oral placebo, B = Inhaled placebo + oral placebo, C = Oral moxifloxacin 400 mg + Inhaled placebo
干预措施: ADASUVE 10 mg 2 doses 2 hours apart (Drug)
Treatment sequence BAC
Treatment: A = Inhaled loxapine (2 doses of 10 mg 2 hours apart) + oral placebo, B = Inhaled placebo + oral placebo, C = Oral moxifloxacin 400 mg + Inhaled placebo
干预措施: Inhaled Placebo (Drug)
Treatment sequence BAC
Treatment: A = Inhaled loxapine (2 doses of 10 mg 2 hours apart) + oral placebo, B = Inhaled placebo + oral placebo, C = Oral moxifloxacin 400 mg + Inhaled placebo
干预措施: Oral moxifloxacin 400 mg (Drug)
Treatment sequence BAC
Treatment: A = Inhaled loxapine (2 doses of 10 mg 2 hours apart) + oral placebo, B = Inhaled placebo + oral placebo, C = Oral moxifloxacin 400 mg + Inhaled placebo
干预措施: Oral placebo (Drug)
Treatment sequence CAB
Treatment: A = Inhaled loxapine (2 doses of 10 mg 2 hours apart) + oral placebo, B = Inhaled placebo + oral placebo, C = Oral moxifloxacin 400 mg + Inhaled placebo
干预措施: ADASUVE 10 mg 2 doses 2 hours apart (Drug)
Treatment sequence CAB
Treatment: A = Inhaled loxapine (2 doses of 10 mg 2 hours apart) + oral placebo, B = Inhaled placebo + oral placebo, C = Oral moxifloxacin 400 mg + Inhaled placebo
干预措施: Inhaled Placebo (Drug)
Treatment sequence CAB
Treatment: A = Inhaled loxapine (2 doses of 10 mg 2 hours apart) + oral placebo, B = Inhaled placebo + oral placebo, C = Oral moxifloxacin 400 mg + Inhaled placebo
干预措施: Oral moxifloxacin 400 mg (Drug)
Treatment sequence CAB
Treatment: A = Inhaled loxapine (2 doses of 10 mg 2 hours apart) + oral placebo, B = Inhaled placebo + oral placebo, C = Oral moxifloxacin 400 mg + Inhaled placebo
干预措施: Oral placebo (Drug)
Treatment sequence CBA
Treatment: A = Inhaled loxapine (2 doses of 10 mg 2 hours apart) + oral placebo, B = Inhaled placebo + oral placebo, C = Oral moxifloxacin 400 mg + Inhaled placebo
干预措施: ADASUVE 10 mg 2 doses 2 hours apart (Drug)
Treatment sequence CBA
Treatment: A = Inhaled loxapine (2 doses of 10 mg 2 hours apart) + oral placebo, B = Inhaled placebo + oral placebo, C = Oral moxifloxacin 400 mg + Inhaled placebo
干预措施: Inhaled Placebo (Drug)
Treatment sequence CBA
Treatment: A = Inhaled loxapine (2 doses of 10 mg 2 hours apart) + oral placebo, B = Inhaled placebo + oral placebo, C = Oral moxifloxacin 400 mg + Inhaled placebo
干预措施: Oral moxifloxacin 400 mg (Drug)
Treatment sequence CBA
Treatment: A = Inhaled loxapine (2 doses of 10 mg 2 hours apart) + oral placebo, B = Inhaled placebo + oral placebo, C = Oral moxifloxacin 400 mg + Inhaled placebo
干预措施: Oral placebo (Drug)
结局指标
主要结局
Maximum Effect of ADASUVE on Cardiac Repolarization (QTc Interval Duration) at the Maximum Clinical Dose Compared to Placebo
时间窗: Predose, 2 min, 1, 1.5 hr, 2 hr 2 min, 2 hr 5 min, 2.5, 3, 5, 8, 12, and 24 hr
Time-matched differences in QTcI values between the maximum of the mean difference from baseline of the QTcI interval after time-matched placebo subtraction for ADASUVE treatment at 12 post-inhalation times.
次要结局
- QTc Versus Loxapine Concentration(Predose, 2 min, 1, 1.5 hr, 2 hr 2 min, 2 hr 5 min, 2.5, 3, 5, 8, 12, and 24 hr)
- Subjects With QTcI > 450 ms(Predose, 2 min, 1, 1.5 hr, 2 hr 2 min, 2 hr 5 min, 2.5, 3, 5, 8, 12, and 24 hr)
- Subjects With QTcI > 480 ms(Predose, 2 min, 1, 1.5 hr, 2 hr 2 min, 2 hr 5 min, 2.5, 3, 5, 8, 12, and 24 hr)
- Subjects With QTcI Increase > 30 ms From Baseline(Predose, 2 min, 1, 1.5 hr, 2 hr 2 min, 2 hr 5 min, 2.5, 3, 5, 8, 12, and 24 hr)
- Subjects With QTcI Increase > 60 ms From Baseline(Predose, 2 min, 1, 1.5 hr, 2 hr 2 min, 2 hr 5 min, 2.5, 3, 5, 8, 12, and 24 hr)