Thorough QT/QTc Study of Staccato® Prochlorperazine for Inhalation in Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- Maximum Effect of Inhaled Prochlorperazine on Cardiac Repolarization (QTc Interval Duration) at the Maximum Clinical Dose Compared to Placebo
研究概览
简要总结
To assess the safety of Staccato Prochlorperazine on cardiac repolarization (QTc interval duration) at 2 dose levels compared to placebo in healthy volunteers.
详细描述
The planned study is a single dose, double-blind, double-dummy, active and placebo controlled, randomized, 4-period cross-over study investigating investigating 2 doses levels of Staccato Prochlorperazine, a positive control with known QT/QTc prolongation (oral moxifloxacin), and 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)
盲法说明
This was a double-blind, double dummy, placebo controlled, randomized 4-period crossover study to assess the effects of single doses of 5 and 10 mg of Staccato Prochlorperazine on QT intervals.
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) ≥21 and ≤
- •Subjects who are willing and able to comply with the study schedule and requirements, and stay at the CRU for a 3-day period and 3 consecutive 2-day periods.
- •Subjects who speak, read, and understand English and are willing and able to provide written informed consent on an IRB approved form prior to the initiation of any study procedures.
- •Subjects who are in good general health prior to study participation as determined by a detailed medical history, physical examination, 12-lead ECG, blood chemistry profile, hematology, urinalysis, and in the opinion of the Principal Investigator.
- •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 one week following the end of the study.
排除标准
- •Subjects who regularly consume large amounts of xanthine-containing substances must be excluded.
- •Subjects who have taken prescription or nonprescription medication within 5 days of Treatment Period 1 must be excluded.
- •Subjects who have had an acute illness within the last 5 days of Treatment Period 1 must be excluded.
- •Subjects who have smoked tobacco within the last year must be excluded.
- •Subjects who have a history of HIV positivity must be excluded.
- •Subjects who have a history of allergy or intolerance to prochlorperazine or phenothiazines must be excluded.
- •Subjects who have a history of contraindication to anticholinergics must be excluded.
- •Subjects who have a history of pheochromocytoma, seizure disorder, Parkinson's disease, or Restless Leg Syndrome must be excluded.
- •Subjects who have an ECG abnormality must be excluded.
- •Subjects who have a history within the past 2 years of drug or alcohol dependence or abuse as defined by DSM-4 must be excluded.
- •Subjects who have a history of syncope, unstable angina, myocardial infarction (within 6 months), congestive heart failure, transient ischemic attack, or pheochromocytoma must be excluded.
- •Subjects who have a history of asthma or chronic obstructive lung disease must be excluded.
- •Subjects who have hypotension (systolic ≤90 mmHg, diastolic ≤50 mmHg), or hypertension (systolic ≥140 mmHg, diastolic blood pressure ≥90 mmHg) must be excluded.
- •Subjects who test positive for alcohol or have a positive urine drug screen must be excluded.
- •Female subjects who have a positive pregnancy test at screening or during randomization visit, or are breastfeeding must be excluded.
- •Subjects who have received an investigational drug within 30 days prior to the Screening Visit must be excluded.
- •Subjects who are considered by the investigator, for any reason, to be an unsuitable candidate for receiving prochlorperazine, or unable to use the inhalation device, must be excluded.
- •Subjects who have any other disease(s), by history, physical examination, or laboratory abnormalities (ALT or AST > 2-fold the upper limit of normal, bilirubin > 1.5 mg/dL, or creatinine > 1.8 mg/dL) or that in the investigator's opinion present undue risk to the subject or may confound the interpretation of study results must be excluded.
研究组 & 干预措施
Treatment Sequence ABCD
Treatment Sequence ABCD where Treatment: A = Inhaled prochlorperazine (10 mg) + oral placebo, B = Inhaled prochlorperazine (5 mg) + oral placebo, C = Inhaled placebo + oral placebo, D = Inhaled placebo + oral moxifloxacin 400 mg
干预措施: Inhaled placebo (Drug)
Treatment Sequence ABCD
Treatment Sequence ABCD where Treatment: A = Inhaled prochlorperazine (10 mg) + oral placebo, B = Inhaled prochlorperazine (5 mg) + oral placebo, C = Inhaled placebo + oral placebo, D = Inhaled placebo + oral moxifloxacin 400 mg
干预措施: Oral placebo (Drug)
Treatment Sequence ABCD
Treatment Sequence ABCD where Treatment: A = Inhaled prochlorperazine (10 mg) + oral placebo, B = Inhaled prochlorperazine (5 mg) + oral placebo, C = Inhaled placebo + oral placebo, D = Inhaled placebo + oral moxifloxacin 400 mg
干预措施: Inhaled prochlorperazine 5 mg (Drug)
Treatment Sequence ABCD
Treatment Sequence ABCD where Treatment: A = Inhaled prochlorperazine (10 mg) + oral placebo, B = Inhaled prochlorperazine (5 mg) + oral placebo, C = Inhaled placebo + oral placebo, D = Inhaled placebo + oral moxifloxacin 400 mg
干预措施: Inhaled prochlorperazine 10 mg (Drug)
Treatment Sequence ABCD
Treatment Sequence ABCD where Treatment: A = Inhaled prochlorperazine (10 mg) + oral placebo, B = Inhaled prochlorperazine (5 mg) + oral placebo, C = Inhaled placebo + oral placebo, D = Inhaled placebo + oral moxifloxacin 400 mg
干预措施: Oral moxifloxacin (Drug)
Treatment Sequence BDAC
Treatment Sequence BDAC where Treatment: A = Inhaled prochlorperazine (10 mg) + oral placebo, B = Inhaled prochlorperazine (5 mg) + oral placebo, C = Inhaled placebo + oral placebo, D = Inhaled placebo + oral moxifloxacin 400 mg
干预措施: Inhaled placebo (Drug)
Treatment Sequence BDAC
Treatment Sequence BDAC where Treatment: A = Inhaled prochlorperazine (10 mg) + oral placebo, B = Inhaled prochlorperazine (5 mg) + oral placebo, C = Inhaled placebo + oral placebo, D = Inhaled placebo + oral moxifloxacin 400 mg
干预措施: Oral placebo (Drug)
Treatment Sequence BDAC
Treatment Sequence BDAC where Treatment: A = Inhaled prochlorperazine (10 mg) + oral placebo, B = Inhaled prochlorperazine (5 mg) + oral placebo, C = Inhaled placebo + oral placebo, D = Inhaled placebo + oral moxifloxacin 400 mg
干预措施: Inhaled prochlorperazine 5 mg (Drug)
Treatment Sequence BDAC
Treatment Sequence BDAC where Treatment: A = Inhaled prochlorperazine (10 mg) + oral placebo, B = Inhaled prochlorperazine (5 mg) + oral placebo, C = Inhaled placebo + oral placebo, D = Inhaled placebo + oral moxifloxacin 400 mg
干预措施: Inhaled prochlorperazine 10 mg (Drug)
Treatment Sequence BDAC
Treatment Sequence BDAC where Treatment: A = Inhaled prochlorperazine (10 mg) + oral placebo, B = Inhaled prochlorperazine (5 mg) + oral placebo, C = Inhaled placebo + oral placebo, D = Inhaled placebo + oral moxifloxacin 400 mg
干预措施: Oral moxifloxacin (Drug)
Treatment Sequence CABD
Treatment Sequence CABD where Treatment: A = Inhaled prochlorperazine (10 mg) + oral placebo, B = Inhaled prochlorperazine (5 mg) + oral placebo, C = Inhaled placebo + oral placebo, D = Inhaled placebo + oral moxifloxacin 400 mg
干预措施: Inhaled placebo (Drug)
Treatment Sequence CABD
Treatment Sequence CABD where Treatment: A = Inhaled prochlorperazine (10 mg) + oral placebo, B = Inhaled prochlorperazine (5 mg) + oral placebo, C = Inhaled placebo + oral placebo, D = Inhaled placebo + oral moxifloxacin 400 mg
干预措施: Oral placebo (Drug)
Treatment Sequence CABD
Treatment Sequence CABD where Treatment: A = Inhaled prochlorperazine (10 mg) + oral placebo, B = Inhaled prochlorperazine (5 mg) + oral placebo, C = Inhaled placebo + oral placebo, D = Inhaled placebo + oral moxifloxacin 400 mg
干预措施: Inhaled prochlorperazine 5 mg (Drug)
Treatment Sequence CABD
Treatment Sequence CABD where Treatment: A = Inhaled prochlorperazine (10 mg) + oral placebo, B = Inhaled prochlorperazine (5 mg) + oral placebo, C = Inhaled placebo + oral placebo, D = Inhaled placebo + oral moxifloxacin 400 mg
干预措施: Inhaled prochlorperazine 10 mg (Drug)
Treatment Sequence CABD
Treatment Sequence CABD where Treatment: A = Inhaled prochlorperazine (10 mg) + oral placebo, B = Inhaled prochlorperazine (5 mg) + oral placebo, C = Inhaled placebo + oral placebo, D = Inhaled placebo + oral moxifloxacin 400 mg
干预措施: Oral moxifloxacin (Drug)
Treatment Sequence DCBA
Treatment Sequence DCBA where Treatment: A = Inhaled prochlorperazine (10 mg) + oral placebo, B = Inhaled prochlorperazine (5 mg) + oral placebo, C = Inhaled placebo + oral placebo, D = Inhaled placebo + oral moxifloxacin 400 mg
干预措施: Inhaled placebo (Drug)
Treatment Sequence DCBA
Treatment Sequence DCBA where Treatment: A = Inhaled prochlorperazine (10 mg) + oral placebo, B = Inhaled prochlorperazine (5 mg) + oral placebo, C = Inhaled placebo + oral placebo, D = Inhaled placebo + oral moxifloxacin 400 mg
干预措施: Oral placebo (Drug)
Treatment Sequence DCBA
Treatment Sequence DCBA where Treatment: A = Inhaled prochlorperazine (10 mg) + oral placebo, B = Inhaled prochlorperazine (5 mg) + oral placebo, C = Inhaled placebo + oral placebo, D = Inhaled placebo + oral moxifloxacin 400 mg
干预措施: Inhaled prochlorperazine 5 mg (Drug)
Treatment Sequence DCBA
Treatment Sequence DCBA where Treatment: A = Inhaled prochlorperazine (10 mg) + oral placebo, B = Inhaled prochlorperazine (5 mg) + oral placebo, C = Inhaled placebo + oral placebo, D = Inhaled placebo + oral moxifloxacin 400 mg
干预措施: Inhaled prochlorperazine 10 mg (Drug)
Treatment Sequence DCBA
Treatment Sequence DCBA where Treatment: A = Inhaled prochlorperazine (10 mg) + oral placebo, B = Inhaled prochlorperazine (5 mg) + oral placebo, C = Inhaled placebo + oral placebo, D = Inhaled placebo + oral moxifloxacin 400 mg
干预措施: Oral moxifloxacin (Drug)
结局指标
主要结局
Maximum Effect of Inhaled Prochlorperazine on Cardiac Repolarization (QTc Interval Duration) at the Maximum Clinical Dose Compared to Placebo
时间窗: 1, 2, 5, 9, 15, 30 min, 1, 3, 6, 10 and 22 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 treatment at 11 post-inhalation times.
次要结局
- Numbers and % of Subjects With QTcI Change > 30 ms(1, 2, 5, 9, 15, 30 min, 1, 3, 6, 10 and 22 hr)
- Numbers and % of Subjects With QTcI > 450 ms(24 hours)
- Numbers and % of Subjects With QTcI > 480 ms(1, 2, 5, 9, 15, 30 min, 1, 3, 6, 10 and 22 hr)
- Numbers and % of Subjects With QTcI Change > 60 ms(1, 2, 5, 9, 15, 30 min, 1, 3, 6, 10 and 22 hr)
- QTcI Versus Prochlorperazine Concentration(1, 2, 5, 9, 15, 30 min, 1, 3, 6, 10 and 22 hr)