A Phase I/IIa, Pharmacokinetic, Dose-response and Safety Study of Inhaled Fentanyl Aerosol (25µg/Dose) in Chinese Patients With Breakthrough Cancer Pain
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 96
- 主要终点
- SPID30
研究概览
简要总结
Breakthrough cancer pain (BTcP) is a common problem in patients with cancer. This is a phase I/IIa, pharmacokinetic, dose-response and safety study of inhaled fentanyl aerosol (25µg/dose) in Chinese patients with breakthrough cancer pain. The study will include two stages.
详细描述
Stage I: dose-response relationship and safety assessment of inhaled fentanyl aerosol in patients with breakthrough cancer pain. placebo-controlled, cross-over, double-blind randomized design is applied in this stage.
Patients meeting the inclusion/exclusion criteria will be treated with inhaled fentanyl aerosol (4 of 6 episodes BTcp) or placebo (2of 6 episodes BTcp).Subjects will inhale fentanyl aerosol or placebo for each episode of BTcp with a starting dose of 25 µg every 4 minutes until adequate pain alleviation. The maximum doses are 6×25 µg.
Stage II: The dosage regimen (number of puffs) will be depended on the data from Stage I. Subjects will inhale fentanyl aerosol not in the episode of breakthrough cancer pain with a starting dose of 25 µg every 4 minutes.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age of 18 to 75years, inclusive.
- •Subjects must be diagnosed with cancer.
- •Subjects must be opioid-tolerant : taking oral morphine more than 60mg and less than 1000mg,or taking other equivalent potency opioids of analgesic doses in one weeks or longer.
- •Subjects must experience persistent pain associated with cancer, and the pain score assessed by NRS should be <4 within 24hour before screening.
- •The breakthrough cancer pain score should be ≥4 assessed by NRS.
- •In the past 7 days, the subject must experience an average of 1 to 4 episodes of breakthrough cancer pain per day, and use 5 mg immediate release morphine at least or equivalent short-acting opioids (e.g., oxycodone, hydrocodone ketones or codeine) to control this pain.
- •ECOG status of 0 to
- •Life expectancy should be longer than 3 months.
- •Subjects must consent to take adequate contraception within the study and 1 months after the study. Women of childbearing potential must show negative in the pregnancy test before dosing.
- •The subject must be able to understand the requirements of the study and provide a written informed consent.
排除标准
- •Allergies, or a history of drug allergies to fentanyl.
- •On intrathecal or epidural opioids.
- •HGB < 80 g/L, NEUT ≤1.5 × l09/L, PLT ≤50 × l09/L；ALT and AST higher than 3 times of ULN;total bilirubin and Cr higher than 1.5 times of ULN;PaO2 <95%;FEV1/FVC<70% and FEV1 accounted for less than 80% of the predicted value.
- •Any uncontrolled disease (e.g., severe mental, neurological, infectious, cardiovascular, respiratory and other systemic diseases).
- •Hepatitis B surface antigen and hepatitis C surface antibody positive. Human T Lymphotropic Virus Type I Positive. HIV positive.
- •Gastrointestinal bleeding or diarrhea presently.
- •Requirement of continuous paracentesis.
- •Tumor infiltration to central nervous system.
- •Subjects are not able to slef evaluate pain intensity using NRS
- •Receive surgery in past 3 weeks.
- •Treatment with any form of radiotherapy winth 1week prior to study entry that could alter pain or response to pain medication.
- •Taking monoamine oxidase inhibitors(MAOIs), CYP3A4 inhibitors or inducers within 14 days of the screening
- •Participated in other clinical trials in past 1months.
- •Pregnancy and breast-feeding women, women of childbearing age ready to conceive, and pregnancy test positive.
- •Other conditions that may affect the informed consent, compliance with the protocol, study results and safety of the subject.
研究组 & 干预措施
Inhaled fentanyl aerosol
Participants in the stage I were randomized to 6 BTP episodes, in which 4 BTP episodes were treated with inhale fentanyl aerosol (with a starting dose of 25 µg every 4 minutes until adequate pain alleviation. The maximum doses are 6×25 µg) and 2 BTP episodes with placebo(0 µg every 4 minutes until adequate pain alleviation. The maximum doses are 6×0µg) in a random sequence.
干预措施: Inhaled fentanyl aerosol (Drug)
Placebo
Participants in the stage I were randomized to 6 BTP episodes, in which 2 BTP episodes were treated with placebo (0 µg every 4 minutes until adequate pain alleviation. The maximum doses are 6×0µg) in a random sequence.
干预措施: Placebo (Drug)
结局指标
主要结局
SPID30
时间窗: During the stage I, at each episode of breakthrough pain, 30 minutes after first dose of study drug.
Weighted sum of pain intensity difference at post dose 30 minutes.Pain intensity at each breakthrough pain (BTP) episode at 0 ,4,8,12,16,20 and 30 minutes after first dose using the 11-point Numerical Rating Scale (NRS) on a scale from 0 to 10, where 0 represents the absence of pain and 10 is "worst possible pain". PID30 is calculated as the difference in pain intensity from time 0 to 30 minutes. A positive value is a decrease (improvement) of the pain.SPID30=PID4\*4+PID8\*4+PID12\*4+PID16\*4+PID20\*4+PID30\*10
次要结局
- Pain intensity at 0, 4,8,12,16,20,30 and 60 minutes post-dose(During the stage I, at each episode of breakthrough pain, 60 minutes after first dose of study drug.)
- SPID60(During the stage I, at each episode of breakthrough pain, 60 minutes after first dose of study drug.)
- Percentage of episodes with NRS≤3(Through study completion, an average of 4 days)
- Percentage of episodes with at least 33% and 50%decrease in pain(Through study completion, an average of 4 days)
- Rescue medication usage(Through study completion, an average of 4 days)