A Dose Titrated Clinical Trial With a Placebo-controlled, Double-blind, Randomised, Cross-over Phase to Demonstrate the Efficacy of 400 μg Intranasal Fentanyl (INFS) Dose Strength, and to Evaluate 12 Weeks Safety and Nasal Tolerability of All Dose Strengths Between 50 μg and 400 μg, in Cancer Patients With Breakthrough Pain.
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 46
- 主要终点
- Induction Phase: Pain Intensity Difference at 10 Minutes (PID10) After Treatment
研究概览
简要总结
The aim of this clinical trial was to demonstrate the efficacy of a 400 μg dose strength of intranasal fentanyl spray (INFS, Instanyl®) and to evaluate the safety and to establish long term tolerability of treatment with INFS doses of 50, 100, 200 and 400 μg.
详细描述
This is a clinical trial with 12 weeks treatment of Intranasal fentanyl (INFS) in cancer patients with breakthrough pain (BTP). It was composed of a dose titrated, placebo-controlled, double-blind, randomised, cross-over efficacy phase, combined with a titration and a tolerability phase assessing the safety and nasal tolerability of INFS. The trial is set up with a screening period and three treatment phases: a titration phase (I), an efficacy phase (II) and a tolerability phase (III). The entire trial period for each completed patient consisted of the one week screening period and 12 weeks treatment with INFS.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •All inclusion criteria were answered 'yes' for a patient to participate in the clinical trial.
- •Is the patient a cancer patient with breakthrough Pain (BTP)?
- •Has the patient received either oral opioids or transdermal fentanyl for treatment of background pain (BGP) within the last month prior to the screening visit?
- •Is the current dose of prescribed opioids (for BGP) equivalent to 60-1000 mg oral morphine/day?
- •Has the patient's BGP for the last 7 days prior to the screening visit been generally stable, and on average controlled to a mild level (defined as ≤ 4 on the 11-point Numerical Rating Scale [NRS])?
- •Does the patient (at the time of the screening visit) experience his/her current BTP episodes to be of such severe pain intensity, that he/she in general needs additional analgesia (i.e. on top of the background opioid treatment)?
- •Has the patient on average for the last 7 days prior to the screening visit had at least three BTP episodes per week, but no more than four BTP episodes per day?
- •Is the patient able to use intranasal drugs?
- •Is the life expectancy of the patient at least 3 months from the date of the screening visit?
排除标准
- •Has the patient had an illicit substance abuse within the last year prior to screening?
- •Does the patient have severe hepatic impairment? - defined as alanine aminotransferase (ALT or) aspartate aminotransferase (AST) levels > 3x upper limit of normal (ULN)
- •Does the patient have severe renal impairment? - defined as serum creatinine ≥ 3.0 mg/dl (265 micromol/L)
- •Has the patient ever had facial radiotherapy or is the patient scheduled to facial radiotherapy?
- •Has the patient been treated with any monoamine oxidase (MAO) inhibitors within the last 14 days prior to the screening visit?
- •Does the patient have severe impaired respiratory function, which may increase the risk of clinically relevant respiratory depression by BTP fentanyl treatment?
- •Is the patient known to be hypersensitive to fentanyl or to other opioids or any of their excipients?
- •Does the patient have any head injury, primary brain tumor or other pathological conditions, which could significantly increase the risk of increased intracranial pressure or impaired consciousness?
研究组 & 干预措施
Intranasal Fentanyl Spray (INFS)
All participants were step-wise titrated to an effective dose of 50, 100, 200 or 400 μg INFS in the Titration Phase (I). Participants titrated to 200 or 400 μg INFS in the Titration Phase were randomized to an 8-spray sequence in the Efficacy Phase (II); 6 BTP episodes were treated with 400 μg INFS and 2 BTP episodes with placebo in a random sequence. Participants entered the Tolerability Phase (III) either directly from the Titration Phase (with an effective dose of 50 or 100 μg) or from the Efficacy Phase (400 μg) and continued with this specific dose, unless adjustment was needed, for a total treatment time of 12 weeks.
干预措施: Intranasal Fentanyl Spray (INFS) (Drug)
Intranasal Fentanyl Spray (INFS)
All participants were step-wise titrated to an effective dose of 50, 100, 200 or 400 μg INFS in the Titration Phase (I). Participants titrated to 200 or 400 μg INFS in the Titration Phase were randomized to an 8-spray sequence in the Efficacy Phase (II); 6 BTP episodes were treated with 400 μg INFS and 2 BTP episodes with placebo in a random sequence. Participants entered the Tolerability Phase (III) either directly from the Titration Phase (with an effective dose of 50 or 100 μg) or from the Efficacy Phase (400 μg) and continued with this specific dose, unless adjustment was needed, for a total treatment time of 12 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
Induction Phase: Pain Intensity Difference at 10 Minutes (PID10) After Treatment
时间窗: During the efficacy phase (II), at each episode of breakthrough pain, at 0 and 10 minutes after first dose of study drug.
During the efficacy phase participants assessed their pain intensity at each breakthrough pain (BTP) episode at 0 and 10 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". PID10 is calculated as the difference in pain intensity from time 0 to 10 minutes. A positive value is a decrease (improvement) of the pain; a ≥ 2-point difference is considered as clinically important.
次要结局
- Efficacy Phase: Sum of Pain Intensity Differences (SPID0-60 and SPID0-30) Derived From PI Scores(During the efficacy phase (II) each episode of breakthrough pain, at 0, 5, 30 and 60 minutes after study drug)
- Efficacy Phase: Proportion of BTP Episodes With a Positive Response Defined as a ≥ 1, 2 or 3 Point Reduction in Pain Intensity(During the efficacy phase (II) each episode of breakthrough pain, at 0, 5, 30 and 60 minutes after study drug)
- Efficacy Phase: Proportion of BTP Episodes With a Positive Response Defined as a ≥ 33% or 50% Reduction in Pain Intensity(During the efficacy phase (II) each episode of breakthrough pain, at 0, 5, 30 and 60 minutes after study drug)
- Efficacy Phase: General Impression (GI) Score at 60 Minutes After First Dose(During the efficacy phase (II), at each episode of breakthrough pain, 60 minutes after first dose of study drug.)
- Number of Participants With Adverse Events (AEs)(12 weeks)
- Incidence of Improvement or Worsening in Nasal Mucosa Sign or Abnormality Score(Baseline and at 12 weeks)
- Efficacy Phase: Pain Intensity Difference (PID) at 5, 30, and 60 Minutes After First Dose of Study Drug(During the efficacy phase (II) each episode of breakthrough pain, at 0, 5, 30 and 60 minutes after study drug.)