Effectiveness and Tolerance of Inhaled Fentanyl Aerosol (25µg/Dose) in Chinese Patients With BTcP

Study Overview
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Brief Summary
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Breakthrough cancer pain (BTcP) is a common problem in patients with cancer. This is a phase IIa dose-response and safety study of inhaled fentanyl aerosol (25µg/dose) in Chinese patients with breakthrough cancer pain.

Official Title
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Effectiveness and Tolerance of Inhaled Fentanyl Aerosol (25µg/Dose) in Chinese Patients With BTcP

Conditions
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Breakthrough Pain

Intervention / Treatment
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* Drug: Fentanyl


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age of 18years or above Subjects must be diagnosed with cancer. Subjects must experience persistent pain associated with cancer, and the pain score assessed by NRS should be <4 within 1week before screening. In the past 7 days, the subject must experience an average of 1 to 4 episodes of breakthrough cancer pain per day,The breakthrough cancer pain score should be ≥4 assessed by NRS ECOG status of 0 to 2. 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. Exclusion Criteria: Allergies, or a history of drug allergies to fentanyl. HGB < 80 g/L, NEUT ≤1.0 × 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). 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: placebo<br>Participants 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 | Drug: Fentanyl<br>* Participants 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.<br>* Other names: Placebo;|
| Experimental: Inhaled fentanyl aerosol<br>Participants 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 | Drug: Fentanyl<br>* Participants 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.<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SPID30 | 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 | at each episode of breakthrough pain, 30 minutes after first dose of study drug. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain intensity at 0, 4,8,12,16,20,30 and 60 minutes post-dose | Pain intensity at each breakthrough pain (BTP) episode at 0 ,4,8,12,16,20, 30 and 60 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.A positive value is a decrease (improvement) of the pain. | at each episode of breakthrough pain, 60 minutes after first dose of study drug. |