Back to resultsEffectiveness and Tolerance of Inhaled Fentanyl Aerosol (25µg/Dose) in Chinese Patients With Breakthrough Cancer Pain
Primary Purpose
Breakthrough Cancer Pain
Status
Unknown status
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Inhaled fentanyl aerosol
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Breakthrough Cancer Pain
Eligibility Criteria
Inclusion Criteria:
- 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 2.
- 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.
Exclusion Criteria:
- 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.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Inhaled fentanyl aerosol
Placebo
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
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.
SPID60
Weighted sum of pain intensity difference at post dose 60 minutes.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". PID60 is calculated as the difference in pain intensity from time 0 to 60 minutes. A positive value is a decrease (improvement) of the pain.SPID60=PID4*4+PID8*4+PID12*4+PID16*4+PID20*4+PID30*10+PID30*30
Percentage of episodes with NRS≤3
Overall responder rate is defined as the proportion of breakthrough pain (BTP) episodes with a positive response to treatment. The following definitions of a positive response were analyzed: greater than or equal to 3 point reduction in PI from time 0. Pain intensity was assessed 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".
Percentage of episodes with at least 33% and 50%decrease in pain
Overall responder rate is defined as the proportion of breakthrough pain (BTP) episodes with a positive response to treatment. The following definitions of a positive response were analyzed: Greater than 33% reduction in PI from time 0;Greater than 50% reduction in PI from time 0. Pain intensity was assessed 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".
Rescue medication usage
Only Morphine for injection to be used as rescue medication
Full Information
NCT ID
NCT04713189
First Posted
January 13, 2021
Last Updated
January 28, 2021
Sponsor
Lee's Pharmaceutical Limited
1. Study Identification
Unique Protocol Identification Number
NCT04713189
Brief Title
Effectiveness and Tolerance of Inhaled Fentanyl Aerosol (25µg/Dose) in Chinese Patients With Breakthrough Cancer Pain
Official Title
A Phase I/IIa, Pharmacokinetic, Dose-response and Safety Study of Inhaled Fentanyl Aerosol (25µg/Dose) in Chinese Patients With Breakthrough Cancer Pain
Study Type
Interventional
2. Study Status
Record Verification Date
January 2021
Overall Recruitment Status
Unknown status
Study Start Date
March 15, 2021 (Anticipated)
Primary Completion Date
December 21, 2021 (Anticipated)
Study Completion Date
December 21, 2021 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Lee's Pharmaceutical Limited
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
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.
Detailed Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breakthrough Cancer Pain
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
96 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Inhaled fentanyl aerosol
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Inhaled fentanyl aerosol
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
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. I
Primary Outcome Measure Information:
Title
SPID30
Description
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
Time Frame
During the stage I, at each episode of breakthrough pain, 30 minutes after first dose of study drug.
Secondary Outcome Measure Information:
Title
Pain intensity at 0, 4,8,12,16,20,30 and 60 minutes post-dose
Description
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.
Time Frame
During the stage I, at each episode of breakthrough pain, 60 minutes after first dose of study drug.
Title
SPID60
Description
Weighted sum of pain intensity difference at post dose 60 minutes.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". PID60 is calculated as the difference in pain intensity from time 0 to 60 minutes. A positive value is a decrease (improvement) of the pain.SPID60=PID4*4+PID8*4+PID12*4+PID16*4+PID20*4+PID30*10+PID30*30
Time Frame
During the stage I, at each episode of breakthrough pain, 60 minutes after first dose of study drug.
Title
Percentage of episodes with NRS≤3
Description
Overall responder rate is defined as the proportion of breakthrough pain (BTP) episodes with a positive response to treatment. The following definitions of a positive response were analyzed: greater than or equal to 3 point reduction in PI from time 0. Pain intensity was assessed 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".
Time Frame
Through study completion, an average of 4 days
Title
Percentage of episodes with at least 33% and 50%decrease in pain
Description
Overall responder rate is defined as the proportion of breakthrough pain (BTP) episodes with a positive response to treatment. The following definitions of a positive response were analyzed: Greater than 33% reduction in PI from time 0;Greater than 50% reduction in PI from time 0. Pain intensity was assessed 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".
Time Frame
Through study completion, an average of 4 days
Title
Rescue medication usage
Description
Only Morphine for injection to be used as rescue medication
Time Frame
Through study completion, an average of 4 days
Other Pre-specified Outcome Measures:
Title
device performance
Description
Success rate of drug stimulation (successful drug inhalation). Normal rate of electronic lock function.
Time Frame
through study completion, an average of 4 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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 2.
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.
Exclusion Criteria:
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.
12. IPD Sharing Statement
Learn more about this trial
Effectiveness and Tolerance of Inhaled Fentanyl Aerosol (25µg/Dose) in Chinese Patients With Breakthrough Cancer Pain
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