Chronic Pain
Conditions
Keywords
Chronic Pain, Chronic Non-Malignant Pain, TTS-fentanyl, Durogesic
Brief summary
The purpose of this study is to evaluate the efficacy and safety of Transdermal Therapeutic System (TTS)-fentanyl patch (transdermal patch containing a drug that is put on the skin so the drug will enter the body through the skin) in Thai participants with chronic (lasting a long time) non-malignant (non-cancerous) pain.
Detailed description
This is an open label (all people know the identity of the intervention), single arm study to assess the efficacy and safety of TTS-fentanyl in Thai participants with chronic non-malignant pain (except for headaches or central spinal cord mediated pain). The study will consist of 2 phases: stabilization phase (up to 7 days before starting the treatment) and treatment phase (30 days). The first patch will be applied by Investigator then by participants themselves until 30 days. All participants will start the treatment with patch releasing 25 micrograms per hour (mcg/h) of fentanyl . The patches will be replaced every 3 days. On Day 3, and every 3 days thereafter, the TTS-fentanyl dose can be titrated (slow increase in drug dosage, guided by participant's responses) as per participant's need. The duration of the treatment will be 30 days after first patch application. The dose of TTS-fentanyl can be slowly increased if needed, by 25 mcg/h to achieve adequate pain control. No increase in TTS-fentanyl dose will be performed within the 72-hour dosing interval. Participants will be allowed the use of oral morphine syrup for the duration of TTS-fentanyl treatment to enable appropriate TTS-fentanyl dose titration. Primary efficacy assessment will be pain control rated by participants. Assessment time points will be Day 0 (Baseline), Day 15 and Day 30 (trial end). At the end of study, global preference on efficacy, side effects and overall satisfaction will also be rated by Investigator and participants. Participants' safety will be monitored throughout the study.
Interventions
DRUGTTS-Fentanyl
Transdermal Therapeutic System (TTS)-fentanyl patches releasing fentanyl in the range of 12.5 to 100 microgram per hour (mcg/hr) rate. The initial dose of fentanyl TTS will be calculated based on each participant's opioid requirement. Patches will be usually replaced every 72 hours. Doses will be escalated in steps of 25 mcg/hr, if pain cannot be controlled. The study duration will be 30 days after first patch application.
DRUGMorphine
Participants will be allowed the use of oral morphine syrup for the duration of TTS-fentanyl treatment to enable appropriate dose titration. It is expected that most of the participants will be titrated to an appropriate dose of TTS-fentanyl within 1 week.
Sponsors
Janssen-Cilag Ltd.,Thailand
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants with chronic non-malignant pain (of any etiology except for headaches or central spinal cord mediated pain) with moderate (medium level of seriousness) to severe (very serious, life threatening) pain that requires treatment with a potent opioid * Participants must also be currently treated with short or long acting opioid medications other than Transdermal Therapeutic System (TTS)-fentanyl at a dose less than or equal to 134 milligram per day (mg/day) of oral morphine (or an equianalgesic dose of another opioid), participants may have been treated with TTS-fentanyl in the past * Participants who had side effects after receiving Non Steroidal Anti-inflammatory Drugs (NSAIDs) * Participants who failed from other treatments such as operation or lack of efficacy of current treatment * Participants with spinal cord stimulators may enroll, provided that they turn the spinal cord stimulator off for the duration of the trial, or leave it continually on for the duration of the trial
Exclusion criteria
* History of allergy, hypersensitivity, or lack of ability to tolerate fentanyl * Skin disease that precludes the use of the transdermal system or which could affect the absorption of fentanyl or local tolerability * History or suspicion of alcohol or drug abuse within the past 5 years * History of narcotic (strong habit-forming drug that stops pain and depresses the central nervous system) therapy * Pregnancy or breast-feeding female
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Pain Intensity Rating at Day 15 | Baseline and Day 15 | Pain intensity was assessed on 11-point Numeric Rating Scale (NRS); score ranges from 0 to 10 where 0=no pain and 10=worst pain. |
| Change From Baseline in Pain Intensity Rating at Day 30 | Baseline and Day 30 | Pain intensity was assessed on 11-point NRS; score ranges from 0 to 10 where 0=no pain and 10=worst pain. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Investigator's Global Assessment | Day 30 | Investigator would complete a global assessment of the participants treatment with respect to pain control using a 9-point scale (-4 to 4; where, -4=100 percent (%) worse, 0=unchanged and 4=100% improvement), safety using 5-point scale (1 to 5; where, 1=no, 2=mild, 3=moderate, 4=severe and 5=most severe side effects) and 5-point overall satisfaction scale (1-5; where, 1=no, 2=mild, 3=moderate, 4=good, 5=excellent). Number of participants with Investigator's assessment with respect to efficacy, safety and overall satisfaction were reported. |
| Number of Participants With Participant's Global Assessment | Day 30 | Participants global assessment with respect to pain control using a 9-point scale (-4 to 4; where, -4=100% worse, 0=unchanged and 4=100% improvement), safety using 5-point scale (1 to 5; where, 1=no, 2=mild, 3=moderate, 4=severe and 5=most severe side effects) and 5-point overall satisfaction scale (1-5; where, 1=no, 2=mild, 3=moderate, 4=good, 5=excellent). Number of participants with participant's global assessment with respect to efficacy, safety and overall satisfaction were reported. |
Countries
Thailand
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Transdermal Therapeutic System (TTS) - Fentanyl Transdermal Therapeutic System (TTS) - fentanyl patches releasing fentanyl in the range of 12.5 to 100 microgram per hour (mcg/hr) rate. The initial dose of fentanyl TTS was calculated based on each participant's opioid requirement. Patches were usually replaced every 72 hours. Doses were escalated in steps of 25 mcg/hr, if pain cannot be controlled. 90 milligram per day (mg/day) of oral morphine was allowed as supplementary analgesic. The study duration was 30 days after first patch application. | 38 |
| Total | 38 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 6 |
| Overall Study | Amputation | 3 |
| Overall Study | Lack of Efficacy | 1 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Not eligible for the study | 1 |
Baseline characteristics
| Characteristic | Transdermal Therapeutic System (TTS) - Fentanyl |
|---|---|
| Age, Continuous | 50.39 Years STANDARD_DEVIATION 16 |
| Pain Intensity Rating | 6.54 units on a scale STANDARD_DEVIATION 2.02 |
| Sex: Female, Male Female | 15 Participants |
| Sex: Female, Male Male | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 25 / 39 |
| serious Total, serious adverse events | 1 / 39 |
Outcome results
Primary
Change From Baseline in Pain Intensity Rating at Day 15
Pain intensity was assessed on 11-point Numeric Rating Scale (NRS); score ranges from 0 to 10 where 0=no pain and 10=worst pain.
Time frame: Baseline and Day 15
Population: Intent-to-treat (ITT) population set included all participants who received at least one dose of study medication and who had at least one post-baseline efficacy assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Transdermal Therapeutic System (TTS) - Fentanyl | Change From Baseline in Pain Intensity Rating at Day 15 | -1.56 Units on a scale | Standard Deviation 3.15 |
Primary
Change From Baseline in Pain Intensity Rating at Day 30
Pain intensity was assessed on 11-point NRS; score ranges from 0 to 10 where 0=no pain and 10=worst pain.
Time frame: Baseline and Day 30
Population: The ITT population set included all participants who received at least one dose of study medication and who had at least one post-baseline efficacy assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Transdermal Therapeutic System (TTS) - Fentanyl | Change From Baseline in Pain Intensity Rating at Day 30 | -1.95 Units on a scale | Standard Deviation 3.28 |
Secondary
Number of Participants With Investigator's Global Assessment
Investigator would complete a global assessment of the participants treatment with respect to pain control using a 9-point scale (-4 to 4; where, -4=100 percent (%) worse, 0=unchanged and 4=100% improvement), safety using 5-point scale (1 to 5; where, 1=no, 2=mild, 3=moderate, 4=severe and 5=most severe side effects) and 5-point overall satisfaction scale (1-5; where, 1=no, 2=mild, 3=moderate, 4=good, 5=excellent). Number of participants with Investigator's assessment with respect to efficacy, safety and overall satisfaction were reported.
Time frame: Day 30
Population: The ITT population set included all participants who received at least one dose of study medication and who had at least one post-baseline efficacy assessment. 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Transdermal Therapeutic System (TTS) - Fentanyl | Number of Participants With Investigator's Global Assessment | Efficacy, 100% Worse | 0 Participants |
| Transdermal Therapeutic System (TTS) - Fentanyl | Number of Participants With Investigator's Global Assessment | Efficacy, 75% Worse | 0 Participants |
| Transdermal Therapeutic System (TTS) - Fentanyl | Number of Participants With Investigator's Global Assessment | Efficacy, 50% Worse | 1 Participants |
| Transdermal Therapeutic System (TTS) - Fentanyl | Number of Participants With Investigator's Global Assessment | Efficacy, 25% Worse | 0 Participants |
| Transdermal Therapeutic System (TTS) - Fentanyl | Number of Participants With Investigator's Global Assessment | Efficacy, Unchanged | 7 Participants |
| Transdermal Therapeutic System (TTS) - Fentanyl | Number of Participants With Investigator's Global Assessment | Efficacy, 25% Improve | 2 Participants |
| Transdermal Therapeutic System (TTS) - Fentanyl | Number of Participants With Investigator's Global Assessment | Efficacy, 50% Improve | 6 Participants |
| Transdermal Therapeutic System (TTS) - Fentanyl | Number of Participants With Investigator's Global Assessment | Efficacy, 75% Improve | 4 Participants |
| Transdermal Therapeutic System (TTS) - Fentanyl | Number of Participants With Investigator's Global Assessment | Efficacy, 100% Improve | 7 Participants |
| Transdermal Therapeutic System (TTS) - Fentanyl | Number of Participants With Investigator's Global Assessment | Safety, No | 16 Participants |
| Transdermal Therapeutic System (TTS) - Fentanyl | Number of Participants With Investigator's Global Assessment | Safety, Mild | 9 Participants |
| Transdermal Therapeutic System (TTS) - Fentanyl | Number of Participants With Investigator's Global Assessment | Safety, Moderate | 2 Participants |
| Transdermal Therapeutic System (TTS) - Fentanyl | Number of Participants With Investigator's Global Assessment | Safety, Severe | 0 Participants |
| Transdermal Therapeutic System (TTS) - Fentanyl | Number of Participants With Investigator's Global Assessment | Safety, Most severe | 0 Participants |
| Transdermal Therapeutic System (TTS) - Fentanyl | Number of Participants With Investigator's Global Assessment | Overall Satisfaction, No | 1 Participants |
| Transdermal Therapeutic System (TTS) - Fentanyl | Number of Participants With Investigator's Global Assessment | Overall Satisfaction, Mild | 7 Participants |
| Transdermal Therapeutic System (TTS) - Fentanyl | Number of Participants With Investigator's Global Assessment | Overall Satisfaction, Moderate | 6 Participants |
| Transdermal Therapeutic System (TTS) - Fentanyl | Number of Participants With Investigator's Global Assessment | Overall Satisfaction, Severe | 8 Participants |
| Transdermal Therapeutic System (TTS) - Fentanyl | Number of Participants With Investigator's Global Assessment | Overall Satisfaction, Most Severe | 5 Participants |
Secondary
Number of Participants With Participant's Global Assessment
Participants global assessment with respect to pain control using a 9-point scale (-4 to 4; where, -4=100% worse, 0=unchanged and 4=100% improvement), safety using 5-point scale (1 to 5; where, 1=no, 2=mild, 3=moderate, 4=severe and 5=most severe side effects) and 5-point overall satisfaction scale (1-5; where, 1=no, 2=mild, 3=moderate, 4=good, 5=excellent). Number of participants with participant's global assessment with respect to efficacy, safety and overall satisfaction were reported.
Time frame: Day 30
Population: The ITT population set included all participants who received at least one dose of study drug and had at least one post-baseline efficacy assessment. 'N' (number of participants analyzed) = participants who were evaluable for this measure and 'n' = participants who were evaluable for this measure at given time points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Transdermal Therapeutic System (TTS) - Fentanyl | Number of Participants With Participant's Global Assessment | Efficacy, 100% Worse (n=34) | 1 Participants |
| Transdermal Therapeutic System (TTS) - Fentanyl | Number of Participants With Participant's Global Assessment | Efficacy, 75% Worse (n=34) | 0 Participants |
| Transdermal Therapeutic System (TTS) - Fentanyl | Number of Participants With Participant's Global Assessment | Efficacy, 50% Worse (n=34) | 2 Participants |
| Transdermal Therapeutic System (TTS) - Fentanyl | Number of Participants With Participant's Global Assessment | Efficacy, 25% Worse (n=34) | 1 Participants |
| Transdermal Therapeutic System (TTS) - Fentanyl | Number of Participants With Participant's Global Assessment | Efficacy, Unchanged (n=34) | 4 Participants |
| Transdermal Therapeutic System (TTS) - Fentanyl | Number of Participants With Participant's Global Assessment | Efficacy, 25% Improve (n=34) | 13 Participants |
| Transdermal Therapeutic System (TTS) - Fentanyl | Number of Participants With Participant's Global Assessment | Efficacy, 50% Improve (n=34) | 11 Participants |
| Transdermal Therapeutic System (TTS) - Fentanyl | Number of Participants With Participant's Global Assessment | Efficacy, 75% Improve (n=34) | 1 Participants |
| Transdermal Therapeutic System (TTS) - Fentanyl | Number of Participants With Participant's Global Assessment | Efficacy, 100% Improve (n=34) | 1 Participants |
| Transdermal Therapeutic System (TTS) - Fentanyl | Number of Participants With Participant's Global Assessment | Safety, No (n=27) | 16 Participants |
| Transdermal Therapeutic System (TTS) - Fentanyl | Number of Participants With Participant's Global Assessment | Safety, Mild (n=27) | 9 Participants |
| Transdermal Therapeutic System (TTS) - Fentanyl | Number of Participants With Participant's Global Assessment | Safety, Moderate (n=27) | 2 Participants |
| Transdermal Therapeutic System (TTS) - Fentanyl | Number of Participants With Participant's Global Assessment | Safety, Severe (n=27) | 0 Participants |
| Transdermal Therapeutic System (TTS) - Fentanyl | Number of Participants With Participant's Global Assessment | Safety, Most severe (n=27) | 0 Participants |
| Transdermal Therapeutic System (TTS) - Fentanyl | Number of Participants With Participant's Global Assessment | Overall Satisfaction, No (n=27) | 1 Participants |
| Transdermal Therapeutic System (TTS) - Fentanyl | Number of Participants With Participant's Global Assessment | Overall Satisfaction, Mild (n=27) | 7 Participants |
| Transdermal Therapeutic System (TTS) - Fentanyl | Number of Participants With Participant's Global Assessment | Overall Satisfaction, Moderate (n=27) | 6 Participants |
| Transdermal Therapeutic System (TTS) - Fentanyl | Number of Participants With Participant's Global Assessment | Overall Satisfaction, Severe (n=27) | 8 Participants |
| Transdermal Therapeutic System (TTS) - Fentanyl | Number of Participants With Participant's Global Assessment | Overall Satisfaction, Most Severe (n=27) | 5 Participants |