Chronic Pain
Conditions
Keywords
Chronic pain, Fentanyl Patch
Brief summary
The purpose of this study is to evaluate the safety and efficacy of fentanyl one-day transdermal patch (JNS020QD, patch containing a drug that is put on the skin so the drug will enter the body through the skin) in participants with chronic (lasting a long time) pain.
Detailed description
This is an open-label (all people know the identity of the intervention), multi-center (conducted in more than one center) and non-comparative study of fentanyl one-day transdermal patch. The study consists of 4 periods: Screening period (3-14 days), Treatment period 1 (4 weeks), Treatment period 2 (48 weeks), Tapering period (0-6 weeks) and Follow-up period (1 week). Treatment will be initiated at 12.5 microgram per hour (mcg/hr). In both Treatment period 1 and 2, the dose will be increased as per the Investigator's discretion, ranging from 12.5 mcg/hr to 100 mcg/hr and the maximum application dose will be 300 mcg/hr. However, in Treatment period 2, the dose will be increased on 7th day before the day of medical examination (only if the participant used rescue treatment for minimum of 3 times per day for minimum of 4 days). The patch will be applied on areas including the chest, abdomen, upper arm and femoral region and replaced daily. Efficacy will primarily be evaluated by visual analog scale (VAS) score. The total duration of the study treatment will be 52 weeks. Participants' safety will be monitored throughout the study.
Interventions
DRUGFentanyl
Fentanyl transdermal patch will be applied daily starting at a dose of 12.5 mcg/hr, and up to 52 weeks. Dose will be increased as per Investigator's discretion.
Sponsors
Janssen Pharmaceutical K.K.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants whose medication for chronic pain meets one of the criteria among a to e (2 or more types of opioid analgesics must not be used): a) Participants who are taking non-opioid analgesic at the normal highest dose or more for at least 14 consecutive days during 12 weeks before the informed consent, but were not continuously taking the non-opioid analgesic during 14 days before the informed consent for medical reasons such as safety b) Participants who are continuously taking an additional analgesic with a certain dosage and administration for at least 14 consecutive days before the informed consent c)Participants who are continuously taking codeine phosphate or dihydrocodeine phosphate less than 270 milligram (mg) daily (except for rescue treatment) for at least 14 consecutive days before the informed consent d) Participants who are continuously taking codeine morphine hydrochloride of oral morphine equivalent dose of less than 45 mg daily (except for rescue treatment) for at least 14 consecutive days before the informed consent (less than 30 mg daily for suppositories and less than 15 mg daily for injections) e) Participants who are continuously taking fentanyl citrate injection of less than 0.3 mg daily (except for rescue treatment) for at least 14 consecutive days before the informed consent * Participants with chronic pain continuing for at least 12 weeks before informed consent * Participants with an average pain intensity of greater than or equal to 50 millimeter (mm) on the Visual Analog Scale in 24-hour daily living before informed consent * Participants who can be hospitalized to the 4th day after the initiation of patch application * Participants who were given a sufficient explanation about the investigational product and the study and gave their own consent to participate in the study
Exclusion criteria
* Participants whose main cause of the pain to be assessed is considered attributable to psychogenic pain * Participants with severe respiratory function disorders * Participants with asthma (breathing disorder in which there is wheezing and difficulty breathing) and bradyarrhythmia (slow, irregular heartbeats) * Participants with hepatic dysfunction function such as fulminant hepatitis (inflammation of the liver) and liver cirrhosis (serious liver disorder in which connective tissue replaces normal liver tissue, and liver failure often occurs), or renal impairment such as nephritic syndrome, acute renal failure, and chronic renal failure * Participants with organic disorder in the brain such as brain tumor who have any of these symptoms: intracranial pressure increased, consciousness disturbance or coma and respiratory disorder
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Rescue Treatments | Week 52 or final evaluation (early discontinuation) | Rescue treatment was used for participants with lack of analgesic efficacy, to have relief from breakthrough pain and in cases where withdrawal symptoms occur. The reference one-time rescue dose used was oral morphine 5 milligram (mg) for the investigational product fentanyl one-day transdermal patch 12.5 mcg per hr. The number of rescue treatments per day were reported. |
| Questionnaire of Opioid Withdrawal Symptoms | Week 52 or endpoint (1 week after last treatment or early discontinuation) | Questionnaire of opioid withdrawal symptoms is a clinician rated 11-item scale that primarily evaluates the physical components of opioid withdrawal and is based on questions and clinical observations. The total score of questionnaire of opioid withdrawal symptoms is the sum of all individual items, with less than (\<) 5 points = no withdrawal, 5 to 12 points = mild withdrawal, 13 to 24 points = moderate withdrawal, 25 to 36 points = moderately severe withdrawal and greater than (\>) 36 points = severe withdrawal. |
| Dependence Questionnaire (DQ) | Week 52 or end point (early discontinuation) | The DQ is a clinician rated 5-item scale that evaluates dependence on drug and based on questions (Q). Based on participant's answer to Q in questionnaire, Investigator assessed whether drug dependence occurred. It comprises 5 Q which are: continuing drug for reason other than pain, using drug in more dosage than prescribed to have effect other than treatment of pain, have ever used drug with more dosage than prescribed for other purpose, anxiety with the thought of stopping drug for reason other than aggravation of symptoms by stopping this drug and feeling to violate law to get this drug. |
| Pain Visual Analogue Scale Score | Week 52 or end point (early discontinuation) | Pain visual analog scale was used to assess the amount of pain experienced by the participant throughout the day by marking a slash through the line of a 100 millimeter (mm) scale measuring pain from no pain (0 mm) to worst possible pain (100 mm). |
| Number of Participants With Pain Assessed by Categorical Scale for Pain | Week 52 or final evaluation (early discontinuation) | Pain intensity was measured by assessing the average intensity of pain experienced by the participant in daily living throughout the day by 4 grades: no pain at all, mild (slightly painful, but not worried), moderate (painful, but bearable) and severe (painful and unbearable). |
| Number of Participants With Total Painful Time Per Day | Week 52 or final evaluation (early discontinuation) | The participants assessed total painful time in 1 day by the following 5 grades: less than 4 hours, 4 hours to less than 8 hours, 8 hours to less than 12 hours, 12 hours or more and all day. |
| Number of Participants With Quality of Sleep | Week 52 or final evaluation (early discontinuation) | The quality of sleep was assessed by participants that how well they have slept from the previous assessment to current assessment time by the following 4 grades: can sleep well, can sleep moderately well, cannot sleep much and cannot sleep at all. |
| Short-Form 36-Item Health Survey (SF-36) Scores | Week 52 or final evaluation (early discontinuation) | The SF-36 is 36-item form related to 8 health concepts (physical functioning, role physical, role emotional, general health, social functioning, bodily pain, vitality, mental health) and 2 summary scores (physical and mental component summary). Physical functioning, role physical and bodily pain contribute to physical component; role emotional, social functioning and mental health contribute to mental component; and social functioning, vitality, and general health contribute to both. All scores are based on a scale from 0 to 100, with higher scores defining more favorable health state. |
| Physician's Global Assessment Scale | Week 52 or final evaluation (early discontinuation) | The treating physician assessed the therapeutic efficacy of the treatment by 2 grades: effective and ineffective. Numbers of participants with effective and ineffective therapeutic efficacy with the treatment were reported. |
| Participants Overall Assessment | Week 52 or final evaluation (early discontinuation) | The participants assessed their satisfaction with therapeutic efficacy by 5 grades: satisfied very much, satisfied, equivocal, dissatisfied and dissatisfied very much. Percentage of participants who were at least satisfied (satisfied, satisfied very much) or at least neither satisfied nor dissatisfied (dissatisfied, dissatisfied very much) were reported. |
| Brief Pain Inventory-Short Form (BPI-SF) Total Score | Week 52 or final evaluation (early discontinuation) | The BPI-SF is a self-report questionnaire designed to assess the severity and impact of pain on daily functions. It includes pain interference score which is mean value for scores for 9 BPI-SF questions ranging between 0 (does not interfere) to 10 (completely interferes) and pain subscale score which is mean value for scores for BPI-SF questions 3 to 6 ranging between 0 (no pain) to 10 (pain as bad as can imagine). Total BPI-SF score is an average of pain interference score and pain subscale score and ranges from 0 to 10; higher score indicates more pain or pain interference. |
Countries
Japan
Participant flow
Pre-assignment details
148 participants were screened, of which 142 participants entered the treatment period.
Participants by arm
| Arm | Count |
|---|---|
| Fentanyl Fentanyl transdermal patch was applied once daily up to 4 weeks in Treatment period 1, releasing at the rate of 12.5 microgram per hour (mcg/hr), maintained for 2 days and for another 48 weeks in Treatment period 2. The dose was increased as per Investigators' discretion in both treatment periods and the maximum applied dose was 300 mcg/hr. Total duration of treatment was 52 weeks. | 142 |
| Total | 142 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Period 1 (up to 4 Weeks) | Adverse Event | 18 |
| Period 1 (up to 4 Weeks) | Ineligible for transfer to period 2 | 9 |
| Period 1 (up to 4 Weeks) | Withdrawal of informed consent | 4 |
| Period 2 (Week 4 to Week 52) | Adverse Event | 13 |
| Period 2 (Week 4 to Week 52) | Aggravated symptoms | 1 |
| Period 2 (Week 4 to Week 52) | Physician Decision | 9 |
| Period 2 (Week 4 to Week 52) | Withdrawal of informed consent | 9 |
Baseline characteristics
| Characteristic | Fentanyl |
|---|---|
| Age Continuous | 61.4 years STANDARD_DEVIATION 14.98 |
| Sex: Female, Male Female | 64 Participants |
| Sex: Female, Male Male | 78 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 140 / 142 |
| serious Total, serious adverse events | 38 / 142 |
Outcome results
Primary
Brief Pain Inventory-Short Form (BPI-SF) Total Score
The BPI-SF is a self-report questionnaire designed to assess the severity and impact of pain on daily functions. It includes pain interference score which is mean value for scores for 9 BPI-SF questions ranging between 0 (does not interfere) to 10 (completely interferes) and pain subscale score which is mean value for scores for BPI-SF questions 3 to 6 ranging between 0 (no pain) to 10 (pain as bad as can imagine). Total BPI-SF score is an average of pain interference score and pain subscale score and ranges from 0 to 10; higher score indicates more pain or pain interference.
Time frame: Week 52 or final evaluation (early discontinuation)
Population: The FAS population included all participants with the exception of participants with violation of eligibility criteria, participants with no treatment with the patch of fentanyl and participants without efficacy data after initiation of patch application. Here 'N' (number of participants analyzed) signifies participants evaluable for this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fentanyl | Brief Pain Inventory-Short Form (BPI-SF) Total Score | 5.1 units on a scale | Standard Deviation 2.24 |
Primary
Dependence Questionnaire (DQ)
The DQ is a clinician rated 5-item scale that evaluates dependence on drug and based on questions (Q). Based on participant's answer to Q in questionnaire, Investigator assessed whether drug dependence occurred. It comprises 5 Q which are: continuing drug for reason other than pain, using drug in more dosage than prescribed to have effect other than treatment of pain, have ever used drug with more dosage than prescribed for other purpose, anxiety with the thought of stopping drug for reason other than aggravation of symptoms by stopping this drug and feeling to violate law to get this drug.
Time frame: Week 52 or end point (early discontinuation)
Population: Safety population included all the participants who received at least one patch application of the investigational product. Here 'N' (number of participants analyzed) signifies participants evaluable for this measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fentanyl | Dependence Questionnaire (DQ) | Q1:Continue to use drug for reason other than pain | 1 units on a scale |
| Fentanyl | Dependence Questionnaire (DQ) | Q 2: Wanted to use more dosage than prescribed | 0 units on a scale |
| Fentanyl | Dependence Questionnaire (DQ) | Q3: Used drug with more dosage than prescribed | 0 units on a scale |
| Fentanyl | Dependence Questionnaire (DQ) | Q4: Anxious with thought of stopping drug | 1 units on a scale |
| Fentanyl | Dependence Questionnaire (DQ) | Q5: Feeling to violate law to get this drug | 0 units on a scale |
| Fentanyl | Dependence Questionnaire (DQ) | Judgment by doctor: Dependent and abuse | 0 units on a scale |
| Fentanyl | Dependence Questionnaire (DQ) | Judgement by doctor: Not dependent and no abuse | 140 units on a scale |
Primary
Number of Participants With Pain Assessed by Categorical Scale for Pain
Pain intensity was measured by assessing the average intensity of pain experienced by the participant in daily living throughout the day by 4 grades: no pain at all, mild (slightly painful, but not worried), moderate (painful, but bearable) and severe (painful and unbearable).
Time frame: Week 52 or final evaluation (early discontinuation)
Population: The FAS population included all participants with the exception of participants with violation of eligibility criteria, participants with no treatment with the patch of fentanyl and participants without efficacy data after initiation of patch application. Here 'N' (number of participants analyzed) signifies participants evaluable for this measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fentanyl | Number of Participants With Pain Assessed by Categorical Scale for Pain | No pain | 1 participants |
| Fentanyl | Number of Participants With Pain Assessed by Categorical Scale for Pain | Mild pain | 21 participants |
| Fentanyl | Number of Participants With Pain Assessed by Categorical Scale for Pain | Moderate pain | 101 participants |
| Fentanyl | Number of Participants With Pain Assessed by Categorical Scale for Pain | Severe pain | 18 participants |
Primary
Number of Participants With Quality of Sleep
The quality of sleep was assessed by participants that how well they have slept from the previous assessment to current assessment time by the following 4 grades: can sleep well, can sleep moderately well, cannot sleep much and cannot sleep at all.
Time frame: Week 52 or final evaluation (early discontinuation)
Population: The FAS population included all participants with the exception of participants with violation of eligibility criteria, participants with no treatment with the patch of fentanyl and participants without efficacy data after initiation of patch application. Here 'N' (number of participants analyzed) signifies participants evaluable for this measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fentanyl | Number of Participants With Quality of Sleep | Can sleep well | 28 participants |
| Fentanyl | Number of Participants With Quality of Sleep | Can sleep moderately well | 67 participants |
| Fentanyl | Number of Participants With Quality of Sleep | Cannot sleep much | 40 participants |
| Fentanyl | Number of Participants With Quality of Sleep | Cannot sleep at all | 6 participants |
Primary
Number of Participants With Total Painful Time Per Day
The participants assessed total painful time in 1 day by the following 5 grades: less than 4 hours, 4 hours to less than 8 hours, 8 hours to less than 12 hours, 12 hours or more and all day.
Time frame: Week 52 or final evaluation (early discontinuation)
Population: The FAS population included all participants with the exception of participants with violation of eligibility criteria, participants with no treatment with the patch of fentanyl and participants without efficacy data after initiation of patch application. Here 'N' (number of participants analyzed) signifies participants evaluable for this measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fentanyl | Number of Participants With Total Painful Time Per Day | Less than 4 hours | 17 participants |
| Fentanyl | Number of Participants With Total Painful Time Per Day | 4 hours to less than 8 hours | 29 participants |
| Fentanyl | Number of Participants With Total Painful Time Per Day | 8 hours to less than 12 hours | 23 participants |
| Fentanyl | Number of Participants With Total Painful Time Per Day | 12 hours or more | 40 participants |
| Fentanyl | Number of Participants With Total Painful Time Per Day | All day | 32 participants |
Primary
Number of Rescue Treatments
Rescue treatment was used for participants with lack of analgesic efficacy, to have relief from breakthrough pain and in cases where withdrawal symptoms occur. The reference one-time rescue dose used was oral morphine 5 milligram (mg) for the investigational product fentanyl one-day transdermal patch 12.5 mcg per hr. The number of rescue treatments per day were reported.
Time frame: Week 52 or final evaluation (early discontinuation)
Population: The FAS population included all the participants with the exception of participants with violation of eligibility criteria, participants with no treatment with the patch of fentanyl and participants without efficacy data after initiation of patch application.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fentanyl | Number of Rescue Treatments | 1.0 treatments per day | Standard Deviation 1.13 |
Primary
Pain Visual Analogue Scale Score
Pain visual analog scale was used to assess the amount of pain experienced by the participant throughout the day by marking a slash through the line of a 100 millimeter (mm) scale measuring pain from no pain (0 mm) to worst possible pain (100 mm).
Time frame: Week 52 or end point (early discontinuation)
Population: Full Analysis Set (FAS) population included all the participants with the exception of participants with violation of eligibility criteria, participants with no treatment with the patch of fentanyl and participants without efficacy data after initiation of patch application.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fentanyl | Pain Visual Analogue Scale Score | 58.3 mm | Standard Deviation 24.72 |
Primary
Participants Overall Assessment
The participants assessed their satisfaction with therapeutic efficacy by 5 grades: satisfied very much, satisfied, equivocal, dissatisfied and dissatisfied very much. Percentage of participants who were at least satisfied (satisfied, satisfied very much) or at least neither satisfied nor dissatisfied (dissatisfied, dissatisfied very much) were reported.
Time frame: Week 52 or final evaluation (early discontinuation)
Population: The FAS population included all participants with the exception of participants with violation of eligibility criteria, participants with no treatment with the patch of fentanyl and participants without efficacy data after initiation of patch application. Here 'N' (number of participants analyzed) signifies participants evaluable for this measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fentanyl | Participants Overall Assessment | Satisfied | 31.2 percentage of participants |
| Fentanyl | Participants Overall Assessment | Neither satisfied nor dissatisfied | 66.7 percentage of participants |
Primary
Physician's Global Assessment Scale
The treating physician assessed the therapeutic efficacy of the treatment by 2 grades: effective and ineffective. Numbers of participants with effective and ineffective therapeutic efficacy with the treatment were reported.
Time frame: Week 52 or final evaluation (early discontinuation)
Population: The FAS population included all the participants with the exception of participants with violation of eligibility criteria, participants with no treatment with the patch of fentanyl and participants without efficacy data after initiation of patch application.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fentanyl | Physician's Global Assessment Scale | Effective | 106 participants |
| Fentanyl | Physician's Global Assessment Scale | Ineffective | 36 participants |
Primary
Questionnaire of Opioid Withdrawal Symptoms
Questionnaire of opioid withdrawal symptoms is a clinician rated 11-item scale that primarily evaluates the physical components of opioid withdrawal and is based on questions and clinical observations. The total score of questionnaire of opioid withdrawal symptoms is the sum of all individual items, with less than (\<) 5 points = no withdrawal, 5 to 12 points = mild withdrawal, 13 to 24 points = moderate withdrawal, 25 to 36 points = moderately severe withdrawal and greater than (\>) 36 points = severe withdrawal.
Time frame: Week 52 or endpoint (1 week after last treatment or early discontinuation)
Population: Safety population included all the participants who received at least one patch application of the investigational product. Here 'N' (number of participants analyzed) signifies participants evaluable for this measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fentanyl | Questionnaire of Opioid Withdrawal Symptoms | < 5 points | 137 participants |
| Fentanyl | Questionnaire of Opioid Withdrawal Symptoms | >=5 to <=12 points | 2 participants |
| Fentanyl | Questionnaire of Opioid Withdrawal Symptoms | >=13 to <=24 points | 1 participants |
| Fentanyl | Questionnaire of Opioid Withdrawal Symptoms | >=25 to <=36 points | 0 participants |
| Fentanyl | Questionnaire of Opioid Withdrawal Symptoms | >=37 points | 0 participants |
Primary
Short-Form 36-Item Health Survey (SF-36) Scores
The SF-36 is 36-item form related to 8 health concepts (physical functioning, role physical, role emotional, general health, social functioning, bodily pain, vitality, mental health) and 2 summary scores (physical and mental component summary). Physical functioning, role physical and bodily pain contribute to physical component; role emotional, social functioning and mental health contribute to mental component; and social functioning, vitality, and general health contribute to both. All scores are based on a scale from 0 to 100, with higher scores defining more favorable health state.
Time frame: Week 52 or final evaluation (early discontinuation)
Population: The FAS population included all participants with the exception of participants with violation of eligibility criteria, participants with no treatment with the patch of fentanyl and participants without efficacy data after initiation of patch application. Here 'N' (number of participants analyzed) signifies participants evaluable for this measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fentanyl | Short-Form 36-Item Health Survey (SF-36) Scores | Physical health (summary score) | 23.0 units on a scale | Standard Deviation 17.49 |
| Fentanyl | Short-Form 36-Item Health Survey (SF-36) Scores | Mental health (summary score) | 42.1 units on a scale | Standard Deviation 9.82 |