Complex Regional Pain Syndromes (CRPS), Postherpetic Neuralgia, Postoperative Pain
Conditions
Keywords
Postherpetic Neuralgia, Complex Regional Pain Syndromes (CRPS), Postoperative Pain, Fentanyl, Patch, transdermal, Opioid analgesics
Brief summary
The purpose of this study is to evaluate the efficacy and safety of fentanyl in opioid-naive participants with post-herpetic neuralgia, complex regional pain syndrome or post-operative pain syndrome who cannot obtain a sufficient analgesic effect by the treatment of non-opioid analgesics (drug used to control pain).
Detailed description
This is a multi-center (conducted in more than one center), double-blind (neither the participant nor the physician knows the assigned study drug), randomized (participants assigned study drug by chance), withdrawal study in opioid-naive participants with post-herpetic neuralgia (intense, typically intermittent pain along the course of a nerve caused by the varicella zoster virus), complex regional pain syndrome or post-operative pain syndrome. The study will consist of titration period (10-29 days) and double-blind period (12 weeks) and the visits will include Day 5-7, 8, 15, 22, 29 in titration period and Day 2-4, 8, 15, 22, 29, 43, 57, 71 and 85 in double-blind period. All the eligible participants will receive one-day adhesive transdermal patch (patch containing a drug that is put on the skin so the drug will enter the body through the skin) of either fentanyl at the dose ranging from 12.5 to 50 microgram/hour or matching placebo. Efficacy will be evaluated primarily by time to withdrawal due to insufficient analgesic efficacy. Participants' safety will be monitored throughout the study.
Interventions
DRUGFentanyl
One-day adhesive transdermal patch containing fentanyl 12.5 to 50 mcg/hr applied to chest, abdomen, upper arm and thigh and replaced every day.
DRUGPlacebo
Placebo patch indistinguishable from one-day adhesive transdermal patch containing fentanyl 12.5 to 50 mcg/hr applied to chest, abdomen, upper arm and thigh and replaced every day.
Sponsors
Janssen Pharmaceutical K.K.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants whose pain because of post-herpetic neuralgia, Complex Regional Pain Syndrome (CRPS) or post-operative pain syndrome is continuing for at least 12 weeks prior to informed consent * Participants who are continuously taking a non-opioid analgesic at the normal highest dose or more for at least 14 consecutive days prior to informed consent, or at a certain dose (except the use on an as-needed base) on consecutive days or participants who are continuously taking an analgesic adjuvant with a certain dosage and administration (except the use on an as-needed base) for at least 14 consecutive days prior to informed consent * Participants showing insufficient therapeutic efficacy of the non-opioid analgesic currently being used, and to requiring a continuous opioid analgesic as per the Investigator or Sub-investigator * Participants with an average pain intensity of 50 millimeter or more on the Visual Analog Scale in 24-hour daily living prior to informed consent * Participants who can be hospitalized to the 4th day after the initiation of titration period
Exclusion criteria
* Participants who had an operation that may affect the assessment within 30 days before informed consent * Participants whose main cause of the pain to be assessed is considered attributable to psychogenic pain (physical pain that is caused, increased, or prolonged by mental, emotional, or behavioral factors) * Participants with asthma, bradyarrhythmia (slow irregular heart beat) and severe respiratory function disorders * Participants complicated with hepatic dysfunction 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 a history of hypersensitivity to fentanyl and other opioid analgesics
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time From the Initial Day of Application in Double-Blind Period to Withdrawal Because of Insufficient Analgesic Efficacy | Day 1 up to Day 85 (double-blind period) and Day 92 (discontinuation of the study) | Time from start of double-blind (researchers and participants were unaware of the treatment) period to withdrawal because of insufficient analgesic efficacy based on any of the pre-defined discontinuation criteria was noted. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pain Visual Analog Scale (VAS) Score - Titration Period | Day 12-14 (Screening period) and Day 27-29 (Titration period) | The intensity of average pain (degree of pain) felt by the participants in daily living throughout the day on a 100-millimeter (mm) VAS scale by drawing a slash. The left margin (0 mm) was considered No pain at all, and the right margin (100 mm) was considered Severer pain than this is inconceivable. The length (mm) from the left margin to the slash is measured. Mean VAS score during 3 days before the end of Screening period and during 3 days before the end of titration period was reported. |
| Pain Visual Analog Scale (VAS) Score - Double-Blind Period | Day 27-29 (Titration period) and Day 83-85 (double-blind period) | The intensity of average pain (degree of pain) felt by the participants in daily living throughout the day on a 100-millimeter (mm) VAS scale by drawing a slash. The left margin (0 mm) was considered No pain at all, and the right margin (100 mm) was considered Severer pain than this is inconceivable. The length (mm) from the left margin to the slash is measured. Mean VAS score during 3 days before the end of titration period and during 3 days before the end of double-blind period was reported. |
| Number of Participants Evaluated as Per Participant's Overall Assessment - Titration Period | Day 1 and 29 or final evaluation (Titration period) | The participant assessed his/her satisfaction with the therapeutic efficacy by the following 5 grades: Extremely satisfied, Satisfied, Neither satisfied nor dissatisfied, Dissatisfied and Dissatisfied very much. The results were reported as Category 1 = At least Neither satisfied nor dissatisfied, which included participants with general evaluation of Extremely satisfied to Neither satisfied nor dissatisfied, and Category 2 = At least Satisfied, which included participants with general evaluation of Extremely satisfied to Satisfied. |
| Number of Participants Evaluated as Per Participant's Overall Assessment - Double-Blind Period | Day 1 and 85 or final evaluation (double-blind period) | The participant assessed his/her satisfaction with the therapeutic efficacy by the following 5 grades: Extremely satisfied, Satisfied, Neither satisfied nor dissatisfied, Dissatisfied and Dissatisfied very much. The results were reported as Category 1 = At least Neither satisfied nor dissatisfied, which included participants with general evaluation of Extremely satisfied to Neither satisfied nor dissatisfied, and Category 2 = At least Satisfied, which included participants with general evaluation of Extremely satisfied to Satisfied. |
| Number of Doses of Rescue Treatment Per Day - Titration Period | Day 1 and 29 or final evaluation (Titration period) | If a breakthrough pain occurred or the analgesic efficacy became insufficient, a fast-acting oral morphine was administered. At such instances, one-time dose of the rescue treatment was administered as per the pre-defined criteria. During hospitalization, Investigator, Sub-investigator or Study Collaborator recorded in the medical record and during the out-patient period, the participants were instructed to describe the name of rescue treatment, date and time of treatment, and one-time dose in the participant's diary. |
| Brief Pain Inventory Short Form (BPI-sf) Score - Double-Blind Period | Day 1 and 85 or final evaluation (double-blind period) | The BPI-sf total score is an average of the pain interference score (mean value for the nine BPI-sf questions \[questions inquiring about the extent of interference with activities by pain, where the extent is ranked from 0 (does not interfere) to 10 (completely interferes)\]) and pain subscale score (mean value for the scores for BPI-sf questions 3, 4, 5 and 6 \[questions inquiring about the extent of pain, where the extent is ranked from 0 (no pain) to 10 (pain as bad as you can imagine)\]). Total score ranges from 0 to 10 with higher values indicating more pain. |
| Brief Pain Inventory Short Form (BPI-sf) Score - Titration Period | Day 1 and 29 or final evaluation (Titration period) | The BPI-sf total score is an average of the pain interference score (mean value for the nine BPI-sf questions \[questions inquiring about the extent of interference with activities by pain, where the extent is ranked from 0 (does not interfere) to 10 (completely interferes)\]) and pain subscale score (mean value for the scores for BPI-sf questions 3, 4, 5 and 6 \[questions inquiring about the extent of pain, where the extent is ranked from 0 (no pain) to 10 (pain as bad as you can imagine)\]). Total score ranges from 0 to 10 with higher values indicating more pain. |
| Short-Form 36-Item Health Survey Version 2.0 (SF-36v2) Score - Titration Period | Day 1 and 29 or final evaluation (Titration period) | The SF-36v2 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. |
| Short-Form 36-Item Health Survey Version 2.0 (SF-36v2) Score - Double-Blind Period | Day 1 and 85 or final evaluation (double-blind period) | The SF-36v2 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. |
| Number of Participants Evaluated as Per Physician's Overall Assessment - Titration Period | Day 29 or final evaluation (Titration period) | Physician's global assessment of therapeutic efficacy (effectiveness) of the study drug was measured on a 2-point scale where 1 = effective and 2 = not effective. |
| Number of Participants Evaluated as Per Physician's Overall Assessment - Double-Blind Period | Day 1 and 85 or final evaluation (double-blind period) | Physician's global assessment of therapeutic efficacy (effectiveness) of the study drug was measured on a 2-point scale where 1 = effective and 2 = not effective. |
| Number of Doses of Rescue Treatment Per Day - Double-Blind Period | Day 1 and 85 or final evaluation (double-blind period) | If a breakthrough pain occurred or the analgesic efficacy became insufficient, a fast-acting oral morphine was administered. At such instances, one-time dose of the rescue treatment was administered as per the pre-defined criteria. During hospitalization, Investigator, Sub-investigator or Study Collaborator recorded in the medical record and during the out-patient period, the participants were instructed to describe the name of rescue treatment, date and time of treatment, and one-time dose in the participant's diary. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Fentanyl (Titration Period) One-day adhesive transdermal patch (patch containing a drug that is put on the skin so the drug will enter the body through the skin) containing fentanyl (JNS020QD) applied to chest, abdomen, upper arm or thigh and replaced every day, starting at the dose of 12.5 microgram per hour (mcg/hr) for at least first 2 days, which was increased by 12.5 mcg/hr at one time based on the medical examination of number of rescue treatments and visual analog scale (VAS) of the participants. The dose was increased up to maximum of 50 mcg/hr. The treatment was continued for 10-29 days and then the eligible participants from this group were randomly assigned to either of the two groups in the double-blind period. | 258 |
| Total | 258 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Period 1 (Titration Period) | Adverse Event | 33 | 0 | 0 |
| Period 1 (Titration Period) | Determined to increase dosage | 3 | 0 | 0 |
| Period 1 (Titration Period) | Not appropriate for this study | 1 | 0 | 0 |
| Period 1 (Titration Period) | Not satisfied criteria to enter Period 2 | 50 | 0 | 0 |
| Period 1 (Titration Period) | Physician Decision | 2 | 0 | 0 |
| Period 1 (Titration Period) | Withdrawal by Subject | 6 | 0 | 0 |
| Period 2 (Double-Blind Period) | Adverse Event | 0 | 14 | 4 |
| Period 2 (Double-Blind Period) | Impossible to perform required tests | 0 | 1 | 0 |
| Period 2 (Double-Blind Period) | Insufficient analgesic efficacy | 0 | 1 | 4 |
| Period 2 (Double-Blind Period) | More than 15mm increase in Mean VAS | 0 | 18 | 35 |
| Period 2 (Double-Blind Period) | More than 3 times a day rescue treatment | 0 | 0 | 1 |
| Period 2 (Double-Blind Period) | Physician Decision | 0 | 1 | 2 |
| Period 2 (Double-Blind Period) | Rescue drugs increased more than 1 times | 0 | 0 | 3 |
| Period 2 (Double-Blind Period) | Withdrawal by Subject | 0 | 2 | 2 |
Baseline characteristics
| Characteristic | Fentanyl (Titration Period) |
|---|---|
| Age Continuous | 66.5 Years STANDARD_DEVIATION 13.89 |
| Sex: Female, Male Female | 124 Participants |
| Sex: Female, Male Male | 134 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 231 / 258 | 71 / 84 | 56 / 79 |
| serious Total, serious adverse events | 13 / 258 | 8 / 84 | 4 / 79 |
Outcome results
Primary
Time From the Initial Day of Application in Double-Blind Period to Withdrawal Because of Insufficient Analgesic Efficacy
Time from start of double-blind (researchers and participants were unaware of the treatment) period to withdrawal because of insufficient analgesic efficacy based on any of the pre-defined discontinuation criteria was noted.
Time frame: Day 1 up to Day 85 (double-blind period) and Day 92 (discontinuation of the study)
Population: Full analysis set (FAS) population included all the randomly assigned participants with the exception of participants with pre-defined criteria.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fentanyl (Double-blind Period) | Time From the Initial Day of Application in Double-Blind Period to Withdrawal Because of Insufficient Analgesic Efficacy | NA Days |
| Placebo (Double-blind Period) | Time From the Initial Day of Application in Double-Blind Period to Withdrawal Because of Insufficient Analgesic Efficacy | 45.0 Days |
p-value: 0.0003Log Rank
Secondary
Brief Pain Inventory Short Form (BPI-sf) Score - Double-Blind Period
The BPI-sf total score is an average of the pain interference score (mean value for the nine BPI-sf questions \[questions inquiring about the extent of interference with activities by pain, where the extent is ranked from 0 (does not interfere) to 10 (completely interferes)\]) and pain subscale score (mean value for the scores for BPI-sf questions 3, 4, 5 and 6 \[questions inquiring about the extent of pain, where the extent is ranked from 0 (no pain) to 10 (pain as bad as you can imagine)\]). Total score ranges from 0 to 10 with higher values indicating more pain.
Time frame: Day 1 and 85 or final evaluation (double-blind period)
Population: The FAS population included all the randomly assigned participants with the exception of participants with pre-defined criteria. 'N' (number of participants analyzed) = participants evaluable for this measure and 'n' = participants evaluable for this measure at given time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fentanyl (Double-blind Period) | Brief Pain Inventory Short Form (BPI-sf) Score - Double-Blind Period | Day 1 (n=84, 79) | 3.3 Units on a scale | Standard Deviation 1.64 |
| Fentanyl (Double-blind Period) | Brief Pain Inventory Short Form (BPI-sf) Score - Double-Blind Period | Day 85/Final evaluation (n=84, 79) | 3.5 Units on a scale | Standard Deviation 2.27 |
| Placebo (Double-blind Period) | Brief Pain Inventory Short Form (BPI-sf) Score - Double-Blind Period | Day 1 (n=84, 79) | 3.1 Units on a scale | Standard Deviation 1.47 |
| Placebo (Double-blind Period) | Brief Pain Inventory Short Form (BPI-sf) Score - Double-Blind Period | Day 85/Final evaluation (n=84, 79) | 3.7 Units on a scale | Standard Deviation 1.98 |
Secondary
Brief Pain Inventory Short Form (BPI-sf) Score - Titration Period
The BPI-sf total score is an average of the pain interference score (mean value for the nine BPI-sf questions \[questions inquiring about the extent of interference with activities by pain, where the extent is ranked from 0 (does not interfere) to 10 (completely interferes)\]) and pain subscale score (mean value for the scores for BPI-sf questions 3, 4, 5 and 6 \[questions inquiring about the extent of pain, where the extent is ranked from 0 (no pain) to 10 (pain as bad as you can imagine)\]). Total score ranges from 0 to 10 with higher values indicating more pain.
Time frame: Day 1 and 29 or final evaluation (Titration period)
Population: The FAS1 population included all the randomly assigned participants with the exception of participants with pre-defined criteria. 'N' (number of participants analyzed) = participants evaluable for this measure and 'n' = participants evaluable for this measure at given time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fentanyl (Double-blind Period) | Brief Pain Inventory Short Form (BPI-sf) Score - Titration Period | Day 1 (n=258) | 5.8 Units on a scale | Standard Deviation 1.66 |
| Fentanyl (Double-blind Period) | Brief Pain Inventory Short Form (BPI-sf) Score - Titration Period | Day 29/Final evaluation (n=257) | 3.9 Units on a scale | Standard Deviation 1.88 |
Secondary
Number of Doses of Rescue Treatment Per Day - Double-Blind Period
If a breakthrough pain occurred or the analgesic efficacy became insufficient, a fast-acting oral morphine was administered. At such instances, one-time dose of the rescue treatment was administered as per the pre-defined criteria. During hospitalization, Investigator, Sub-investigator or Study Collaborator recorded in the medical record and during the out-patient period, the participants were instructed to describe the name of rescue treatment, date and time of treatment, and one-time dose in the participant's diary.
Time frame: Day 1 and 85 or final evaluation (double-blind period)
Population: The FAS population included all the randomly assigned participants with the exception of participants with pre-defined criteria. 'N' (number of participants analyzed) = participants evaluable for this measure and 'n' = participants evaluable for this measure at given time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fentanyl (Double-blind Period) | Number of Doses of Rescue Treatment Per Day - Double-Blind Period | Day 1 (n=84, 79) | 0.1 Treatments per day | Standard Deviation 0.33 |
| Fentanyl (Double-blind Period) | Number of Doses of Rescue Treatment Per Day - Double-Blind Period | Day 85/Final evaluation (n=84, 79) | 0.4 Treatments per day | Standard Deviation 0.68 |
| Placebo (Double-blind Period) | Number of Doses of Rescue Treatment Per Day - Double-Blind Period | Day 1 (n=84, 79) | 0.1 Treatments per day | Standard Deviation 0.47 |
| Placebo (Double-blind Period) | Number of Doses of Rescue Treatment Per Day - Double-Blind Period | Day 85/Final evaluation (n=84, 79) | 0.7 Treatments per day | Standard Deviation 0.86 |
Secondary
Number of Doses of Rescue Treatment Per Day - Titration Period
If a breakthrough pain occurred or the analgesic efficacy became insufficient, a fast-acting oral morphine was administered. At such instances, one-time dose of the rescue treatment was administered as per the pre-defined criteria. During hospitalization, Investigator, Sub-investigator or Study Collaborator recorded in the medical record and during the out-patient period, the participants were instructed to describe the name of rescue treatment, date and time of treatment, and one-time dose in the participant's diary.
Time frame: Day 1 and 29 or final evaluation (Titration period)
Population: The FAS1 population included all the randomly assigned participants with the exception of participants with pre-defined criteria. 'N' (number of participants analyzed) = participants evaluable for this measure and 'n' = participants evaluable for this measure at given time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fentanyl (Double-blind Period) | Number of Doses of Rescue Treatment Per Day - Titration Period | Day 1 (n=258) | 0.1 Treatments per day | Standard Deviation 0.41 |
| Fentanyl (Double-blind Period) | Number of Doses of Rescue Treatment Per Day - Titration Period | Day 29/Final evaluation (n=258) | 0.5 Treatments per day | Standard Deviation 0.72 |
Secondary
Number of Participants Evaluated as Per Participant's Overall Assessment - Double-Blind Period
The participant assessed his/her satisfaction with the therapeutic efficacy by the following 5 grades: Extremely satisfied, Satisfied, Neither satisfied nor dissatisfied, Dissatisfied and Dissatisfied very much. The results were reported as Category 1 = At least Neither satisfied nor dissatisfied, which included participants with general evaluation of Extremely satisfied to Neither satisfied nor dissatisfied, and Category 2 = At least Satisfied, which included participants with general evaluation of Extremely satisfied to Satisfied.
Time frame: Day 1 and 85 or final evaluation (double-blind period)
Population: The FAS population included all the randomly assigned participants with the exception of participants with pre-defined criteria. 'N' (number of participants analyzed) = participants evaluable for this measure and 'n' = participants evaluable for this measure at given time points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fentanyl (Double-blind Period) | Number of Participants Evaluated as Per Participant's Overall Assessment - Double-Blind Period | Day 1, Category 1 (n=84, 79) | 82 Participants |
| Fentanyl (Double-blind Period) | Number of Participants Evaluated as Per Participant's Overall Assessment - Double-Blind Period | Day 1, Category 2 (n=84, 79) | 61 Participants |
| Fentanyl (Double-blind Period) | Number of Participants Evaluated as Per Participant's Overall Assessment - Double-Blind Period | Day 85/Final evaluation, Category 1 (n=84, 78) | 69 Participants |
| Fentanyl (Double-blind Period) | Number of Participants Evaluated as Per Participant's Overall Assessment - Double-Blind Period | Day 85/Final evaluation, Category 2 (n=84, 78) | 49 Participants |
| Placebo (Double-blind Period) | Number of Participants Evaluated as Per Participant's Overall Assessment - Double-Blind Period | Day 85/Final evaluation, Category 2 (n=84, 78) | 32 Participants |
| Placebo (Double-blind Period) | Number of Participants Evaluated as Per Participant's Overall Assessment - Double-Blind Period | Day 1, Category 1 (n=84, 79) | 79 Participants |
| Placebo (Double-blind Period) | Number of Participants Evaluated as Per Participant's Overall Assessment - Double-Blind Period | Day 85/Final evaluation, Category 1 (n=84, 78) | 56 Participants |
| Placebo (Double-blind Period) | Number of Participants Evaluated as Per Participant's Overall Assessment - Double-Blind Period | Day 1, Category 2 (n=84, 79) | 67 Participants |
Secondary
Number of Participants Evaluated as Per Participant's Overall Assessment - Titration Period
The participant assessed his/her satisfaction with the therapeutic efficacy by the following 5 grades: Extremely satisfied, Satisfied, Neither satisfied nor dissatisfied, Dissatisfied and Dissatisfied very much. The results were reported as Category 1 = At least Neither satisfied nor dissatisfied, which included participants with general evaluation of Extremely satisfied to Neither satisfied nor dissatisfied, and Category 2 = At least Satisfied, which included participants with general evaluation of Extremely satisfied to Satisfied.
Time frame: Day 1 and 29 or final evaluation (Titration period)
Population: The FAS1 population included all the randomly assigned participants with the exception of participants with pre-defined criteria. 'N' (number of participants analyzed) = participants evaluable for this measure and 'n' = participants evaluable for this measure at given time points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fentanyl (Double-blind Period) | Number of Participants Evaluated as Per Participant's Overall Assessment - Titration Period | Day 1, Category 1 (n=258) | 85 Participants |
| Fentanyl (Double-blind Period) | Number of Participants Evaluated as Per Participant's Overall Assessment - Titration Period | Day 1, Category 2 (n=258) | 15 Participants |
| Fentanyl (Double-blind Period) | Number of Participants Evaluated as Per Participant's Overall Assessment - Titration Period | Day 29/Final evaluation, Category 1 (n=257) | 220 Participants |
| Fentanyl (Double-blind Period) | Number of Participants Evaluated as Per Participant's Overall Assessment - Titration Period | Day 29/ Final evaluation, Category 2 (n=257) | 146 Participants |
Secondary
Number of Participants Evaluated as Per Physician's Overall Assessment - Double-Blind Period
Physician's global assessment of therapeutic efficacy (effectiveness) of the study drug was measured on a 2-point scale where 1 = effective and 2 = not effective.
Time frame: Day 1 and 85 or final evaluation (double-blind period)
Population: The FAS population included all the randomly assigned participants with the exception of participants with pre-defined criteria. 'N' (number of participants analyzed) = participants evaluable for this measure and 'n' = participants evaluable for this measure at given time points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fentanyl (Double-blind Period) | Number of Participants Evaluated as Per Physician's Overall Assessment - Double-Blind Period | Day 1, Effective (n= 84, 79) | 84 Participants |
| Fentanyl (Double-blind Period) | Number of Participants Evaluated as Per Physician's Overall Assessment - Double-Blind Period | Day 1, Ineffective (n= 84, 79) | 0 Participants |
| Fentanyl (Double-blind Period) | Number of Participants Evaluated as Per Physician's Overall Assessment - Double-Blind Period | Day 85/Final evaluation, Effective (n= 84, 79) | 70 Participants |
| Fentanyl (Double-blind Period) | Number of Participants Evaluated as Per Physician's Overall Assessment - Double-Blind Period | Day 85/Final evaluation, Ineffective (n= 84, 79) | 14 Participants |
| Placebo (Double-blind Period) | Number of Participants Evaluated as Per Physician's Overall Assessment - Double-Blind Period | Day 85/Final evaluation, Ineffective (n= 84, 79) | 32 Participants |
| Placebo (Double-blind Period) | Number of Participants Evaluated as Per Physician's Overall Assessment - Double-Blind Period | Day 1, Effective (n= 84, 79) | 79 Participants |
| Placebo (Double-blind Period) | Number of Participants Evaluated as Per Physician's Overall Assessment - Double-Blind Period | Day 85/Final evaluation, Effective (n= 84, 79) | 47 Participants |
| Placebo (Double-blind Period) | Number of Participants Evaluated as Per Physician's Overall Assessment - Double-Blind Period | Day 1, Ineffective (n= 84, 79) | 0 Participants |
Secondary
Number of Participants Evaluated as Per Physician's Overall Assessment - Titration Period
Physician's global assessment of therapeutic efficacy (effectiveness) of the study drug was measured on a 2-point scale where 1 = effective and 2 = not effective.
Time frame: Day 29 or final evaluation (Titration period)
Population: The FAS1 population included all the randomly assigned participants with the exception of participants with pre-defined criteria.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fentanyl (Double-blind Period) | Number of Participants Evaluated as Per Physician's Overall Assessment - Titration Period | Effective | 214 Participants |
| Fentanyl (Double-blind Period) | Number of Participants Evaluated as Per Physician's Overall Assessment - Titration Period | Ineffective | 44 Participants |
Secondary
Pain Visual Analog Scale (VAS) Score - Double-Blind Period
The intensity of average pain (degree of pain) felt by the participants in daily living throughout the day on a 100-millimeter (mm) VAS scale by drawing a slash. The left margin (0 mm) was considered No pain at all, and the right margin (100 mm) was considered Severer pain than this is inconceivable. The length (mm) from the left margin to the slash is measured. Mean VAS score during 3 days before the end of titration period and during 3 days before the end of double-blind period was reported.
Time frame: Day 27-29 (Titration period) and Day 83-85 (double-blind period)
Population: The FAS population included all the randomly assigned participants with the exception of participants with pre-defined criteria. 'N' (number of participants analyzed) = participants evaluable for this measure and 'n' = participants evaluable for this measure at given time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fentanyl (Double-blind Period) | Pain Visual Analog Scale (VAS) Score - Double-Blind Period | Baseline (n=84, 79) | 30.1 mm | Standard Deviation 11.5 |
| Fentanyl (Double-blind Period) | Pain Visual Analog Scale (VAS) Score - Double-Blind Period | Last 3 days in double-blind period (n=83, 79) | 29.6 mm | Standard Deviation 21.71 |
| Placebo (Double-blind Period) | Pain Visual Analog Scale (VAS) Score - Double-Blind Period | Baseline (n=84, 79) | 27.5 mm | Standard Deviation 11.23 |
| Placebo (Double-blind Period) | Pain Visual Analog Scale (VAS) Score - Double-Blind Period | Last 3 days in double-blind period (n=83, 79) | 37.1 mm | Standard Deviation 20.19 |
Secondary
Pain Visual Analog Scale (VAS) Score - Titration Period
The intensity of average pain (degree of pain) felt by the participants in daily living throughout the day on a 100-millimeter (mm) VAS scale by drawing a slash. The left margin (0 mm) was considered No pain at all, and the right margin (100 mm) was considered Severer pain than this is inconceivable. The length (mm) from the left margin to the slash is measured. Mean VAS score during 3 days before the end of Screening period and during 3 days before the end of titration period was reported.
Time frame: Day 12-14 (Screening period) and Day 27-29 (Titration period)
Population: Full analysis set in Period 1 (FAS1) population included all the randomly assigned participants with the exception of participants with pre-defined criteria. 'N' (number of participants analyzed) = participants evaluable for this measure and 'n' = participants evaluable for this measure at given time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fentanyl (Double-blind Period) | Pain Visual Analog Scale (VAS) Score - Titration Period | Baseline (n=258) | 73.5 mm | Standard Deviation 12.81 |
| Fentanyl (Double-blind Period) | Pain Visual Analog Scale (VAS) Score - Titration Period | Last 3 days in titration period (n=257) | 39.5 mm | Standard Deviation 20.02 |
Secondary
Short-Form 36-Item Health Survey Version 2.0 (SF-36v2) Score - Double-Blind Period
The SF-36v2 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: Day 1 and 85 or final evaluation (double-blind period)
Population: The FAS population included all the randomly assigned participants with the exception of participants with pre-defined criteria. 'N' (number of participants analyzed) = participants evaluable for this measure and 'n' = participants evaluable for this measure at given time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fentanyl (Double-blind Period) | Short-Form 36-Item Health Survey Version 2.0 (SF-36v2) Score - Double-Blind Period | Day 1, Mental Component Score (n=84, 79) | 47.3 Units on a scale | Standard Deviation 9.22 |
| Fentanyl (Double-blind Period) | Short-Form 36-Item Health Survey Version 2.0 (SF-36v2) Score - Double-Blind Period | Day 1, Physical Component Score (n=84, 79) | 28.0 Units on a scale | Standard Deviation 16.97 |
| Fentanyl (Double-blind Period) | Short-Form 36-Item Health Survey Version 2.0 (SF-36v2) Score - Double-Blind Period | Day 85/Final, Physical Component Score (n=84, 79) | 29.9 Units on a scale | Standard Deviation 17.39 |
| Fentanyl (Double-blind Period) | Short-Form 36-Item Health Survey Version 2.0 (SF-36v2) Score - Double-Blind Period | Day 85/Final, Mental Component Score (n=84, 79) | 47.1 Units on a scale | Standard Deviation 11.07 |
| Placebo (Double-blind Period) | Short-Form 36-Item Health Survey Version 2.0 (SF-36v2) Score - Double-Blind Period | Day 85/Final, Mental Component Score (n=84, 79) | 47.2 Units on a scale | Standard Deviation 9.61 |
| Placebo (Double-blind Period) | Short-Form 36-Item Health Survey Version 2.0 (SF-36v2) Score - Double-Blind Period | Day 85/Final, Physical Component Score (n=84, 79) | 27.6 Units on a scale | Standard Deviation 16.24 |
| Placebo (Double-blind Period) | Short-Form 36-Item Health Survey Version 2.0 (SF-36v2) Score - Double-Blind Period | Day 1, Physical Component Score (n=84, 79) | 29.4 Units on a scale | Standard Deviation 16.98 |
| Placebo (Double-blind Period) | Short-Form 36-Item Health Survey Version 2.0 (SF-36v2) Score - Double-Blind Period | Day 1, Mental Component Score (n=84, 79) | 47.7 Units on a scale | Standard Deviation 8.89 |
Secondary
Short-Form 36-Item Health Survey Version 2.0 (SF-36v2) Score - Titration Period
The SF-36v2 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: Day 1 and 29 or final evaluation (Titration period)
Population: The FAS1 population included all the randomly assigned participants with the exception of participants with pre-defined criteria. 'N' (number of participants analyzed) = participants evaluable for this measure and 'n' = participants evaluable for this measure at given time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fentanyl (Double-blind Period) | Short-Form 36-Item Health Survey Version 2.0 (SF-36v2) Score - Titration Period | Day 29/Final, Physical Component Score (n=257) | 26.0 Units on a scale | Standard Deviation 17.55 |
| Fentanyl (Double-blind Period) | Short-Form 36-Item Health Survey Version 2.0 (SF-36v2) Score - Titration Period | Day 1, Physical Component Score (n=258) | 23.1 Units on a scale | Standard Deviation 16.67 |
| Fentanyl (Double-blind Period) | Short-Form 36-Item Health Survey Version 2.0 (SF-36v2) Score - Titration Period | Day 1, Mental Component Score (n=258) | 41.7 Units on a scale | Standard Deviation 9.75 |
| Fentanyl (Double-blind Period) | Short-Form 36-Item Health Survey Version 2.0 (SF-36v2) Score - Titration Period | Day 29/Final, Mental Component Score (n=257) | 45.8 Units on a scale | Standard Deviation 9.77 |