A Confirmatory Study of Fentanyl in Participants With Osteoarthritis or Low Back Pain
Sponsor
Janssen Pharmaceutical K.K. (Industry)
Overall Status
Completed
CT.gov ID
NCT01008618
Collaborator
(none)
218
59
3
13
3.7
0.3
Study Details
Study Description
Brief Summary
The purpose of this study is to evaluate efficacy and safety of fentanyl in opioid-naive participants with osteoarthritis (disorder, which is seen mostly in older persons, in which the joints become painful and stuff) or low back pain who cannot obtain a sufficient analgesic effect by the treatment of non-opioid analgesics (drug used to control pain).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
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 osteoarthritis or low back pain. 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, 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 per hour (mcg/hr) 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.
Study Design
Study Type:
Interventional
Actual Enrollment
:
218 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Verification Study of JNS020QD in Patients With Osteoarthritis or Low Back Pain
Study Start Date
:
Jan 1, 2009
Actual Primary Completion Date
:
Feb 1, 2010
Actual Study Completion Date
:
Feb 1, 2010
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Fentanyl (Titration period) One-day adhesive transdermal patch containing fentanyl (JNS020QD) applied to chest, abdomen, upper arm and thigh and replaced every day, starting at the dose of 12.5 microgram per hour (mcg/hr) for at least first 2 days, which will be increased by 12.5 mcg/hr at one time based on the medical examination of number of rescue treatments and visual analog scale (VAS) score of the participants. The dose will be increased up to maximum of 50 mcg/hr. The treatment will be continued for 10-29 days and then the eligible participants from this group will be randomly assigned to either of the two groups in the double-blind period. |
Drug: Fentanyl
One-day adhesive transdermal patch containing fentanyl 12.5 to 50 mcg/hr applied to chest, abdomen, upper arm or thigh and replaced every day.
|
| Experimental: Fentanyl (Double-blind period) Participants meeting the pre-defined criteria for transfer from titration period to double-blind period and randomly assigned to fentanyl group, will be administered one-day adhesive transdermal patch containing fentanyl, applied to chest, abdomen, upper arm and thigh and replaced every day, the dose of which will be same as the final application dose in the titration period (in the range of 12.5 to 50 mcg/hr). The treatment will be continued for 12 weeks. |
Drug: Fentanyl
One-day adhesive transdermal patch containing fentanyl 12.5 to 50 mcg/hr applied to chest, abdomen, upper arm or thigh and replaced every day.
|
| Placebo Comparator: Placebo (Double-blind period) Participants meeting the pre-defined criteria for transfer from titration period to double-blind period and randomly assigned to placebo group, will be administered one-day adhesive transdermal placebo patch indistinguishable from fentanyl in appearance, applied to chest, abdomen, upper arm and thigh and replaced every day. The dose of fentanyl (from titration period) will be gradually decreased to prevent withdrawal symptoms and the dose of the matching placebo will be gradually increased up to same dose as the final application dose in the titration period (in the range of 12.5 to 50 mcg/hr). The treatment will continue for 12 weeks. |
Drug: Placebo
Placebo patch indistinguishable from one-day adhesive transdermal patch containing fentanyl 12.5 to 50 mcg/hr applied to chest, abdomen, upper arm or thigh and replaced every day.
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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. The mean number of treatments per day at each assessment time was reported.
- 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. The mean number of treatments per day at each assessment time was reported.
- 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.
- 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.
- Short-Form 36-Item Health Survey Version 2.0 (SF-36v2) - 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) - 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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
20 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Participants whose pain because of osteoarthritis or low back pain 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 participant at a certain dose (except the use on an as-needed base) on consecutive days
-
Participants showing insufficient therapeutic efficacy of the non-opioid analgesic currently being used, and 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 (VAS) 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:
-
In cases of low back pain, participants with severe pain of lower extremities due to radiculopathy (a problem in which one or more nerves are affected) than that of low back pain, or participants with disc herniation (a medical condition affecting the spine due to trauma, lifting injuries, or idiopathic [unknown] causes) requiring an operation
-
In cases of low back pain, participants with pain due to compression fracture
-
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Aki | Japan | |||
| 2 | Ako | Japan | |||
| 3 | Amagasaki | Japan | |||
| 4 | Anan | Japan | |||
| 5 | Annaka | Japan | |||
| 6 | Chiba | Japan | |||
| 7 | Chiisagata | Japan | |||
| 8 | Fuchu | Japan | |||
| 9 | Fukuoka | Japan | |||
| 10 | Fukuyama | Japan | |||
| 11 | Hamamatsu | Japan | |||
| 12 | Hiki | Japan | |||
| 13 | Himeji | Japan | |||
| 14 | Hiratsuka | Japan | |||
| 15 | Hitachinaka | Japan | |||
| 16 | Ichikawa N/A | Japan | |||
| 17 | Ikeda N/A | Japan | |||
| 18 | Ikoma | Japan | |||
| 19 | Ito | Japan | |||
| 20 | Izumo | Japan | |||
| 21 | Kagoshima | Japan | |||
| 22 | Kanazawa | Japan | |||
| 23 | Kasama | Japan | |||
| 24 | Kitakyushu | Japan | |||
| 25 | Kochi | Japan | |||
| 26 | Koga | Japan | |||
| 27 | Komatsu | Japan | |||
| 28 | Kure | Japan | |||
| 29 | Kurume | Japan | |||
| 30 | Kyoto | Japan | |||
| 31 | Maebaru | Japan | |||
| 32 | Matsudo | Japan | |||
| 33 | Matsumoto | Japan | |||
| 34 | Miyazaki | Japan | |||
| 35 | Nagano | Japan | |||
| 36 | Nagoya | Japan | |||
| 37 | Niihama | Japan | |||
| 38 | Ohkawa | Japan | |||
| 39 | Ohmuta | Japan | |||
| 40 | Ohta-Ku | Japan | |||
| 41 | Ohtsu | Japan | |||
| 42 | Oita | Japan | |||
| 43 | Osaka | Japan | |||
| 44 | Otaru | Japan | |||
| 45 | Sagamihara | Japan | |||
| 46 | Saga | Japan | |||
| 47 | Sapporo | Japan | |||
| 48 | Sendai | Japan | |||
| 49 | Suginami-Ku | Japan | |||
| 50 | Takaoka | Japan | |||
| 51 | Takasaki | Japan | |||
| 52 | Takayama | Japan | |||
| 53 | Tatebayashi | Japan | |||
| 54 | Tokushima N/A | Japan | |||
| 55 | Tokyo | Japan | |||
| 56 | Toshima-Ku | Japan | |||
| 57 | Toyama | Japan | |||
| 58 | Ube | Japan | |||
| 59 | Yokohama | Japan |
Sponsors and Collaborators
- Janssen Pharmaceutical K.K.
Investigators
- Study Director: Janssen Pharmaceutical K.K., Japan Clinical Trial, Janssen Pharmaceutical K.K.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Janssen Pharmaceutical K.K.
ClinicalTrials.gov Identifier:
NCT01008618
Other Study ID Numbers:
- CR015541
- JNS020QD-JPN-N01
First Posted:
Nov 6, 2009
Last Update Posted:
Dec 25, 2013
Last Verified:
Nov 1, 2013
Keywords provided by Janssen Pharmaceutical K.K.
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Fentanyl (Titration Period) | Fentanyl (Double-blind Period) | Placebo (Double-blind Period) |
|---|---|---|---|
| Arm/Group Description | 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. | Participants meeting the pre-defined criteria for transfer from titration period to double-blind period and randomly assigned to fentanyl group, were administered one-day adhesive transdermal patch containing fentanyl, applied to chest, abdomen, upper arm or thigh and replaced every day, the dose of which was same as the final application dose in the titration period (in the range of 12.5 to 50 mcg/hr). The treatment was continued for 12 weeks. | Participants meeting the pre-defined criteria for transfer from titration period to double-blind period and randomly assigned to placebo group, were administered one-day adhesive transdermal placebo patch indistinguishable from fentanyl in appearance, applied to chest, abdomen, upper arm or thigh and replaced every day. The dose of fentanyl (from titration period) was gradually decreased to prevent withdrawal symptoms and the dose of the matching placebo was gradually increased up to same dose as the final application dose in the titration period (in the range of 12.5 to 50 mcg/hr). The treatment was continued for 12 weeks. |
| Period Title: Period 1 (Titration Period) | |||
| STARTED | 218 | 0 | 0 |
| COMPLETED | 150 | 0 | 0 |
| NOT COMPLETED | 68 | 0 | 0 |
| Period Title: Period 1 (Titration Period) | |||
| STARTED | 0 | 73 | 77 |
| COMPLETED | 0 | 37 | 39 |
| NOT COMPLETED | 0 | 36 | 38 |
Baseline Characteristics
| Arm/Group Title | Fentanyl (Titration Period) |
|---|---|
| Arm/Group Description | 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. |
| Overall Participants | 218 |
| Age (Years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [Years] |
66.8
(13.09)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
145
66.5%
|
| Male |
73
33.5%
|
Outcome Measures
| Title | Time From the Initial Day of Application in Double-Blind Period to Withdrawal Because of Insufficient Analgesic Efficacy |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set (FAS) population included all the randomly assigned participants with the exception of participants with pre-defined criteria. |
| Arm/Group Title | Fentanyl (Double-blind Period) | Placebo (Double-blind Period) |
|---|---|---|
| Arm/Group Description | Participants meeting the pre-defined criteria for transfer from titration period to double-blind period and randomly assigned to fentanyl group, were administered one-day adhesive transdermal patch containing fentanyl, applied to chest, abdomen, upper arm and thigh and replaced every day, the dose of which was same as the final application dose in the titration period (in the range of 12.5 to 50 mcg/hr). The treatment was continued for 12 weeks. | Participants meeting the pre-defined criteria for transfer from titration period to double-blind period and randomly assigned to placebo group, were administered one-day adhesive transdermal placebo patch indistinguishable from fentanyl in appearance, applied to chest, abdomen, upper arm and thigh and replaced every day. The dose of fentanyl (from titration period) was gradually decreased to prevent withdrawal symptoms and the dose of the matching placebo was gradually increased up to same dose as the final application dose in the titration period (in the range of 12.5 to 50 mcg/hr). The treatment was continued for 12 weeks. |
| Measure Participants | 73 | 77 |
| Median (95% Confidence Interval) [Days] |
NA
|
NA
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Fentanyl (Double-blind Period), Placebo (Double-blind Period) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0846 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Title | Pain Visual Analog Scale (VAS) Score - Titration Period |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Fentanyl (Titration Period) |
|---|---|
| Arm/Group Description | 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 and 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) score 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. |
| Measure Participants | 218 |
| Last 3 days in Screening period (n=218) |
74.1
(12.37)
|
| Last 3 days in titration period (n=216) |
39.71
(21.41)
|
| Title | Pain Visual Analog Scale (VAS) Score - Double-Blind Period |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Fentanyl (Double-blind Period) | Placebo (Double-blind Period) |
|---|---|---|
| Arm/Group Description | Participants meeting the pre-defined criteria for transfer from titration period to double-blind period and randomly assigned to fentanyl group, were administered one-day adhesive transdermal patch containing fentanyl, applied to chest, abdomen, upper arm and thigh and replaced every day, the dose of which was same as the final application dose in the titration period (in the range of 12.5 to 50 mcg/hr). The treatment was continued for 12 weeks. | Participants meeting the pre-defined criteria for transfer from titration period to double-blind period and randomly assigned to placebo group, were administered one-day adhesive transdermal placebo patch indistinguishable from fentanyl in appearance, applied to chest, abdomen, upper arm and thigh and replaced every day. The dose of fentanyl (from titration period) was gradually decreased to prevent withdrawal symptoms and the dose of the matching placebo was gradually increased up to same dose as the final application dose in the titration period (in the range of 12.5 to 50 mcg/hr). The treatment was continued for 12 weeks. |
| Measure Participants | 73 | 77 |
| Last 3 days in titration period (n=73, 77) |
28.9
(12.71)
|
29.6
(12.05)
|
| Last 3 days in double-blind period (n=72, 77) |
28.9
(18.99)
|
36.5
(22.29)
|
| Title | Number of Participants Evaluated as Per Participant's Overall Assessment - Titration Period |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Fentanyl (Titration Period) |
|---|---|
| Arm/Group Description | One-day adhesive transdermal patch containing fentanyl applied to chest, abdomen, upper arm and thigh and replaced every day, starting at the dose of 12.5 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 VAS score 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. |
| Measure Participants | 218 |
| Day 1, Category 1 (n=218) |
77
35.3%
|
| Day 1, Category 2 (n=218) |
11
5%
|
| Day 29/Final evaluation, Category 1 (n=218) |
183
83.9%
|
| Day 29/ Final evaluation, Category 2 (n=218) |
124
56.9%
|
| Title | Number of Participants Evaluated as Per Participant's Overall Assessment - Double-Blind Period |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Fentanyl (Double-blind Period) | Placebo (Double-blind Period) |
|---|---|---|
| Arm/Group Description | Participants meeting the pre-defined criteria for transfer from titration period to double-blind period and randomly assigned to fentanyl group, were administered one-day adhesive transdermal patch containing fentanyl, applied to chest, abdomen, upper arm and thigh and replaced every day, the dose of which was same as the final application dose in the titration period (in the range of 12.5 to 50 mcg/hr). The treatment was continued for 12 weeks. | Participants meeting the pre-defined criteria for transfer from titration period to double-blind period and randomly assigned to placebo group, were administered one-day adhesive transdermal placebo patch indistinguishable from fentanyl in appearance, applied to chest, abdomen, upper arm and thigh and replaced every day. The dose of fentanyl (from titration period) was gradually decreased to prevent withdrawal symptoms and the dose of the matching placebo was gradually increased up to same dose as the final application dose in the titration period (in the range of 12.5 to 50 mcg/hr). The treatment was continued for 12 weeks. |
| Measure Participants | 73 | 77 |
| Day 1, Category 1 (n=73, 77) |
71
32.6%
|
76
NaN
|
| Day 1, Category 2 (n=73, 77) |
57
26.1%
|
63
NaN
|
| Day 85/Final evaluation, Category 1 (n=73, 77) |
63
28.9%
|
56
NaN
|
| Day 85/Final evaluation, Category 2 (n=73, 77) |
42
19.3%
|
35
NaN
|
| Title | Number of Doses of Rescue Treatment Per Day - Titration Period |
|---|---|
| Description | 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. The mean number of treatments per day at each assessment time was reported. |
| Time Frame | Day 1 and 29 or final evaluation (Titration period) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Fentanyl (Titration Period) |
|---|---|
| Arm/Group Description | One-day adhesive transdermal patch containing fentanyl applied to chest, abdomen, upper arm and thigh and replaced every day, starting at the dose of 12.5 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 VAS score 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. |
| Measure Participants | 218 |
| Day 1 (n=218) |
0.0
(0.19)
|
| Day 29/Final evaluation (n=218) |
0.2
(0.45)
|
| Title | Number of Doses of Rescue Treatment Per Day - Double-Blind Period |
|---|---|
| Description | 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. The mean number of treatments per day at each assessment time was reported. |
| Time Frame | Day 1 and 85 or final evaluation (double-blind period) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Fentanyl (Double-blind Period) | Placebo (Double-blind Period) |
|---|---|---|
| Arm/Group Description | Participants meeting the pre-defined criteria for transfer from titration period to double-blind period and randomly assigned to fentanyl group, were administered one-day adhesive transdermal patch containing fentanyl, applied to chest, abdomen, upper arm and thigh and replaced every day, the dose of which was same as the final application dose in the titration period (in the range of 12.5 to 50 mcg/hr). The treatment was continued for 12 weeks. | Participants meeting the pre-defined criteria for transfer from titration period to double-blind period and randomly assigned to placebo group, were administered one-day adhesive transdermal placebo patch indistinguishable from fentanyl in appearance, applied to chest, abdomen, upper arm and thigh and replaced every day. The dose of fentanyl (from titration period) was gradually decreased to prevent withdrawal symptoms and the dose of the matching placebo was gradually increased up to same dose as the final application dose in the titration period (in the range of 12.5 to 50 mcg/hr). The treatment was continued for 12 weeks. |
| Measure Participants | 73 | 77 |
| Day 1 (n=73, 77) |
0.0
(0.16)
|
0.0
(0.11)
|
| Day 85/Final evaluation (n=72, 77) |
0.2
(0.49)
|
0.2
(0.42)
|
| Title | Brief Pain Inventory Short Form (BPI-sf) Score - Titration Period |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Fentanyl (Titration Period) |
|---|---|
| Arm/Group Description | One-day adhesive transdermal patch containing fentanyl applied to chest, abdomen, upper arm and thigh and replaced every day, starting at the dose of 12.5 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 VAS score 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. |
| Measure Participants | 218 |
| Day 1 (n=218) |
5.9
(1.66)
|
| Day 29/Final evaluation (n=217) |
4.0
(2.19)
|
| Title | Brief Pain Inventory Short Form (BPI-sf) Score - Double-Blind Period |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Fentanyl (Double-blind Period) | Placebo (Double-blind Period) |
|---|---|---|
| Arm/Group Description | Participants meeting the pre-defined criteria for transfer from titration period to double-blind period and randomly assigned to fentanyl group, were administered one-day adhesive transdermal patch containing fentanyl, applied to chest, abdomen, upper arm and thigh and replaced every day, the dose of which was same as the final application dose in the titration period (in the range of 12.5 to 50 mcg/hr). The treatment was continued for 12 weeks. | Participants meeting the pre-defined criteria for transfer from titration period to double-blind period and randomly assigned to placebo group, were administered one-day adhesive transdermal placebo patch indistinguishable from fentanyl in appearance, applied to chest, abdomen, upper arm and thigh and replaced every day. The dose of fentanyl (from titration period) was gradually decreased to prevent withdrawal symptoms and the dose of the matching placebo was gradually increased up to same dose as the final application dose in the titration period (in the range of 12.5 to 50 mcg/hr). The treatment was continued for 12 weeks. |
| Measure Participants | 73 | 77 |
| Day 1 (n=73, 77) |
3.2
(1.65)
|
3.2
(1.66)
|
| Day 85/Final evaluation (n=73, 77) |
3.2
(1.83)
|
3.9
(2.08)
|
| Title | Short-Form 36-Item Health Survey Version 2.0 (SF-36v2) - Titration Period |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Fentanyl (Titration Period) |
|---|---|
| Arm/Group Description | One-day adhesive transdermal patch containing fentanyl applied to chest, abdomen, upper arm and thigh and replaced every day, starting at the dose of 12.5 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 VAS score 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. |
| Measure Participants | 218 |
| Day 1, Physical Component Score (n=218) |
17.1
(14.91)
|
| Day 1, Mental Component Score (n=218) |
48.2
(9.92)
|
| Day 29/Final, Physical Component Score (n=217) |
23.3
(15.56)
|
| Day 29/Final, Mental Component Score (n=217) |
48.5
(9.57)
|
| Title | Short-Form 36-Item Health Survey Version 2.0 (SF-36v2) - Double-Blind Period: |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Fentanyl (Double-blind Period) | Placebo (Double-blind Period) |
|---|---|---|
| Arm/Group Description | Participants meeting the pre-defined criteria for transfer from titration period to double-blind period and randomly assigned to fentanyl group, were administered one-day adhesive transdermal patch containing fentanyl, applied to chest, abdomen, upper arm and thigh and replaced every day, the dose of which was same as the final application dose in the titration period (in the range of 12.5 to 50 mcg/hr). The treatment was continued for 12 weeks. | Participants meeting the pre-defined criteria for transfer from titration period to double-blind period and randomly assigned to placebo group, were administered one-day adhesive transdermal placebo patch indistinguishable from fentanyl in appearance, applied to chest, abdomen, upper arm and thigh and replaced every day. The dose of fentanyl (from titration period) was gradually decreased to prevent withdrawal symptoms and the dose of the matching placebo was gradually increased up to same dose as the final application dose in the titration period (in the range of 12.5 to 50 mcg/hr). The treatment was continued for 12 weeks. |
| Measure Participants | 73 | 77 |
| Day 1, Physical Component Score (n=73, 77) |
25.8
(14.71)
|
22.8
(14.30)
|
| Day 1, Mental Component Score (n=73, 77) |
50.1
(8.29)
|
50.8
(9.13)
|
| Day 85/Final, Physical Component Score (n=73, 77) |
24.3
(16.11)
|
22.5
(14.64)
|
| Day 85/Final, Mental Component Score (n=73, 77) |
49.9
(9.82)
|
51.0
(10.41)
|
| Title | Number of Participants Evaluated as Per Physician's Overall Assessment - Titration Period |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The FAS1 population included all the randomly assigned participants with the exception of participants with pre-defined criteria. |
| Arm/Group Title | Fentanyl (Titration Period) |
|---|---|
| Arm/Group Description | One-day adhesive transdermal patch containing fentanyl applied to chest, abdomen, upper arm and thigh and replaced every day, starting at the dose of 12.5 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 VAS score 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. |
| Measure Participants | 218 |
| Effective |
185
84.9%
|
| Ineffective |
33
15.1%
|
| Title | Number of Participants Evaluated as Per Physician's Overall Assessment - Double-Blind Period |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Fentanyl (Double-blind Period) | Placebo (Double-blind Period) |
|---|---|---|
| Arm/Group Description | Participants meeting the pre-defined criteria for transfer from titration period to double-blind period and randomly assigned to fentanyl group, were administered one-day adhesive transdermal patch containing fentanyl, applied to chest, abdomen, upper arm and thigh and replaced every day, the dose of which was same as the final application dose in the titration period (in the range of 12.5 to 50 mcg/hr). The treatment was continued for 12 weeks. | Participants meeting the pre-defined criteria for transfer from titration period to double-blind period and randomly assigned to placebo group, were administered one-day adhesive transdermal placebo patch indistinguishable from fentanyl in appearance, applied to chest, abdomen, upper arm and thigh and replaced every day. The dose of fentanyl (from titration period) was gradually decreased to prevent withdrawal symptoms and the dose of the matching placebo was gradually increased up to same dose as the final application dose in the titration period (in the range of 12.5 to 50 mcg/hr). The treatment was continued for 12 weeks. |
| Measure Participants | 73 | 77 |
| Day 1, Effective (n= 73, 77) |
73
33.5%
|
77
NaN
|
| Day 1, Ineffective (n= 73, 77) |
0
0%
|
0
NaN
|
| Day 85/Final evaluation, Effective (n= 73, 77) |
64
29.4%
|
51
NaN
|
| Day 85/Final evaluation, Ineffective (n= 73, 77) |
9
4.1%
|
26
NaN
|
Adverse Events
| Time Frame | From Screening period up to the Follow-up period | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||
| Arm/Group Title | Fentanyl (Titration Period) | Fentanyl (Double-blind Period) | Placebo (Double-blind Period) | |||
| Arm/Group Description | 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. | Participants meeting the pre-defined criteria for transfer from titration period to double-blind period and randomly assigned to fentanyl group, were administered one-day adhesive transdermal patch containing fentanyl, applied to chest, abdomen, upper arm or thigh and replaced every day, the dose of which was same as the final application dose in the titration period (in the range of 12.5 to 50 mcg/hr). The treatment was continued for 12 weeks. | Participants meeting the pre-defined criteria for transfer from titration period to double-blind period and randomly assigned to placebo group, were administered one-day adhesive transdermal placebo patch indistinguishable from fentanyl in appearance, applied to chest, abdomen, upper arm or thigh and replaced every day. The dose of fentanyl (from titration period) was gradually decreased to prevent withdrawal symptoms and the dose of the matching placebo was gradually increased up to same dose as the final application dose in the titration period (in the range of 12.5 to 50 mcg/hr). The treatment was continued for 12 weeks. | |||
All Cause Mortality |
||||||
| Fentanyl (Titration Period) | Fentanyl (Double-blind Period) | Placebo (Double-blind Period) | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| Fentanyl (Titration Period) | Fentanyl (Double-blind Period) | Placebo (Double-blind Period) | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 12/218 (5.5%) | 3/73 (4.1%) | 2/77 (2.6%) | |||
| Ear and labyrinth disorders | ||||||
| Positional vertigo | 1/218 (0.5%) | 0/73 (0%) | 0/77 (0%) | |||
| Gastrointestinal disorders | ||||||
| Nausea | 3/218 (1.4%) | 0/73 (0%) | 0/77 (0%) | |||
| Abdominal pain | 1/218 (0.5%) | 0/73 (0%) | 0/77 (0%) | |||
| Vomiting | 1/218 (0.5%) | 0/73 (0%) | 0/77 (0%) | |||
| Gastric discomfort | 0/218 (0%) | 1/73 (1.4%) | 0/77 (0%) | |||
| Gastric ulcer | 0/218 (0%) | 1/73 (1.4%) | 0/77 (0%) | |||
| General disorders | ||||||
| Pain | 1/218 (0.5%) | 1/73 (1.4%) | 0/77 (0%) | |||
| Lassitude | 0/218 (0%) | 0/73 (0%) | 1/77 (1.3%) | |||
| Death | 1/218 (0.5%) | 0/73 (0%) | 0/77 (0%) | |||
| Infections and infestations | ||||||
| Aspiration pneumonia | 0/218 (0%) | 1/73 (1.4%) | 0/77 (0%) | |||
| Nervous system disorders | ||||||
| Dizziness | 1/218 (0.5%) | 0/73 (0%) | 0/77 (0%) | |||
| Somnolence | 1/218 (0.5%) | 0/73 (0%) | 0/77 (0%) | |||
| Psychiatric disorders | ||||||
| Delirium | 1/218 (0.5%) | 0/73 (0%) | 0/77 (0%) | |||
| Hallucinations | 1/218 (0.5%) | 0/73 (0%) | 0/77 (0%) | |||
| Anxiety | 0/218 (0%) | 0/73 (0%) | 1/77 (1.3%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Asthma | 1/218 (0.5%) | 0/73 (0%) | 0/77 (0%) | |||
| Vascular disorders | ||||||
| Chronic heart failure | 1/218 (0.5%) | 0/73 (0%) | 0/77 (0%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| Fentanyl (Titration Period) | Fentanyl (Double-blind Period) | Placebo (Double-blind Period) | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 177/218 (81.2%) | 50/73 (68.5%) | 35/77 (45.5%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 1/218 (0.5%) | 3/73 (4.1%) | 0/77 (0%) | |||
| Cardiac disorders | ||||||
| Palpitations | 2/218 (0.9%) | 0/73 (0%) | 0/77 (0%) | |||
| Angina pectoris | 0/218 (0%) | 1/73 (1.4%) | 0/77 (0%) | |||
| Atrial fibrillation | 0/218 (0%) | 0/73 (0%) | 1/77 (1.3%) | |||
| Sinus bradycardia | 0/218 (0%) | 1/73 (1.4%) | 0/77 (0%) | |||
| Ventricular extrasystoles | 0/218 (0%) | 0/73 (0%) | 1/77 (1.3%) | |||
| Ear and labyrinth disorders | ||||||
| Vertigo | 2/218 (0.9%) | 0/73 (0%) | 0/77 (0%) | |||
| Tinnitus | 0/218 (0%) | 0/73 (0%) | 1/77 (1.3%) | |||
| Eye disorders | ||||||
| Diplopia | 1/218 (0.5%) | 0/73 (0%) | 0/77 (0%) | |||
| Lacrimation increased | 1/218 (0.5%) | 0/73 (0%) | 0/77 (0%) | |||
| Vision blurred | 1/218 (0.5%) | 0/73 (0%) | 0/77 (0%) | |||
| Abnormal sensation in eye | 0/218 (0%) | 1/73 (1.4%) | 0/77 (0%) | |||
| Cataract | 0/218 (0%) | 0/73 (0%) | 1/77 (1.3%) | |||
| Posterior capsule opacification | 0/218 (0%) | 0/73 (0%) | 1/77 (1.3%) | |||
| Gastrointestinal disorders | ||||||
| Nausea | 91/218 (41.7%) | 5/73 (6.8%) | 6/77 (7.8%) | |||
| Constipation | 66/218 (30.3%) | 6/73 (8.2%) | 3/77 (3.9%) | |||
| Vomiting | 29/218 (13.3%) | 3/73 (4.1%) | 1/77 (1.3%) | |||
| Abdominal discomfort | 11/218 (5%) | 1/73 (1.4%) | 1/77 (1.3%) | |||
| Diarrhoea | 9/218 (4.1%) | 0/73 (0%) | 1/77 (1.3%) | |||
| Abdominal pain | 2/218 (0.9%) | 1/73 (1.4%) | 0/77 (0%) | |||
| Stomatitis | 2/218 (0.9%) | 1/73 (1.4%) | 1/77 (1.3%) | |||
| Abdominal pain upper | 1/218 (0.5%) | 2/73 (2.7%) | 0/77 (0%) | |||
| Dyspepsia | 1/218 (0.5%) | 0/73 (0%) | 1/77 (1.3%) | |||
| Eructation | 1/218 (0.5%) | 0/73 (0%) | 0/77 (0%) | |||
| Faeces hard | 1/218 (0.5%) | 0/73 (0%) | 0/77 (0%) | |||
| Gastritis | 1/218 (0.5%) | 2/73 (2.7%) | 0/77 (0%) | |||
| Periodontitis | 1/218 (0.5%) | 0/73 (0%) | 0/77 (0%) | |||
| Epigastric discomfort | 1/218 (0.5%) | 0/73 (0%) | 0/77 (0%) | |||
| Gingivitis | 0/218 (0%) | 2/73 (2.7%) | 0/77 (0%) | |||
| Toothache | 0/218 (0%) | 1/73 (1.4%) | 1/77 (1.3%) | |||
| Dental caries | 0/218 (0%) | 0/73 (0%) | 1/77 (1.3%) | |||
| Gastritis atrophic | 0/218 (0%) | 1/73 (1.4%) | 0/77 (0%) | |||
| Oral discomfort | 0/218 (0%) | 0/73 (0%) | 1/77 (1.3%) | |||
| Salivary hypersecretion | 0/218 (0%) | 0/73 (0%) | 1/77 (1.3%) | |||
| General disorders | ||||||
| Application site pruritus | 12/218 (5.5%) | 0/73 (0%) | 0/77 (0%) | |||
| Malaise | 9/218 (4.1%) | 3/73 (4.1%) | 3/77 (3.9%) | |||
| Thirst | 4/218 (1.8%) | 0/73 (0%) | 3/77 (3.9%) | |||
| Application site dermatitis | 3/218 (1.4%) | 1/73 (1.4%) | 1/77 (1.3%) | |||
| Feeling abnormal | 3/218 (1.4%) | 1/73 (1.4%) | 1/77 (1.3%) | |||
| Application site erythema | 2/218 (0.9%) | 1/73 (1.4%) | 0/77 (0%) | |||
| Drug withdrawal syndrome | 2/218 (0.9%) | 4/73 (5.5%) | 1/77 (1.3%) | |||
| Hypothermia | 2/218 (0.9%) | 0/73 (0%) | 0/77 (0%) | |||
| Oedema | 2/218 (0.9%) | 0/73 (0%) | 0/77 (0%) | |||
| Pyrexia | 2/218 (0.9%) | 2/73 (2.7%) | 1/77 (1.3%) | |||
| Application site pain | 1/218 (0.5%) | 0/73 (0%) | 0/77 (0%) | |||
| Application site rash | 1/218 (0.5%) | 0/73 (0%) | 0/77 (0%) | |||
| Chest pain | 1/218 (0.5%) | 0/73 (0%) | 0/77 (0%) | |||
| Oedema peripheral | 1/218 (0.5%) | 2/73 (2.7%) | 1/77 (1.3%) | |||
| Temperature regulation disorder | 1/218 (0.5%) | 0/73 (0%) | 0/77 (0%) | |||
| Sensation of foreign body | 1/218 (0.5%) | 0/73 (0%) | 0/77 (0%) | |||
| Application site discomfort | 1/218 (0.5%) | 0/73 (0%) | 0/77 (0%) | |||
| Application site reaction | 0/218 (0%) | 1/73 (1.4%) | 0/77 (0%) | |||
| Chest discomfort | 0/218 (0%) | 0/73 (0%) | 1/77 (1.3%) | |||
| Facial pain | 0/218 (0%) | 1/73 (1.4%) | 0/77 (0%) | |||
| Fatigue | 0/218 (0%) | 1/73 (1.4%) | 0/77 (0%) | |||
| Injection site extravasation | 0/218 (0%) | 1/73 (1.4%) | 0/77 (0%) | |||
| Irritability | 0/218 (0%) | 0/73 (0%) | 1/77 (1.3%) | |||
| Pain | 0/218 (0%) | 1/73 (1.4%) | 0/77 (0%) | |||
| Application site eczema | 0/218 (0%) | 0/73 (0%) | 1/77 (1.3%) | |||
| Hepatobiliary disorders | ||||||
| Hepatic function abnormal | 4/218 (1.8%) | 0/73 (0%) | 2/77 (2.6%) | |||
| Liver disorder | 1/218 (0.5%) | 0/73 (0%) | 0/77 (0%) | |||
| Immune system disorders | ||||||
| Seasonal allergy | 0/218 (0%) | 1/73 (1.4%) | 0/77 (0%) | |||
| Infections and infestations | ||||||
| Nasopharyngitis | 6/218 (2.8%) | 10/73 (13.7%) | 8/77 (10.4%) | |||
| Chronic sinusitis | 1/218 (0.5%) | 0/73 (0%) | 0/77 (0%) | |||
| Impetigo | 1/218 (0.5%) | 0/73 (0%) | 0/77 (0%) | |||
| Tinea pedis | 1/218 (0.5%) | 0/73 (0%) | 0/77 (0%) | |||
| Urinary tract infection | 1/218 (0.5%) | 0/73 (0%) | 0/77 (0%) | |||
| Gastroenteritis bacterial | 1/218 (0.5%) | 0/73 (0%) | 0/77 (0%) | |||
| Cystitis | 0/218 (0%) | 1/73 (1.4%) | 1/77 (1.3%) | |||
| Bronchitis | 0/218 (0%) | 0/73 (0%) | 1/77 (1.3%) | |||
| Herpes zoster | 0/218 (0%) | 0/73 (0%) | 1/77 (1.3%) | |||
| Pneumonia | 0/218 (0%) | 1/73 (1.4%) | 0/77 (0%) | |||
| Anal abscess | 0/218 (0%) | 1/73 (1.4%) | 0/77 (0%) | |||
| Injury, poisoning and procedural complications | ||||||
| Fall | 2/218 (0.9%) | 2/73 (2.7%) | 1/77 (1.3%) | |||
| Animal bite | 1/218 (0.5%) | 0/73 (0%) | 0/77 (0%) | |||
| Spinal compression fracture | 1/218 (0.5%) | 0/73 (0%) | 0/77 (0%) | |||
| Contusion | 1/218 (0.5%) | 0/73 (0%) | 0/77 (0%) | |||
| Arthropod sting | 0/218 (0%) | 1/73 (1.4%) | 0/77 (0%) | |||
| Wound | 0/218 (0%) | 1/73 (1.4%) | 0/77 (0%) | |||
| Skeletal injury | 0/218 (0%) | 0/73 (0%) | 1/77 (1.3%) | |||
| Investigations | ||||||
| Blood pressure increased | 5/218 (2.3%) | 0/73 (0%) | 2/77 (2.6%) | |||
| Aspartate aminotransferase increased | 2/218 (0.9%) | 0/73 (0%) | 0/77 (0%) | |||
| Gamma-glutamyltransferase increased | 2/218 (0.9%) | 0/73 (0%) | 1/77 (1.3%) | |||
| White blood cell count increased | 2/218 (0.9%) | 1/73 (1.4%) | 0/77 (0%) | |||
| Alanine aminotransferase increased | 1/218 (0.5%) | 0/73 (0%) | 0/77 (0%) | |||
| Blood creatinine increased | 1/218 (0.5%) | 1/73 (1.4%) | 2/77 (2.6%) | |||
| Blood pressure decreased | 1/218 (0.5%) | 0/73 (0%) | 0/77 (0%) | |||
| Blood urea increased | 1/218 (0.5%) | 1/73 (1.4%) | 1/77 (1.3%) | |||
| C-reactive protein increased | 1/218 (0.5%) | 0/73 (0%) | 0/77 (0%) | |||
| Electrocardiogram ST segment elevation | 1/218 (0.5%) | 0/73 (0%) | 0/77 (0%) | |||
| Glucose urine present | 1/218 (0.5%) | 1/73 (1.4%) | 0/77 (0%) | |||
| Laboratory test abnormal | 1/218 (0.5%) | 0/73 (0%) | 0/77 (0%) | |||
| Liver function test abnormal | 1/218 (0.5%) | 0/73 (0%) | 0/77 (0%) | |||
| Blood alkaline phosphatase increased | 1/218 (0.5%) | 0/73 (0%) | 0/77 (0%) | |||
| Weight decreased | 0/218 (0%) | 0/73 (0%) | 2/77 (2.6%) | |||
| Blood potassium decreased | 0/218 (0%) | 1/73 (1.4%) | 0/77 (0%) | |||
| Electrocardiogram QT prolonged | 0/218 (0%) | 1/73 (1.4%) | 0/77 (0%) | |||
| Eosinophil count increased | 0/218 (0%) | 1/73 (1.4%) | 0/77 (0%) | |||
| Blood urine present | 0/218 (0%) | 1/73 (1.4%) | 0/77 (0%) | |||
| Monocyte count increased | 0/218 (0%) | 1/73 (1.4%) | 0/77 (0%) | |||
| Protein urine present | 0/218 (0%) | 0/73 (0%) | 1/77 (1.3%) | |||
| Metabolism and nutrition disorders | ||||||
| Decreased appetite | 3/218 (1.4%) | 2/73 (2.7%) | 5/77 (6.5%) | |||
| Hypophagia | 1/218 (0.5%) | 0/73 (0%) | 0/77 (0%) | |||
| Dehydration | 0/218 (0%) | 1/73 (1.4%) | 0/77 (0%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Myalgia | 2/218 (0.9%) | 0/73 (0%) | 0/77 (0%) | |||
| Pain in extremity | 2/218 (0.9%) | 0/73 (0%) | 2/77 (2.6%) | |||
| Arthritis | 1/218 (0.5%) | 0/73 (0%) | 1/77 (1.3%) | |||
| Back pain | 1/218 (0.5%) | 0/73 (0%) | 1/77 (1.3%) | |||
| Bursitis | 1/218 (0.5%) | 0/73 (0%) | 0/77 (0%) | |||
| Chondrocalcinosis pyrophosphate | 1/218 (0.5%) | 0/73 (0%) | 0/77 (0%) | |||
| Lumbar spinal stenosis | 1/218 (0.5%) | 0/73 (0%) | 0/77 (0%) | |||
| Muscular weakness | 1/218 (0.5%) | 0/73 (0%) | 0/77 (0%) | |||
| Musculoskeletal pain | 1/218 (0.5%) | 0/73 (0%) | 0/77 (0%) | |||
| Neck pain | 1/218 (0.5%) | 1/73 (1.4%) | 0/77 (0%) | |||
| Osteoarthritis | 1/218 (0.5%) | 0/73 (0%) | 0/77 (0%) | |||
| Spinal osteoarthritis | 1/218 (0.5%) | 0/73 (0%) | 0/77 (0%) | |||
| Musculoskeletal stiffness | 1/218 (0.5%) | 1/73 (1.4%) | 1/77 (1.3%) | |||
| Arthralgia | 0/218 (0%) | 0/73 (0%) | 1/77 (1.3%) | |||
| Bone pain | 0/218 (0%) | 0/73 (0%) | 1/77 (1.3%) | |||
| Muscle spasms | 0/218 (0%) | 0/73 (0%) | 1/77 (1.3%) | |||
| Periarthritis | 0/218 (0%) | 0/73 (0%) | 1/77 (1.3%) | |||
| Neck mass | 0/218 (0%) | 0/73 (0%) | 1/77 (1.3%) | |||
| Tenosynovitis stenosans | 0/218 (0%) | 1/73 (1.4%) | 0/77 (0%) | |||
| Spondylolisthesis | 0/218 (0%) | 0/73 (0%) | 1/77 (1.3%) | |||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Uterine leiomyoma | 1/218 (0.5%) | 0/73 (0%) | 0/77 (0%) | |||
| Nervous system disorders | ||||||
| Somnolence | 59/218 (27.1%) | 3/73 (4.1%) | 0/77 (0%) | |||
| Dizziness | 27/218 (12.4%) | 1/73 (1.4%) | 2/77 (2.6%) | |||
| Headache | 15/218 (6.9%) | 0/73 (0%) | 1/77 (1.3%) | |||
| Dysgeusia | 2/218 (0.9%) | 0/73 (0%) | 0/77 (0%) | |||
| Dysarthria | 1/218 (0.5%) | 0/73 (0%) | 0/77 (0%) | |||
| Head discomfort | 1/218 (0.5%) | 0/73 (0%) | 0/77 (0%) | |||
| Hypoaesthesia | 1/218 (0.5%) | 0/73 (0%) | 1/77 (1.3%) | |||
| Myelopathy | 1/218 (0.5%) | 0/73 (0%) | 0/77 (0%) | |||
| Tremor | 1/218 (0.5%) | 0/73 (0%) | 0/77 (0%) | |||
| Extrapyramidal disorder | 0/218 (0%) | 1/73 (1.4%) | 0/77 (0%) | |||
| Mental impairment | 0/218 (0%) | 0/73 (0%) | 1/77 (1.3%) | |||
| Visual field defect | 0/218 (0%) | 0/73 (0%) | 1/77 (1.3%) | |||
| Psychiatric disorders | ||||||
| Insomnia | 5/218 (2.3%) | 7/73 (9.6%) | 3/77 (3.9%) | |||
| Hallucination | 3/218 (1.4%) | 0/73 (0%) | 0/77 (0%) | |||
| Delirium | 1/218 (0.5%) | 0/73 (0%) | 0/77 (0%) | |||
| Hallucination, visual | 1/218 (0.5%) | 0/73 (0%) | 0/77 (0%) | |||
| Abnormal behaviour | 1/218 (0.5%) | 0/73 (0%) | 0/77 (0%) | |||
| Anxiety | 0/218 (0%) | 0/73 (0%) | 2/77 (2.6%) | |||
| Renal and urinary disorders | ||||||
| Dysuria | 2/218 (0.9%) | 1/73 (1.4%) | 0/77 (0%) | |||
| Pollakiuria | 2/218 (0.9%) | 0/73 (0%) | 0/77 (0%) | |||
| Haematuria | 1/218 (0.5%) | 1/73 (1.4%) | 0/77 (0%) | |||
| Urinary retention | 0/218 (0%) | 1/73 (1.4%) | 0/77 (0%) | |||
| Benign prostatic hyperplasia | 0/218 (0%) | 1/73 (1.4%) | 0/77 (0%) | |||
| Reproductive system and breast disorders | ||||||
| Sexual dysfunction | 1/218 (0.5%) | 0/73 (0%) | 0/77 (0%) | |||
| Genital haemorrhage | 1/218 (0.5%) | 0/73 (0%) | 0/77 (0%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Dyspnoea | 4/218 (1.8%) | 3/73 (4.1%) | 0/77 (0%) | |||
| Dysphonia | 1/218 (0.5%) | 0/73 (0%) | 0/77 (0%) | |||
| Epistaxis | 1/218 (0.5%) | 0/73 (0%) | 0/77 (0%) | |||
| Hypoxia | 1/218 (0.5%) | 0/73 (0%) | 0/77 (0%) | |||
| Pleurisy | 1/218 (0.5%) | 0/73 (0%) | 0/77 (0%) | |||
| Productive cough | 1/218 (0.5%) | 0/73 (0%) | 0/77 (0%) | |||
| Upper respiratory tract inflammation | 1/218 (0.5%) | 0/73 (0%) | 1/77 (1.3%) | |||
| Oropharyngeal pain | 1/218 (0.5%) | 0/73 (0%) | 0/77 (0%) | |||
| Rhinitis allergic | 0/218 (0%) | 0/73 (0%) | 1/77 (1.3%) | |||
| Rhinorrhoea | 0/218 (0%) | 1/73 (1.4%) | 0/77 (0%) | |||
| Oropharyngeal discomfort | 0/218 (0%) | 1/73 (1.4%) | 0/77 (0%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| Pruritus | 6/218 (2.8%) | 0/73 (0%) | 2/77 (2.6%) | |||
| Pruritus generalised | 6/218 (2.8%) | 0/73 (0%) | 0/77 (0%) | |||
| Rash | 5/218 (2.3%) | 0/73 (0%) | 0/77 (0%) | |||
| Dermatitis contact | 3/218 (1.4%) | 0/73 (0%) | 0/77 (0%) | |||
| Eczema | 2/218 (0.9%) | 3/73 (4.1%) | 0/77 (0%) | |||
| Hyperhidrosis | 2/218 (0.9%) | 0/73 (0%) | 0/77 (0%) | |||
| Heat rash | 1/218 (0.5%) | 0/73 (0%) | 0/77 (0%) | |||
| Night sweats | 1/218 (0.5%) | 0/73 (0%) | 0/77 (0%) | |||
| Rash generalised | 1/218 (0.5%) | 0/73 (0%) | 0/77 (0%) | |||
| Rash papular | 1/218 (0.5%) | 0/73 (0%) | 0/77 (0%) | |||
| Skin exfoliation | 1/218 (0.5%) | 0/73 (0%) | 0/77 (0%) | |||
| Urticaria | 1/218 (0.5%) | 0/73 (0%) | 1/77 (1.3%) | |||
| Xeroderma | 1/218 (0.5%) | 0/73 (0%) | 0/77 (0%) | |||
| Decubitus ulcer | 0/218 (0%) | 1/73 (1.4%) | 0/77 (0%) | |||
| Photosensitivity reaction | 0/218 (0%) | 1/73 (1.4%) | 0/77 (0%) | |||
| Piloerection | 0/218 (0%) | 0/73 (0%) | 1/77 (1.3%) | |||
| Vascular disorders | ||||||
| Flushing | 1/218 (0.5%) | 0/73 (0%) | 0/77 (0%) | |||
| Hypertension | 1/218 (0.5%) | 0/73 (0%) | 0/77 (0%) | |||
| Raynaud's phenomenon | 1/218 (0.5%) | 0/73 (0%) | 0/77 (0%) | |||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Results Point of Contact
| Name/Title | Director, Clinical Research |
|---|---|
| Organization | Janssen Research & Development, L.L.C. USA |
| Phone | 1 609 730-3387 |
Responsible Party:
Janssen Pharmaceutical K.K.
ClinicalTrials.gov Identifier:
NCT01008618
Other Study ID Numbers:
- CR015541
- JNS020QD-JPN-N01
First Posted:
Nov 6, 2009
Last Update Posted:
Dec 25, 2013
Last Verified:
Nov 1, 2013