Trial Outcomes & Findings for A Confirmatory Study of Fentanyl in Participants With Post-herpetic Neuralgia, Complex Regional Pain Syndrome or Postoperative Pain Syndrome (NCT NCT01008553)
NCT ID: NCT01008553
Last Updated: 2013-07-25
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
258 participants
Primary outcome timeframe
Day 1 up to Day 85 (double-blind period) and Day 92 (discontinuation of the study)
Results posted on
2013-07-25
Participant Flow
Participant milestones
| Measure |
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.
|
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, 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.
|
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, 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 1 (Titration Period)
STARTED
|
258
|
0
|
0
|
|
Period 1 (Titration Period)
COMPLETED
|
163
|
0
|
0
|
|
Period 1 (Titration Period)
NOT COMPLETED
|
95
|
0
|
0
|
|
Period 2 (Double-Blind Period)
STARTED
|
0
|
84
|
79
|
|
Period 2 (Double-Blind Period)
COMPLETED
|
0
|
47
|
28
|
|
Period 2 (Double-Blind Period)
NOT COMPLETED
|
0
|
37
|
51
|
Reasons for withdrawal
| Measure |
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.
|
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, 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.
|
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, 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 1 (Titration Period)
Physician Decision
|
2
|
0
|
0
|
|
Period 1 (Titration Period)
Adverse Event
|
33
|
0
|
0
|
|
Period 1 (Titration Period)
Withdrawal by Subject
|
6
|
0
|
0
|
|
Period 1 (Titration Period)
Determined to increase dosage
|
3
|
0
|
0
|
|
Period 1 (Titration Period)
Not satisfied criteria to enter Period 2
|
50
|
0
|
0
|
|
Period 1 (Titration Period)
Not appropriate for this study
|
1
|
0
|
0
|
|
Period 2 (Double-Blind Period)
Physician Decision
|
0
|
1
|
2
|
|
Period 2 (Double-Blind Period)
Adverse Event
|
0
|
14
|
4
|
|
Period 2 (Double-Blind Period)
Withdrawal by Subject
|
0
|
2
|
2
|
|
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)
Rescue drugs increased more than 1 times
|
0
|
0
|
3
|
|
Period 2 (Double-Blind Period)
More than 3 times a day rescue treatment
|
0
|
0
|
1
|
|
Period 2 (Double-Blind Period)
More than 15mm increase in Mean VAS
|
0
|
18
|
35
|
Baseline Characteristics
A Confirmatory Study of Fentanyl in Participants With Post-herpetic Neuralgia, Complex Regional Pain Syndrome or Postoperative Pain Syndrome
Baseline characteristics by cohort
| Measure |
Fentanyl (Titration Period)
n=258 Participants
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.
|
|---|---|
|
Age Continuous
|
66.5 Years
STANDARD_DEVIATION 13.89 • n=5 Participants
|
|
Sex: Female, Male
Female
|
124 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
134 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
Fentanyl (Double-blind Period)
n=84 Participants
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.
|
Placebo (Double-blind Period)
n=79 Participants
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.
|
|---|---|---|
|
Time From the Initial Day of Application in Double-Blind Period to Withdrawal Because of Insufficient Analgesic Efficacy
|
NA Days
The data was not estimable due to the high number of participants censored for this outcome measure.
|
45.0 Days
Interval 16.0 to
The upper limit of 95% confidence interval was not estimable due to the high number of participants censored for this outcome measure.
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
Fentanyl (Double-blind Period)
n=258 Participants
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.
|
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, 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.
|
|---|---|---|
|
Pain Visual Analog Scale (VAS) Score - Titration Period
Baseline (n=258)
|
73.5 mm
Standard Deviation 12.81
|
—
|
|
Pain Visual Analog Scale (VAS) Score - Titration Period
Last 3 days in titration period (n=257)
|
39.5 mm
Standard Deviation 20.02
|
—
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
Fentanyl (Double-blind Period)
n=84 Participants
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.
|
Placebo (Double-blind Period)
n=79 Participants
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.
|
|---|---|---|
|
Pain Visual Analog Scale (VAS) Score - Double-Blind Period
Baseline (n=84, 79)
|
30.1 mm
Standard Deviation 11.50
|
27.5 mm
Standard Deviation 11.23
|
|
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
|
37.1 mm
Standard Deviation 20.19
|
SECONDARY outcome
Timeframe: 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.
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".
Outcome measures
| Measure |
Fentanyl (Double-blind Period)
n=258 Participants
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.
|
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, 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.
|
|---|---|---|
|
Number of Participants Evaluated as Per Participant's Overall Assessment - Titration Period
Day 1, Category 1 (n=258)
|
85 Participants
|
—
|
|
Number of Participants Evaluated as Per Participant's Overall Assessment - Titration Period
Day 1, Category 2 (n=258)
|
15 Participants
|
—
|
|
Number of Participants Evaluated as Per Participant's Overall Assessment - Titration Period
Day 29/Final evaluation, Category 1 (n=257)
|
220 Participants
|
—
|
|
Number of Participants Evaluated as Per Participant's Overall Assessment - Titration Period
Day 29/ Final evaluation, Category 2 (n=257)
|
146 Participants
|
—
|
SECONDARY outcome
Timeframe: 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.
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".
Outcome measures
| Measure |
Fentanyl (Double-blind Period)
n=84 Participants
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.
|
Placebo (Double-blind Period)
n=79 Participants
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.
|
|---|---|---|
|
Number of Participants Evaluated as Per Participant's Overall Assessment - Double-Blind Period
Day 1, Category 1 (n=84, 79)
|
82 Participants
|
79 Participants
|
|
Number of Participants Evaluated as Per Participant's Overall Assessment - Double-Blind Period
Day 1, Category 2 (n=84, 79)
|
61 Participants
|
67 Participants
|
|
Number of Participants Evaluated as Per Participant's Overall Assessment - Double-Blind Period
Day 85/Final evaluation, Category 1 (n=84, 78)
|
69 Participants
|
56 Participants
|
|
Number of Participants Evaluated as Per Participant's Overall Assessment - Double-Blind Period
Day 85/Final evaluation, Category 2 (n=84, 78)
|
49 Participants
|
32 Participants
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
Fentanyl (Double-blind Period)
n=258 Participants
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.
|
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, 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.
|
|---|---|---|
|
Number of Doses of Rescue Treatment Per Day - Titration Period
Day 1 (n=258)
|
0.1 Treatments per day
Standard Deviation 0.41 • Interval 0.0 to 4.0
|
—
|
|
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 outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
Fentanyl (Double-blind Period)
n=84 Participants
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.
|
Placebo (Double-blind Period)
n=79 Participants
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.
|
|---|---|---|
|
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
|
0.1 Treatments per day
Standard Deviation 0.47
|
|
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
|
0.7 Treatments per day
Standard Deviation 0.86
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
Fentanyl (Double-blind Period)
n=258 Participants
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.
|
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, 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.
|
|---|---|---|
|
Brief Pain Inventory Short Form (BPI-sf) Score - Titration Period
Day 1 (n=258)
|
5.8 Units on a scale
Standard Deviation 1.66
|
—
|
|
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 outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
Fentanyl (Double-blind Period)
n=84 Participants
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.
|
Placebo (Double-blind Period)
n=79 Participants
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.
|
|---|---|---|
|
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
|
3.1 Units on a scale
Standard Deviation 1.47
|
|
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
|
3.7 Units on a scale
Standard Deviation 1.98
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
Fentanyl (Double-blind Period)
n=258 Participants
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.
|
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, 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.
|
|---|---|---|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
Fentanyl (Double-blind Period)
n=84 Participants
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.
|
Placebo (Double-blind Period)
n=79 Participants
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.
|
|---|---|---|
|
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
|
29.4 Units on a scale
Standard Deviation 16.98
|
|
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
|
47.7 Units on a scale
Standard Deviation 8.89
|
|
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
|
27.6 Units on a scale
Standard Deviation 16.24
|
|
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
|
47.2 Units on a scale
Standard Deviation 9.61
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
Fentanyl (Double-blind Period)
n=258 Participants
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.
|
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, 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.
|
|---|---|---|
|
Number of Participants Evaluated as Per Physician's Overall Assessment - Titration Period
Effective
|
214 Participants
|
—
|
|
Number of Participants Evaluated as Per Physician's Overall Assessment - Titration Period
Ineffective
|
44 Participants
|
—
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
Fentanyl (Double-blind Period)
n=84 Participants
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.
|
Placebo (Double-blind Period)
n=79 Participants
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.
|
|---|---|---|
|
Number of Participants Evaluated as Per Physician's Overall Assessment - Double-Blind Period
Day 1, Effective (n= 84, 79)
|
84 Participants
|
79 Participants
|
|
Number of Participants Evaluated as Per Physician's Overall Assessment - Double-Blind Period
Day 1, Ineffective (n= 84, 79)
|
0 Participants
|
0 Participants
|
|
Number of Participants Evaluated as Per Physician's Overall Assessment - Double-Blind Period
Day 85/Final evaluation, Effective (n= 84, 79)
|
70 Participants
|
47 Participants
|
|
Number of Participants Evaluated as Per Physician's Overall Assessment - Double-Blind Period
Day 85/Final evaluation, Ineffective (n= 84, 79)
|
14 Participants
|
32 Participants
|
Adverse Events
Fentanyl (Titration Period)
Serious events: 13 serious events
Other events: 231 other events
Deaths: 0 deaths
Fentanyl (Double-blind Period)
Serious events: 8 serious events
Other events: 71 other events
Deaths: 0 deaths
Placebo (Double-blind Period)
Serious events: 4 serious events
Other events: 56 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Fentanyl (Titration Period)
n=258 participants at risk
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.
|
Fentanyl (Double-blind Period)
n=84 participants at risk
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.
|
Placebo (Double-blind Period)
n=79 participants at risk
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.
|
|---|---|---|---|
|
Infections and infestations
Pneumonia
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
1.3%
1/79 • From Screening period up to the Follow-up period
|
|
Infections and infestations
Urinary tract infection
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Endocrine disorders
Inappropriate antidiuretic hormone secretion
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Psychiatric disorders
Disorientation
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Psychiatric disorders
Abnormal behaviour
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Nervous system disorders
Dizziness
|
0.78%
2/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Nervous system disorders
Amnesia
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Cardiac disorders
Cardiac failure congestive
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Gastrointestinal disorders
Haemorrhoids
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Gastrointestinal disorders
Nausea
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
1.2%
1/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Gastrointestinal disorders
Reflux oesophagitis
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Musculoskeletal and connective tissue disorders
Chondrocalcinosis pyrophosphate
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Renal and urinary disorders
Dysuria
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
General disorders
Pyrexia
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pancreatic carcinoma
|
0.00%
0/258 • From Screening period up to the Follow-up period
|
1.2%
1/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Vascular disorders
Arteriosclerosis obliterans
|
0.00%
0/258 • From Screening period up to the Follow-up period
|
1.2%
1/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Gastrointestinal disorders
Gastric ulcer haemorrhage
|
0.00%
0/258 • From Screening period up to the Follow-up period
|
1.2%
1/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Renal and urinary disorders
Urinary retention
|
0.00%
0/258 • From Screening period up to the Follow-up period
|
1.2%
1/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Renal and urinary disorders
Renal impairment
|
0.00%
0/258 • From Screening period up to the Follow-up period
|
1.2%
1/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
General disorders
Asthenia
|
0.00%
0/258 • From Screening period up to the Follow-up period
|
1.2%
1/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
General disorders
Drug interaction
|
0.00%
0/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
1.3%
1/79 • From Screening period up to the Follow-up period
|
|
General disorders
Drug withdrawal syndrome
|
0.00%
0/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
1.3%
1/79 • From Screening period up to the Follow-up period
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
1.3%
1/79 • From Screening period up to the Follow-up period
|
|
Injury, poisoning and procedural complications
Muscle rupture
|
0.00%
0/258 • From Screening period up to the Follow-up period
|
1.2%
1/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
Other adverse events
| Measure |
Fentanyl (Titration Period)
n=258 participants at risk
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.
|
Fentanyl (Double-blind Period)
n=84 participants at risk
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.
|
Placebo (Double-blind Period)
n=79 participants at risk
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.
|
|---|---|---|---|
|
Skin and subcutaneous tissue disorders
Dermatitis contact
|
3.1%
8/258 • From Screening period up to the Follow-up period
|
1.2%
1/84 • From Screening period up to the Follow-up period
|
1.3%
1/79 • From Screening period up to the Follow-up period
|
|
Skin and subcutaneous tissue disorders
Eczema
|
3.1%
8/258 • From Screening period up to the Follow-up period
|
3.6%
3/84 • From Screening period up to the Follow-up period
|
1.3%
1/79 • From Screening period up to the Follow-up period
|
|
Skin and subcutaneous tissue disorders
Pruritus generalised
|
2.7%
7/258 • From Screening period up to the Follow-up period
|
1.2%
1/84 • From Screening period up to the Follow-up period
|
1.3%
1/79 • From Screening period up to the Follow-up period
|
|
Skin and subcutaneous tissue disorders
Erythema
|
1.6%
4/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
2.5%
2/79 • From Screening period up to the Follow-up period
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
1.2%
3/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Skin and subcutaneous tissue disorders
Heat rash
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Skin and subcutaneous tissue disorders
Photosensitivity reaction
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Skin and subcutaneous tissue disorders
Skin exfoliation
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
1.2%
3/258 • From Screening period up to the Follow-up period
|
2.4%
2/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
1.2%
3/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
2.5%
2/79 • From Screening period up to the Follow-up period
|
|
Skin and subcutaneous tissue disorders
Rash
|
3.9%
10/258 • From Screening period up to the Follow-up period
|
2.4%
2/84 • From Screening period up to the Follow-up period
|
2.5%
2/79 • From Screening period up to the Follow-up period
|
|
Infections and infestations
Nasopharyngitis
|
4.7%
12/258 • From Screening period up to the Follow-up period
|
6.0%
5/84 • From Screening period up to the Follow-up period
|
7.6%
6/79 • From Screening period up to the Follow-up period
|
|
Infections and infestations
Cystitis
|
0.78%
2/258 • From Screening period up to the Follow-up period
|
1.2%
1/84 • From Screening period up to the Follow-up period
|
1.3%
1/79 • From Screening period up to the Follow-up period
|
|
Infections and infestations
Gastroenteritis
|
0.78%
2/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Infections and infestations
Herpes simplex
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Infections and infestations
Hordeolum
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Infections and infestations
Pharyngitis
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Infections and infestations
Urinary tract infection
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Blood and lymphatic system disorders
Anaemia
|
0.78%
2/258 • From Screening period up to the Follow-up period
|
1.2%
1/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Immune system disorders
Seasonal allergy
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Metabolism and nutrition disorders
Decreased appetite
|
6.6%
17/258 • From Screening period up to the Follow-up period
|
8.3%
7/84 • From Screening period up to the Follow-up period
|
5.1%
4/79 • From Screening period up to the Follow-up period
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.78%
2/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Psychiatric disorders
Delirium
|
2.7%
7/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Psychiatric disorders
Insomnia
|
2.7%
7/258 • From Screening period up to the Follow-up period
|
3.6%
3/84 • From Screening period up to the Follow-up period
|
1.3%
1/79 • From Screening period up to the Follow-up period
|
|
Psychiatric disorders
Disorientation
|
0.78%
2/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Psychiatric disorders
Hallucination
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
1.2%
1/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Psychiatric disorders
Hallucination, visual
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Psychiatric disorders
Middle insomnia
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Psychiatric disorders
Nightmare
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Psychiatric disorders
Restlessness
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Psychiatric disorders
Sleep disorder
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Psychiatric disorders
Abulia
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Nervous system disorders
Somnolence
|
45.7%
118/258 • From Screening period up to the Follow-up period
|
14.3%
12/84 • From Screening period up to the Follow-up period
|
6.3%
5/79 • From Screening period up to the Follow-up period
|
|
Nervous system disorders
Dizziness
|
20.2%
52/258 • From Screening period up to the Follow-up period
|
7.1%
6/84 • From Screening period up to the Follow-up period
|
3.8%
3/79 • From Screening period up to the Follow-up period
|
|
Nervous system disorders
Headache
|
2.3%
6/258 • From Screening period up to the Follow-up period
|
1.2%
1/84 • From Screening period up to the Follow-up period
|
1.3%
1/79 • From Screening period up to the Follow-up period
|
|
Nervous system disorders
Tremor
|
1.6%
4/258 • From Screening period up to the Follow-up period
|
1.2%
1/84 • From Screening period up to the Follow-up period
|
1.3%
1/79 • From Screening period up to the Follow-up period
|
|
Nervous system disorders
Amnesia
|
1.2%
3/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Nervous system disorders
Dysarthria
|
0.78%
2/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
1.3%
1/79 • From Screening period up to the Follow-up period
|
|
Nervous system disorders
Cerebral infarction
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Nervous system disorders
Disturbance in attention
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Nervous system disorders
Dyslalia
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Nervous system disorders
Hypoaesthesia
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Nervous system disorders
Memory impairment
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Nervous system disorders
Parkinsonism
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Nervous system disorders
Parkinsonian gait
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Eye disorders
Photophobia
|
0.78%
2/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Eye disorders
Cataract
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Eye disorders
Iritis
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Eye disorders
Uveitis
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Eye disorders
Visual impairment
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Eye disorders
Vitreous floaters
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Ear and labyrinth disorders
Tinnitus
|
0.78%
2/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
1.3%
1/79 • From Screening period up to the Follow-up period
|
|
Ear and labyrinth disorders
Vertigo positional
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Ear and labyrinth disorders
Ear discomfort
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Cardiac disorders
Palpitations
|
1.6%
4/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Cardiac disorders
Tachycardia
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Vascular disorders
Hypertension
|
0.78%
2/258 • From Screening period up to the Follow-up period
|
1.2%
1/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
1.2%
3/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal discomfort
|
0.78%
2/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
1.2%
1/84 • From Screening period up to the Follow-up period
|
1.3%
1/79 • From Screening period up to the Follow-up period
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
1.2%
1/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Gastrointestinal disorders
Constipation
|
48.1%
124/258 • From Screening period up to the Follow-up period
|
14.3%
12/84 • From Screening period up to the Follow-up period
|
12.7%
10/79 • From Screening period up to the Follow-up period
|
|
Gastrointestinal disorders
Nausea
|
39.9%
103/258 • From Screening period up to the Follow-up period
|
14.3%
12/84 • From Screening period up to the Follow-up period
|
12.7%
10/79 • From Screening period up to the Follow-up period
|
|
Gastrointestinal disorders
Vomiting
|
9.7%
25/258 • From Screening period up to the Follow-up period
|
6.0%
5/84 • From Screening period up to the Follow-up period
|
1.3%
1/79 • From Screening period up to the Follow-up period
|
|
Gastrointestinal disorders
Diarrhoea
|
6.6%
17/258 • From Screening period up to the Follow-up period
|
6.0%
5/84 • From Screening period up to the Follow-up period
|
11.4%
9/79 • From Screening period up to the Follow-up period
|
|
Gastrointestinal disorders
Stomatitis
|
1.6%
4/258 • From Screening period up to the Follow-up period
|
1.2%
1/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Gastrointestinal disorders
Abdominal discomfort
|
1.2%
3/258 • From Screening period up to the Follow-up period
|
2.4%
2/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Gastrointestinal disorders
Gastritis
|
1.2%
3/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Gastrointestinal disorders
Abdominal distension
|
0.78%
2/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.78%
2/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
1.3%
1/79 • From Screening period up to the Follow-up period
|
|
Gastrointestinal disorders
Gingivitis
|
0.78%
2/258 • From Screening period up to the Follow-up period
|
1.2%
1/84 • From Screening period up to the Follow-up period
|
1.3%
1/79 • From Screening period up to the Follow-up period
|
|
Gastrointestinal disorders
Abdominal pain
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Gastrointestinal disorders
Cheilitis
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Gastrointestinal disorders
Dyspepsia
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Gastrointestinal disorders
Dysphagia
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Gastrointestinal disorders
Gingival pain
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Gastrointestinal disorders
Oral discomfort
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Gastrointestinal disorders
Hypoaesthesia oral
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
2.4%
2/84 • From Screening period up to the Follow-up period
|
1.3%
1/79 • From Screening period up to the Follow-up period
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
5.0%
13/258 • From Screening period up to the Follow-up period
|
6.0%
5/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.78%
2/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
2.5%
2/79 • From Screening period up to the Follow-up period
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal stiffness
|
0.78%
2/258 • From Screening period up to the Follow-up period
|
1.2%
1/84 • From Screening period up to the Follow-up period
|
2.5%
2/79 • From Screening period up to the Follow-up period
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
1.2%
1/84 • From Screening period up to the Follow-up period
|
1.3%
1/79 • From Screening period up to the Follow-up period
|
|
Renal and urinary disorders
Dysuria
|
1.6%
4/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Renal and urinary disorders
Urinary retention
|
0.78%
2/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Renal and urinary disorders
Pollakiuria
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
General disorders
Application site pruritus
|
5.8%
15/258 • From Screening period up to the Follow-up period
|
2.4%
2/84 • From Screening period up to the Follow-up period
|
1.3%
1/79 • From Screening period up to the Follow-up period
|
|
General disorders
Thirst
|
5.8%
15/258 • From Screening period up to the Follow-up period
|
3.6%
3/84 • From Screening period up to the Follow-up period
|
1.3%
1/79 • From Screening period up to the Follow-up period
|
|
General disorders
Malaise
|
4.7%
12/258 • From Screening period up to the Follow-up period
|
8.3%
7/84 • From Screening period up to the Follow-up period
|
5.1%
4/79 • From Screening period up to the Follow-up period
|
|
General disorders
Application site erythema
|
3.1%
8/258 • From Screening period up to the Follow-up period
|
1.2%
1/84 • From Screening period up to the Follow-up period
|
1.3%
1/79 • From Screening period up to the Follow-up period
|
|
General disorders
Pyrexia
|
3.1%
8/258 • From Screening period up to the Follow-up period
|
1.2%
1/84 • From Screening period up to the Follow-up period
|
2.5%
2/79 • From Screening period up to the Follow-up period
|
|
General disorders
Application site dermatitis
|
1.6%
4/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
1.3%
1/79 • From Screening period up to the Follow-up period
|
|
General disorders
Feeling abnormal
|
1.6%
4/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
General disorders
Oedema peripheral
|
1.6%
4/258 • From Screening period up to the Follow-up period
|
1.2%
1/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
General disorders
Application site rash
|
1.2%
3/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
General disorders
Drug withdrawal syndrome
|
1.2%
3/258 • From Screening period up to the Follow-up period
|
2.4%
2/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
General disorders
Oedema
|
1.2%
3/258 • From Screening period up to the Follow-up period
|
2.4%
2/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
General disorders
Chest pain
|
0.78%
2/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
1.3%
1/79 • From Screening period up to the Follow-up period
|
|
General disorders
Chills
|
0.78%
2/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
1.3%
1/79 • From Screening period up to the Follow-up period
|
|
General disorders
Pain
|
0.78%
2/258 • From Screening period up to the Follow-up period
|
1.2%
1/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
General disorders
Discomfort
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
General disorders
Puncture site pain
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Investigations
Blood pressure increased
|
3.1%
8/258 • From Screening period up to the Follow-up period
|
1.2%
1/84 • From Screening period up to the Follow-up period
|
1.3%
1/79 • From Screening period up to the Follow-up period
|
|
Investigations
Aspartate aminotransferase increased
|
1.2%
3/258 • From Screening period up to the Follow-up period
|
1.2%
1/84 • From Screening period up to the Follow-up period
|
1.3%
1/79 • From Screening period up to the Follow-up period
|
|
Investigations
Blood urea increased
|
1.2%
3/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Investigations
Alanine aminotransferase increased
|
0.78%
2/258 • From Screening period up to the Follow-up period
|
1.2%
1/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Investigations
Blood creatinine increased
|
0.78%
2/258 • From Screening period up to the Follow-up period
|
2.4%
2/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Investigations
Weight decreased
|
0.78%
2/258 • From Screening period up to the Follow-up period
|
2.4%
2/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Investigations
Blood creatine phosphokinase increased
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Investigations
Blood lactate dehydrogenase increased
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Investigations
Blood potassium increased
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Investigations
Blood pressure decreased
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Investigations
Gamma-glutamyltransferase increased
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Investigations
Haemoglobin decreased
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Investigations
Liver function test abnormal
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Investigations
Monocyte count increased
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Investigations
Red blood cell count decreased
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Investigations
Weight increased
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Investigations
Lymphocyte percentage decreased
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Investigations
Protein urine present
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Injury, poisoning and procedural complications
Fall
|
0.78%
2/258 • From Screening period up to the Follow-up period
|
3.6%
3/84 • From Screening period up to the Follow-up period
|
2.5%
2/79 • From Screening period up to the Follow-up period
|
|
Injury, poisoning and procedural complications
Arthropod bite
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Injury, poisoning and procedural complications
Joint dislocation
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Injury, poisoning and procedural complications
Contusion
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
1.2%
1/84 • From Screening period up to the Follow-up period
|
1.3%
1/79 • From Screening period up to the Follow-up period
|
|
Injury, poisoning and procedural complications
Wound
|
0.39%
1/258 • From Screening period up to the Follow-up period
|
1.2%
1/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Infections and infestations
Anal candidiasis
|
0.00%
0/258 • From Screening period up to the Follow-up period
|
1.2%
1/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Infections and infestations
Onychomycosis
|
0.00%
0/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
1.3%
1/79 • From Screening period up to the Follow-up period
|
|
Infections and infestations
Pneumonia
|
0.00%
0/258 • From Screening period up to the Follow-up period
|
1.2%
1/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
0.00%
0/258 • From Screening period up to the Follow-up period
|
1.2%
1/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Metabolism and nutrition disorders
Gout
|
0.00%
0/258 • From Screening period up to the Follow-up period
|
1.2%
1/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Metabolism and nutrition disorders
Hyperuricaemia
|
0.00%
0/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
1.3%
1/79 • From Screening period up to the Follow-up period
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/258 • From Screening period up to the Follow-up period
|
2.4%
2/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Psychiatric disorders
Apathy
|
0.00%
0/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
1.3%
1/79 • From Screening period up to the Follow-up period
|
|
Psychiatric disorders
Depression
|
0.00%
0/258 • From Screening period up to the Follow-up period
|
1.2%
1/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Psychiatric disorders
Euphoric mood
|
0.00%
0/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
1.3%
1/79 • From Screening period up to the Follow-up period
|
|
Psychiatric disorders
Depressive symptom
|
0.00%
0/258 • From Screening period up to the Follow-up period
|
1.2%
1/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Nervous system disorders
Loss of consciousness
|
0.00%
0/258 • From Screening period up to the Follow-up period
|
1.2%
1/84 • From Screening period up to the Follow-up period
|
1.3%
1/79 • From Screening period up to the Follow-up period
|
|
Nervous system disorders
Autonomic nervous system imbalance
|
0.00%
0/258 • From Screening period up to the Follow-up period
|
1.2%
1/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Nervous system disorders
Dyskinesia
|
0.00%
0/258 • From Screening period up to the Follow-up period
|
1.2%
1/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Nervous system disorders
Extrapyramidal disorder
|
0.00%
0/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
1.3%
1/79 • From Screening period up to the Follow-up period
|
|
Nervous system disorders
Migraine
|
0.00%
0/258 • From Screening period up to the Follow-up period
|
1.2%
1/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Nervous system disorders
Speech disorder
|
0.00%
0/258 • From Screening period up to the Follow-up period
|
1.2%
1/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Eye disorders
Conjunctivitis allergic
|
0.00%
0/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
1.3%
1/79 • From Screening period up to the Follow-up period
|
|
Eye disorders
Dry eye
|
0.00%
0/258 • From Screening period up to the Follow-up period
|
1.2%
1/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Eye disorders
Keratitis
|
0.00%
0/258 • From Screening period up to the Follow-up period
|
1.2%
1/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Eye disorders
Vision blurred
|
0.00%
0/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
1.3%
1/79 • From Screening period up to the Follow-up period
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
1.3%
1/79 • From Screening period up to the Follow-up period
|
|
Cardiac disorders
Bundle branch block right
|
0.00%
0/258 • From Screening period up to the Follow-up period
|
1.2%
1/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Cardiac disorders
Supraventricular extrasystoles
|
0.00%
0/258 • From Screening period up to the Follow-up period
|
1.2%
1/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Vascular disorders
Haematoma
|
0.00%
0/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
1.3%
1/79 • From Screening period up to the Follow-up period
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract inflammation
|
0.00%
0/258 • From Screening period up to the Follow-up period
|
1.2%
1/84 • From Screening period up to the Follow-up period
|
1.3%
1/79 • From Screening period up to the Follow-up period
|
|
Respiratory, thoracic and mediastinal disorders
Bronchitis chronic
|
0.00%
0/258 • From Screening period up to the Follow-up period
|
1.2%
1/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Gastrointestinal disorders
Salivary hypersecretion
|
0.00%
0/258 • From Screening period up to the Follow-up period
|
2.4%
2/84 • From Screening period up to the Follow-up period
|
1.3%
1/79 • From Screening period up to the Follow-up period
|
|
Gastrointestinal disorders
Gastrointestinal disorder
|
0.00%
0/258 • From Screening period up to the Follow-up period
|
1.2%
1/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Gastrointestinal disorders
Periodontal disease
|
0.00%
0/258 • From Screening period up to the Follow-up period
|
1.2%
1/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Hepatobiliary disorders
Hepatic function abnormal
|
0.00%
0/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
5.1%
4/79 • From Screening period up to the Follow-up period
|
|
Skin and subcutaneous tissue disorders
Decubitus ulcer
|
0.00%
0/258 • From Screening period up to the Follow-up period
|
1.2%
1/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
0.00%
0/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
1.3%
1/79 • From Screening period up to the Follow-up period
|
|
Skin and subcutaneous tissue disorders
Sweat gland disorder
|
0.00%
0/258 • From Screening period up to the Follow-up period
|
1.2%
1/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
0.00%
0/258 • From Screening period up to the Follow-up period
|
1.2%
1/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
1.3%
1/79 • From Screening period up to the Follow-up period
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.00%
0/258 • From Screening period up to the Follow-up period
|
1.2%
1/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Renal and urinary disorders
Haematuria
|
0.00%
0/258 • From Screening period up to the Follow-up period
|
1.2%
1/84 • From Screening period up to the Follow-up period
|
1.3%
1/79 • From Screening period up to the Follow-up period
|
|
Renal and urinary disorders
Renal impairment
|
0.00%
0/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
2.5%
2/79 • From Screening period up to the Follow-up period
|
|
General disorders
Irritability
|
0.00%
0/258 • From Screening period up to the Follow-up period
|
2.4%
2/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
General disorders
Chest discomfort
|
0.00%
0/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
1.3%
1/79 • From Screening period up to the Follow-up period
|
|
General disorders
Drug interaction
|
0.00%
0/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
1.3%
1/79 • From Screening period up to the Follow-up period
|
|
General disorders
Loss of control of legs
|
0.00%
0/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
1.3%
1/79 • From Screening period up to the Follow-up period
|
|
General disorders
Puncture site reaction
|
0.00%
0/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
1.3%
1/79 • From Screening period up to the Follow-up period
|
|
Investigations
Eosinophil count increased
|
0.00%
0/258 • From Screening period up to the Follow-up period
|
1.2%
1/84 • From Screening period up to the Follow-up period
|
2.5%
2/79 • From Screening period up to the Follow-up period
|
|
Investigations
Blood alkaline phosphatase increased
|
0.00%
0/258 • From Screening period up to the Follow-up period
|
2.4%
2/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Investigations
Blood glucose increased
|
0.00%
0/258 • From Screening period up to the Follow-up period
|
1.2%
1/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Investigations
Electrocardiogram abnormal
|
0.00%
0/258 • From Screening period up to the Follow-up period
|
1.2%
1/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Investigations
Glucose urine present
|
0.00%
0/258 • From Screening period up to the Follow-up period
|
1.2%
1/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Investigations
Neutrophil count increased
|
0.00%
0/258 • From Screening period up to the Follow-up period
|
1.2%
1/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Investigations
Electrocardiogram ST-T segment abnormal
|
0.00%
0/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
1.3%
1/79 • From Screening period up to the Follow-up period
|
|
Investigations
Urine output decreased
|
0.00%
0/258 • From Screening period up to the Follow-up period
|
1.2%
1/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Injury, poisoning and procedural complications
Arthropod sting
|
0.00%
0/258 • From Screening period up to the Follow-up period
|
2.4%
2/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Injury, poisoning and procedural complications
Joint sprain
|
0.00%
0/258 • From Screening period up to the Follow-up period
|
2.4%
2/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Injury, poisoning and procedural complications
Animal bite
|
0.00%
0/258 • From Screening period up to the Follow-up period
|
1.2%
1/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Injury, poisoning and procedural complications
Rib fracture
|
0.00%
0/258 • From Screening period up to the Follow-up period
|
0.00%
0/84 • From Screening period up to the Follow-up period
|
1.3%
1/79 • From Screening period up to the Follow-up period
|
|
Injury, poisoning and procedural complications
Muscle strain
|
0.00%
0/258 • From Screening period up to the Follow-up period
|
1.2%
1/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Injury, poisoning and procedural complications
Thermal burn
|
0.00%
0/258 • From Screening period up to the Follow-up period
|
1.2%
1/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
|
Skin and subcutaneous tissue disorders
Dermatitis
|
0.00%
0/258 • From Screening period up to the Follow-up period
|
1.2%
1/84 • From Screening period up to the Follow-up period
|
0.00%
0/79 • From Screening period up to the Follow-up period
|
Additional Information
Director, Clinical Research
Janssen Research & Development, L.L.C. USA
Phone: 1 609 730-3387
Results disclosure agreements
- Principal investigator is a sponsor employee The disclosure restriction on PI is that the Sponsor can review results communications prior to public release and can embargo communications regarding results for a period as the Sponsor requires.
- Publication restrictions are in place
Restriction type: OTHER