Trial Outcomes & Findings for Fentanyl Buccal Tablets Versus Immediate Release Oxycodone for Breakthrough Pain in Patients With Chronic Pain (NCT NCT00813488)
NCT ID: NCT00813488
Last Updated: 2012-05-28
Results Overview
Pain intensity (PI) scores were assessed on an 11-point numerical rating scale from 0 = no pain to 10 = pain as bad as you can imagine after each episode of breakthrough pain during the double-blind treatment period. The PID15 is the difference between the PI scores from the episode baseline (immediately prior to study drug administration)and 15 minutes after the administration of the study drug. Least squared mean was from an analysis of variance (ANOVA) with treatment as randomized, phase, and sequence as fixed factors and patient as a random factor using compound symmetry.
COMPLETED
PHASE3
213 participants
Immediately pre-dose and 15 minutes after dosing
2012-05-28
Participant Flow
Subjects with chronic pain who had been receiving opioid therapy for the previous 7 days and reported on average 1 to 5 breakthrough pain episodes per day were recruited from 50 different study sites throughout the United States beginning December 2008 and completing in November 2009.
Prior to the double-blind treatment period, subjects participated in two titration periods to identify a "successful" and tolerated dose of FBT and immediate-release oxycodone. Subjects who did not titrate to a successful and tolerated dose were excluded from further participation in the study.
Participant milestones
| Measure |
FBT First Immediate Release Oxycodone Second
Subjects in this treatment group were assigned 200 mcg FBT during the first titration period and then 15 mg oxycodone during the second titration period. Standard rescue medication could be taken if pain relief was unsuccessful. If more than one dose was required for at least 1 of 3 breakthrough pain episodes in one day, the next day the dose was increased (in 200 mcg increments for FBT and 15 mg increments for oxycodone). The maximum allowable dose was 800 mcg for FBT (4 tablets) and 60 mg (4 capsules) for oxycodone. If a dose was not tolerated the dose was lowered to the previous tolerated dose. Titration completed when successful analgesia was achieved with a tolerated dose or maximum dose was reached. If unsuccessful at maximum dose subject was discontinued from proceeding further in the study. Subjects who successfully titrated were randomized.
|
Immediate-Release Oxycodone First FBT Second
Subjects in this treatment group were assigned 15 mg oxycodone during the first titration period and then 200 mcg FBT during the second titration period. Standard rescue medication could be taken if pain relief was unsuccessful. If more than one dose was required for at least 1 of 3 breakthrough pain episodes in one day, the next day the dose was increased (in 200 mcg increments for FBT and 15 mg increments for oxycodone). The maximum allowable dose was 800 mcg for FBT (4 tablets) and 60 mg (4 capsules) for oxycodone. If a dose was not tolerated the dose was lowered to the previous tolerated dose. Titration completed when successful analgesia was achieved with a tolerated dose or maximum dose was reached. If unsuccessful at maximum dose subject was discontinued from proceeding further in the study. Subjects who successfully titrated were randomized.
|
|---|---|---|
|
Titration Period 1
STARTED
|
107
|
106
|
|
Titration Period 1
COMPLETED
|
80
|
89
|
|
Titration Period 1
NOT COMPLETED
|
27
|
17
|
|
Titration Period 2
STARTED
|
80
|
89
|
|
Titration Period 2
COMPLETED
|
64
|
79
|
|
Titration Period 2
NOT COMPLETED
|
16
|
10
|
|
Double-blind Treatment Period 1
STARTED
|
72
|
71
|
|
Double-blind Treatment Period 1
COMPLETED
|
71
|
66
|
|
Double-blind Treatment Period 1
NOT COMPLETED
|
1
|
5
|
|
Double-blind Treatment Period 2
STARTED
|
71
|
66
|
|
Double-blind Treatment Period 2
COMPLETED
|
66
|
65
|
|
Double-blind Treatment Period 2
NOT COMPLETED
|
5
|
1
|
|
Open-label Extension
STARTED
|
65
|
66
|
|
Open-label Extension
COMPLETED
|
53
|
59
|
|
Open-label Extension
NOT COMPLETED
|
12
|
7
|
Reasons for withdrawal
| Measure |
FBT First Immediate Release Oxycodone Second
Subjects in this treatment group were assigned 200 mcg FBT during the first titration period and then 15 mg oxycodone during the second titration period. Standard rescue medication could be taken if pain relief was unsuccessful. If more than one dose was required for at least 1 of 3 breakthrough pain episodes in one day, the next day the dose was increased (in 200 mcg increments for FBT and 15 mg increments for oxycodone). The maximum allowable dose was 800 mcg for FBT (4 tablets) and 60 mg (4 capsules) for oxycodone. If a dose was not tolerated the dose was lowered to the previous tolerated dose. Titration completed when successful analgesia was achieved with a tolerated dose or maximum dose was reached. If unsuccessful at maximum dose subject was discontinued from proceeding further in the study. Subjects who successfully titrated were randomized.
|
Immediate-Release Oxycodone First FBT Second
Subjects in this treatment group were assigned 15 mg oxycodone during the first titration period and then 200 mcg FBT during the second titration period. Standard rescue medication could be taken if pain relief was unsuccessful. If more than one dose was required for at least 1 of 3 breakthrough pain episodes in one day, the next day the dose was increased (in 200 mcg increments for FBT and 15 mg increments for oxycodone). The maximum allowable dose was 800 mcg for FBT (4 tablets) and 60 mg (4 capsules) for oxycodone. If a dose was not tolerated the dose was lowered to the previous tolerated dose. Titration completed when successful analgesia was achieved with a tolerated dose or maximum dose was reached. If unsuccessful at maximum dose subject was discontinued from proceeding further in the study. Subjects who successfully titrated were randomized.
|
|---|---|---|
|
Titration Period 1
Adverse Event
|
6
|
1
|
|
Titration Period 1
Lack of Efficacy
|
9
|
7
|
|
Titration Period 1
Withdrawal by Subject
|
2
|
2
|
|
Titration Period 1
Protocol Violation
|
4
|
3
|
|
Titration Period 1
Non-compliance to study medication
|
4
|
1
|
|
Titration Period 1
Non-compliance to study procedures
|
2
|
2
|
|
Titration Period 1
Technical Difficulties
|
0
|
1
|
|
Titration Period 2
Adverse Event
|
2
|
3
|
|
Titration Period 2
Lack of Efficacy
|
8
|
4
|
|
Titration Period 2
Protocol Violation
|
3
|
2
|
|
Titration Period 2
Lost to Follow-up
|
1
|
0
|
|
Titration Period 2
Non-compliance with study procedures
|
2
|
1
|
|
Double-blind Treatment Period 1
Adverse Event
|
1
|
1
|
|
Double-blind Treatment Period 1
Withdrawal by Subject
|
0
|
1
|
|
Double-blind Treatment Period 1
Protocol Violation
|
0
|
2
|
|
Double-blind Treatment Period 1
Lost to Follow-up
|
0
|
1
|
|
Double-blind Treatment Period 2
Adverse Event
|
1
|
0
|
|
Double-blind Treatment Period 2
Withdrawal by Subject
|
1
|
1
|
|
Double-blind Treatment Period 2
Protocol Violation
|
2
|
0
|
|
Double-blind Treatment Period 2
Other
|
1
|
0
|
|
Open-label Extension
Adverse Event
|
1
|
2
|
|
Open-label Extension
Lack of Efficacy
|
3
|
0
|
|
Open-label Extension
Withdrawal by Subject
|
0
|
2
|
|
Open-label Extension
Protocol Violation
|
1
|
2
|
|
Open-label Extension
Non-compliance study medication
|
4
|
0
|
|
Open-label Extension
Non-compliance study procedures
|
2
|
1
|
|
Open-label Extension
Other
|
1
|
0
|
Baseline Characteristics
Fentanyl Buccal Tablets Versus Immediate Release Oxycodone for Breakthrough Pain in Patients With Chronic Pain
Baseline characteristics by cohort
| Measure |
Total Number of Patients
n=213 Participants
|
|---|---|
|
Age Continuous
|
51.0 years
STANDARD_DEVIATION 9.97 • n=5 Participants
|
|
Sex: Female, Male
Female
|
120 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
93 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
10 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
195 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
8 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
19 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
191 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
213 participants
n=5 Participants
|
|
Body Mass Index (BMI)
|
30.1 kg/m^2
STANDARD_DEVIATION 7.25 • n=5 Participants
|
PRIMARY outcome
Timeframe: Immediately pre-dose and 15 minutes after dosingPopulation: Full Analysis Set defined as having at least one evaluable episode of breakthrough pain treated with FBT and at least one with oxycodone. An episode was evaluable if it had a valid pain intensity measurement immediately prior to drug administration. No imputation for missing breakthrough pain episodes, but LOCF was applied for missing PI scores.
Pain intensity (PI) scores were assessed on an 11-point numerical rating scale from 0 = no pain to 10 = pain as bad as you can imagine after each episode of breakthrough pain during the double-blind treatment period. The PID15 is the difference between the PI scores from the episode baseline (immediately prior to study drug administration)and 15 minutes after the administration of the study drug. Least squared mean was from an analysis of variance (ANOVA) with treatment as randomized, phase, and sequence as fixed factors and patient as a random factor using compound symmetry.
Outcome measures
| Measure |
Fentanyl Buccal Tablet (FBT)
n=1342 Breakthrough pain episodes
FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.
PTs were initially titrated with FBT during the 1st titration period and immediate release oxycodone during the 2nd titration period or immediate-release oxycodone in the 1st titration period then FBT in the 2nd titration period.
During the 12-week open-label extension period, pts randomized to FBT treatment were initially dispensed single tablets at the dose found to be successful during the titration period.
|
Immediate-release Oxycodone (OXY)
n=1334 Breakthrough pain episodes
Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Patients were initially titrated to immediate-release oxycodone during the 1st titration period and to FBT during the 2nd titration period or to FBT during the 1st titration period and immediate-release oxycodone during the 2nd titration period.
|
|---|---|---|
|
Pain Intensity Difference (PID) at 15 Minutes Post-treatment (PID15)
|
0.88 Units on scale
Standard Error 0.09
|
0.76 Units on scale
Standard Error 0.09
|
SECONDARY outcome
Timeframe: Immediately pre-dose and 5 minutes after dosingPopulation: Full Analysis Set defined as having at least one evaluable episode of breakthrough pain treated with FBT and at least one with oxycodone. An episode was evaluable if it had a valid pain intensity measurement immediately prior to drug administration. No imputation for missing breakthrough pain episodes, but LOCF was applied for missing PI scores.
Pain intensity (PI) scores were assessed on an 11-point numerical rating scale from 0 = no pain to 10 = pain as bad as you can imagine after each episode of breakthrough pain during the double-blind treatment period. The PID5 is the difference between the PI score from the episode baseline (immediately prior to study drug administration) and 5 minutes after the administration of the study drug. Least squared mean was from an analysis of variance (ANOVA) with treatment as randomized, phase, and sequence as fixed factors and patient as a random factor using compound symmetry.
Outcome measures
| Measure |
Fentanyl Buccal Tablet (FBT)
n=1342 Breakthrough pain episodes
FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.
PTs were initially titrated with FBT during the 1st titration period and immediate release oxycodone during the 2nd titration period or immediate-release oxycodone in the 1st titration period then FBT in the 2nd titration period.
During the 12-week open-label extension period, pts randomized to FBT treatment were initially dispensed single tablets at the dose found to be successful during the titration period.
|
Immediate-release Oxycodone (OXY)
n=1334 Breakthrough pain episodes
Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Patients were initially titrated to immediate-release oxycodone during the 1st titration period and to FBT during the 2nd titration period or to FBT during the 1st titration period and immediate-release oxycodone during the 2nd titration period.
|
|---|---|---|
|
Pain Intensity Difference (PID) at 5 Minutes Post-treatment
|
.08 Units on a scale
Standard Error .02
|
.06 Units on a scale
Standard Error .02
|
SECONDARY outcome
Timeframe: Immediately pre-dose and 10 minutes after dosingPopulation: Full Analysis Set defined as having at least one evaluable episode of breakthrough pain treated with FBT and at least one with oxycodone. An episode was evaluable if it had a valid pain intensity measurement immediately prior to drug administration. No imputation for missing breakthrough pain episodes, but LOCF was applied for missing PI scores.
Pain intensity (PI) scores were assessed on an 11-point numerical rating scale from 0 = no pain to 10 = pain as bad as you can imagine after each episode of breakthrough pain during the double-blind treatment period. The PID10 is the difference between the PI score from the episode baseline (immediately prior to study drug administration) and 10 minutes after the administration of the study drug. Least squared mean was from an analysis of variance (ANOVA) with treatment as randomized, phase, and sequence as fixed factors and patient as a random factor using compound symmetry.
Outcome measures
| Measure |
Fentanyl Buccal Tablet (FBT)
n=1342 Breakthrough pain episodes
FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.
PTs were initially titrated with FBT during the 1st titration period and immediate release oxycodone during the 2nd titration period or immediate-release oxycodone in the 1st titration period then FBT in the 2nd titration period.
During the 12-week open-label extension period, pts randomized to FBT treatment were initially dispensed single tablets at the dose found to be successful during the titration period.
|
Immediate-release Oxycodone (OXY)
n=1334 Breakthrough pain episodes
Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Patients were initially titrated to immediate-release oxycodone during the 1st titration period and to FBT during the 2nd titration period or to FBT during the 1st titration period and immediate-release oxycodone during the 2nd titration period.
|
|---|---|---|
|
Pain Intensity Difference (PID) at 10 Minutes Post-treatment
|
.35 Units on a scale
Standard Error .05
|
.29 Units on a scale
Standard Error .05
|
SECONDARY outcome
Timeframe: Immediately pre-dose and 30 minutes after dosingPopulation: Full Analysis Set defined as having at least one evaluable episode of breakthrough pain treated with FBT and at least one with oxycodone. An episode was evaluable if it had a valid pain intensity measurement immediately prior to drug administration. No imputation for missing breakthrough pain episodes, but LOCF was applied for missing PI scores.
Pain intensity (PI) scores were assessed on an 11-point numerical rating scale from 0 = no pain to 10 = pain as bad as you can imagine after each episode of breakthrough pain during the double-blind treatment period. The PID30 is the difference between the PI score from the episode baseline (immediately prior to study drug administration) and 30 minutes after the administration of the study drug. Least squared mean was from an analysis of variance (ANOVA) with treatment as randomized, phase, and sequence as fixed factors and patient as a random factor using compound symmetry.
Outcome measures
| Measure |
Fentanyl Buccal Tablet (FBT)
n=1342 Breakthrough pain episodes
FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.
PTs were initially titrated with FBT during the 1st titration period and immediate release oxycodone during the 2nd titration period or immediate-release oxycodone in the 1st titration period then FBT in the 2nd titration period.
During the 12-week open-label extension period, pts randomized to FBT treatment were initially dispensed single tablets at the dose found to be successful during the titration period.
|
Immediate-release Oxycodone (OXY)
n=1334 Breakthrough pain episodes
Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Patients were initially titrated to immediate-release oxycodone during the 1st titration period and to FBT during the 2nd titration period or to FBT during the 1st titration period and immediate-release oxycodone during the 2nd titration period.
|
|---|---|---|
|
Pain Intensity Difference (PID) at 30 Minutes Post-treatment
|
2.10 Units on a scale
Standard Error 0.12
|
1.79 Units on a scale
Standard Error 0.12
|
SECONDARY outcome
Timeframe: Immediately pre-dose and 45 minutes after dosingPopulation: Full Analysis Set defined as having at least one evaluable episode of breakthrough pain treated with FBT and at least one with oxycodone. An episode was evaluable if it had a valid pain intensity measurement immediately prior to drug administration. No imputation for missing breakthrough pain episodes, but LOCF was applied for missing PI scores.
Pain intensity (PI) scores were assessed on an 11-point numerical rating scale from 0 = no pain to 10 = pain as bad as you can imagine after each episode of breakthrough pain during the double-blind treatment period. The PID45 is the difference between the PI score from the episode baseline (immediately prior to study drug administration) and 45 minutes after the administration of the study drug. Least squared mean was from an analysis of variance (ANOVA) with treatment as randomized, phase, and sequence as fixed factors and patient as a random factor using compound symmetry.
Outcome measures
| Measure |
Fentanyl Buccal Tablet (FBT)
n=1342 Breakthrough pain episodes
FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.
PTs were initially titrated with FBT during the 1st titration period and immediate release oxycodone during the 2nd titration period or immediate-release oxycodone in the 1st titration period then FBT in the 2nd titration period.
During the 12-week open-label extension period, pts randomized to FBT treatment were initially dispensed single tablets at the dose found to be successful during the titration period.
|
Immediate-release Oxycodone (OXY)
n=1334 Breakthrough pain episodes
Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Patients were initially titrated to immediate-release oxycodone during the 1st titration period and to FBT during the 2nd titration period or to FBT during the 1st titration period and immediate-release oxycodone during the 2nd titration period.
|
|---|---|---|
|
Pain Intensity Difference (PID) at 45 Minutes Post-treatment
|
3.13 Units on a scale
Standard Error 0.14
|
2.85 Units on a scale
Standard Error 0.14
|
SECONDARY outcome
Timeframe: Immediately pre-dose and 60 minutes after dosingPopulation: Full Analysis Set defined as having at least one evaluable episode of breakthrough pain treated with FBT and at least one with oxycodone. An episode was evaluable if it had a valid pain intensity measurement immediately prior to drug administration. No imputation for missing breakthrough pain episodes, but LOCF was applied for missing PI scores.
Pain intensity (PI) scores were assessed on an 11-point numerical rating scale from 0 = no pain to 10 = pain as bad as you can imagine after each episode of breakthrough pain during the double-blind treatment period. The PID60 is the difference between the PI score from the episode baseline (immediately prior to study drug administration) and 60 minutes after the administration of the study drug. Least squared mean was from an analysis of variance (ANOVA) with treatment as randomized, phase, and sequence as fixed factors and patient as a random factor using compound symmetry.
Outcome measures
| Measure |
Fentanyl Buccal Tablet (FBT)
n=1342 Breakthrough pain episodes
FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.
PTs were initially titrated with FBT during the 1st titration period and immediate release oxycodone during the 2nd titration period or immediate-release oxycodone in the 1st titration period then FBT in the 2nd titration period.
During the 12-week open-label extension period, pts randomized to FBT treatment were initially dispensed single tablets at the dose found to be successful during the titration period.
|
Immediate-release Oxycodone (OXY)
n=1334 Breakthrough pain episodes
Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Patients were initially titrated to immediate-release oxycodone during the 1st titration period and to FBT during the 2nd titration period or to FBT during the 1st titration period and immediate-release oxycodone during the 2nd titration period.
|
|---|---|---|
|
Pain Intensity Difference (PID) at 60 Minutes Post-treatment
|
3.65 Units on a scale
Standard Error 0.15
|
3.48 Units on a scale
Standard Error 0.15
|
SECONDARY outcome
Timeframe: Immediately pre-dose and 5 minutes after dosingPopulation: Full Analysis Set defined as having at least one evaluable episode of breakthrough pain treated with FBT and at least one with oxycodone. An episode was evaluable if it had a valid pain intensity measurement immediately prior to drug administration. No imputation for missing breakthrough pain episodes, but LOCF was applied for missing PI scores.
Pain intensity (PI) scores were assessed on an 11-point numerical rating scale from 0 = no pain to 10 = pain as bad as you can imagine after each episode of breakthrough pain during the double-blind treatment period. The PID5 is the difference between the PI scores from the episode baseline (immediately prior to study drug administration)and 5 minutes after the administration of the study drug. The difference is calculated and assessed as a percentage of the baseline pain intensity score.
Outcome measures
| Measure |
Fentanyl Buccal Tablet (FBT)
n=137 Participants
FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.
PTs were initially titrated with FBT during the 1st titration period and immediate release oxycodone during the 2nd titration period or immediate-release oxycodone in the 1st titration period then FBT in the 2nd titration period.
During the 12-week open-label extension period, pts randomized to FBT treatment were initially dispensed single tablets at the dose found to be successful during the titration period.
|
Immediate-release Oxycodone (OXY)
n=137 Participants
Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Patients were initially titrated to immediate-release oxycodone during the 1st titration period and to FBT during the 2nd titration period or to FBT during the 1st titration period and immediate-release oxycodone during the 2nd titration period.
|
|---|---|---|
|
Percentage Change in Pain Intensity Difference (% PID) at 5 Minutes Post-treatment
|
1.01 Percentage change
Standard Deviation 4.50
|
0.73 Percentage change
Standard Deviation 3.02
|
SECONDARY outcome
Timeframe: Immediately before treatment and 10 minutes after treatment.Population: Full Analysis Set defined as having at least one evaluable episode of breakthrough pain treated with FBT and at least one with oxycodone. An episode was evaluable if it had a valid pain intensity measurement immediately prior to drug administration. No imputation for missing breakthrough pain episodes, but LOCF was applied for missing PI scores.
Pain intensity (PI) scores were assessed on an 11-point numerical rating scale from 0 = no pain to 10 = pain as bad as you can imagine after each episode of breakthrough pain. The PID10 is the difference between the PI scores from the episode baseline (immediately prior to study drug administration)and 10 minutes after the administration of the study drug. The difference is calculated and assessed as a percentage of the baseline pain intensity score. This was assessed during the double-blind treatment period.
Outcome measures
| Measure |
Fentanyl Buccal Tablet (FBT)
n=137 Participants
FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.
PTs were initially titrated with FBT during the 1st titration period and immediate release oxycodone during the 2nd titration period or immediate-release oxycodone in the 1st titration period then FBT in the 2nd titration period.
During the 12-week open-label extension period, pts randomized to FBT treatment were initially dispensed single tablets at the dose found to be successful during the titration period.
|
Immediate-release Oxycodone (OXY)
n=137 Participants
Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Patients were initially titrated to immediate-release oxycodone during the 1st titration period and to FBT during the 2nd titration period or to FBT during the 1st titration period and immediate-release oxycodone during the 2nd titration period.
|
|---|---|---|
|
Percentage Change in Pain Intensity Difference (% PID) at 10 Minutes Post-treatment
|
4.83 Percentage change
Standard Deviation 11.21
|
3.89 Percentage change
Standard Deviation 8.30
|
SECONDARY outcome
Timeframe: Baseline (immediately pre-dose) and 15 minutes after dosingPopulation: Full Analysis Set defined as having at least one evaluable episode of breakthrough pain treated with FBT and at least one with oxycodone. An episode was evaluable if it had a valid pain intensity measurement immediately prior to drug administration. No imputation for missing breakthrough pain episodes, but LOCF was applied for missing PI scores.
Pain intensity (PI) scores were assessed during the double-blind treatment period on an 11-point numerical rating scale from 0 = no pain to 10 = pain as bad as you can imagine after each episode of breakthrough pain. The PID15 is the difference between the PI scores from the episode baseline (immediately prior to study drug administration)and 15 minutes after the administration of the study drug. The difference is calculated and assessed as a percentage of the baseline pain intensity score.
Outcome measures
| Measure |
Fentanyl Buccal Tablet (FBT)
n=137 Participants
FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.
PTs were initially titrated with FBT during the 1st titration period and immediate release oxycodone during the 2nd titration period or immediate-release oxycodone in the 1st titration period then FBT in the 2nd titration period.
During the 12-week open-label extension period, pts randomized to FBT treatment were initially dispensed single tablets at the dose found to be successful during the titration period.
|
Immediate-release Oxycodone (OXY)
n=137 Participants
Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Patients were initially titrated to immediate-release oxycodone during the 1st titration period and to FBT during the 2nd titration period or to FBT during the 1st titration period and immediate-release oxycodone during the 2nd titration period.
|
|---|---|---|
|
Percentage Change in Pain Intensity Difference (% PID) at 15 Minutes Post-treatment
|
12.38 Percentage change
Standard Deviation 17.08
|
10.38 Percentage change
Standard Deviation 15.43
|
SECONDARY outcome
Timeframe: Pre-dose and 30 minutes after dosingPopulation: Full Analysis Set defined as having at least one evaluable episode of breakthrough pain treated with FBT and at least one with oxycodone. An episode was evaluable if it had a valid pain intensity measurement immediately prior to drug administration. No imputation for missing breakthrough pain episodes, but LOCF was applied for missing PI scores.
Pain intensity (PI) scores were assessed on an 11-point numerical rating scale from 0 = no pain to 10 = pain as bad as you can imagine after each episode of breakthrough pain during the double-blind treatment period. The PID30 is the difference between the PI scores from the episode baseline (immediately prior to study drug administration)and 30 minutes after the administration of the study drug. The difference is calculated and assessed as a percentage of the baseline pain intensity score.
Outcome measures
| Measure |
Fentanyl Buccal Tablet (FBT)
n=137 Participants
FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.
PTs were initially titrated with FBT during the 1st titration period and immediate release oxycodone during the 2nd titration period or immediate-release oxycodone in the 1st titration period then FBT in the 2nd titration period.
During the 12-week open-label extension period, pts randomized to FBT treatment were initially dispensed single tablets at the dose found to be successful during the titration period.
|
Immediate-release Oxycodone (OXY)
n=137 Participants
Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Patients were initially titrated to immediate-release oxycodone during the 1st titration period and to FBT during the 2nd titration period or to FBT during the 1st titration period and immediate-release oxycodone during the 2nd titration period.
|
|---|---|---|
|
Percentage Change in Pain Intensity Difference (% PID) at 30 Minutes Post-treatment
|
29.72 Percentage change
Standard Deviation 21.30
|
25.03 Percentage change
Standard Deviation 20.42
|
SECONDARY outcome
Timeframe: Immediately pre-dose and 45 minutes after dosingPopulation: Full Analysis Set defined as having at least one evaluable episode of breakthrough pain treated with FBT and at least one with oxycodone. An episode was evaluable if it had a valid pain intensity measurement immediately prior to drug administration. No imputation for missing breakthrough pain episodes, but LOCF was applied for missing PI scores.
Pain intensity (PI) scores were assessed on an 11-point numerical rating scale from 0 = no pain to 10 = pain as bad as you can imagine after each episode of breakthrough pain during the double-blind treatment period. The PID45 is the difference between the PI scores from the episode baseline (immediately prior to study drug administration)and 45 minutes after the administration of the study drug. The difference is calculated and assessed as a percentage of the baseline pain intensity score.
Outcome measures
| Measure |
Fentanyl Buccal Tablet (FBT)
n=137 Participants
FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.
PTs were initially titrated with FBT during the 1st titration period and immediate release oxycodone during the 2nd titration period or immediate-release oxycodone in the 1st titration period then FBT in the 2nd titration period.
During the 12-week open-label extension period, pts randomized to FBT treatment were initially dispensed single tablets at the dose found to be successful during the titration period.
|
Immediate-release Oxycodone (OXY)
n=137 Participants
Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Patients were initially titrated to immediate-release oxycodone during the 1st titration period and to FBT during the 2nd titration period or to FBT during the 1st titration period and immediate-release oxycodone during the 2nd titration period.
|
|---|---|---|
|
Percentage Change in Pain Intensity Difference (% PID) at 45 Minutes Post-treatment
|
44.84 Percentage change
Standard Deviation 23.36
|
40.49 Percentage change
Standard Deviation 22.68
|
SECONDARY outcome
Timeframe: Immediately pre-dose and 60 minutes after dosingPopulation: Full Analysis Set defined as having at least one evaluable episode of breakthrough pain treated with FBT and at least one with oxycodone. An episode was evaluable if it had a valid pain intensity measurement immediately prior to drug administration. No imputation for missing breakthrough pain episodes, but LOCF was applied for missing PI scores.
Pain intensity (PI) scores were assessed on an 11-point numerical rating scale from 0 = no pain to 10 = pain as bad as you can imagine after each episode of breakthrough pain during the double-blind treatment period. The PID60 is the difference between the PI scores from the episode baseline (immediately prior to study drug administration)and 60 minutes after the administration of the study drug. The difference is calculated and assessed as a percentage of the baseline pain intensity score.
Outcome measures
| Measure |
Fentanyl Buccal Tablet (FBT)
n=137 Participants
FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.
PTs were initially titrated with FBT during the 1st titration period and immediate release oxycodone during the 2nd titration period or immediate-release oxycodone in the 1st titration period then FBT in the 2nd titration period.
During the 12-week open-label extension period, pts randomized to FBT treatment were initially dispensed single tablets at the dose found to be successful during the titration period.
|
Immediate-release Oxycodone (OXY)
n=137 Participants
Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Patients were initially titrated to immediate-release oxycodone during the 1st titration period and to FBT during the 2nd titration period or to FBT during the 1st titration period and immediate-release oxycodone during the 2nd titration period.
|
|---|---|---|
|
Percentage Change in Pain Intensity Difference (% PID) at 60 Minutes Post-treatment
|
52.61 Percentage change
Standard Deviation 24.33
|
49.47 Percentage change
Standard Deviation 24.19
|
SECONDARY outcome
Timeframe: From 5 minutes after dosing through 30 minutes after dosingPopulation: Full Analysis Set defined as having at least one evaluable episode of breakthrough pain treated with FBT and at least one with oxycodone. An episode was evaluable if it had a valid pain intensity measurement immediately prior to drug administration. No imputation for missing breakthrough pain episodes, but LOCF was applied for missing PI scores.
PI scores were assessed on an 11-point numerical rating scale from 0 = no pain to 10 = pain as bad as you can imagine. SPID30 were derived from PID values. The SPID30 scores during the double-blind treatment phase were calculated as the time- weighted sum of the PID scores from 5 through 30 minutes,after the administration of study drug. SPID30 = (⅓ x PID5) + (⅓ x PID10) + (⅓ x PID15) + PID30. Least squared mean was from an analysis of variance (ANOVA) with treatment as randomized, phase, and sequence as fixed factors and patient as a random factor using compound symmetry.
Outcome measures
| Measure |
Fentanyl Buccal Tablet (FBT)
n=1342 Breakthrough pain episodes
FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.
PTs were initially titrated with FBT during the 1st titration period and immediate release oxycodone during the 2nd titration period or immediate-release oxycodone in the 1st titration period then FBT in the 2nd titration period.
During the 12-week open-label extension period, pts randomized to FBT treatment were initially dispensed single tablets at the dose found to be successful during the titration period.
|
Immediate-release Oxycodone (OXY)
n=1334 Breakthrough pain episodes
Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Patients were initially titrated to immediate-release oxycodone during the 1st titration period and to FBT during the 2nd titration period or to FBT during the 1st titration period and immediate-release oxycodone during the 2nd titration period.
|
|---|---|---|
|
Sum of Pain Intensity Difference at 30 Minutes Post-treatment (SPID30)
|
2.54 Units on a scale
Standard Error 0.17
|
2.16 Units on a scale
Standard Error 0.17
|
SECONDARY outcome
Timeframe: From 5 minutes after dosing through 60 minutes after dosingPopulation: Full Analysis Set defined as having at least one evaluable episode of breakthrough pain treated with FBT and at least one with oxycodone. An episode was evaluable if it had a valid pain intensity measurement immediately prior to drug administration. No imputation for missing breakthrough pain episodes, but LOCF was applied for missing PI scores.
PI scores were assessed on an 11-point numerical rating scale from 0=no pain to 10=pain as bad as you can imagine during the double-blind treatment period. The SPID60 was derived from PID values. The SPID60 scores during the double-blind treatment phase were calculated as the time- weighted sum of the PID scores from 5 through 60 minutes,after the administration of the study drug. SPID60 = SPID30 + PID45 + PID60. Least squared mean was from an analysis of variance (ANOVA) with treatment as randomized, phase, and sequence as fixed factors and patient as a random factor using compound symmetry.
Outcome measures
| Measure |
Fentanyl Buccal Tablet (FBT)
n=1342 Breakthrough pain episodes
FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.
PTs were initially titrated with FBT during the 1st titration period and immediate release oxycodone during the 2nd titration period or immediate-release oxycodone in the 1st titration period then FBT in the 2nd titration period.
During the 12-week open-label extension period, pts randomized to FBT treatment were initially dispensed single tablets at the dose found to be successful during the titration period.
|
Immediate-release Oxycodone (OXY)
n=1334 Breakthrough pain episodes
Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Patients were initially titrated to immediate-release oxycodone during the 1st titration period and to FBT during the 2nd titration period or to FBT during the 1st titration period and immediate-release oxycodone during the 2nd titration period.
|
|---|---|---|
|
Sum of Pain Intensity Difference at 60 Minutes Post-treatment (SPID60)
|
9.32 Units on a scale
Standard Error 0.44
|
8.50 Units on a scale
Standard Error 0.44
|
SECONDARY outcome
Timeframe: 5 minutes after treatmentPopulation: Full Analysis Set defined as having at least one evaluable episode of breakthrough pain treated with FBT and at least one with oxycodone. An episode was evaluable if it had a valid pain intensity measurement immediately prior to drug administration. No imputation for missing breakthrough pain episodes, but LOCF was applied for missing PR scores.
The PR score 5 minutes after the administration of study drug during the double-blind treatment phase was recorded in the patient's diary. The PR scale is a 5-point categorical scale of 0-4 (0=none, 1=slight, 2=moderate, 3=a lot, 4=complete).
Outcome measures
| Measure |
Fentanyl Buccal Tablet (FBT)
n=137 Participants
FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.
PTs were initially titrated with FBT during the 1st titration period and immediate release oxycodone during the 2nd titration period or immediate-release oxycodone in the 1st titration period then FBT in the 2nd titration period.
During the 12-week open-label extension period, pts randomized to FBT treatment were initially dispensed single tablets at the dose found to be successful during the titration period.
|
Immediate-release Oxycodone (OXY)
n=137 Participants
Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Patients were initially titrated to immediate-release oxycodone during the 1st titration period and to FBT during the 2nd titration period or to FBT during the 1st titration period and immediate-release oxycodone during the 2nd titration period.
|
|---|---|---|
|
Pain Relief (PR) Score at 5 Minutes Post-treatment
|
0.11 Units on a scale
Standard Deviation 0.41
|
0.10 Units on a scale
Standard Deviation 0.36
|
SECONDARY outcome
Timeframe: 10 minutes after treatment with study drugPopulation: Full Analysis Set defined as having at least one evaluable episode of breakthrough pain treated with FBT and at least one with oxycodone. An episode was evaluable if it had a valid pain intensity measurement immediately prior to drug administration. No imputation for missing breakthrough pain episodes, but LOCF was applied for missing PR scores.
The PR score 10 minutes after the administration of study drug during the double-blind treatment phase was recorded in the patient's diary. The PR scale is a 5-point categorical scale of 0-4 (0=none, 1=slight, 2=moderate, 3=a lot, 4=complete).
Outcome measures
| Measure |
Fentanyl Buccal Tablet (FBT)
n=137 Participants
FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.
PTs were initially titrated with FBT during the 1st titration period and immediate release oxycodone during the 2nd titration period or immediate-release oxycodone in the 1st titration period then FBT in the 2nd titration period.
During the 12-week open-label extension period, pts randomized to FBT treatment were initially dispensed single tablets at the dose found to be successful during the titration period.
|
Immediate-release Oxycodone (OXY)
n=137 Participants
Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Patients were initially titrated to immediate-release oxycodone during the 1st titration period and to FBT during the 2nd titration period or to FBT during the 1st titration period and immediate-release oxycodone during the 2nd titration period.
|
|---|---|---|
|
Pain Relief Score at 10 Minutes Post-treatment
|
0.32 Units on a scale
Standard Deviation 0.61
|
0.26 Units on a scale
Standard Deviation 0.49
|
SECONDARY outcome
Timeframe: 15 minutes after treatment with study drugPopulation: Full Analysis Set defined as having at least one evaluable episode of breakthrough pain treated with FBT and at least one with oxycodone. An episode was evaluable if it had a valid pain intensity measurement immediately prior to drug administration. No imputation for missing breakthrough pain episodes, but LOCF was applied for missing PR scores.
The PR score 15 minutes after the administration of study drug during the double-blind treatment phase was recorded in the patient's diary. The PR scale is a 5-point categorical scale of 0-4 (0=none, 1=slight, 2=moderate, 3=a lot, 4=complete).
Outcome measures
| Measure |
Fentanyl Buccal Tablet (FBT)
n=137 Participants
FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.
PTs were initially titrated with FBT during the 1st titration period and immediate release oxycodone during the 2nd titration period or immediate-release oxycodone in the 1st titration period then FBT in the 2nd titration period.
During the 12-week open-label extension period, pts randomized to FBT treatment were initially dispensed single tablets at the dose found to be successful during the titration period.
|
Immediate-release Oxycodone (OXY)
n=137 Participants
Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Patients were initially titrated to immediate-release oxycodone during the 1st titration period and to FBT during the 2nd titration period or to FBT during the 1st titration period and immediate-release oxycodone during the 2nd titration period.
|
|---|---|---|
|
Pain Relief Score at 15 Minutes Post-treatment
|
0.68 Units on a scale
Standard Deviation 0.74
|
0.56 Units on a scale
Standard Deviation 0.70
|
SECONDARY outcome
Timeframe: 30 minutes after treatment with study drugPopulation: Full Analysis Set defined as having at least one evaluable episode of breakthrough pain treated with FBT and at least one with oxycodone. An episode was evaluable if it had a valid pain intensity measurement immediately prior to drug administration. No imputation for missing breakthrough pain episodes, but LOCF was applied for missing PR scores.
The PR score 30 minutes after the administration of study drug during the double-blind treatment phase was recorded in the patient's diary. The PR scale is a 5-point categorical scale of 0-4 (0=none, 1=slight, 2=moderate, 3=a lot, 4=complete).
Outcome measures
| Measure |
Fentanyl Buccal Tablet (FBT)
n=137 Participants
FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.
PTs were initially titrated with FBT during the 1st titration period and immediate release oxycodone during the 2nd titration period or immediate-release oxycodone in the 1st titration period then FBT in the 2nd titration period.
During the 12-week open-label extension period, pts randomized to FBT treatment were initially dispensed single tablets at the dose found to be successful during the titration period.
|
Immediate-release Oxycodone (OXY)
n=137 Participants
Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Patients were initially titrated to immediate-release oxycodone during the 1st titration period and to FBT during the 2nd titration period or to FBT during the 1st titration period and immediate-release oxycodone during the 2nd titration period.
|
|---|---|---|
|
Pain Relief Score at 30 Minutes Post-treatment
|
1.48 Units on a scale
Standard Deviation 0.83
|
1.22 Units on a scale
Standard Deviation 0.81
|
SECONDARY outcome
Timeframe: 45 minutes after treatment with study drugPopulation: Full Analysis Set defined as having at least one evaluable episode of breakthrough pain treated with FBT and at least one with oxycodone. An episode was evaluable if it had a valid pain intensity measurement immediately prior to drug administration. No imputation for missing breakthrough pain episodes, but LOCF was applied for missing PR scores.
The PR score 45 minutes after the administration of study drug during the double-blind treatment phase was recorded in the patient's diary. The PR scale is a 5-point categorical scale of 0-4 (0=none, 1=slight, 2=moderate, 3=a lot, 4=complete).
Outcome measures
| Measure |
Fentanyl Buccal Tablet (FBT)
n=137 Participants
FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.
PTs were initially titrated with FBT during the 1st titration period and immediate release oxycodone during the 2nd titration period or immediate-release oxycodone in the 1st titration period then FBT in the 2nd titration period.
During the 12-week open-label extension period, pts randomized to FBT treatment were initially dispensed single tablets at the dose found to be successful during the titration period.
|
Immediate-release Oxycodone (OXY)
n=137 Participants
Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Patients were initially titrated to immediate-release oxycodone during the 1st titration period and to FBT during the 2nd titration period or to FBT during the 1st titration period and immediate-release oxycodone during the 2nd titration period.
|
|---|---|---|
|
Pain Relief Score at 45 Minutes Post-treatment
|
2.14 Units on a scale
Standard Deviation 0.82
|
1.90 Units on a scale
Standard Deviation 0.82
|
SECONDARY outcome
Timeframe: 60 minutes after treatment with study drugPopulation: Full Analysis Set defined as having at least one evaluable episode of breakthrough pain treated with FBT and at least one with oxycodone. An episode was evaluable if it had a valid pain intensity measurement immediately prior to drug administration. No imputation for missing breakthrough pain episodes, but LOCF was applied for missing PR scores.
The PR score 60 minutes after the administration of study drug during the double-blind treatment phase was recorded in the patient's diary. The PR scale is a 5-point categorical scale of 0-4 (0=none, 1=slight, 2=moderate, 3=a lot, 4=complete).
Outcome measures
| Measure |
Fentanyl Buccal Tablet (FBT)
n=137 Participants
FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.
PTs were initially titrated with FBT during the 1st titration period and immediate release oxycodone during the 2nd titration period or immediate-release oxycodone in the 1st titration period then FBT in the 2nd titration period.
During the 12-week open-label extension period, pts randomized to FBT treatment were initially dispensed single tablets at the dose found to be successful during the titration period.
|
Immediate-release Oxycodone (OXY)
n=137 Participants
Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Patients were initially titrated to immediate-release oxycodone during the 1st titration period and to FBT during the 2nd titration period or to FBT during the 1st titration period and immediate-release oxycodone during the 2nd titration period.
|
|---|---|---|
|
Pain Relief Score at 60 Minutes Post-treatment
|
2.44 Units on a scale
Standard Deviation 0.83
|
2.27 Units on a scale
Standard Deviation 0.82
|
SECONDARY outcome
Timeframe: From 5 minutes to 60 minutes after dosingPopulation: Full Analysis Set defined as having at least one evaluable episode of breakthrough pain treated with FBT and at least one with oxycodone. An episode was evaluable if it had a valid pain intensity measurement immediately prior to drug administration. No imputation for missing breakthrough pain episodes, but LOCF was applied for missing PR scores.
The mean TOTPAR at 60 minutes will be calculated for each episode as the weighted sum of Pain Relief (PR) scores (5-point Likert scale, 0 = none to 4 = complete) at each assessment of PR (during the double-blind treatment period) until 60 minutes after study drug administration, as follows: TOTPAR60 =(⅓ x PR5)+ (⅓ x PR10) +(⅓ x PR15)+ PR30 + PR45 + PR60. Least squared mean was from an analysis of variance (ANOVA) with treatment as randomized, phase, and sequence as fixed factors and patient as a random factor using compound symmetry.
Outcome measures
| Measure |
Fentanyl Buccal Tablet (FBT)
n=137 Participants
FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.
PTs were initially titrated with FBT during the 1st titration period and immediate release oxycodone during the 2nd titration period or immediate-release oxycodone in the 1st titration period then FBT in the 2nd titration period.
During the 12-week open-label extension period, pts randomized to FBT treatment were initially dispensed single tablets at the dose found to be successful during the titration period.
|
Immediate-release Oxycodone (OXY)
n=137 Participants
Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Patients were initially titrated to immediate-release oxycodone during the 1st titration period and to FBT during the 2nd titration period or to FBT during the 1st titration period and immediate-release oxycodone during the 2nd titration period.
|
|---|---|---|
|
Total Pain Relief at 60 Minutes (TOTPAR60)
|
6.43 units on a scale
Standard Error 0.20
|
5.70 units on a scale
Standard Error 0.20
|
SECONDARY outcome
Timeframe: From 5 minutes through 60 minutes after study drug treatmentPopulation: Full Analysis Set defined as having at least one evaluable episode of breakthrough pain treated with FBT and at least one with oxycodone. An episode was evaluable if it had a valid pain intensity measurement immediately prior to drug administration. No imputation for missing breakthrough pain episodes, but LOCF was applied for missing PR scores.
The PR score at set intervals after the administration of study drug during the double-blind treatment phase was recorded in the patient's diary. The PR scale is a 5-point categorical scale of 0-4 (0=none, 1=slight, 2=moderate, 3=a lot, 4=complete). The maximum TOTPAR score that could be achieved at 60 minutes is equal to 16; thus, %TOTPAR at 60 minutes is (TOTPAR60 /16) x 100.The % TOTPAR achieved 60 minutes after the administration of study drug was calculated during the double-blind treatment phase.
Outcome measures
| Measure |
Fentanyl Buccal Tablet (FBT)
n=137 Participants
FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.
PTs were initially titrated with FBT during the 1st titration period and immediate release oxycodone during the 2nd titration period or immediate-release oxycodone in the 1st titration period then FBT in the 2nd titration period.
During the 12-week open-label extension period, pts randomized to FBT treatment were initially dispensed single tablets at the dose found to be successful during the titration period.
|
Immediate-release Oxycodone (OXY)
n=137 Participants
Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Patients were initially titrated to immediate-release oxycodone during the 1st titration period and to FBT during the 2nd titration period or to FBT during the 1st titration period and immediate-release oxycodone during the 2nd titration period.
|
|---|---|---|
|
Percent Total Pain Relief at 60 Minutes Posttreatment (%TOTPAR)
|
40.11 Percentage change
Standard Deviation 16.32
|
35.59 Percentage change
Standard Deviation 15.78
|
SECONDARY outcome
Timeframe: From time study drug was taken until 5 minutes after treatmentPopulation: Full Analysis Set defined by at least one episode of breakthrough pain treated with FBT and at least one with oxycodone. No imputation was done if subject never answered APR/MPR question. If responded only as no, remaining missing imputed as no. If at least 1 yes, remaining missing imputed as yes.
Time to APR (subjective perception of any reduction in pain intensity) was measured by stopwatch and by scheduled questions at each time point up to 60 minutes during double-blind treatment period. No pain relief was defined as: patient indicated no pain relief experienced, rescue medication was used,or missing data. For each category (\<5, \<10, \<15, \<30, \<45, \<60 minutes, No APR-rescue medication used, and No APR-no rescue medication used)the number of episodes which time to APR fell in that category was compared. Number of episodes where APR was achieved in 5 minutes or less was compared.
Outcome measures
| Measure |
Fentanyl Buccal Tablet (FBT)
n=1342 Breakthrough pain episodes
FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.
PTs were initially titrated with FBT during the 1st titration period and immediate release oxycodone during the 2nd titration period or immediate-release oxycodone in the 1st titration period then FBT in the 2nd titration period.
During the 12-week open-label extension period, pts randomized to FBT treatment were initially dispensed single tablets at the dose found to be successful during the titration period.
|
Immediate-release Oxycodone (OXY)
n=1334 Breakthrough pain episodes
Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Patients were initially titrated to immediate-release oxycodone during the 1st titration period and to FBT during the 2nd titration period or to FBT during the 1st titration period and immediate-release oxycodone during the 2nd titration period.
|
|---|---|---|
|
Time to Any Pain Relief (APR) by Treatment - <= 5 Minutes
|
55 Episodes
|
50 Episodes
|
SECONDARY outcome
Timeframe: From study drug treatment until 10 minutes after treatmentPopulation: Full Analysis Set defined by at least one episode of breakthrough pain treated with FBT and at least one with oxycodone. No imputation was done if subject never answered APR/MPR question. If responded only as no, remaining missing imputed as no. If at least 1 yes, remaining missing imputed as yes.
Time to APR (subjective perception of any reduction in pain intensity) was measured by stopwatch and by scheduled questions at each time point up to 60 minutes during double-blind treatment period. No pain relief was defined as: patient indicated no pain relief experienced, rescue medication was used,or missing data. For each category (\<5, \<10, \<15, \<30, \<45, \<60 minutes, No APR-rescue medication used, and No APR-no rescue medication used)the number of episodes which time to APR fell in that category was compared. Number of episodes where APR was achieved in 10 minutes or less was compared.
Outcome measures
| Measure |
Fentanyl Buccal Tablet (FBT)
n=1342 Breakthrough pain episodes
FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.
PTs were initially titrated with FBT during the 1st titration period and immediate release oxycodone during the 2nd titration period or immediate-release oxycodone in the 1st titration period then FBT in the 2nd titration period.
During the 12-week open-label extension period, pts randomized to FBT treatment were initially dispensed single tablets at the dose found to be successful during the titration period.
|
Immediate-release Oxycodone (OXY)
n=1334 Breakthrough pain episodes
Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Patients were initially titrated to immediate-release oxycodone during the 1st titration period and to FBT during the 2nd titration period or to FBT during the 1st titration period and immediate-release oxycodone during the 2nd titration period.
|
|---|---|---|
|
Time to Any Pain Relief (APR) by Treatment <=10 Minutes
|
226 Episodes
|
219 Episodes
|
SECONDARY outcome
Timeframe: From study drug administration to 15 minutes after treatmentPopulation: Full Analysis Set defined by at least one episode of breakthrough pain treated with FBT and at least one with oxycodone. No imputation was done if subject never answered APR/MPR question. If responded only as no, remaining missing imputed as no. If at least 1 yes, remaining missing imputed as yes.
Time to APR (subjective perception of any reduction in pain intensity) was measured by stopwatch and by scheduled questions at each time point up to 60 minutes during double-blind treatment period. No pain relief was defined as: patient indicated no pain relief experienced, rescue medication was used,or missing data. For each category (\<5, \<10, \<15, \<30, \<45, \<60 minutes, No APR-rescue medication used, and No APR-no rescue medication used)the number of episodes which time to APR fell in that category was compared. Number of episodes where APR was achieved in 15 minutes or less was compared.
Outcome measures
| Measure |
Fentanyl Buccal Tablet (FBT)
n=1342 Breakthrough pain episodes
FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.
PTs were initially titrated with FBT during the 1st titration period and immediate release oxycodone during the 2nd titration period or immediate-release oxycodone in the 1st titration period then FBT in the 2nd titration period.
During the 12-week open-label extension period, pts randomized to FBT treatment were initially dispensed single tablets at the dose found to be successful during the titration period.
|
Immediate-release Oxycodone (OXY)
n=1334 Breakthrough pain episodes
Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Patients were initially titrated to immediate-release oxycodone during the 1st titration period and to FBT during the 2nd titration period or to FBT during the 1st titration period and immediate-release oxycodone during the 2nd titration period.
|
|---|---|---|
|
Time to Any Pain Relief (APR) by Treatment <=15 Minutes
|
515 Episodes
|
451 Episodes
|
SECONDARY outcome
Timeframe: Time of study drug administration till 30 minutes after treatmentPopulation: Full Analysis Set defined by at least one episode of breakthrough pain treated with FBT and at least one with oxycodone. No imputation was done if subject never answered APR/MPR question. If responded only as no, remaining missing imputed as no. If at least 1 yes, remaining missing imputed as yes.
Time to APR (subjective perception of any reduction in pain intensity) was measured by stopwatch and by scheduled questions at each time point up to 60 minutes during double-blind treatment period. No pain relief was defined as: patient indicated no pain relief experienced, rescue medication was used,or missing data. For each category (\<5, \<10, \<15, \<30, \<45, \<60 minutes, No APR-rescue medication used, and No APR-no rescue medication used)the number of episodes which time to APR fell in that category was compared. Number of episodes where APR was achieved in 30 minutes or less was compared.
Outcome measures
| Measure |
Fentanyl Buccal Tablet (FBT)
n=1342 Breakthrough pain episodes
FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.
PTs were initially titrated with FBT during the 1st titration period and immediate release oxycodone during the 2nd titration period or immediate-release oxycodone in the 1st titration period then FBT in the 2nd titration period.
During the 12-week open-label extension period, pts randomized to FBT treatment were initially dispensed single tablets at the dose found to be successful during the titration period.
|
Immediate-release Oxycodone (OXY)
n=1334 Breakthrough pain episodes
Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Patients were initially titrated to immediate-release oxycodone during the 1st titration period and to FBT during the 2nd titration period or to FBT during the 1st titration period and immediate-release oxycodone during the 2nd titration period.
|
|---|---|---|
|
Time to Any Pain Relief (APR) by Treatment <=30 Minutes
|
1004 Episodes
|
877 Episodes
|
SECONDARY outcome
Timeframe: Time of study drug treatment until 45 minutes after treatmentPopulation: Full Analysis Set defined by at least one episode of breakthrough pain treated with FBT and at least one with oxycodone. No imputation was done if subject never answered APR/MPR question. If responded only as no, remaining missing imputed as no. If at least 1 yes, remaining missing imputed as yes.
Time to APR (subjective perception of any reduction in pain intensity) was measured by stopwatch and by scheduled questions at each time point up to 60 minutes during double-blind treatment period. No pain relief was defined as: patient indicated no pain relief experienced, rescue medication was used,or missing data. For each category (\<5, \<10, \<15, \<30, \<45, \<60 minutes, No APR-rescue medication used, and No APR-no rescue medication used)the number of episodes which time to APR fell in that category was compared. Number of episodes where APR was achieved in 45 minutes or less was compared.
Outcome measures
| Measure |
Fentanyl Buccal Tablet (FBT)
n=1342 breakthrough pain episodes
FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.
PTs were initially titrated with FBT during the 1st titration period and immediate release oxycodone during the 2nd titration period or immediate-release oxycodone in the 1st titration period then FBT in the 2nd titration period.
During the 12-week open-label extension period, pts randomized to FBT treatment were initially dispensed single tablets at the dose found to be successful during the titration period.
|
Immediate-release Oxycodone (OXY)
n=1334 breakthrough pain episodes
Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Patients were initially titrated to immediate-release oxycodone during the 1st titration period and to FBT during the 2nd titration period or to FBT during the 1st titration period and immediate-release oxycodone during the 2nd titration period.
|
|---|---|---|
|
Time to Any Pain Relief (APR) by Treatment <=45 Minutes
|
1217 Episodes
|
1150 Episodes
|
SECONDARY outcome
Timeframe: Time of study drug treatment until 60 minutes after treatmentPopulation: Full Analysis Set defined by at least one episode of breakthrough pain treated with FBT and at least one with oxycodone. No imputation was done if subject never answered APR/MPR question. If responded only as no, remaining missing imputed as no. If at least 1 yes, remaining missing imputed as yes.
Time to APR (subjective perception of any reduction in pain intensity) was measured by stopwatch and by scheduled questions at each time point up to 60 minutes during double-blind treatment period. No pain relief was defined as: patient indicated no pain relief experienced, rescue medication was used,or missing data. For each category (\<5, \<10, \<15, \<30, \<45, \<60 minutes, No APR-rescue medication used, and No APR-no rescue medication used)the number of episodes which time to APR fell in that category was compared. Number of episodes where APR was achieved in 60 minutes or less was compared.
Outcome measures
| Measure |
Fentanyl Buccal Tablet (FBT)
n=1342 breakthrough pain episodes
FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.
PTs were initially titrated with FBT during the 1st titration period and immediate release oxycodone during the 2nd titration period or immediate-release oxycodone in the 1st titration period then FBT in the 2nd titration period.
During the 12-week open-label extension period, pts randomized to FBT treatment were initially dispensed single tablets at the dose found to be successful during the titration period.
|
Immediate-release Oxycodone (OXY)
n=1334 breakthrough pain episodes
Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Patients were initially titrated to immediate-release oxycodone during the 1st titration period and to FBT during the 2nd titration period or to FBT during the 1st titration period and immediate-release oxycodone during the 2nd titration period.
|
|---|---|---|
|
Time to Any Pain Relief (APR) by Treatment <=60 Minutes
|
1271 Episodes
|
1239 Episodes
|
SECONDARY outcome
Timeframe: From time study drug was taken until 5 minutes after treatmentPopulation: Full Analysis Set defined by at least one episode of breakthrough pain treated with FBT and at least one with oxycodone. No imputation was done if subject never answered APR/MPR question. If responded only as no, remaining missing imputed as no. If at least 1 yes, remaining missing imputed as yes.
Time to MPR (subjective perception of meaningful reduction in pain intensity) was measured by stopwatch and by scheduled questions at each time point up to 60 minutes during double-blind treatment period. No pain relief was defined as: patient indicated no pain relief experienced, rescue medication was used,or missing data. For each category (\<5, \<10, \<15, \<30, \<45, \<60 minutes, No MPR-rescue medication used, and No MPR-no rescue medication used)the number of episodes which time to MPR fell in that category was compared.
Outcome measures
| Measure |
Fentanyl Buccal Tablet (FBT)
n=1342 breakthrough pain episodes
FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.
PTs were initially titrated with FBT during the 1st titration period and immediate release oxycodone during the 2nd titration period or immediate-release oxycodone in the 1st titration period then FBT in the 2nd titration period.
During the 12-week open-label extension period, pts randomized to FBT treatment were initially dispensed single tablets at the dose found to be successful during the titration period.
|
Immediate-release Oxycodone (OXY)
n=1334 breakthrough pain episodes
Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Patients were initially titrated to immediate-release oxycodone during the 1st titration period and to FBT during the 2nd titration period or to FBT during the 1st titration period and immediate-release oxycodone during the 2nd titration period.
|
|---|---|---|
|
Time to Meaningful Pain Relief (MPR) by Treatment - <= 5 Minutes
|
21 Episodes
|
26 Episodes
|
SECONDARY outcome
Timeframe: Time of study drug treatment until 10 minutes after treatmentPopulation: Full Analysis Set defined by at least one episode of breakthrough pain treated with FBT and at least one with oxycodone. No imputation was done if subject never answered APR/MPR question. If responded only as no, remaining missing imputed as no. If at least 1 yes, remaining missing imputed as yes.
Time to MPR(subjective perception of meaningful reduction in pain intensity) was measured by stopwatch and by scheduled questions at each time point during double-blind treatment period. No pain relief was defined as: patient indicated no pain relief experienced, rescue medication was used,or missing data. For each category (\<5, \<10, \<15, \<30, \<45, \<60 minutes, No MPR-rescue medication used, and No MPR-no rescue medication used)the number of episodes which time to MPR fell in that category was compared. Number of episodes in which MPR was achieved in 10 minutes or less was compared.
Outcome measures
| Measure |
Fentanyl Buccal Tablet (FBT)
n=1342 breakthrough pain episodes
FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.
PTs were initially titrated with FBT during the 1st titration period and immediate release oxycodone during the 2nd titration period or immediate-release oxycodone in the 1st titration period then FBT in the 2nd titration period.
During the 12-week open-label extension period, pts randomized to FBT treatment were initially dispensed single tablets at the dose found to be successful during the titration period.
|
Immediate-release Oxycodone (OXY)
n=1334 breakthrough pain episodes
Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Patients were initially titrated to immediate-release oxycodone during the 1st titration period and to FBT during the 2nd titration period or to FBT during the 1st titration period and immediate-release oxycodone during the 2nd titration period.
|
|---|---|---|
|
Time to Meaningful Pain Relief (MPR) by Treatment <=10 Minutes
|
88 Episodes
|
91 Episodes
|
SECONDARY outcome
Timeframe: Time of study drug administration until 15 minutes after treatmentPopulation: Full Analysis Set defined by at least one episode of breakthrough pain treated with FBT and at least one with oxycodone. No imputation was done if subject never answered APR/MPR question. If responded only as no, remaining missing imputed as no. If at least 1 yes, remaining missing imputed as yes.
Time to MPR(subjective perception of meaningful reduction in pain intensity) was measured by stopwatch and by scheduled questions at each time point during double-blind treatment period. No pain relief was defined as: patient indicated no pain relief experienced, rescue medication was used,or missing data. For each category (\<5, \<10, \<15, \<30, \<45, \<60 minutes, No MPR-rescue medication used, and No MPR-no rescue medication used)the number of episodes which time to MPR fell in that category was compared. Number of episodes in which MPR was achieved in 15 minutes or less was compared.
Outcome measures
| Measure |
Fentanyl Buccal Tablet (FBT)
n=1342 breakthrough pain episodes
FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.
PTs were initially titrated with FBT during the 1st titration period and immediate release oxycodone during the 2nd titration period or immediate-release oxycodone in the 1st titration period then FBT in the 2nd titration period.
During the 12-week open-label extension period, pts randomized to FBT treatment were initially dispensed single tablets at the dose found to be successful during the titration period.
|
Immediate-release Oxycodone (OXY)
n=1334 breakthrough pain episodes
Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Patients were initially titrated to immediate-release oxycodone during the 1st titration period and to FBT during the 2nd titration period or to FBT during the 1st titration period and immediate-release oxycodone during the 2nd titration period.
|
|---|---|---|
|
Time to Meaningful Pain Relief (MPR) by Treatment <=15 Minutes
|
230 Episodes
|
212 Episodes
|
SECONDARY outcome
Timeframe: Time of study drug administration until 30 minutes after treatmentPopulation: Full Analysis Set defined by at least one episode of breakthrough pain treated with FBT and at least one with oxycodone. No imputation was done if subject never answered APR/MPR question. If responded only as no, remaining missing imputed as no. If at least 1 yes, remaining missing imputed as yes.
Time to MPR(subjective perception of meaningful reduction in pain intensity) was measured by stopwatch and by scheduled questions at each time point during double-blind treatment period. No pain relief was defined as: patient indicated no pain relief experienced, rescue medication was used,or missing data. For each category (\<5, \<10, \<15, \<30, \<45, \<60 minutes, No MPR-rescue medication used, and No MPR-no rescue medication used)the number of episodes which time to MPR fell in that category was compared. Number of episodes in which MPR was achieved in 30 minutes or less was compared.
Outcome measures
| Measure |
Fentanyl Buccal Tablet (FBT)
n=1342 breakthrough pain episodes
FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.
PTs were initially titrated with FBT during the 1st titration period and immediate release oxycodone during the 2nd titration period or immediate-release oxycodone in the 1st titration period then FBT in the 2nd titration period.
During the 12-week open-label extension period, pts randomized to FBT treatment were initially dispensed single tablets at the dose found to be successful during the titration period.
|
Immediate-release Oxycodone (OXY)
n=1334 breakthrough pain episodes
Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Patients were initially titrated to immediate-release oxycodone during the 1st titration period and to FBT during the 2nd titration period or to FBT during the 1st titration period and immediate-release oxycodone during the 2nd titration period.
|
|---|---|---|
|
Time to Meaningful Pain Relief (MPR) by Treatment <=30 Minutes
|
613 Episodes
|
503 Episodes
|
SECONDARY outcome
Timeframe: From study drug administration until 45 minutes after treatmentPopulation: Full Analysis Set defined by at least one episode of breakthrough pain treated with FBT and at least one with oxycodone. No imputation was done if subject never answered APR/MPR question. If responded only as no, remaining missing imputed as no. If at least 1 yes, remaining missing imputed as yes.
Time to MPR(subjective perception of meaningful reduction in pain intensity) was measured by stopwatch and by scheduled questions at each time point during double-blind treatment period. No pain relief was defined as: patient indicated no pain relief experienced, rescue medication was used,or missing data. For each category (\<5, \<10, \<15, \<30, \<45, \<60 minutes, No MPR-rescue medication used, and No MPR-no rescue medication used)the number of episodes which time to MPR fell in that category was compared. Number of episodes in which MPR was achieved in 45 minutes or less was compared.
Outcome measures
| Measure |
Fentanyl Buccal Tablet (FBT)
n=1342 breakthrough pain episodes
FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.
PTs were initially titrated with FBT during the 1st titration period and immediate release oxycodone during the 2nd titration period or immediate-release oxycodone in the 1st titration period then FBT in the 2nd titration period.
During the 12-week open-label extension period, pts randomized to FBT treatment were initially dispensed single tablets at the dose found to be successful during the titration period.
|
Immediate-release Oxycodone (OXY)
n=1334 breakthrough pain episodes
Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Patients were initially titrated to immediate-release oxycodone during the 1st titration period and to FBT during the 2nd titration period or to FBT during the 1st titration period and immediate-release oxycodone during the 2nd titration period.
|
|---|---|---|
|
Time to Meaningful Pain Relief (MPR) by Treatment <=45 Minutes
|
983 Episodes
|
864 Episodes
|
SECONDARY outcome
Timeframe: Time of study drug administration until 60 minutes after treatmentPopulation: Full Analysis Set defined by at least one episode of breakthrough pain treated with FBT and at least one with oxycodone. No imputation was done if subject never answered APR/MPR question. If responded only as no, remaining missing imputed as no. If at least 1 yes, remaining missing imputed as yes.
Time to MPR(subjective perception of meaningful reduction in pain intensity) was measured by stopwatch and by scheduled questions at each time point during double-blind treatment period. No pain relief was defined as: patient indicated no pain relief experienced, rescue medication was used,or missing data. For each category (\<5, \<10, \<15, \<30, \<45, \<60 minutes, No MPR-rescue medication used, and No MPR-no rescue medication used)the number of episodes which time to MPR fell in that category was compared. Number of episodes in which MPR was achieved in 60 minutes or less was compared.
Outcome measures
| Measure |
Fentanyl Buccal Tablet (FBT)
n=1342 breakthrough pain episodes
FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.
PTs were initially titrated with FBT during the 1st titration period and immediate release oxycodone during the 2nd titration period or immediate-release oxycodone in the 1st titration period then FBT in the 2nd titration period.
During the 12-week open-label extension period, pts randomized to FBT treatment were initially dispensed single tablets at the dose found to be successful during the titration period.
|
Immediate-release Oxycodone (OXY)
n=1334 breakthrough pain episodes
Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Patients were initially titrated to immediate-release oxycodone during the 1st titration period and to FBT during the 2nd titration period or to FBT during the 1st titration period and immediate-release oxycodone during the 2nd titration period.
|
|---|---|---|
|
Time to Meaningful Pain Relief (MPR) by Treatment <=60 Minutes
|
1139 Episodes
|
1047 Episodes
|
SECONDARY outcome
Timeframe: Throughout the double-blind treatment periodPopulation: Full Analysis Set defined as having at least one evaluable episode of breakthrough pain treated with FBT and at least one with oxycodone. An episode was evaluable if it had a valid pain intensity measurement immediately prior to drug administration. No imputation for missing breakthrough pain episodes, but LOCF was applied for missing PR scores.
Any use of standard rescue medication after the administration of study drug for relief of Breakthrough Pain (BTP) during the double-blind treatment phase was recorded in the patient's diary. The number of breakthrough pain episodes for which study drug treatment was administered and which required rescue medication use was recorded.
Outcome measures
| Measure |
Fentanyl Buccal Tablet (FBT)
n=1342 breakthrough pain episodes
FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.
PTs were initially titrated with FBT during the 1st titration period and immediate release oxycodone during the 2nd titration period or immediate-release oxycodone in the 1st titration period then FBT in the 2nd titration period.
During the 12-week open-label extension period, pts randomized to FBT treatment were initially dispensed single tablets at the dose found to be successful during the titration period.
|
Immediate-release Oxycodone (OXY)
n=1334 breakthrough pain episodes
Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Patients were initially titrated to immediate-release oxycodone during the 1st titration period and to FBT during the 2nd titration period or to FBT during the 1st titration period and immediate-release oxycodone during the 2nd titration period.
|
|---|---|---|
|
Use of Standard Rescue Medication
|
39 Episodes
|
41 Episodes
|
SECONDARY outcome
Timeframe: 30 minutes post-treatmentPopulation: Full Analysis Set defined as having at least one evaluable episode of breakthrough pain treated with FBT and at least one with oxycodone. An episode was evaluable if it had a valid pain intensity measurement immediately prior to drug administration. No imputation for missing breakthrough pain episodes, but LOCF was applied for missing PR scores.
The medication performance assessment assessed study drug performance on a 5-point categorical scale of 0-4 (0=poor, 1=fair,2=good, 3=very good, 4=excellent) 30 minutes after administration of study drug during the double-blind treatment periods and for the first 5 BTP episodes after each visit during the open-label extension period were recorded in the patient's paper diary. Patients were asked "How well did your study medication perform in controlling this breakthrough pain episode?" The number of episodes rated for each category were recorded.
Outcome measures
| Measure |
Fentanyl Buccal Tablet (FBT)
n=1342 breakthrough pain episodes
FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.
PTs were initially titrated with FBT during the 1st titration period and immediate release oxycodone during the 2nd titration period or immediate-release oxycodone in the 1st titration period then FBT in the 2nd titration period.
During the 12-week open-label extension period, pts randomized to FBT treatment were initially dispensed single tablets at the dose found to be successful during the titration period.
|
Immediate-release Oxycodone (OXY)
n=1334 breakthrough pain episodes
Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Patients were initially titrated to immediate-release oxycodone during the 1st titration period and to FBT during the 2nd titration period or to FBT during the 1st titration period and immediate-release oxycodone during the 2nd titration period.
|
|---|---|---|
|
Medication Performance Assessment 30 Minutes Post-treatment
Excellent
|
49 Episodes
|
16 Episodes
|
|
Medication Performance Assessment 30 Minutes Post-treatment
Very Good
|
125 Episodes
|
104 Episodes
|
|
Medication Performance Assessment 30 Minutes Post-treatment
Good
|
378 Episodes
|
304 Episodes
|
|
Medication Performance Assessment 30 Minutes Post-treatment
Fair
|
416 Episodes
|
391 Episodes
|
|
Medication Performance Assessment 30 Minutes Post-treatment
Poor
|
341 Episodes
|
489 Episodes
|
|
Medication Performance Assessment 30 Minutes Post-treatment
No Response
|
33 Episodes
|
30 Episodes
|
SECONDARY outcome
Timeframe: 60 minutes post-treatmentPopulation: Full Analysis Set defined as having at least one evaluable episode of breakthrough pain treated with FBT and at least one with oxycodone. An episode was evaluable if it had a valid pain intensity measurement immediately prior to drug administration. No imputation for missing breakthrough pain episodes, but LOCF was applied for missing PR scores.
The medication performance assessment assessed study drug performance on a 5-point categorical scale of 0-4 (0=poor, 1=fair,2=good, 3=very good, 4=excellent) 60 minutes after administration of study drug during the double-blind treatment periods and for the first 5 BTP episodes after each visit during the open-label extension period were recorded in the patient's paper diary. Patients were asked "How well did your study medication perform in controlling this breakthrough pain episode?" The number of episodes rated for each category were recorded.
Outcome measures
| Measure |
Fentanyl Buccal Tablet (FBT)
n=1342 breakthrough pain episodes
FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.
PTs were initially titrated with FBT during the 1st titration period and immediate release oxycodone during the 2nd titration period or immediate-release oxycodone in the 1st titration period then FBT in the 2nd titration period.
During the 12-week open-label extension period, pts randomized to FBT treatment were initially dispensed single tablets at the dose found to be successful during the titration period.
|
Immediate-release Oxycodone (OXY)
n=1334 breakthrough pain episodes
Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Patients were initially titrated to immediate-release oxycodone during the 1st titration period and to FBT during the 2nd titration period or to FBT during the 1st titration period and immediate-release oxycodone during the 2nd titration period.
|
|---|---|---|
|
Medication Performance Assessment 60 Minutes Post-treatment
Excellent
|
160 Episodes
|
119 Episodes
|
|
Medication Performance Assessment 60 Minutes Post-treatment
Very Good
|
371 Episodes
|
313 Episodes
|
|
Medication Performance Assessment 60 Minutes Post-treatment
Good
|
508 Episodes
|
565 Episodes
|
|
Medication Performance Assessment 60 Minutes Post-treatment
Fair
|
181 Episodes
|
179 Episodes
|
|
Medication Performance Assessment 60 Minutes Post-treatment
Poor
|
92 Episodes
|
136 Episodes
|
|
Medication Performance Assessment 60 Minutes Post-treatment
No Response
|
30 Episodes
|
22 Episodes
|
SECONDARY outcome
Timeframe: At Visit 6 ( up to 42 days depending upon how long it takes the patient to manage their BTP) after completion of both double-blind treatment periods.Population: Double-blind safety analysis set: 143 subjects who received both study drugs in this crossover study completed the Breakthrough Pain Preference Questionnaire after completing treatment
The BTP preference questionnaire is a questionnaire used to measure patients' preference for FBT or immediate-release oxycodone for management of BTP. The question is used to determine a patient's preference between the study drugs given in the 2 double-blind treatment periods. The patient was asked to select 1 of the following: 1, a preference for study drug used in the 1st double-blind treatment period; 2, a preference for study drug used in the 2nd double-blind treatment period; or 3, no preference.
Outcome measures
| Measure |
Fentanyl Buccal Tablet (FBT)
n=143 Participants
FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.
PTs were initially titrated with FBT during the 1st titration period and immediate release oxycodone during the 2nd titration period or immediate-release oxycodone in the 1st titration period then FBT in the 2nd titration period.
During the 12-week open-label extension period, pts randomized to FBT treatment were initially dispensed single tablets at the dose found to be successful during the titration period.
|
Immediate-release Oxycodone (OXY)
Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Patients were initially titrated to immediate-release oxycodone during the 1st titration period and to FBT during the 2nd titration period or to FBT during the 1st titration period and immediate-release oxycodone during the 2nd titration period.
|
|---|---|---|
|
Breakthrough Pain Preference Questionnaire
Preferred FBT
|
62 Participants
|
—
|
|
Breakthrough Pain Preference Questionnaire
Preferred Oxycodone
|
46 Participants
|
—
|
|
Breakthrough Pain Preference Questionnaire
No Preference
|
23 Participants
|
—
|
|
Breakthrough Pain Preference Questionnaire
Missing
|
12 Participants
|
—
|
SECONDARY outcome
Timeframe: One month after start of open-label treatmentPopulation: Open-Label Efficacy Assessment Set includes all subjects who were randomly assigned to the open-label treatments in the extension period and had an efficacy assessment for at least one of the efficacy questionnaires.
The PGIC is a standardized self-report tool that measures the change in a patient's overall status rating since the start of the open-label extension period. The 7-point scale includes very much worse= -3, much worse= -2, minimally worse= -1, no change=0, minimally improved= +1, much improved= +2, and very much improved= +3. This was assessed 1 month after start of the open-label extension period.
Outcome measures
| Measure |
Fentanyl Buccal Tablet (FBT)
n=55 Participants
FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.
PTs were initially titrated with FBT during the 1st titration period and immediate release oxycodone during the 2nd titration period or immediate-release oxycodone in the 1st titration period then FBT in the 2nd titration period.
During the 12-week open-label extension period, pts randomized to FBT treatment were initially dispensed single tablets at the dose found to be successful during the titration period.
|
Immediate-release Oxycodone (OXY)
n=61 Participants
Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Patients were initially titrated to immediate-release oxycodone during the 1st titration period and to FBT during the 2nd titration period or to FBT during the 1st titration period and immediate-release oxycodone during the 2nd titration period.
|
|---|---|---|
|
Patient Global Impression of Change (PGIC) at Visit 7- 1 Month After Open Label Treatment
|
1.5 Unit on a scale
Standard Deviation 0.88
|
0.6 Unit on a scale
Standard Deviation 0.99
|
SECONDARY outcome
Timeframe: 2 months after start of open-label extension periodPopulation: Open-Label Efficacy Assessment Set includes all subjects who were randomly assigned to the open-label treatments in the extension period and had an efficacy assessment for at least one of the efficacy questionnaires.
The PGIC is a standardized self-report tool that measures the change in a patient's overall status rating since the start of the open-label extension period. The 7-point scale includes very much worse= -3, much worse= -2, minimally worse= -1, no change=0, minimally improved= +1, much improved= +2, and very much improved= +3. Here it was assessed 2 months after the start of the open-label extension period.
Outcome measures
| Measure |
Fentanyl Buccal Tablet (FBT)
n=54 Participants
FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.
PTs were initially titrated with FBT during the 1st titration period and immediate release oxycodone during the 2nd titration period or immediate-release oxycodone in the 1st titration period then FBT in the 2nd titration period.
During the 12-week open-label extension period, pts randomized to FBT treatment were initially dispensed single tablets at the dose found to be successful during the titration period.
|
Immediate-release Oxycodone (OXY)
n=60 Participants
Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Patients were initially titrated to immediate-release oxycodone during the 1st titration period and to FBT during the 2nd titration period or to FBT during the 1st titration period and immediate-release oxycodone during the 2nd titration period.
|
|---|---|---|
|
Patient Global Impression of Change (PGIC) at Visit 8- 2 Months After Open Label Treatment
|
1.5 Units on scale
Standard Deviation 0.99
|
0.8 Units on scale
Standard Deviation 0.99
|
SECONDARY outcome
Timeframe: 3 months after start of open-label extension periodPopulation: Open-Label Efficacy Assessment Set includes all subjects who were randomly assigned to the open-label treatments in the extension period and had an efficacy assessment for at least one of the efficacy questionnaires.
The PGIC is a standardized self-report tool that measures the change in a patient's overall status rating since the start of the open-label extension period. The 7-point scale includes very much worse= -3, much worse= -2, minimally worse= -1, no change=0, minimally improved= +1, much improved= +2, and very much improved= +3. Here it was assessed 3 months after the start of the open-label extension period.
Outcome measures
| Measure |
Fentanyl Buccal Tablet (FBT)
n=53 Participants
FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.
PTs were initially titrated with FBT during the 1st titration period and immediate release oxycodone during the 2nd titration period or immediate-release oxycodone in the 1st titration period then FBT in the 2nd titration period.
During the 12-week open-label extension period, pts randomized to FBT treatment were initially dispensed single tablets at the dose found to be successful during the titration period.
|
Immediate-release Oxycodone (OXY)
n=59 Participants
Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Patients were initially titrated to immediate-release oxycodone during the 1st titration period and to FBT during the 2nd titration period or to FBT during the 1st titration period and immediate-release oxycodone during the 2nd titration period.
|
|---|---|---|
|
Patient Global Impression of Change (PGIC) at Visit 9- 3 Months After Open Label Treatment
|
1.7 Units on scale
Standard Deviation 0.86
|
0.8 Units on scale
Standard Deviation 1.09
|
SECONDARY outcome
Timeframe: At conclusion of open-label extension periodPopulation: Open-Label Efficacy Assessment Set includes all subjects who were randomly assigned to the open-label treatments in the extension period and had an efficacy assessment for at least one of the efficacy questionnaires.
The PGIC is a standardized self-report tool that measures the change in a patient's overall status rating since the start of the open-label extension period. The 7-point scale includes very much worse= -3, much worse= -2, minimally worse= -1, no change=0, minimally improved= +1, much improved= +2, and very much improved= +3. Here it was assessed at the conclusion of the open-label extension period.
Outcome measures
| Measure |
Fentanyl Buccal Tablet (FBT)
n=65 Participants
FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.
PTs were initially titrated with FBT during the 1st titration period and immediate release oxycodone during the 2nd titration period or immediate-release oxycodone in the 1st titration period then FBT in the 2nd titration period.
During the 12-week open-label extension period, pts randomized to FBT treatment were initially dispensed single tablets at the dose found to be successful during the titration period.
|
Immediate-release Oxycodone (OXY)
n=65 Participants
Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Patients were initially titrated to immediate-release oxycodone during the 1st titration period and to FBT during the 2nd titration period or to FBT during the 1st titration period and immediate-release oxycodone during the 2nd titration period.
|
|---|---|---|
|
Patient Global Impression of Change (PGIC) Endpoint
|
1.5 Units on a scale
Standard Deviation 1.02
|
0.9 Units on a scale
Standard Deviation 1.09
|
SECONDARY outcome
Timeframe: One month after start of open-label extensionPopulation: Open-Label Efficacy Assessment Set includes all subjects who were randomly assigned to the open-label treatments in the extension period and had an efficacy assessment for at least one of the efficacy questionnaires.
The CGIC is a standardized tool that measures the change in a patient's overall status rating since the start of the open-label extension period, in the opinion of the clinician. The 7-point scale includes very much worse=-3, much worse=-2, minimally worse=-1,no change=0, minimally improved=+1, much improved=+2, and very much improved=+3. The CGIC was completed by the clinicians at visits 7, 8, and 9 (or early termination) which correspond to 1, 2, or 3 months after the start of the open-label extension period.
Outcome measures
| Measure |
Fentanyl Buccal Tablet (FBT)
n=57 Participants
FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.
PTs were initially titrated with FBT during the 1st titration period and immediate release oxycodone during the 2nd titration period or immediate-release oxycodone in the 1st titration period then FBT in the 2nd titration period.
During the 12-week open-label extension period, pts randomized to FBT treatment were initially dispensed single tablets at the dose found to be successful during the titration period.
|
Immediate-release Oxycodone (OXY)
n=63 Participants
Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Patients were initially titrated to immediate-release oxycodone during the 1st titration period and to FBT during the 2nd titration period or to FBT during the 1st titration period and immediate-release oxycodone during the 2nd titration period.
|
|---|---|---|
|
Clinician Global Impression of Change at Visit 7- 1 Month After Open Label Treatment
|
1.4 Unit on a scale
Standard Deviation 0.79
|
0.6 Unit on a scale
Standard Deviation 0.91
|
SECONDARY outcome
Timeframe: Two months after start of open-label extension periodPopulation: Open-Label Efficacy Assessment Set includes all subjects who were randomly assigned to the open-label treatments in the extension period and had an efficacy assessment for at least one of the efficacy questionnaires.
The CGIC is a standardized tool that measures the change in a patient's overall status rating since the start of the open-label extension period, in the opinion of the clinician. The 7-point scale includes very much worse=-3, much worse=-2, minimally worse=-1,no change=0, minimally improved=+1, much improved=+2, and very much improved=+3. Here it was assessed 2 months after the start of the open-label extension period. The CGIC was completed by the clinicians at visits 7, 8, and 9 (or early termination).
Outcome measures
| Measure |
Fentanyl Buccal Tablet (FBT)
n=54 Participants
FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.
PTs were initially titrated with FBT during the 1st titration period and immediate release oxycodone during the 2nd titration period or immediate-release oxycodone in the 1st titration period then FBT in the 2nd titration period.
During the 12-week open-label extension period, pts randomized to FBT treatment were initially dispensed single tablets at the dose found to be successful during the titration period.
|
Immediate-release Oxycodone (OXY)
n=60 Participants
Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Patients were initially titrated to immediate-release oxycodone during the 1st titration period and to FBT during the 2nd titration period or to FBT during the 1st titration period and immediate-release oxycodone during the 2nd titration period.
|
|---|---|---|
|
Clinician Global Impression of Change (CGIC) at Visit 8- 2 Months After Open Label Treatment
|
1.4 Units on a scale
Standard Deviation 0.96
|
0.7 Units on a scale
Standard Deviation 0.88
|
SECONDARY outcome
Timeframe: 3 months after start of open-label extension periodPopulation: Open-Label Efficacy Assessment Set includes all subjects who were randomly assigned to the open-label treatments in the extension period and had an efficacy assessment for at least one of the efficacy questionnaires.
The CGIC is a standardized tool that measures the change in a patient's overall status rating since the start of the open-label extension period, in the opinion of the clinician. The 7-point scale includes very much worse=-3, much worse=-2, minimally worse=-1,no change=0, minimally improved=+1, much improved=+2, and very much improved=+3. The CGIC was completed by the clinicians at visits 7, 8, and 9 (or early termination), which correspond to 1, 2, or 3 months after the start of the open-label extension period.
Outcome measures
| Measure |
Fentanyl Buccal Tablet (FBT)
n=53 Participants
FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.
PTs were initially titrated with FBT during the 1st titration period and immediate release oxycodone during the 2nd titration period or immediate-release oxycodone in the 1st titration period then FBT in the 2nd titration period.
During the 12-week open-label extension period, pts randomized to FBT treatment were initially dispensed single tablets at the dose found to be successful during the titration period.
|
Immediate-release Oxycodone (OXY)
n=59 Participants
Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Patients were initially titrated to immediate-release oxycodone during the 1st titration period and to FBT during the 2nd titration period or to FBT during the 1st titration period and immediate-release oxycodone during the 2nd titration period.
|
|---|---|---|
|
Clinician Global Impression of Change (CGIC) at Visit 9- 3 Months After Open Label Treatment
|
1.6 Units on a scale
Standard Deviation 0.81
|
0.7 Units on a scale
Standard Deviation 1.02
|
SECONDARY outcome
Timeframe: End of open-label extension periodPopulation: Open-Label Efficacy Assessment Set includes all subjects who were randomly assigned to the open-label treatments in the extension period and had an efficacy assessment for at least one of the efficacy questionnaires.
The CGIC is a standardized tool that measures the change in a patient's overall status rating since the start of the open-label extension period, in the opinion of the clinician. The 7-point scale includes very much worse=-3, much worse=-2, minimally worse=-1,no change=0, minimally improved=+1, much improved=+2, and very much improved=+3. The CGIC was completed by the clinicians at visits 7, 8, and 9 (or early termination).
Outcome measures
| Measure |
Fentanyl Buccal Tablet (FBT)
n=65 Participants
FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.
PTs were initially titrated with FBT during the 1st titration period and immediate release oxycodone during the 2nd titration period or immediate-release oxycodone in the 1st titration period then FBT in the 2nd titration period.
During the 12-week open-label extension period, pts randomized to FBT treatment were initially dispensed single tablets at the dose found to be successful during the titration period.
|
Immediate-release Oxycodone (OXY)
n=65 Participants
Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Patients were initially titrated to immediate-release oxycodone during the 1st titration period and to FBT during the 2nd titration period or to FBT during the 1st titration period and immediate-release oxycodone during the 2nd titration period.
|
|---|---|---|
|
Clinician Global Impression of Change (CGIC)Endpoint
|
1.4 Units on a scale
Standard Deviation 1.01
|
0.7 Units on a scale
Standard Deviation 1.05
|
Adverse Events
Fentanyl Buccal Tablet
Oxycodone
Standard of Care
Serious adverse events
| Measure |
Fentanyl Buccal Tablet
n=196 participants at risk
This was a crossover study in which subjects were first randomized to receive Fentanyl Buccal Tablet (FBT) or oxycodone in two titration periods of the study (titrated once with one drug and again with the other) and then were randomized to double-blind treatment first with one drug then the other. As a result, all subjects were exposed to both FBT and oxycodone at different times except for subjects who discontinued before the second titration period. 213 subjects began the first titration period and of those 17 discontinued before exposure to FBT. Including Titration Periods, Double-blind Treatment Periods and Open-Label Extension Periods 196 subjects had exposure to FBT
|
Oxycodone
n=186 participants at risk
This was a crossover study in which subjects were first randomized to receive Fentanyl Buccal Tablet (FBT) or oxycodone in two titration periods of the study (titrated once with one drug and again with the other) and then were randomized to double-blind treatment first with one drug then the other. As a result, all subjects were exposed to both FBT and oxycodone at different times except for subjects who discontinued before the second titration period (they were only exposed to one drug). 213 subjects began the first titration period and of those 27 discontinued before exposure to oxycodone. Including Titration Periods, Double-blind Treatment Periods and Open-Label Extension Periods 186 subjects had exposure to oxycodone
|
Standard of Care
n=21 participants at risk
21 subjects received standard of care analgesics apart from oxycodone or FBT during the Open-Label Extension Period. Subjects who took oxycodone during SOC are listed under Oxycodone.
|
|---|---|---|---|
|
Cardiac disorders
Cyanosis
|
0.51%
1/196 • Number of events 1
|
0.00%
0/186
|
0.00%
0/21
|
|
Cardiac disorders
Myocardial infarction
|
0.00%
0/196
|
0.54%
1/186 • Number of events 1
|
0.00%
0/21
|
|
Gastrointestinal disorders
Oesophageal mass
|
0.51%
1/196 • Number of events 1
|
0.00%
0/186
|
0.00%
0/21
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/196
|
0.00%
0/186
|
4.8%
1/21 • Number of events 1
|
|
General disorders
Chest pain
|
0.00%
0/196
|
0.54%
1/186 • Number of events 1
|
0.00%
0/21
|
|
General disorders
Drug withdrawal syndrome
|
0.51%
1/196 • Number of events 1
|
0.00%
0/186
|
0.00%
0/21
|
|
Infections and infestations
Cystitis
|
0.51%
1/196 • Number of events 1
|
0.00%
0/186
|
0.00%
0/21
|
|
Infections and infestations
Sepsis syndrome
|
0.00%
0/196
|
0.00%
0/186
|
4.8%
1/21 • Number of events 1
|
|
Investigations
Blood creatinine increased
|
0.51%
1/196 • Number of events 1
|
0.00%
0/186
|
0.00%
0/21
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/196
|
0.00%
0/186
|
4.8%
1/21 • Number of events 1
|
|
Metabolism and nutrition disorders
Malnutrition
|
0.00%
0/196
|
0.00%
0/186
|
4.8%
1/21 • Number of events 1
|
|
Nervous system disorders
Unresponsive to stimuli
|
0.51%
1/196 • Number of events 1
|
0.54%
1/186 • Number of events 1
|
0.00%
0/21
|
|
Nervous system disorders
Syncope
|
0.51%
1/196 • Number of events 1
|
0.00%
0/186
|
0.00%
0/21
|
|
Renal and urinary disorders
Renal failure acute
|
0.51%
1/196 • Number of events 1
|
0.00%
0/186
|
0.00%
0/21
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.51%
1/196 • Number of events 1
|
0.00%
0/186
|
0.00%
0/21
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia aspiration
|
0.00%
0/196
|
0.00%
0/186
|
4.8%
1/21 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.00%
0/196
|
0.54%
1/186 • Number of events 1
|
0.00%
0/21
|
Other adverse events
| Measure |
Fentanyl Buccal Tablet
n=196 participants at risk
This was a crossover study in which subjects were first randomized to receive Fentanyl Buccal Tablet (FBT) or oxycodone in two titration periods of the study (titrated once with one drug and again with the other) and then were randomized to double-blind treatment first with one drug then the other. As a result, all subjects were exposed to both FBT and oxycodone at different times except for subjects who discontinued before the second titration period. 213 subjects began the first titration period and of those 17 discontinued before exposure to FBT. Including Titration Periods, Double-blind Treatment Periods and Open-Label Extension Periods 196 subjects had exposure to FBT
|
Oxycodone
n=186 participants at risk
This was a crossover study in which subjects were first randomized to receive Fentanyl Buccal Tablet (FBT) or oxycodone in two titration periods of the study (titrated once with one drug and again with the other) and then were randomized to double-blind treatment first with one drug then the other. As a result, all subjects were exposed to both FBT and oxycodone at different times except for subjects who discontinued before the second titration period (they were only exposed to one drug). 213 subjects began the first titration period and of those 27 discontinued before exposure to oxycodone. Including Titration Periods, Double-blind Treatment Periods and Open-Label Extension Periods 186 subjects had exposure to oxycodone
|
Standard of Care
n=21 participants at risk
21 subjects received standard of care analgesics apart from oxycodone or FBT during the Open-Label Extension Period. Subjects who took oxycodone during SOC are listed under Oxycodone.
|
|---|---|---|---|
|
Gastrointestinal disorders
Nausea
|
4.6%
9/196
|
3.8%
7/186
|
0.00%
0/21
|
|
Gastrointestinal disorders
Vomiting
|
3.1%
6/196
|
2.7%
5/186
|
4.8%
1/21
|
|
Gastrointestinal disorders
Constipation
|
1.5%
3/196
|
0.54%
1/186
|
9.5%
2/21
|
|
Infections and infestations
Urinary tract infection
|
1.5%
3/196
|
2.2%
4/186
|
9.5%
2/21
|
|
Infections and infestations
Influenza
|
1.5%
3/196
|
1.1%
2/186
|
9.5%
2/21
|
|
Injury, poisoning and procedural complications
Fall
|
0.51%
1/196
|
1.1%
2/186
|
9.5%
2/21
|
|
Investigations
Liver function test abnormal
|
0.00%
0/196
|
0.00%
0/186
|
9.5%
2/21
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
4.1%
8/196
|
4.3%
8/186
|
9.5%
2/21
|
|
Nervous system disorders
Somnolence
|
4.6%
9/196
|
4.8%
9/186
|
0.00%
0/21
|
|
Nervous system disorders
Headache
|
4.1%
8/196
|
3.2%
6/186
|
4.8%
1/21
|
Additional Information
Sponsor's Medical Expert, Clinical Research
Cephalon, Inc.
Results disclosure agreements
- Principal investigator is a sponsor employee All unpublished information given to an investigator by Cephalon shall not be published or disclosed to a third party without the prior written consent of Cephalon.
- Publication restrictions are in place
Restriction type: OTHER