Trial Outcomes & Findings for Efficacy and Safety of Fentanyl Buccal Tablets Compared With Oxycodone for the Management of Break Through Pain (NCT NCT00463047)

NCT ID: NCT00463047

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.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 323 participants
• Primary outcome timeframe: Immediately pre-dose and fifteen minutes after administration of study drug
• Results posted on: 2012-05-28

Participant Flow

Subjects 18 to 80 years of age with chronic pain for at least 3 months, were opioid tolerant, on around-the-clock opioid therapy, with 1-4 breakthrough pain episodes a day were recruited from 46 centers in the United States. First participant screened: June 2007. Last participant last visit: February 2009.

Prior to the double-blind treatment period, subjects participated in two titration periods to identify a "successful" and tolerated dose of Fentanyl Buccal Tablets (FBT) and immediate-release oxycodone. Subjects who did not titrate successfully were excluded from further participation in the study.

Participant milestones

Measure	FBT First Immediate Release Oxycodone Second Patients were randomized 1:1 to titrate Fentanyl Buccal Tablet (FBT) during the first titration period and then titrated immediate-release oxycodone during the second period or the reverse. Titration began with either 200 mcg FBT or 15 mg oxycodone taken as needed for breakthrough pain. If after 30 minutes pain relief was unsuccessful, a second dose could be taken. 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 Patients were randomly assigned 1:1 to either titrate FBT during the first titration period and then titrated immediate-release oxycodone during the second period or the reverse. Titration began with either 200 mcg FBT or 15 mg oxycodone taken as needed for breakthrough pain. If after 30 minutes pain relief was unsuccessful, a second dose could be taken. 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	160	160
Titration Period 1 COMPLETED	123	121
Titration Period 1 NOT COMPLETED	37	39
Titration Period 2 STARTED	123	121
Titration Period 2 COMPLETED	93	98
Titration Period 2 NOT COMPLETED	30	23
Double-Blind Treatment Period 1 STARTED	96	94
Double-Blind Treatment Period 1 COMPLETED	93	90
Double-Blind Treatment Period 1 NOT COMPLETED	3	4
Double-Blind Treatment Period 2 STARTED	93	90
Double-Blind Treatment Period 2 COMPLETED	92	88
Double-Blind Treatment Period 2 NOT COMPLETED	1	2

Reasons for withdrawal

Measure	FBT First Immediate Release Oxycodone Second Patients were randomized 1:1 to titrate Fentanyl Buccal Tablet (FBT) during the first titration period and then titrated immediate-release oxycodone during the second period or the reverse. Titration began with either 200 mcg FBT or 15 mg oxycodone taken as needed for breakthrough pain. If after 30 minutes pain relief was unsuccessful, a second dose could be taken. 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 Patients were randomly assigned 1:1 to either titrate FBT during the first titration period and then titrated immediate-release oxycodone during the second period or the reverse. Titration began with either 200 mcg FBT or 15 mg oxycodone taken as needed for breakthrough pain. If after 30 minutes pain relief was unsuccessful, a second dose could be taken. 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	10	8
Titration Period 1 Lack of Efficacy	10	4
Titration Period 1 Lost to Follow-up	2	0
Titration Period 1 Non-compliance with study medication	3	5
Titration Period 1 Protocol Violation	5	5
Titration Period 1 Withdrawal by Subject	3	5
Titration Period 1 Non-compliance procedures	4	10
Titration Period 1 Other	0	2
Titration Period 2 Adverse Event	9	9
Titration Period 2 Lack of Efficacy	6	4
Titration Period 2 Withdrawal by Subject	1	0
Titration Period 2 Protocol Violation	2	3
Titration Period 2 Lost to Follow-up	1	2
Titration Period 2 Non-compliance study medication	4	2
Titration Period 2 Non-compliance procedures	4	1
Titration Period 2 Other	3	2
Double-Blind Treatment Period 1 Adverse Event	0	2
Double-Blind Treatment Period 1 Protocol Violation	1	2
Double-Blind Treatment Period 1 Non-compliance with procedures	1	0
Double-Blind Treatment Period 1 Other	1	0
Double-Blind Treatment Period 2 Adverse Event	0	1
Double-Blind Treatment Period 2 Withdrawal by Subject	0	1
Double-Blind Treatment Period 2 Non-compliance with procedures	1	0

Baseline Characteristics

Efficacy and Safety of Fentanyl Buccal Tablets Compared With Oxycodone for the Management of Break Through Pain

Baseline characteristics by cohort

Measure	Total Number of Patients n=323 Participants Fentanyl Buccal Tablets (FBT) and Immediate-Release Oxycodone crossover. The total number of patients (323) reflect the number that were enrolled to participate in the study prior to the first titration period. Three subjects withdrew before receiving any study drug so they are not listed as being assigned to either dosing arm in the titration studies, leaving only 320 subjects who were evenly divided between the two groups.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	323 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age Continuous	50.2 years STANDARD_DEVIATION 9.81 • n=5 Participants
Sex: Female, Male Female	188 Participants n=5 Participants
Sex: Female, Male Male	135 Participants n=5 Participants
Region of Enrollment United States	323 participants n=5 Participants

PRIMARY outcome

Timeframe: Immediately pre-dose and fifteen minutes after administration of study drug

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 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 Tablets (FBT) n=1764 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.	Immediate-Release Oxycodone n=1758 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.
Pain Intensity Difference (PID15) At 15 Minutes	0.82 Units on a scale Standard Error 0.07	0.59 Units on a scale Standard Error 0.07

SECONDARY outcome

Timeframe: Immediately before and 5 minutes after study drug administration

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 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 Tablets (FBT) n=1764 Episodes of breakthrough pain 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.	Immediate-Release Oxycodone n=1758 Episodes of breakthrough pain 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.
Pain Intensity Difference (PID 5) at 5 Minutes	0.08 Units on a scale Standard Error 0.03	0.05 Units on a scale Standard Error 0.03

SECONDARY outcome

Timeframe: Immediately before and 10 minutes after administration of study drug

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 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 Tablets (FBT) n=1764 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.	Immediate-Release Oxycodone n=1758 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.
Pain Intensity Difference (PID 10) at 10 Minutes	0.30 Units on a scale Standard Error 0.04	0.22 Units on a scale Standard Error 0.04

SECONDARY outcome

Timeframe: Immediately before and 10 minutes after study drug administration

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 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 Tablets (FBT) n=1764 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.	Immediate-Release Oxycodone n=1758 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.
Pain Intensity Difference (PID 30) at 30 Minutes	1.96 Units on a scale Standard Error 0.09	1.58 Units on a scale Standard Error 0.09

SECONDARY outcome

Timeframe: Immediately before and 45 minutes after study drug administration

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 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 Tablets (FBT) n=1764 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.	Immediate-Release Oxycodone n=1758 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.
Pain Intensity Difference (PID 45) at 45 Minutes	2.87 Units on a scale Standard Error 0.12	2.59 Units on a scale Standard Error 0.12

SECONDARY outcome

Timeframe: Immediately before and 60 minutes after administration of study drug

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 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 Tablets (FBT) n=1764 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.	Immediate-Release Oxycodone n=1758 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.
Pain Intensity Difference (PID 60) at 60 Minutes	3.35 Units on a scale Standard Error 0.13	3.19 Units on a scale Standard Error 0.13

SECONDARY outcome

Timeframe: Immediately before and 5 minutes after administration of study drug

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 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. The percentage is calculated as the PID at 5 minutes divided by the baseline PI score times 100.

Outcome measures

Measure	Fentanyl Buccal Tablets (FBT) n=183 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.	Immediate-Release Oxycodone n=183 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.
Percentage Change in Pain Intensity Difference (% PID) at 5 Minutes Post-treatment	1.11 Percent change in units on a scale Standard Error 0.45	0.73 Percent change in units on a scale Standard Error 0.37

SECONDARY outcome

Timeframe: Immediately before and 10 minutes after study drug administration

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 during the double-blind treatment period. 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. The percentage is calculated as the PID at 10 minutes divided by the baseline PI score times 100.

Outcome measures

Measure	Fentanyl Buccal Tablets (FBT) n=183 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.	Immediate-Release Oxycodone n=183 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.
Percentage Change in Pain Intensity Difference (%PID) at 10 Minutes	4.08 Percentage change in units on a scale Standard Error 0.76	3.16 Percentage change in units on a scale Standard Error 0.57

SECONDARY outcome

Timeframe: Immediately before and 15 minutes after administration of study drug

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 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. The difference is calculated and assessed as a percentage of the baseline pain intensity score. The percentage is calculated as the PID at 15 minutes divided by the baseline PI score times 100.

Outcome measures

Measure	Fentanyl Buccal Tablets (FBT) n=183 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.	Immediate-Release Oxycodone n=183 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.
Percentage Change in Pain Intensity Difference (%PID) at 15 Minutes	11.40 Percent change in units on a scale Standard Error 1.15	8.59 Percent change in units on a scale Standard Error 0.94

SECONDARY outcome

Timeframe: Immediately before and 30 minutes after study drug administration

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 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. The percentage is calculated as the PID at 30 minutes divided by the baseline PI score times 100.

Outcome measures

Measure	Fentanyl Buccal Tablets (FBT) n=183 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.	Immediate-Release Oxycodone n=183 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.
Percentage Change in Pain Intensity Difference (%PID) at 30 Minutes	27.83 Percent change in units on a scale Standard Error 1.50	23.06 Percent change in units on a scale Standard Error 1.33

SECONDARY outcome

Timeframe: Immediately before and 45 minutes after study drug administration

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 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. The percentage is calculated as the PID at 45 minutes divided by the baseline PI score times 100.

Outcome measures

Measure	Fentanyl Buccal Tablets (FBT) n=183 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.	Immediate-Release Oxycodone n=183 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.
Percentage Change in Pain Intensity Difference (% PID) at 45 Minutes	40.94 Percent change in units on scale Standard Error 1.76	37.56 Percent change in units on scale Standard Error 1.57

SECONDARY outcome

Timeframe: Immediately before and 60 minutes after study drug administration

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 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. The percentage is calculated as the PID at 60 minutes divided by the baseline PI score times 100.

Outcome measures

Measure	Fentanyl Buccal Tablets (FBT) n=183 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.	Immediate-Release Oxycodone n=183 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.
Percentage Change in Pain Intensity Difference (%PID) at 60 Minutes	48.08 Percent change in units on a scale Standard Error 1.85	46.16 Percent change in units on a scale Standard Error 1.75

SECONDARY outcome

Timeframe: From 5 minutes after dosing through 30 minutes after dosing

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.

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 Tablets (FBT) n=1764 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.	Immediate-Release Oxycodone n=1758 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.
Sum of Pain Intensity Difference at 30 Minutes Post-treatment (SPID30)	2.36 Units on a scale Standard Error 0.13	1.87 Units on a scale Standard Error 0.13

SECONDARY outcome

Timeframe: From 5 minutes after dosing through 60 minutes after dosing

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.

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 Tablets (FBT) n=1764 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.	Immediate-Release Oxycodone n=1758 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.
Sum of Pain Intensity Difference at 60 Minutes Post-treatment (SPID60)	8.58 Units on a scale Standard Error 0.34	7.65 Units on a scale Standard Error 0.34

SECONDARY outcome

Timeframe: Five minutes after administration of study drug

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 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 Tablets (FBT) n=178 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.	Immediate-Release Oxycodone n=178 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.
Pain Relief (PR) Score at 5 Minutes	0.10 Units on a scale Standard Deviation 0.43	0.09 Units on a scale Standard Deviation 0.40

SECONDARY outcome

Timeframe: 10 minutes after treatment with study drug

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 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 Tablets (FBT) n=178 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.	Immediate-Release Oxycodone n=178 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.
Pain Relief Score (PR) at 10 Minutes	0.30 Units on a scale Standard Deviation 0.57	0.25 Units on a scale Standard Deviation 0.53

SECONDARY outcome

Timeframe: 15 minutes after treatment with study drug

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 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 Tablets (FBT) n=178 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.	Immediate-Release Oxycodone n=178 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.
Pain Relief Score (PR) at 15 Minutes	0.69 Units on a scale Standard Deviation 0.74	0.53 Units on a scale Standard Deviation 0.67

SECONDARY outcome

Timeframe: 30 minutes after treatment with study drug

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 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 Tablets (FBT) n=178 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.	Immediate-Release Oxycodone n=178 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.
Pain Relief Score (PR) at 30 Minutes	1.50 Units on a scale Standard Deviation 0.83	1.23 Units on a scale Standard Deviation 0.76

SECONDARY outcome

Timeframe: 45 minutes after treatment with study drug

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 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 Tablets (FBT) n=178 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.	Immediate-Release Oxycodone n=178 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.
Pain Relief Score (PR) at 45 Minutes	2.08 Units on a scale Standard Deviation 0.80	1.89 Units on a scale Standard Deviation 0.74

SECONDARY outcome

Timeframe: 60 minutes after treatment with study drug

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 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 Tablets (FBT) n=178 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.	Immediate-Release Oxycodone n=178 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.
Pain Relief Score (PR) at 60 Minutes	2.38 Units on a scale Standard Deviation 0.76	2.24 Units on a scale Standard Deviation 0.75

SECONDARY outcome

Timeframe: From 5 minutes to 60 minutes after dosing

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 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 Tablets (FBT) n=1676 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.	Immediate-Release Oxycodone n=1687 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.
Total Pain Relief (TOTPAR60) at 60 Minutes	6.32 Units on a scale Standard Error 0.16	5.63 Units on a scale Standard Error 0.16

SECONDARY outcome

Timeframe: From 5 minutes through 60 minutes after study drug 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 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) times 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 Tablets (FBT) n=178 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.	Immediate-Release Oxycodone n=178 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.
Percent Total Pain Relief at 60 Minutes Posttreatment (%TOTPAR)	39.48 Percent change in units on a scale Standard Deviation 15.67	35.28 Percent change in units on a scale Standard Deviation 14.27

SECONDARY outcome

Timeframe: From time was administered to 5 minutes after treatment

Population: 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 was measured by stopwatch and by scheduled questions at each time point up to 60 minutes after baseline during double-blind treatment period. Any pain relief was defined as any subjective reduction in pain severity, even if not meaningful to patient. 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 for which the time to APR fell into that category was compared. Here the number of episodes in which APR was achieved in less than or equal to 5 minutes was compared.

Outcome measures

Measure	Fentanyl Buccal Tablets (FBT) n=1764 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.	Immediate-Release Oxycodone n=1758 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.
Time to Any Pain Relief (APR) by Treatment, <= 5 Minutes	48 Number of episodes treated	33 Number of episodes treated

SECONDARY outcome

Timeframe: From study drug treatment until 10 minutes after treatment

Population: 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.

The time to APR was measured by stopwatch and scheduled questions at each time point up to 60 minutes after baseline during the double-blind treatment periods. Any pain relief was defined as any subjective reduction in pain severity, even if not meaningful to patient. 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 for which the time to APR fell into that category was compared. Here the number of episodes in which APR was achieved in less than or equal to 10 minutes was compared.

Outcome measures

Measure	Fentanyl Buccal Tablets (FBT) n=1764 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.	Immediate-Release Oxycodone n=1758 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.
Time to Any Pain Relief (APR) by Treatment, <=10 Minutes	286 Number of episodes treated	215 Number of episodes treated

SECONDARY outcome

Timeframe: From study drug administration to 15 minutes after treatment

Population: 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.

The time to APR was measured by stopwatch and scheduled questions at each time point up to 60 minutes after baseline during double-blind treatment periods. Any pain relief was defined as any subjective reduction in pain severity, even if not meaningful to patient. 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 for which the time to APR fell into that category was compared. Here the number of episodes in which APR was achieved in less than or equal to 15 minutes was compared.

Outcome measures

Measure	Fentanyl Buccal Tablets (FBT) n=1764 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.	Immediate-Release Oxycodone n=1758 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.
Time to Any Pain Relief (APR) by Treatment, <=15 Minutes	687 Number of episodes treated	540 Number of episodes treated

SECONDARY outcome

Timeframe: Time of study drug administration till 30 minutes after treatment

Population: 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.

The time to APR was measured by stopwatch and scheduled questions at each time point up to 60 minutes after baseline during double-blind treatment periods. Any pain relief was defined as any subjective reduction in pain severity, even if not meaningful to patient. 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 for which the time to APRfell into that category was compared. Here the number of episodes in which APR was achieved in less than or equal to 30 minutes was compared.

Outcome measures

Measure	Fentanyl Buccal Tablets (FBT) n=1764 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.	Immediate-Release Oxycodone n=1758 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.
Time to Any Pain Relief (APR) by Treatment, <=30 Minutes	1259 Number of episodes treated	1157 Number of episodes treated

SECONDARY outcome

Timeframe: Time of study drug treatment until 45 minutes after treatment

Population: 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.

The time to APR was measured by stopwatch and scheduled questions at each time point up to 60 minutes after baseline during double-blind treatment periods. Any pain relief was defined as any subjective reduction in pain severity, even if not meaningful to patient. 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 for which the time to APRfell into that category was compared. Here the number of episodes in which APR was achieved in less than or equal to 45 minutes was compared.

Outcome measures

Measure	Fentanyl Buccal Tablets (FBT) n=1764 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.	Immediate-Release Oxycodone n=1758 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.
Time to Any Pain Relief (APR) by Treatment, <=45 Minutes	1499 Number of episodes treated	1480 Number of episodes treated

SECONDARY outcome

Timeframe: Time of study drug treatment until 60 minutes after treatment

Population: 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.

The time to APR was measured by stopwatch and scheduled questions at each time point up to 60 minutes after baseline during double-blind treatment periods. Any pain relief was defined as any subjective reduction in pain severity, even if not meaningful to patient. 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 for which the time to APRfell into that category was compared. Here the number of episodes in which APR was achieved in less than or equal to 60 minutes was compared.

Outcome measures

Measure	Fentanyl Buccal Tablets (FBT) n=1764 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.	Immediate-Release Oxycodone n=1758 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.
Time to Any Pain Relief (APR) by Treatment, <=60 Minutes	1559 Number of episodes treated	1565 Number of episodes treated

SECONDARY outcome

Timeframe: From time study drug was taken until 5 minutes after treatment

Population: 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 was measured by stopwatch and by scheduled questions at each time point up to 60 minutes after baseline during the double-blind treatment period. Meaningful pain relief was defined as a subject reduction of pain intensity that the subject found to be meaningful (substantive). 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 for which the time to meaningful pain relief fell into that category was compared.

Outcome measures

Measure	Fentanyl Buccal Tablets (FBT) n=1764 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.	Immediate-Release Oxycodone n=1758 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.
Time to Meaningful Pain Relief (MPR) by Treatment, <= 5 Minutes	9 Number of episodes treated	18 Number of episodes treated

SECONDARY outcome

Timeframe: Time of study drug treatment until 10 minutes after treatment

Population: 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.

The time to MPR was measured by stopwatch and scheduled questions at each time point up to 60 minutes after baseline during double-blind treatment periods. Meaningful pain relief was defined as a subject reduction of pain intensity that the subject found to be meaningful (substantive). For each category (<5, <10, <15, <30, <45, <60 min, No MPR-rescue medication used, and No MPR-no rescue medication used)the number of episodes for which the time to MPR fell into that category was compared. Here the number of episodes in which MPR was achieved in less than or equal to 10 minutes was compared.

Outcome measures

Measure	Fentanyl Buccal Tablets (FBT) n=1764 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.	Immediate-Release Oxycodone n=1758 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.
Time to Meaningful Pain Relief (MPR) by Treatment, <=10 Minutes	92 Number of episodes treated	83 Number of episodes treated

SECONDARY outcome

Timeframe: Time of study drug administration until 15 minutes after treatment

Population: 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.

The time to MPR was measured by stopwatch and scheduled questions at each time point up to 60 minutes after baseline during double-blind treatment periods. Meaningful pain relief was defined as a subject reduction of pain intensity that the subject found to be meaningful (substantive). For each category (<5, <10, <15, <30, <45, <60 min, No MPR-rescue medication used, and No MPR-no rescue medication used)the number of episodes for which the time to MPR fell into that category was compared. Here the number of episodes in which MPR was achieved in less than or equal to 15 minutes was compared.

Outcome measures

Measure	Fentanyl Buccal Tablets (FBT) n=1764 breakthrough 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.	Immediate-Release Oxycodone n=1758 breakthrough 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.
Time to Meaningful Pain Relief (MPR) by Treatment, <=15 Minutes	286 Number of episodes treated	211 Number of episodes treated

SECONDARY outcome

Timeframe: Time of study drug administration until 30 minutes after treatment

Population: 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.

The time to MPR was measured by stopwatch and scheduled questions at each time point up to 60 minutes after baseline during double-blind treatment periods. Meaningful pain relief was defined as a subject reduction of pain intensity that the subject found to be meaningful (substantive). For each category (<5, <10, <15, <30, <45, <60 min, No MPR-rescue medication used, and No MPR-no rescue medication used)the number of episodes for which the time to MPR fell into that category was compared. Here the number of episodes in which MPR was achieved in less than or equal to 30 minutes was compared.

Outcome measures

Measure	Fentanyl Buccal Tablets (FBT) n=1764 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.	Immediate-Release Oxycodone n=1758 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.
Time to Meaningful Pain Relief (MPR) by Treatment, <=30 Minutes	787 Number of episodes treated	636 Number of episodes treated

SECONDARY outcome

Timeframe: From study drug administration until 45 minutes after treatment

Population: 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.

The time to MPR was measured by stopwatch and scheduled questions at each time point up to 60 minutes after baseline during double-blind treatment periods. Meaningful pain relief was defined as a subject reduction of pain intensity that the subject found to be meaningful (substantive). For each category (<5, <10, <15, <30, <45, <60 min, No MPR-rescue medication used, and No MPR-no rescue medication used)the number of episodes for which the time to MPR fell into that category was compared. Here the number of episodes in which MPR was achieved in less than or equal to 45 minutes was compared.

Outcome measures

Measure	Fentanyl Buccal Tablets (FBT) n=1764 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.	Immediate-Release Oxycodone n=1758 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.
Time to Meaningful Pain Relief (MPR) by Treatment, <=45 Minutes	1179 Number of episodes treated	1060 Number of episodes treated

SECONDARY outcome

Timeframe: Time of study drug administration until 60 minutes after treatment

Population: 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.

The time to MPR was measured by stopwatch and scheduled questions at each time point up to 60 minutes after baseline during double-blind treatment periods. Meaningful pain relief was defined as a subject reduction of pain intensity that the subject found to be meaningful (substantive). For each category (<5, <10, <15, <30, <45, <60 min, No MPR-rescue medication used, and No MPR-no rescue medication used)the number of episodes for which the time to MPR fell into that category was compared. Here the number of episodes in which MPR was achieved in less than or equal to 60 minutes was compared.

Outcome measures

Measure	Fentanyl Buccal Tablets (FBT) n=1764 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.	Immediate-Release Oxycodone n=1758 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.
Time to Meaningful Pain Relief (MPR) by Treatment, <=60 Minutes	1359 Number of episodes treated	1313 Number of episodes treated

SECONDARY outcome

Timeframe: During the administration of study drug during the double blind treatment periods.

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 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 Tablets (FBT) n=1764 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.	Immediate-Release Oxycodone n=1758 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.
Standard Rescue Medication Usage	144 Number of episodes treated	131 Number of episodes treated

SECONDARY outcome

Timeframe: 30 minutes post-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 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 Tablets (FBT) n=1764 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.	Immediate-Release Oxycodone n=1758 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.
Medication Performance Assessment 30 Minutes After-treatment Excellent	45 Number of episodes treated	18 Number of episodes treated
Medication Performance Assessment 30 Minutes After-treatment Very good	153 Number of episodes treated	104 Number of episodes treated
Medication Performance Assessment 30 Minutes After-treatment Good	533 Number of episodes treated	343 Number of episodes treated
Medication Performance Assessment 30 Minutes After-treatment Fair	450 Number of episodes treated	566 Number of episodes treated
Medication Performance Assessment 30 Minutes After-treatment Poor	334 Number of episodes treated	489 Number of episodes treated
Medication Performance Assessment 30 Minutes After-treatment No response	249 Number of episodes treated	238 Number of episodes treated

SECONDARY outcome

Timeframe: 60 minutes post-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 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 Tablets (FBT) n=1764 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.	Immediate-Release Oxycodone n=1758 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.
Medication Performance Assessment 60 Minutes After-treatment Excellent	158 Number of episodes treated	101 Number of episodes treated
Medication Performance Assessment 60 Minutes After-treatment Very good	562 Number of episodes treated	424 Number of episodes treated
Medication Performance Assessment 60 Minutes After-treatment Good	679 Number of episodes treated	726 Number of episodes treated
Medication Performance Assessment 60 Minutes After-treatment Fair	210 Number of episodes treated	335 Number of episodes treated
Medication Performance Assessment 60 Minutes After-treatment Poor	128 Number of episodes treated	146 Number of episodes treated
Medication Performance Assessment 60 Minutes After-treatment No response	27 Number of episodes treated	26 Number of episodes treated

SECONDARY outcome

Timeframe: After completion of both double-blind treatment periods or early termination

Population: Double-blind safety analysis set: 190 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 Tablets (FBT) n=190 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.	Immediate-Release Oxycodone 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.
Breakthrough Pain Preference Questionnaire Preferred Fentanyl Buccal Tablet (FBT)	99 Participants	—
Breakthrough Pain Preference Questionnaire Preferred Immediate-Release Oxycodone	63 Participants	—
Breakthrough Pain Preference Questionnaire No preference	15 Participants	—
Breakthrough Pain Preference Questionnaire Missing	13 Participants	—

SECONDARY outcome

Timeframe: The end of the first double-blind treatment period.

Population: Double-blind safety analysis set: 88 subjects who received FBT and 90 subjects who received Oxycodone in the first double-blind period

The PFTS is used to measure patient's satisfaction with study drug. Although the full scale has 25 questions, the question that is most useful (and least redundant with prior scales) for assessing the efficacy of the study drug is Question 21 which states: Which medication would you prefer to use when treating your pain flares? The subject can choose either: Prior medication, Study medication, or No preference. The number of subjects in each treatment group at the end of the first double-blind treatment period (Visit 5) who responded to each option is presented.

Outcome measures

Measure	Fentanyl Buccal Tablets (FBT) n=88 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.	Immediate-Release Oxycodone n=90 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.
Pain Flare Treatment Satisfaction (PFTS) Questionnaire - Question 21 at the End of the First Double-blind Treatment Period (Visit 5) Prior Medication	15 Participants	22 Participants
Pain Flare Treatment Satisfaction (PFTS) Questionnaire - Question 21 at the End of the First Double-blind Treatment Period (Visit 5) Study Medication	61 Participants	50 Participants
Pain Flare Treatment Satisfaction (PFTS) Questionnaire - Question 21 at the End of the First Double-blind Treatment Period (Visit 5) No Preference	12 Participants	18 Participants

SECONDARY outcome

Timeframe: At the end of the second double-blind treatment period (Visit 6)

Population: Double-blind safety analysis set: 83 subjects who received FBT and 87 subjects who received Oxycodone in the second double-blind period

The PFTS is used to measure patient's satisfaction with study drug. Although the full scale has 25 questions, the question that is most useful (and least redundant with prior scales) for assessing the efficacy of the study drug is Question 21 which states: Which medication would you prefer to use when treating your pain flares? The subject can choose either: Prior medication, Study medication, or No preference. The number of subjects in each treatment group at the end of the second double-blind treatment period (Visit 6) who responded to each option is presented.

Outcome measures

Measure	Fentanyl Buccal Tablets (FBT) n=83 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.	Immediate-Release Oxycodone n=87 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.
Pain Flare Treatment Satisfaction (PFTS) Questionnaire - Question 21 at the End of the Second Double-blind Treatment Period (Visit 6) Prior Medication	10 Participants	19 Participants
Pain Flare Treatment Satisfaction (PFTS) Questionnaire - Question 21 at the End of the Second Double-blind Treatment Period (Visit 6) Study Medication	63 Participants	59 Participants
Pain Flare Treatment Satisfaction (PFTS) Questionnaire - Question 21 at the End of the Second Double-blind Treatment Period (Visit 6) No Preference	10 Participants	9 Participants

SECONDARY outcome

Timeframe: Endpoint (End of second double-blind treatment period or last observation after start of treatment period)

Population: Double-blind safety analysis set: 88 subjects who received FBT and 94 subjects who received Oxycodone at any time during the double-blind treatment period who completed the PFTS questionnaire

The PFTS is used to measure patient's satisfaction with study drug. Although the full scale has 25 questions, the question that is most useful (and least redundant with prior scales) for assessing the efficacy of the study drug is Question 21 which states: Which medication would you prefer to use when treating your pain flares? The subject can choose either: Prior medication, Study medication, or No preference. The number of subjects in each treatment group at the Endpoint (time of the last observation during the treatment period)who responded to each option is presented.

Outcome measures

Measure	Fentanyl Buccal Tablets (FBT) n=183 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.	Immediate-Release Oxycodone n=183 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.
Pain Flare Treatment Satisfaction (PFTS) Questionnaire - Question 21 at Endpoint (End of Second Double-blind Treatment Period or Last Observation After Start of Treatment Period) Prior Medication	11 Participants	19 Participants
Pain Flare Treatment Satisfaction (PFTS) Questionnaire - Question 21 at Endpoint (End of Second Double-blind Treatment Period or Last Observation After Start of Treatment Period) Study Medication	66 Participants	63 Participants
Pain Flare Treatment Satisfaction (PFTS) Questionnaire - Question 21 at Endpoint (End of Second Double-blind Treatment Period or Last Observation After Start of Treatment Period) No Preference	12 Participants	12 Participants

Adverse Events

Fentanyl Buccal Tablets (FBT)

Serious events: 1 serious events

Other events: 79 other events

Deaths: 0 deaths

Immediate-Release Oxycodone

Serious events: 0 serious events

Other events: 49 other events

Deaths: 0 deaths

Serious adverse events

Measure	Fentanyl Buccal Tablets (FBT) n=281 participants at risk 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. This group includes all subjects in this study who had taken at least one dose of FBT in the course of the study, including both titration periods and both double-blind treatment periods. 320 subjects were randomized to titrate either FBT or oxycodone. 39 subjects received only oxycodone before discontinuing leaving 281 who received FBT during the study. 36 subjects received only FBT before discontinuing, leaving only 284 who received oxycodone.	Immediate-Release Oxycodone n=284 participants at risk 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. This arm represents all subjects who had exposure to at least one dose of immediate-release oxycodone either during the titration periods or double-blind periods. 320 subjects were randomized to titrate either FBT or oxycodone. 39 subjects received only oxycodone before discontinuing leaving 281 who received FBT during the study. 36 subjects received only FBT before discontinuing, leaving only 284 who received oxycodone.
Infections and infestations Pneumonia	0.36% 1/281 • Number of events 2 • Adverse events were monitored throughout the two titration periods and double-blind treatment periods. Each titration period was 7-10 days in length and each double-blind treatment period was 7-17 days. The average duration of treatment was 24.2 days. 323 subjects were enrolled, 3 discontinued before receiving any study drug. 320 were randomized to titrate either FBT or oxycodone in first titration period. 36 received only FBT and discontinued (leaving 284 who received oxycodone), 39 received only oxycodone and discontinued leaving 281 who received FBT).	0.00% 0/284 • Adverse events were monitored throughout the two titration periods and double-blind treatment periods. Each titration period was 7-10 days in length and each double-blind treatment period was 7-17 days. The average duration of treatment was 24.2 days. 323 subjects were enrolled, 3 discontinued before receiving any study drug. 320 were randomized to titrate either FBT or oxycodone in first titration period. 36 received only FBT and discontinued (leaving 284 who received oxycodone), 39 received only oxycodone and discontinued leaving 281 who received FBT).

Other adverse events

Measure	Fentanyl Buccal Tablets (FBT) n=281 participants at risk 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. This group includes all subjects in this study who had taken at least one dose of FBT in the course of the study, including both titration periods and both double-blind treatment periods. 320 subjects were randomized to titrate either FBT or oxycodone. 39 subjects received only oxycodone before discontinuing leaving 281 who received FBT during the study. 36 subjects received only FBT before discontinuing, leaving only 284 who received oxycodone.	Immediate-Release Oxycodone n=284 participants at risk 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. This arm represents all subjects who had exposure to at least one dose of immediate-release oxycodone either during the titration periods or double-blind periods. 320 subjects were randomized to titrate either FBT or oxycodone. 39 subjects received only oxycodone before discontinuing leaving 281 who received FBT during the study. 36 subjects received only FBT before discontinuing, leaving only 284 who received oxycodone.
Gastrointestinal disorders Nausea	9.3% 26/281 • Adverse events were monitored throughout the two titration periods and double-blind treatment periods. Each titration period was 7-10 days in length and each double-blind treatment period was 7-17 days. The average duration of treatment was 24.2 days. 323 subjects were enrolled, 3 discontinued before receiving any study drug. 320 were randomized to titrate either FBT or oxycodone in first titration period. 36 received only FBT and discontinued (leaving 284 who received oxycodone), 39 received only oxycodone and discontinued leaving 281 who received FBT).	3.9% 11/284 • Adverse events were monitored throughout the two titration periods and double-blind treatment periods. Each titration period was 7-10 days in length and each double-blind treatment period was 7-17 days. The average duration of treatment was 24.2 days. 323 subjects were enrolled, 3 discontinued before receiving any study drug. 320 were randomized to titrate either FBT or oxycodone in first titration period. 36 received only FBT and discontinued (leaving 284 who received oxycodone), 39 received only oxycodone and discontinued leaving 281 who received FBT).
Gastrointestinal disorders Diarrhea	2.1% 6/281 • Adverse events were monitored throughout the two titration periods and double-blind treatment periods. Each titration period was 7-10 days in length and each double-blind treatment period was 7-17 days. The average duration of treatment was 24.2 days. 323 subjects were enrolled, 3 discontinued before receiving any study drug. 320 were randomized to titrate either FBT or oxycodone in first titration period. 36 received only FBT and discontinued (leaving 284 who received oxycodone), 39 received only oxycodone and discontinued leaving 281 who received FBT).	1.1% 3/284 • Adverse events were monitored throughout the two titration periods and double-blind treatment periods. Each titration period was 7-10 days in length and each double-blind treatment period was 7-17 days. The average duration of treatment was 24.2 days. 323 subjects were enrolled, 3 discontinued before receiving any study drug. 320 were randomized to titrate either FBT or oxycodone in first titration period. 36 received only FBT and discontinued (leaving 284 who received oxycodone), 39 received only oxycodone and discontinued leaving 281 who received FBT).
Gastrointestinal disorders Vomiting	1.4% 4/281 • Adverse events were monitored throughout the two titration periods and double-blind treatment periods. Each titration period was 7-10 days in length and each double-blind treatment period was 7-17 days. The average duration of treatment was 24.2 days. 323 subjects were enrolled, 3 discontinued before receiving any study drug. 320 were randomized to titrate either FBT or oxycodone in first titration period. 36 received only FBT and discontinued (leaving 284 who received oxycodone), 39 received only oxycodone and discontinued leaving 281 who received FBT).	1.1% 3/284 • Adverse events were monitored throughout the two titration periods and double-blind treatment periods. Each titration period was 7-10 days in length and each double-blind treatment period was 7-17 days. The average duration of treatment was 24.2 days. 323 subjects were enrolled, 3 discontinued before receiving any study drug. 320 were randomized to titrate either FBT or oxycodone in first titration period. 36 received only FBT and discontinued (leaving 284 who received oxycodone), 39 received only oxycodone and discontinued leaving 281 who received FBT).
Gastrointestinal disorders Constipation	0.36% 1/281 • Adverse events were monitored throughout the two titration periods and double-blind treatment periods. Each titration period was 7-10 days in length and each double-blind treatment period was 7-17 days. The average duration of treatment was 24.2 days. 323 subjects were enrolled, 3 discontinued before receiving any study drug. 320 were randomized to titrate either FBT or oxycodone in first titration period. 36 received only FBT and discontinued (leaving 284 who received oxycodone), 39 received only oxycodone and discontinued leaving 281 who received FBT).	1.4% 4/284 • Adverse events were monitored throughout the two titration periods and double-blind treatment periods. Each titration period was 7-10 days in length and each double-blind treatment period was 7-17 days. The average duration of treatment was 24.2 days. 323 subjects were enrolled, 3 discontinued before receiving any study drug. 320 were randomized to titrate either FBT or oxycodone in first titration period. 36 received only FBT and discontinued (leaving 284 who received oxycodone), 39 received only oxycodone and discontinued leaving 281 who received FBT).
Gastrointestinal disorders Dry mouth	0.36% 1/281 • Adverse events were monitored throughout the two titration periods and double-blind treatment periods. Each titration period was 7-10 days in length and each double-blind treatment period was 7-17 days. The average duration of treatment was 24.2 days. 323 subjects were enrolled, 3 discontinued before receiving any study drug. 320 were randomized to titrate either FBT or oxycodone in first titration period. 36 received only FBT and discontinued (leaving 284 who received oxycodone), 39 received only oxycodone and discontinued leaving 281 who received FBT).	1.1% 3/284 • Adverse events were monitored throughout the two titration periods and double-blind treatment periods. Each titration period was 7-10 days in length and each double-blind treatment period was 7-17 days. The average duration of treatment was 24.2 days. 323 subjects were enrolled, 3 discontinued before receiving any study drug. 320 were randomized to titrate either FBT or oxycodone in first titration period. 36 received only FBT and discontinued (leaving 284 who received oxycodone), 39 received only oxycodone and discontinued leaving 281 who received FBT).
Gastrointestinal disorders Stomach discomfort	1.1% 3/281 • Adverse events were monitored throughout the two titration periods and double-blind treatment periods. Each titration period was 7-10 days in length and each double-blind treatment period was 7-17 days. The average duration of treatment was 24.2 days. 323 subjects were enrolled, 3 discontinued before receiving any study drug. 320 were randomized to titrate either FBT or oxycodone in first titration period. 36 received only FBT and discontinued (leaving 284 who received oxycodone), 39 received only oxycodone and discontinued leaving 281 who received FBT).	0.00% 0/284 • Adverse events were monitored throughout the two titration periods and double-blind treatment periods. Each titration period was 7-10 days in length and each double-blind treatment period was 7-17 days. The average duration of treatment was 24.2 days. 323 subjects were enrolled, 3 discontinued before receiving any study drug. 320 were randomized to titrate either FBT or oxycodone in first titration period. 36 received only FBT and discontinued (leaving 284 who received oxycodone), 39 received only oxycodone and discontinued leaving 281 who received FBT).
General disorders Application site pain	4.6% 13/281 • Adverse events were monitored throughout the two titration periods and double-blind treatment periods. Each titration period was 7-10 days in length and each double-blind treatment period was 7-17 days. The average duration of treatment was 24.2 days. 323 subjects were enrolled, 3 discontinued before receiving any study drug. 320 were randomized to titrate either FBT or oxycodone in first titration period. 36 received only FBT and discontinued (leaving 284 who received oxycodone), 39 received only oxycodone and discontinued leaving 281 who received FBT).	0.00% 0/284 • Adverse events were monitored throughout the two titration periods and double-blind treatment periods. Each titration period was 7-10 days in length and each double-blind treatment period was 7-17 days. The average duration of treatment was 24.2 days. 323 subjects were enrolled, 3 discontinued before receiving any study drug. 320 were randomized to titrate either FBT or oxycodone in first titration period. 36 received only FBT and discontinued (leaving 284 who received oxycodone), 39 received only oxycodone and discontinued leaving 281 who received FBT).
General disorders Application site ulcer	3.9% 11/281 • Adverse events were monitored throughout the two titration periods and double-blind treatment periods. Each titration period was 7-10 days in length and each double-blind treatment period was 7-17 days. The average duration of treatment was 24.2 days. 323 subjects were enrolled, 3 discontinued before receiving any study drug. 320 were randomized to titrate either FBT or oxycodone in first titration period. 36 received only FBT and discontinued (leaving 284 who received oxycodone), 39 received only oxycodone and discontinued leaving 281 who received FBT).	0.00% 0/284 • Adverse events were monitored throughout the two titration periods and double-blind treatment periods. Each titration period was 7-10 days in length and each double-blind treatment period was 7-17 days. The average duration of treatment was 24.2 days. 323 subjects were enrolled, 3 discontinued before receiving any study drug. 320 were randomized to titrate either FBT or oxycodone in first titration period. 36 received only FBT and discontinued (leaving 284 who received oxycodone), 39 received only oxycodone and discontinued leaving 281 who received FBT).
General disorders Fatigue	0.71% 2/281 • Adverse events were monitored throughout the two titration periods and double-blind treatment periods. Each titration period was 7-10 days in length and each double-blind treatment period was 7-17 days. The average duration of treatment was 24.2 days. 323 subjects were enrolled, 3 discontinued before receiving any study drug. 320 were randomized to titrate either FBT or oxycodone in first titration period. 36 received only FBT and discontinued (leaving 284 who received oxycodone), 39 received only oxycodone and discontinued leaving 281 who received FBT).	1.4% 4/284 • Adverse events were monitored throughout the two titration periods and double-blind treatment periods. Each titration period was 7-10 days in length and each double-blind treatment period was 7-17 days. The average duration of treatment was 24.2 days. 323 subjects were enrolled, 3 discontinued before receiving any study drug. 320 were randomized to titrate either FBT or oxycodone in first titration period. 36 received only FBT and discontinued (leaving 284 who received oxycodone), 39 received only oxycodone and discontinued leaving 281 who received FBT).
General disorders Application site erythema	1.8% 5/281 • Adverse events were monitored throughout the two titration periods and double-blind treatment periods. Each titration period was 7-10 days in length and each double-blind treatment period was 7-17 days. The average duration of treatment was 24.2 days. 323 subjects were enrolled, 3 discontinued before receiving any study drug. 320 were randomized to titrate either FBT or oxycodone in first titration period. 36 received only FBT and discontinued (leaving 284 who received oxycodone), 39 received only oxycodone and discontinued leaving 281 who received FBT).	0.00% 0/284 • Adverse events were monitored throughout the two titration periods and double-blind treatment periods. Each titration period was 7-10 days in length and each double-blind treatment period was 7-17 days. The average duration of treatment was 24.2 days. 323 subjects were enrolled, 3 discontinued before receiving any study drug. 320 were randomized to titrate either FBT or oxycodone in first titration period. 36 received only FBT and discontinued (leaving 284 who received oxycodone), 39 received only oxycodone and discontinued leaving 281 who received FBT).
Infections and infestations Nasopharyngitis	1.4% 4/281 • Adverse events were monitored throughout the two titration periods and double-blind treatment periods. Each titration period was 7-10 days in length and each double-blind treatment period was 7-17 days. The average duration of treatment was 24.2 days. 323 subjects were enrolled, 3 discontinued before receiving any study drug. 320 were randomized to titrate either FBT or oxycodone in first titration period. 36 received only FBT and discontinued (leaving 284 who received oxycodone), 39 received only oxycodone and discontinued leaving 281 who received FBT).	1.1% 3/284 • Adverse events were monitored throughout the two titration periods and double-blind treatment periods. Each titration period was 7-10 days in length and each double-blind treatment period was 7-17 days. The average duration of treatment was 24.2 days. 323 subjects were enrolled, 3 discontinued before receiving any study drug. 320 were randomized to titrate either FBT or oxycodone in first titration period. 36 received only FBT and discontinued (leaving 284 who received oxycodone), 39 received only oxycodone and discontinued leaving 281 who received FBT).
Injury, poisoning and procedural complications Fall	0.71% 2/281 • Adverse events were monitored throughout the two titration periods and double-blind treatment periods. Each titration period was 7-10 days in length and each double-blind treatment period was 7-17 days. The average duration of treatment was 24.2 days. 323 subjects were enrolled, 3 discontinued before receiving any study drug. 320 were randomized to titrate either FBT or oxycodone in first titration period. 36 received only FBT and discontinued (leaving 284 who received oxycodone), 39 received only oxycodone and discontinued leaving 281 who received FBT).	1.1% 3/284 • Adverse events were monitored throughout the two titration periods and double-blind treatment periods. Each titration period was 7-10 days in length and each double-blind treatment period was 7-17 days. The average duration of treatment was 24.2 days. 323 subjects were enrolled, 3 discontinued before receiving any study drug. 320 were randomized to titrate either FBT or oxycodone in first titration period. 36 received only FBT and discontinued (leaving 284 who received oxycodone), 39 received only oxycodone and discontinued leaving 281 who received FBT).
Nervous system disorders Headache	4.3% 12/281 • Adverse events were monitored throughout the two titration periods and double-blind treatment periods. Each titration period was 7-10 days in length and each double-blind treatment period was 7-17 days. The average duration of treatment was 24.2 days. 323 subjects were enrolled, 3 discontinued before receiving any study drug. 320 were randomized to titrate either FBT or oxycodone in first titration period. 36 received only FBT and discontinued (leaving 284 who received oxycodone), 39 received only oxycodone and discontinued leaving 281 who received FBT).	2.8% 8/284 • Adverse events were monitored throughout the two titration periods and double-blind treatment periods. Each titration period was 7-10 days in length and each double-blind treatment period was 7-17 days. The average duration of treatment was 24.2 days. 323 subjects were enrolled, 3 discontinued before receiving any study drug. 320 were randomized to titrate either FBT or oxycodone in first titration period. 36 received only FBT and discontinued (leaving 284 who received oxycodone), 39 received only oxycodone and discontinued leaving 281 who received FBT).
Nervous system disorders Dizziness	3.2% 9/281 • Adverse events were monitored throughout the two titration periods and double-blind treatment periods. Each titration period was 7-10 days in length and each double-blind treatment period was 7-17 days. The average duration of treatment was 24.2 days. 323 subjects were enrolled, 3 discontinued before receiving any study drug. 320 were randomized to titrate either FBT or oxycodone in first titration period. 36 received only FBT and discontinued (leaving 284 who received oxycodone), 39 received only oxycodone and discontinued leaving 281 who received FBT).	0.70% 2/284 • Adverse events were monitored throughout the two titration periods and double-blind treatment periods. Each titration period was 7-10 days in length and each double-blind treatment period was 7-17 days. The average duration of treatment was 24.2 days. 323 subjects were enrolled, 3 discontinued before receiving any study drug. 320 were randomized to titrate either FBT or oxycodone in first titration period. 36 received only FBT and discontinued (leaving 284 who received oxycodone), 39 received only oxycodone and discontinued leaving 281 who received FBT).
Nervous system disorders Somnolence	2.1% 6/281 • Adverse events were monitored throughout the two titration periods and double-blind treatment periods. Each titration period was 7-10 days in length and each double-blind treatment period was 7-17 days. The average duration of treatment was 24.2 days. 323 subjects were enrolled, 3 discontinued before receiving any study drug. 320 were randomized to titrate either FBT or oxycodone in first titration period. 36 received only FBT and discontinued (leaving 284 who received oxycodone), 39 received only oxycodone and discontinued leaving 281 who received FBT).	1.8% 5/284 • Adverse events were monitored throughout the two titration periods and double-blind treatment periods. Each titration period was 7-10 days in length and each double-blind treatment period was 7-17 days. The average duration of treatment was 24.2 days. 323 subjects were enrolled, 3 discontinued before receiving any study drug. 320 were randomized to titrate either FBT or oxycodone in first titration period. 36 received only FBT and discontinued (leaving 284 who received oxycodone), 39 received only oxycodone and discontinued leaving 281 who received FBT).
Nervous system disorders Sedation	1.1% 3/281 • Adverse events were monitored throughout the two titration periods and double-blind treatment periods. Each titration period was 7-10 days in length and each double-blind treatment period was 7-17 days. The average duration of treatment was 24.2 days. 323 subjects were enrolled, 3 discontinued before receiving any study drug. 320 were randomized to titrate either FBT or oxycodone in first titration period. 36 received only FBT and discontinued (leaving 284 who received oxycodone), 39 received only oxycodone and discontinued leaving 281 who received FBT).	0.70% 2/284 • Adverse events were monitored throughout the two titration periods and double-blind treatment periods. Each titration period was 7-10 days in length and each double-blind treatment period was 7-17 days. The average duration of treatment was 24.2 days. 323 subjects were enrolled, 3 discontinued before receiving any study drug. 320 were randomized to titrate either FBT or oxycodone in first titration period. 36 received only FBT and discontinued (leaving 284 who received oxycodone), 39 received only oxycodone and discontinued leaving 281 who received FBT).
Psychiatric disorders Euphoric mood	0.36% 1/281 • Adverse events were monitored throughout the two titration periods and double-blind treatment periods. Each titration period was 7-10 days in length and each double-blind treatment period was 7-17 days. The average duration of treatment was 24.2 days. 323 subjects were enrolled, 3 discontinued before receiving any study drug. 320 were randomized to titrate either FBT or oxycodone in first titration period. 36 received only FBT and discontinued (leaving 284 who received oxycodone), 39 received only oxycodone and discontinued leaving 281 who received FBT).	1.1% 3/284 • Adverse events were monitored throughout the two titration periods and double-blind treatment periods. Each titration period was 7-10 days in length and each double-blind treatment period was 7-17 days. The average duration of treatment was 24.2 days. 323 subjects were enrolled, 3 discontinued before receiving any study drug. 320 were randomized to titrate either FBT or oxycodone in first titration period. 36 received only FBT and discontinued (leaving 284 who received oxycodone), 39 received only oxycodone and discontinued leaving 281 who received FBT).
Skin and subcutaneous tissue disorders Pruritus	0.71% 2/281 • Adverse events were monitored throughout the two titration periods and double-blind treatment periods. Each titration period was 7-10 days in length and each double-blind treatment period was 7-17 days. The average duration of treatment was 24.2 days. 323 subjects were enrolled, 3 discontinued before receiving any study drug. 320 were randomized to titrate either FBT or oxycodone in first titration period. 36 received only FBT and discontinued (leaving 284 who received oxycodone), 39 received only oxycodone and discontinued leaving 281 who received FBT).	2.5% 7/284 • Adverse events were monitored throughout the two titration periods and double-blind treatment periods. Each titration period was 7-10 days in length and each double-blind treatment period was 7-17 days. The average duration of treatment was 24.2 days. 323 subjects were enrolled, 3 discontinued before receiving any study drug. 320 were randomized to titrate either FBT or oxycodone in first titration period. 36 received only FBT and discontinued (leaving 284 who received oxycodone), 39 received only oxycodone and discontinued leaving 281 who received FBT).
Skin and subcutaneous tissue disorders Hyperhidrosis	1.1% 3/281 • Adverse events were monitored throughout the two titration periods and double-blind treatment periods. Each titration period was 7-10 days in length and each double-blind treatment period was 7-17 days. The average duration of treatment was 24.2 days. 323 subjects were enrolled, 3 discontinued before receiving any study drug. 320 were randomized to titrate either FBT or oxycodone in first titration period. 36 received only FBT and discontinued (leaving 284 who received oxycodone), 39 received only oxycodone and discontinued leaving 281 who received FBT).	0.35% 1/284 • Adverse events were monitored throughout the two titration periods and double-blind treatment periods. Each titration period was 7-10 days in length and each double-blind treatment period was 7-17 days. The average duration of treatment was 24.2 days. 323 subjects were enrolled, 3 discontinued before receiving any study drug. 320 were randomized to titrate either FBT or oxycodone in first titration period. 36 received only FBT and discontinued (leaving 284 who received oxycodone), 39 received only oxycodone and discontinued leaving 281 who received FBT).
General disorders Application site irritation	2.8% 8/281 • Adverse events were monitored throughout the two titration periods and double-blind treatment periods. Each titration period was 7-10 days in length and each double-blind treatment period was 7-17 days. The average duration of treatment was 24.2 days. 323 subjects were enrolled, 3 discontinued before receiving any study drug. 320 were randomized to titrate either FBT or oxycodone in first titration period. 36 received only FBT and discontinued (leaving 284 who received oxycodone), 39 received only oxycodone and discontinued leaving 281 who received FBT).	0.00% 0/284 • Adverse events were monitored throughout the two titration periods and double-blind treatment periods. Each titration period was 7-10 days in length and each double-blind treatment period was 7-17 days. The average duration of treatment was 24.2 days. 323 subjects were enrolled, 3 discontinued before receiving any study drug. 320 were randomized to titrate either FBT or oxycodone in first titration period. 36 received only FBT and discontinued (leaving 284 who received oxycodone), 39 received only oxycodone and discontinued leaving 281 who received FBT).

Additional Information

Medical Monitor

Cephalon, Inc.

Phone: 1-800-896-5855

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: GT60