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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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).

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).

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).

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).

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).

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).

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.