Fentanyl Buccal Tablets Versus Immediate Release Oxycodone for Breakthrough Pain in Patients With Chronic Pain

Pain Intensity Difference (PID) at 30 Minutes Post-treatment

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.

Time frame: Immediately pre-dose and 30 minutes after dosing

Pain Intensity Difference (PID) at 45 Minutes Post-treatment

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.

Time frame: Immediately pre-dose and 45 minutes after dosing

Pain Intensity Difference (PID) at 60 Minutes Post-treatment

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.

Time frame: Immediately pre-dose and 60 minutes after dosing

Percentage Change in Pain Intensity Difference (% PID) at 5 Minutes Post-treatment

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.

Time frame: Immediately pre-dose and 5 minutes after dosing

Percentage Change in Pain Intensity Difference (% PID) at 10 Minutes Post-treatment

Pain intensity (PI) scores were assessed on an 11-point numerical rating scale from 0 = no pain to 10 = pain as bad as you can imagine after each episode of breakthrough pain. The PID10 is the difference between the PI scores from the episode baseline (immediately prior to study drug administration)and 10 minutes after the administration of the study drug. The difference is calculated and assessed as a percentage of the baseline pain intensity score. This was assessed during the double-blind treatment period.

Time frame: Immediately before treatment and 10 minutes after treatment.

Percentage Change in Pain Intensity Difference (% PID) at 15 Minutes Post-treatment

Pain intensity (PI) scores were assessed during the double-blind treatment period on an 11-point numerical rating scale from 0 = no pain to 10 = pain as bad as you can imagine after each episode of breakthrough pain. The PID15 is the difference between the PI scores from the episode baseline (immediately prior to study drug administration)and 15 minutes after the administration of the study drug. The difference is calculated and assessed as a percentage of the baseline pain intensity score.

Time frame: Baseline (immediately pre-dose) and 15 minutes after dosing

Percentage Change in Pain Intensity Difference (% PID) at 30 Minutes Post-treatment

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.

Time frame: Pre-dose and 30 minutes after dosing

Percentage Change in Pain Intensity Difference (% PID) at 45 Minutes Post-treatment

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.

Time frame: Immediately pre-dose and 45 minutes after dosing

Percentage Change in Pain Intensity Difference (% PID) at 60 Minutes Post-treatment

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.

Time frame: Immediately pre-dose and 60 minutes after dosing

Sum of Pain Intensity Difference at 30 Minutes Post-treatment (SPID30)

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.

Time frame: From 5 minutes after dosing through 30 minutes after dosing

Sum of Pain Intensity Difference at 60 Minutes Post-treatment (SPID60)

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.

Time frame: From 5 minutes after dosing through 60 minutes after dosing

Pain Relief (PR) Score at 5 Minutes Post-treatment

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).

Time frame: 5 minutes after treatment

Pain Relief Score at 10 Minutes Post-treatment

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).

Time frame: 10 minutes after treatment with study drug

Pain Relief Score at 15 Minutes Post-treatment

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).

Time frame: 15 minutes after treatment with study drug

Pain Relief Score at 30 Minutes Post-treatment

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).

Time frame: 30 minutes after treatment with study drug

Pain Relief Score at 45 Minutes Post-treatment

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).

Time frame: 45 minutes after treatment with study drug

Pain Relief Score at 60 Minutes Post-treatment

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).

Time frame: 60 minutes after treatment with study drug

Total Pain Relief at 60 Minutes (TOTPAR60)

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.

Time frame: From 5 minutes to 60 minutes after dosing

Percent Total Pain Relief at 60 Minutes Posttreatment (%TOTPAR)

The PR score at set intervals after the administration of study drug during the double-blind treatment phase was recorded in the patient's diary. The PR scale is a 5-point categorical scale of 0-4 (0=none, 1=slight, 2=moderate, 3=a lot, 4=complete). The maximum TOTPAR score that could be achieved at 60 minutes is equal to 16; thus, %TOTPAR at 60 minutes is (TOTPAR60 /16) x 100.The % TOTPAR achieved 60 minutes after the administration of study drug was calculated during the double-blind treatment phase.

Time frame: From 5 minutes through 60 minutes after study drug treatment

Time to Any Pain Relief (APR) by Treatment - <= 5 Minutes

Time to APR (subjective perception of any reduction in pain intensity) was measured by stopwatch and by scheduled questions at each time point up to 60 minutes during double-blind treatment period. No pain relief was defined as: patient indicated no pain relief experienced, rescue medication was used,or missing data. For each category (\<5, \<10, \<15, \<30, \<45, \<60 minutes, No APR-rescue medication used, and No APR-no rescue medication used)the number of episodes which time to APR fell in that category was compared. Number of episodes where APR was achieved in 5 minutes or less was compared.

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

Time to Any Pain Relief (APR) by Treatment <=10 Minutes

Time to APR (subjective perception of any reduction in pain intensity) was measured by stopwatch and by scheduled questions at each time point up to 60 minutes during double-blind treatment period. No pain relief was defined as: patient indicated no pain relief experienced, rescue medication was used,or missing data. For each category (\<5, \<10, \<15, \<30, \<45, \<60 minutes, No APR-rescue medication used, and No APR-no rescue medication used)the number of episodes which time to APR fell in that category was compared. Number of episodes where APR was achieved in 10 minutes or less was compared.

Time frame: From study drug treatment until 10 minutes after treatment

Time to Any Pain Relief (APR) by Treatment <=15 Minutes

Time to APR (subjective perception of any reduction in pain intensity) was measured by stopwatch and by scheduled questions at each time point up to 60 minutes during double-blind treatment period. No pain relief was defined as: patient indicated no pain relief experienced, rescue medication was used,or missing data. For each category (\<5, \<10, \<15, \<30, \<45, \<60 minutes, No APR-rescue medication used, and No APR-no rescue medication used)the number of episodes which time to APR fell in that category was compared. Number of episodes where APR was achieved in 15 minutes or less was compared.

Time frame: From study drug administration to 15 minutes after treatment

Time to Any Pain Relief (APR) by Treatment <=30 Minutes

Time to APR (subjective perception of any reduction in pain intensity) was measured by stopwatch and by scheduled questions at each time point up to 60 minutes during double-blind treatment period. No pain relief was defined as: patient indicated no pain relief experienced, rescue medication was used,or missing data. For each category (\<5, \<10, \<15, \<30, \<45, \<60 minutes, No APR-rescue medication used, and No APR-no rescue medication used)the number of episodes which time to APR fell in that category was compared. Number of episodes where APR was achieved in 30 minutes or less was compared.

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

Time to Any Pain Relief (APR) by Treatment <=45 Minutes

Time to APR (subjective perception of any reduction in pain intensity) was measured by stopwatch and by scheduled questions at each time point up to 60 minutes during double-blind treatment period. No pain relief was defined as: patient indicated no pain relief experienced, rescue medication was used,or missing data. For each category (\<5, \<10, \<15, \<30, \<45, \<60 minutes, No APR-rescue medication used, and No APR-no rescue medication used)the number of episodes which time to APR fell in that category was compared. Number of episodes where APR was achieved in 45 minutes or less was compared.

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

Time to Any Pain Relief (APR) by Treatment <=60 Minutes

Time to APR (subjective perception of any reduction in pain intensity) was measured by stopwatch and by scheduled questions at each time point up to 60 minutes during double-blind treatment period. No pain relief was defined as: patient indicated no pain relief experienced, rescue medication was used,or missing data. For each category (\<5, \<10, \<15, \<30, \<45, \<60 minutes, No APR-rescue medication used, and No APR-no rescue medication used)the number of episodes which time to APR fell in that category was compared. Number of episodes where APR was achieved in 60 minutes or less was compared.

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

Time to Meaningful Pain Relief (MPR) by Treatment - <= 5 Minutes

Time to MPR (subjective perception of meaningful reduction in pain intensity) was measured by stopwatch and by scheduled questions at each time point up to 60 minutes during double-blind treatment period. No pain relief was defined as: patient indicated no pain relief experienced, rescue medication was used,or missing data. For each category (\<5, \<10, \<15, \<30, \<45, \<60 minutes, No MPR-rescue medication used, and No MPR-no rescue medication used)the number of episodes which time to MPR fell in that category was compared.

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

Time to Meaningful Pain Relief (MPR) by Treatment <=10 Minutes

Time to MPR(subjective perception of meaningful reduction in pain intensity) was measured by stopwatch and by scheduled questions at each time point during double-blind treatment period. No pain relief was defined as: patient indicated no pain relief experienced, rescue medication was used,or missing data. For each category (\<5, \<10, \<15, \<30, \<45, \<60 minutes, No MPR-rescue medication used, and No MPR-no rescue medication used)the number of episodes which time to MPR fell in that category was compared. Number of episodes in which MPR was achieved in 10 minutes or less was compared.

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

Time to Meaningful Pain Relief (MPR) by Treatment <=15 Minutes

Time to MPR(subjective perception of meaningful reduction in pain intensity) was measured by stopwatch and by scheduled questions at each time point during double-blind treatment period. No pain relief was defined as: patient indicated no pain relief experienced, rescue medication was used,or missing data. For each category (\<5, \<10, \<15, \<30, \<45, \<60 minutes, No MPR-rescue medication used, and No MPR-no rescue medication used)the number of episodes which time to MPR fell in that category was compared. Number of episodes in which MPR was achieved in 15 minutes or less was compared.

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

Time to Meaningful Pain Relief (MPR) by Treatment <=30 Minutes

Time to MPR(subjective perception of meaningful reduction in pain intensity) was measured by stopwatch and by scheduled questions at each time point during double-blind treatment period. No pain relief was defined as: patient indicated no pain relief experienced, rescue medication was used,or missing data. For each category (\<5, \<10, \<15, \<30, \<45, \<60 minutes, No MPR-rescue medication used, and No MPR-no rescue medication used)the number of episodes which time to MPR fell in that category was compared. Number of episodes in which MPR was achieved in 30 minutes or less was compared.

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

Time to Meaningful Pain Relief (MPR) by Treatment <=45 Minutes

Time to MPR(subjective perception of meaningful reduction in pain intensity) was measured by stopwatch and by scheduled questions at each time point during double-blind treatment period. No pain relief was defined as: patient indicated no pain relief experienced, rescue medication was used,or missing data. For each category (\<5, \<10, \<15, \<30, \<45, \<60 minutes, No MPR-rescue medication used, and No MPR-no rescue medication used)the number of episodes which time to MPR fell in that category was compared. Number of episodes in which MPR was achieved in 45 minutes or less was compared.

Time frame: From study drug administration until 45 minutes after treatment

Time to Meaningful Pain Relief (MPR) by Treatment <=60 Minutes

Time to MPR(subjective perception of meaningful reduction in pain intensity) was measured by stopwatch and by scheduled questions at each time point during double-blind treatment period. No pain relief was defined as: patient indicated no pain relief experienced, rescue medication was used,or missing data. For each category (\<5, \<10, \<15, \<30, \<45, \<60 minutes, No MPR-rescue medication used, and No MPR-no rescue medication used)the number of episodes which time to MPR fell in that category was compared. Number of episodes in which MPR was achieved in 60 minutes or less was compared.

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

Use of Standard Rescue Medication

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.

Time frame: Throughout the double-blind treatment period

Medication Performance Assessment 30 Minutes Post-treatment

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.

Time frame: 30 minutes post-treatment

Medication Performance Assessment 60 Minutes Post-treatment

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.

Time frame: 60 minutes post-treatment

Breakthrough Pain Preference Questionnaire

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.

Time frame: At Visit 6 ( up to 42 days depending upon how long it takes the patient to manage their BTP) after completion of both double-blind treatment periods.

Patient Global Impression of Change (PGIC) at Visit 7- 1 Month After Open Label Treatment

The PGIC is a standardized self-report tool that measures the change in a patient's overall status rating since the start of the open-label extension period. The 7-point scale includes very much worse= -3, much worse= -2, minimally worse= -1, no change=0, minimally improved= +1, much improved= +2, and very much improved= +3. This was assessed 1 month after start of the open-label extension period.

Time frame: One month after start of open-label treatment

Patient Global Impression of Change (PGIC) at Visit 8- 2 Months After Open Label Treatment

The PGIC is a standardized self-report tool that measures the change in a patient's overall status rating since the start of the open-label extension period. The 7-point scale includes very much worse= -3, much worse= -2, minimally worse= -1, no change=0, minimally improved= +1, much improved= +2, and very much improved= +3. Here it was assessed 2 months after the start of the open-label extension period.

Time frame: 2 months after start of open-label extension period

Patient Global Impression of Change (PGIC) at Visit 9- 3 Months After Open Label Treatment

The PGIC is a standardized self-report tool that measures the change in a patient's overall status rating since the start of the open-label extension period. The 7-point scale includes very much worse= -3, much worse= -2, minimally worse= -1, no change=0, minimally improved= +1, much improved= +2, and very much improved= +3. Here it was assessed 3 months after the start of the open-label extension period.

Time frame: 3 months after start of open-label extension period

Patient Global Impression of Change (PGIC) Endpoint

The PGIC is a standardized self-report tool that measures the change in a patient's overall status rating since the start of the open-label extension period. The 7-point scale includes very much worse= -3, much worse= -2, minimally worse= -1, no change=0, minimally improved= +1, much improved= +2, and very much improved= +3. Here it was assessed at the conclusion of the open-label extension period.

Time frame: At conclusion of open-label extension period

Clinician Global Impression of Change at Visit 7- 1 Month After Open Label Treatment

The CGIC is a standardized tool that measures the change in a patient's overall status rating since the start of the open-label extension period, in the opinion of the clinician. The 7-point scale includes very much worse=-3, much worse=-2, minimally worse=-1,no change=0, minimally improved=+1, much improved=+2, and very much improved=+3. The CGIC was completed by the clinicians at visits 7, 8, and 9 (or early termination) which correspond to 1, 2, or 3 months after the start of the open-label extension period.

Time frame: One month after start of open-label extension

Clinician Global Impression of Change (CGIC) at Visit 8- 2 Months After Open Label Treatment

The CGIC is a standardized tool that measures the change in a patient's overall status rating since the start of the open-label extension period, in the opinion of the clinician. The 7-point scale includes very much worse=-3, much worse=-2, minimally worse=-1,no change=0, minimally improved=+1, much improved=+2, and very much improved=+3. Here it was assessed 2 months after the start of the open-label extension period. The CGIC was completed by the clinicians at visits 7, 8, and 9 (or early termination).

Time frame: Two months after start of open-label extension period

Clinician Global Impression of Change (CGIC) at Visit 9- 3 Months After Open Label Treatment

The CGIC is a standardized tool that measures the change in a patient's overall status rating since the start of the open-label extension period, in the opinion of the clinician. The 7-point scale includes very much worse=-3, much worse=-2, minimally worse=-1,no change=0, minimally improved=+1, much improved=+2, and very much improved=+3. The CGIC was completed by the clinicians at visits 7, 8, and 9 (or early termination), which correspond to 1, 2, or 3 months after the start of the open-label extension period.

Time frame: 3 months after start of open-label extension period

Clinician Global Impression of Change (CGIC)Endpoint

The CGIC is a standardized tool that measures the change in a patient's overall status rating since the start of the open-label extension period, in the opinion of the clinician. The 7-point scale includes very much worse=-3, much worse=-2, minimally worse=-1,no change=0, minimally improved=+1, much improved=+2, and very much improved=+3. The CGIC was completed by the clinicians at visits 7, 8, and 9 (or early termination).

Time frame: End of open-label extension period