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

A Randomized, Double-Blind, Active-Controlled Crossover Study to Evaluate the Efficacy and Safety of Fentanyl Buccal Tablets Compared With Immediate-release Oxycodone for the Management of Breakthrough Pain in Opioid-Tolerant Patient With Chronic Pain

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00463047

Enrollment

323

Registered

2007-04-19

Start date

2007-07-31

Completion date

2009-02-28

Last updated

2012-05-28

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Chronic Pain

Keywords

Breakthrough pain, Opioid-tolerant, Chronic pain

Brief summary

Evaluate the efficacy of treatment with Fentanyl Buccal Tablets (FBT) compared with immediate release oxycodone in alleviating breakthrough pain in opioid tolerant patients with chronic pain.

Interventions

DRUGFentanyl Buccal Tablets Compared With Immediate-Release Oxycodone

Patients will be randomly assigned in a 1:1 ratio either to titrate immediate-release oxycodone first and to titrate FBT second, or to titrate FBT first and immediate-release oxycodone second, followed by 2 double-blind crossover treatment periods (in randomized order). For the double-blind treatment period of the study involving FBT administration, a patient is randomly assigned to receive FBT at the 200, 400, 600, or 800 mcg strength found to be successful during open-label titration. For the double-blind treatment period of the study to which a patient is randomly assigned to receive immediate-release oxycodone, the patient will receive immediate-release oxycodone at the strength (15, 30, 45, or 60 mg) found to be successful during open-label titration.

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to 80 Years

Healthy volunteers

Inclusion criteria

* The patient has chronic pain of at least 3 months duration associated with: diabetic peripheral neuropathy, postherpetic neuralgia, traumatic injury, complex regional pain syndrome, back pain, neck pain,fibromyalgia, chronic pancreatitis, osteoarthritis,or cancer. * The patient is currently using 1 of the following: at least 60 mg of oral morphine/day, or at least 25 mcg of transdermal fentanyl/hour, or at least 30 mg of oxycodone/day, or at least 8 mg of hydromorphone/day, or an equianalgesic dose of another opioid/day as around-the-clock (ATC) therapy for at least 7 days before administration of the first dose of study drug * The patient is willing to provide written informed consent to participate in this study. * The patient is 18 through 80 years of age. * Women must be surgically sterile, 2 years postmenopausal, or, if of childbearing potential, using a medically accepted method of birth control and agree to continued use of this method for the duration of the study. * Any patient with cancer should have a life expectancy of at least 3 months. * The patient reports an average Pain Intensity (PI) score, over the prior 24 hours, of 6 or less (0=no pain through 10=pain as bad as you can imagine) for their chronic pain. * The patient experiences, on average, 1 to 4 breakthrough pain (BTP) episodes per day while taking ATC opioid therapy, and on average, the duration of each BTP episode is less than 4 hours. * The patient currently uses opioid therapy for alleviation of BTP episodes, occurring at the location of the chronic pain, and achieves at least partial relief. * The patient must be willing and able to successfully self-administer the study drug,comply with study restrictions, complete the electronic diary, and return to the clinic for scheduled study visits as specified in this protocol.

Exclusion criteria

* The patient has uncontrolled or rapidly escalating pain as determined by the investigator (i.e., the around-the-clock (ATC) therapy may be expected to change between the first and last treatments with study drug), or has pain uncontrolled by therapy that could adversely impact the safety of the patient or that could be compromised by treatment with study drug. * The patient has a recent history (within 5 years) or current evidence of alcohol or other substance abuse. * The patient has known or suspected hypersensitivities, allergies, or other contraindications to any ingredient in either study drug. * The patient has cardiopulmonary disease that would, in the opinion of the investigator, significantly increase the risk of treatment with potent synthetic opioids. * The patient has medical or psychiatric disease that, in the opinion of the investigator, would compromise collected data. * The patient is expected to have surgery during the study that will impact the patient's chronic pain and/or BTP. * The patient has had therapy before study drug treatment that, in the opinion of the investigator, could alter pain or response to pain medication. * The patient is pregnant or lactating. * The patient has participated in a previous study with FBT. * The patient has participated in a study involving an investigational drug in the prior 30 days. * The patient is currently using prescription FBT or immediate-release oxycodone for BTP and is unwilling to undergo re-titration. * The patient has received a monoamine oxidase inhibitor (MAOI) within 14 days before the first treatment with study drug. * The patient has any other medical condition or is receiving concomitant medication/therapy (eg, regional nerve block) that could, in the opinion of the investigator, compromise the patient's safety or compliance with the study protocol,or compromise collected data. * The patient is involved in active litigation in regard to the chronic pain currently being treated. * The patient has a positive urine drug screen (UDS) for an illicit drug or a medication not prescribed for him/her or which is not medically explainable.

Design outcomes

Primary

Measure	Time frame	Description
Pain Intensity Difference (PID15) At 15 Minutes	Immediately pre-dose and fifteen minutes after administration of study drug	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.

Secondary

Measure	Time frame	Description
Pain Intensity Difference (PID 10) at 10 Minutes	Immediately before and 10 minutes after administration of study drug	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 Difference (PID 30) at 30 Minutes	Immediately before and 10 minutes after study drug administration	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 Difference (PID 45) at 45 Minutes	Immediately before and 45 minutes after study drug administration	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 Difference (PID 60) at 60 Minutes	Immediately before and 60 minutes after administration of study drug	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.
Percentage Change in Pain Intensity Difference (% PID) at 5 Minutes Post-treatment	Immediately before and 5 minutes after administration of study drug	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.
Percentage Change in Pain Intensity Difference (%PID) at 10 Minutes	Immediately before and 10 minutes after study drug administration	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.
Percentage Change in Pain Intensity Difference (%PID) at 15 Minutes	Immediately before and 15 minutes after administration of study drug	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.
Percentage Change in Pain Intensity Difference (%PID) at 30 Minutes	Immediately before and 30 minutes after study drug administration	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.
Percentage Change in Pain Intensity Difference (% PID) at 45 Minutes	Immediately before and 45 minutes after study drug administration	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.
Percentage Change in Pain Intensity Difference (%PID) at 60 Minutes	Immediately before and 60 minutes after study drug administration	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.
Sum of Pain Intensity Difference at 30 Minutes Post-treatment (SPID30)	From 5 minutes after dosing through 30 minutes after dosing	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.
Sum of Pain Intensity Difference at 60 Minutes Post-treatment (SPID60)	From 5 minutes after dosing through 60 minutes after dosing	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.
Pain Relief (PR) Score at 5 Minutes	Five minutes after administration of study drug	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).
Pain Relief Score (PR) at 10 Minutes	10 minutes after treatment with study drug	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).
Pain Relief Score (PR) at 15 Minutes	15 minutes after treatment with study drug	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).
Pain Relief Score (PR) at 30 Minutes	30 minutes after treatment with study drug	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).
Pain Relief Score (PR) at 45 Minutes	45 minutes after treatment with study drug	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).
Pain Relief Score (PR) at 60 Minutes	60 minutes after treatment with study drug	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).
Total Pain Relief (TOTPAR60) at 60 Minutes	From 5 minutes to 60 minutes after dosing	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.
Percent Total Pain Relief at 60 Minutes Posttreatment (%TOTPAR)	From 5 minutes through 60 minutes after study drug treatment	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 Any Pain Relief (APR) by Treatment, <= 5 Minutes	From time was administered to 5 minutes after treatment	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.
Time to Any Pain Relief (APR) by Treatment, <=10 Minutes	From study drug treatment until 10 minutes after treatment	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.
Time to Any Pain Relief (APR) by Treatment, <=15 Minutes	From study drug administration to 15 minutes after treatment	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.
Time to Any Pain Relief (APR) by Treatment, <=30 Minutes	Time of study drug administration till 30 minutes after treatment	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.
Time to Any Pain Relief (APR) by Treatment, <=45 Minutes	Time of study drug treatment until 45 minutes after treatment	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.
Time to Any Pain Relief (APR) by Treatment, <=60 Minutes	Time of study drug treatment until 60 minutes after treatment	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 Meaningful Pain Relief (MPR) by Treatment, <= 5 Minutes	From time study drug was taken until 5 minutes after treatment	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.
Time to Meaningful Pain Relief (MPR) by Treatment, <=10 Minutes	Time of study drug treatment until 10 minutes after treatment	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.
Time to Meaningful Pain Relief (MPR) by Treatment, <=15 Minutes	Time of study drug administration until 15 minutes after treatment	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.
Time to Meaningful Pain Relief (MPR) by Treatment, <=30 Minutes	Time of study drug administration until 30 minutes after treatment	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.
Time to Meaningful Pain Relief (MPR) by Treatment, <=45 Minutes	From study drug administration until 45 minutes after treatment	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.
Time to Meaningful Pain Relief (MPR) by Treatment, <=60 Minutes	Time of study drug administration until 60 minutes after treatment	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.
Standard Rescue Medication Usage	During the administration of study drug during the double blind treatment periods.	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.
Medication Performance Assessment 30 Minutes After-treatment	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.
Pain Intensity Difference (PID 5) at 5 Minutes	Immediately before and 5 minutes after study drug administration	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.
Breakthrough Pain Preference Questionnaire	After completion of both double-blind treatment periods or early termination	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.
Pain Flare Treatment Satisfaction (PFTS) Questionnaire - Question 21 at the End of the First Double-blind Treatment Period (Visit 5)	The end of the first double-blind treatment 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.
Pain Flare Treatment Satisfaction (PFTS) Questionnaire - Question 21 at the End of the Second Double-blind Treatment Period (Visit 6)	At the end of the second double-blind treatment period (Visit 6)	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.
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)	Endpoint (End of second double-blind treatment period or last observation after start of treatment 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 Endpoint (time of the last observation during the treatment period)who responded to each option is presented.
Medication Performance Assessment 60 Minutes After-treatment	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.

Countries

United States

Participant flow

Recruitment details

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.

Pre-assignment details

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.

Participants by arm

Arm	Count
Total Number of Patients 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.	323
Total	323

Arm

Count

Total Number of Patients

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.

323

Total

323

Withdrawals & dropouts

Period	Reason	FG000	FG001
Double-Blind Treatment Period 1	Adverse Event	0	2
Double-Blind Treatment Period 1	Non-compliance with procedures	1	0
Double-Blind Treatment Period 1	Other	1	0
Double-Blind Treatment Period 1	Protocol Violation	1	2
Double-Blind Treatment Period 2	Adverse Event	0	1
Double-Blind Treatment Period 2	Non-compliance with procedures	1	0
Double-Blind Treatment Period 2	Withdrawal by Subject	0	1
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 procedures	4	10
Titration Period 1	Non-compliance with study medication	3	5
Titration Period 1	Other	0	2
Titration Period 1	Protocol Violation	5	5
Titration Period 1	Withdrawal by Subject	3	5
Titration Period 2	Adverse Event	9	9
Titration Period 2	Lack of Efficacy	6	4
Titration Period 2	Lost to Follow-up	1	2
Titration Period 2	Non-compliance procedures	4	1
Titration Period 2	Non-compliance study medication	4	2
Titration Period 2	Other	3	2
Titration Period 2	Protocol Violation	2	3
Titration Period 2	Withdrawal by Subject	1	0

Baseline characteristics

Characteristic	Total Number of Patients
Age, Categorical <=18 years	0 Participants
Age, Categorical >=65 years	0 Participants
Age, Categorical Between 18 and 65 years	323 Participants
Age Continuous	50.2 years STANDARD_DEVIATION 9.81
Region of Enrollment United States	323 participants
Sex: Female, Male Female	188 Participants
Sex: Female, Male Male	135 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	79 / 281	49 / 284
serious Total, serious adverse events	1 / 281	0 / 284

Outcome results

Primary

Pain Intensity Difference (PID15) At 15 Minutes

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.

Time frame: 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.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Fentanyl Buccal Tablets (FBT)	Pain Intensity Difference (PID15) At 15 Minutes	0.82 Units on a scale	Standard Error 0.07
Immediate-Release Oxycodone	Pain Intensity Difference (PID15) At 15 Minutes	0.59 Units on a scale	Standard Error 0.07

Comparison: The statistical hypothesis to be tested was:HO: µFBT = µOXY versus Ha: µFBT ≠ µoxy where µFBT and µOXY denote the mean PID15 for double-blind episodes for which patients use FBT and oxycodone (OXY), respectively. The primary variable was analyzed using a mixed effects ANOVA crossover model, with treatment as randomized (FBT or OXY), period, and treatment sequence (as randomized) as fixed factors and patient as a random factor, using compound symmetry for the variance-covariance matrix.p-value: <0.000195% CI: [0.18, 0.29]Mixed effects ANOVA

Secondary

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: 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

Arm	Measure	Group	Value (NUMBER)
Fentanyl Buccal Tablets (FBT)	Breakthrough Pain Preference Questionnaire	Missing	13 Participants
Fentanyl Buccal Tablets (FBT)	Breakthrough Pain Preference Questionnaire	Preferred Fentanyl Buccal Tablet (FBT)	99 Participants
Fentanyl Buccal Tablets (FBT)	Breakthrough Pain Preference Questionnaire	Preferred Immediate-Release Oxycodone	63 Participants
Fentanyl Buccal Tablets (FBT)	Breakthrough Pain Preference Questionnaire	No preference	15 Participants

Secondary

Medication Performance Assessment 30 Minutes After-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

Arm	Measure	Group	Value (NUMBER)
Fentanyl Buccal Tablets (FBT)	Medication Performance Assessment 30 Minutes After-treatment	Fair	450 Number of episodes treated
Fentanyl Buccal Tablets (FBT)	Medication Performance Assessment 30 Minutes After-treatment	Very good	153 Number of episodes treated
Fentanyl Buccal Tablets (FBT)	Medication Performance Assessment 30 Minutes After-treatment	Poor	334 Number of episodes treated
Fentanyl Buccal Tablets (FBT)	Medication Performance Assessment 30 Minutes After-treatment	Good	533 Number of episodes treated
Fentanyl Buccal Tablets (FBT)	Medication Performance Assessment 30 Minutes After-treatment	No response	249 Number of episodes treated
Fentanyl Buccal Tablets (FBT)	Medication Performance Assessment 30 Minutes After-treatment	Excellent	45 Number of episodes treated
Immediate-Release Oxycodone	Medication Performance Assessment 30 Minutes After-treatment	No response	238 Number of episodes treated
Immediate-Release Oxycodone	Medication Performance Assessment 30 Minutes After-treatment	Excellent	18 Number of episodes treated
Immediate-Release Oxycodone	Medication Performance Assessment 30 Minutes After-treatment	Good	343 Number of episodes treated
Immediate-Release Oxycodone	Medication Performance Assessment 30 Minutes After-treatment	Fair	566 Number of episodes treated
Immediate-Release Oxycodone	Medication Performance Assessment 30 Minutes After-treatment	Poor	489 Number of episodes treated
Immediate-Release Oxycodone	Medication Performance Assessment 30 Minutes After-treatment	Very good	104 Number of episodes treated

Comparison: Analysis is based on a generalized estimating equation model with treatment as a fixed effect and patient as a random effect. A cumulative logit link function and independent working correlation were applied in this model. Treatment differences for each time point were measured across all categories of responses.p-value: <0.000195% CI: [1.7, 2.2]Generalized estimating equation

Secondary

Medication Performance Assessment 60 Minutes After-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

Arm	Measure	Group	Value (NUMBER)
Fentanyl Buccal Tablets (FBT)	Medication Performance Assessment 60 Minutes After-treatment	Excellent	158 Number of episodes treated
Fentanyl Buccal Tablets (FBT)	Medication Performance Assessment 60 Minutes After-treatment	Very good	562 Number of episodes treated
Fentanyl Buccal Tablets (FBT)	Medication Performance Assessment 60 Minutes After-treatment	Good	679 Number of episodes treated
Fentanyl Buccal Tablets (FBT)	Medication Performance Assessment 60 Minutes After-treatment	Fair	210 Number of episodes treated
Fentanyl Buccal Tablets (FBT)	Medication Performance Assessment 60 Minutes After-treatment	Poor	128 Number of episodes treated
Fentanyl Buccal Tablets (FBT)	Medication Performance Assessment 60 Minutes After-treatment	No response	27 Number of episodes treated
Immediate-Release Oxycodone	Medication Performance Assessment 60 Minutes After-treatment	Poor	146 Number of episodes treated
Immediate-Release Oxycodone	Medication Performance Assessment 60 Minutes After-treatment	Excellent	101 Number of episodes treated
Immediate-Release Oxycodone	Medication Performance Assessment 60 Minutes After-treatment	Fair	335 Number of episodes treated
Immediate-Release Oxycodone	Medication Performance Assessment 60 Minutes After-treatment	Very good	424 Number of episodes treated
Immediate-Release Oxycodone	Medication Performance Assessment 60 Minutes After-treatment	No response	26 Number of episodes treated
Immediate-Release Oxycodone	Medication Performance Assessment 60 Minutes After-treatment	Good	726 Number of episodes treated

Secondary

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)

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.

Time frame: 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

Arm	Measure	Group	Value (NUMBER)
Fentanyl Buccal Tablets (FBT)	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
Fentanyl Buccal Tablets (FBT)	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
Fentanyl Buccal Tablets (FBT)	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
Immediate-Release Oxycodone	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	63 Participants
Immediate-Release Oxycodone	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
Immediate-Release Oxycodone	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	19 Participants

Secondary

Pain Flare Treatment Satisfaction (PFTS) Questionnaire - Question 21 at the End of the First Double-blind Treatment Period (Visit 5)

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.

Time frame: 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

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

Secondary

Pain Flare Treatment Satisfaction (PFTS) Questionnaire - Question 21 at the End of the Second Double-blind Treatment Period (Visit 6)

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.

Time frame: 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

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

Secondary

Pain Intensity Difference (PID 10) at 10 Minutes

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.

Time frame: Immediately before and 10 minutes after administration of study drug

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Fentanyl Buccal Tablets (FBT)	Pain Intensity Difference (PID 10) at 10 Minutes	0.30 Units on a scale	Standard Error 0.04
Immediate-Release Oxycodone	Pain Intensity Difference (PID 10) at 10 Minutes	0.22 Units on a scale	Standard Error 0.04

Comparison: The statistical hypothesis to be tested was: HO: µFBT = µOXY versus Ha: µFBT ≠ µoxy where µFBT and µOXY denote the mean PID10 for double-blind episodes for which patients use FBT and OXY, respectively. The primary variable was analyzed using a mixed effects ANOVA crossover model, with treatment as randomized (FBT or OXY), period, and treatment sequence (as randomized) as fixed factors and patient as a random factor, using compound symmetry for the variance-covariance matrix.p-value: <0.000195% CI: [0.05, 0.13]ANOVA

Secondary

Pain Intensity Difference (PID 30) at 30 Minutes

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 before and 10 minutes after study drug administration

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Fentanyl Buccal Tablets (FBT)	Pain Intensity Difference (PID 30) at 30 Minutes	1.96 Units on a scale	Standard Error 0.09
Immediate-Release Oxycodone	Pain Intensity Difference (PID 30) at 30 Minutes	1.58 Units on a scale	Standard Error 0.09

Secondary

Pain Intensity Difference (PID 45) at 45 Minutes

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 before and 45 minutes after study drug administration

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Fentanyl Buccal Tablets (FBT)	Pain Intensity Difference (PID 45) at 45 Minutes	2.87 Units on a scale	Standard Error 0.12
Immediate-Release Oxycodone	Pain Intensity Difference (PID 45) at 45 Minutes	2.59 Units on a scale	Standard Error 0.12

Comparison: The statistical hypothesis to be tested was: HO: µFBT = µOXY versus Ha: µFBT ≠ µoxy where µFBT and µOXY denote the mean PID45 for double-blind episodes for which patients use FBT and OXY, respectively. The primary variable was analyzed using a mixed effects ANOVA crossover model, with treatment as randomized (FBT or OXY), period, and treatment sequence (as randomized) as fixed factors and patient as a random factor, using compound symmetry for the variance-covariance matrix.p-value: <0.000195% CI: [0.2, 0.35]ANOVA

Secondary

Pain Intensity Difference (PID 5) at 5 Minutes

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.

Time frame: Immediately before and 5 minutes after study drug administration

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Fentanyl Buccal Tablets (FBT)	Pain Intensity Difference (PID 5) at 5 Minutes	0.08 Units on a scale	Standard Error 0.03
Immediate-Release Oxycodone	Pain Intensity Difference (PID 5) at 5 Minutes	0.05 Units on a scale	Standard Error 0.03

Comparison: The statistical hypothesis to be tested was: HO: µFBT = µOXY versus Ha: µFBT ≠ µoxy where µFBT and µOXY denote the mean PID5 for double-blind episodes for which patients use FBT and OXY, respectively. The primary variable was analyzed using a mixed effects ANOVA crossover model, with treatment as randomized (FBT or OXY), period, and treatment sequence (as randomized) as fixed factors and patient as a random factor, using compound symmetry for the variance-covariance matrix.p-value: 0.008195% CI: [0.01, 0.05]ANOVA

Secondary

Pain Intensity Difference (PID 60) at 60 Minutes

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 before and 60 minutes after administration of study drug

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Fentanyl Buccal Tablets (FBT)	Pain Intensity Difference (PID 60) at 60 Minutes	3.35 Units on a scale	Standard Error 0.13
Immediate-Release Oxycodone	Pain Intensity Difference (PID 60) at 60 Minutes	3.19 Units on a scale	Standard Error 0.13

Comparison: The statistical hypothesis to be tested was: HO: µFBT = µOXY versus Ha: µFBT ≠ µoxy where µFBT and µOXY denote the mean PID60 for double-blind episodes for which patients use FBT and OXY, respectively. The primary variable was analyzed using a mixed effects ANOVA crossover model, with treatment as randomized (FBT or OXY), period, and treatment sequence (as randomized) as fixed factors and patient as a random factor, using compound symmetry for the variance-covariance matrix.p-value: <0.000195% CI: [0.08, 0.25]ANOVA

Secondary

Pain Relief (PR) Score at 5 Minutes

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: Five minutes after administration of study drug

Arm	Measure	Value (MEAN)	Dispersion
Fentanyl Buccal Tablets (FBT)	Pain Relief (PR) Score at 5 Minutes	0.10 Units on a scale	Standard Deviation 0.43
Immediate-Release Oxycodone	Pain Relief (PR) Score at 5 Minutes	0.09 Units on a scale	Standard Deviation 0.4

p-value: 0.1966Wilcoxon (Mann-Whitney)

Secondary

Pain Relief Score (PR) at 10 Minutes

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

Arm	Measure	Value (MEAN)	Dispersion
Fentanyl Buccal Tablets (FBT)	Pain Relief Score (PR) at 10 Minutes	0.30 Units on a scale	Standard Deviation 0.57
Immediate-Release Oxycodone	Pain Relief Score (PR) at 10 Minutes	0.25 Units on a scale	Standard Deviation 0.53

p-value: 0.0275Wilcoxon (Mann-Whitney)

Secondary

Pain Relief Score (PR) at 15 Minutes

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

Arm	Measure	Value (MEAN)	Dispersion
Fentanyl Buccal Tablets (FBT)	Pain Relief Score (PR) at 15 Minutes	0.69 Units on a scale	Standard Deviation 0.74
Immediate-Release Oxycodone	Pain Relief Score (PR) at 15 Minutes	0.53 Units on a scale	Standard Deviation 0.67

p-value: 0.0001Wilcoxon (Mann-Whitney)

Secondary

Pain Relief Score (PR) at 30 Minutes

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

Arm	Measure	Value (MEAN)	Dispersion
Fentanyl Buccal Tablets (FBT)	Pain Relief Score (PR) at 30 Minutes	1.50 Units on a scale	Standard Deviation 0.83
Immediate-Release Oxycodone	Pain Relief Score (PR) at 30 Minutes	1.23 Units on a scale	Standard Deviation 0.76

p-value: <0.0001Wilcoxon (Mann-Whitney)

Secondary

Pain Relief Score (PR) at 45 Minutes

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

Arm	Measure	Value (MEAN)	Dispersion
Fentanyl Buccal Tablets (FBT)	Pain Relief Score (PR) at 45 Minutes	2.08 Units on a scale	Standard Deviation 0.8
Immediate-Release Oxycodone	Pain Relief Score (PR) at 45 Minutes	1.89 Units on a scale	Standard Deviation 0.74

p-value: 0.0004Wilcoxon (Mann-Whitney)

Secondary

Pain Relief Score (PR) at 60 Minutes

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

Arm	Measure	Value (MEAN)	Dispersion
Fentanyl Buccal Tablets (FBT)	Pain Relief Score (PR) at 60 Minutes	2.38 Units on a scale	Standard Deviation 0.76
Immediate-Release Oxycodone	Pain Relief Score (PR) at 60 Minutes	2.24 Units on a scale	Standard Deviation 0.75

p-value: 0.0074Wilcoxon (Mann-Whitney)

Secondary

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

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.

Time frame: Immediately before and 10 minutes after study drug administration

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

Secondary

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

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.

Time frame: Immediately before and 15 minutes after administration of study drug

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

Secondary

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

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.

Time frame: Immediately before and 30 minutes after study drug administration

Arm	Measure	Value (MEAN)	Dispersion
Fentanyl Buccal Tablets (FBT)	Percentage Change in Pain Intensity Difference (%PID) at 30 Minutes	27.83 Percent change in units on a scale	Standard Error 1.5
Immediate-Release Oxycodone	Percentage Change in Pain Intensity Difference (%PID) at 30 Minutes	23.06 Percent change in units on a scale	Standard Error 1.33

Secondary

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

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.

Time frame: Immediately before and 45 minutes after study drug administration

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

Secondary

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

Time frame: Immediately before and 5 minutes after administration of study drug

Arm	Measure	Value (MEAN)	Dispersion
Fentanyl Buccal Tablets (FBT)	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
Immediate-Release Oxycodone	Percentage Change in Pain Intensity Difference (% PID) at 5 Minutes Post-treatment	0.73 Percent change in units on a scale	Standard Error 0.37

Secondary

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

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.

Time frame: Immediately before and 60 minutes after study drug administration

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

Secondary

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) times 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

Arm	Measure	Value (MEAN)	Dispersion
Fentanyl Buccal Tablets (FBT)	Percent Total Pain Relief at 60 Minutes Posttreatment (%TOTPAR)	39.48 Percent change in units on a scale	Standard Deviation 15.67
Immediate-Release Oxycodone	Percent Total Pain Relief at 60 Minutes Posttreatment (%TOTPAR)	35.28 Percent change in units on a scale	Standard Deviation 14.27

Secondary

Standard Rescue Medication Usage

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

Arm	Measure	Value (NUMBER)
Fentanyl Buccal Tablets (FBT)	Standard Rescue Medication Usage	144 Number of episodes treated
Immediate-Release Oxycodone	Standard Rescue Medication Usage	131 Number of episodes treated

Comparison: Analysis is based on a generalized estimating equation model with treatment as a fixed effect and patient as a random effect. A logit link function and compound symmetry working correlation were applied in this model.p-value: 0.580895% CI: [0.7, 1.2]Generalized estimating equation

Secondary

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

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Fentanyl Buccal Tablets (FBT)	Sum of Pain Intensity Difference at 30 Minutes Post-treatment (SPID30)	2.36 Units on a scale	Standard Error 0.13
Immediate-Release Oxycodone	Sum of Pain Intensity Difference at 30 Minutes Post-treatment (SPID30)	1.87 Units on a scale	Standard Error 0.13

p-value: <0.000195% CI: [0.39, 0.58]ANOVA

Secondary

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

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Fentanyl Buccal Tablets (FBT)	Sum of Pain Intensity Difference at 60 Minutes Post-treatment (SPID60)	8.58 Units on a scale	Standard Error 0.34
Immediate-Release Oxycodone	Sum of Pain Intensity Difference at 60 Minutes Post-treatment (SPID60)	7.65 Units on a scale	Standard Error 0.34

p-value: <0.000195% CI: [0.7, 1.16]ANOVA

Secondary

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

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.

Time frame: 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.

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

Comparison: Analysis is based on a generalized estimating equation model with treatment as a fixed effect and patient as a random effect. A logit link function and compound symmetry working correlation were applied in this model.p-value: 0.026895% CI: [1, 1.9]Generalized estimating equation

Secondary

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

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.

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

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

Comparison: Analysis is based on a generalized estimating equation model with treatment as a fixed effect and patient as a random effect. A logit link function and compound symmetry working correlation were applied in this model.p-value: 0.000895% CI: [1.2, 1.8]Generalized estimating equation

Secondary

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

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.

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

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

Comparison: Analysis is based on a generalized estimating equation model with treatment as a fixed effect and patient as a random effect. A logit link function and compound symmetry working correlation were applied in this model.p-value: 0.008495% CI: [1.1, 1.6]Generalized estimating equation

Secondary

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

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.

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

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

Comparison: Analysis is based on a generalized estimating equation model with treatment as a fixed effect and patient as a random effect. A logit link function and compound symmetry working correlation were applied in this model.p-value: 0.528395% CI: [0.9, 1.4]Generalize estimating equation

Secondary

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

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.

Time frame: From time was administered to 5 minutes after treatment

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

Comparison: Analysis is based on a generalized estimating equation model with treatment as a fixed effect and patient as a random effect. A logit link function and compound symmetry working correlation were applied in this model.p-value: 0.302295% CI: [0.7, 3.3]Generalized estimating equation

Secondary

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

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

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

Comparison: Analysis is based on a generalized estimating equation model with treatment as a fixed effect and patient as a random effect. A logit link function and compound symmetry working correlation were applied in this model.p-value: 0.71195% CI: [0.7, 1.3]Generalized estimating equation

Secondary

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

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.

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

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

Comparison: Analysis is based on a generalized estimating equation model with treatment as a fixed effect and patient as a random effect. A logit link function and compound symmetry working correlation were applied in this model.p-value: 0.514595% CI: [0.8, 1.7]Generalized estimating equation

Secondary

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

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

Arm	Measure	Value (NUMBER)
Fentanyl Buccal Tablets (FBT)	Time to Meaningful Pain Relief (MPR) by Treatment, <=15 Minutes	286 Number of episodes treated
Immediate-Release Oxycodone	Time to Meaningful Pain Relief (MPR) by Treatment, <=15 Minutes	211 Number of episodes treated

Comparison: Analysis is based on a generalized estimating equation model with treatment as a fixed effect and patient as a random effect. A logit link function and compound symmetry working correlation were applied in this model.p-value: 0.019195% CI: [1.1, 2]Generalized estimating equation

Secondary

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

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

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

Comparison: Analysis is based on a generalized estimating equation model with treatment as a fixed effect and patient as a random effect. A logit link function and compound symmetry working correlation were applied in this model.p-value: 0.000695% CI: [1.2, 1.8]Generalized estimating equation

Secondary

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

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

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

Comparison: Analysis is based on a generalized estimating equation model with treatment as a fixed effect and patient as a random effect. A logit link function and compound symmetry working correlation were applied in this model.p-value: 0.004495% CI: [1.1, 1.6]Generalized estimating equation

Secondary

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

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.

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

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

Comparison: Analysis is based on a generalized estimating equation model with treatment as a fixed effect and patient as a random effect. A logit link function and compound symmetry working correlation were applied in this model.p-value: 0.328895% CI: [0.2, 1.9]Generalized estimating equation

Secondary

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

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

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

Comparison: Analysis is based on a generalized estimating equation model with treatment as a fixed effect and patient as a random effect. A logit link function and compound symmetry working correlation were applied in this model.p-value: 0.218495% CI: [0.9, 1.4]Generalized estimating equation

Secondary

Total Pain Relief (TOTPAR60) at 60 Minutes

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

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Fentanyl Buccal Tablets (FBT)	Total Pain Relief (TOTPAR60) at 60 Minutes	6.32 Units on a scale	Standard Error 0.16
Immediate-Release Oxycodone	Total Pain Relief (TOTPAR60) at 60 Minutes	5.63 Units on a scale	Standard Error 0.16

p-value: <0.000195% CI: [0.55, 0.83]ANOVA

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026

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

Conditions

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Brief summary

Related papers

Interventions

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Study design

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Exclusion criteria

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Primary

Secondary

Countries

Participant flow

Recruitment details

Pre-assignment details

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Pain Intensity Difference (PID15) At 15 Minutes

Breakthrough Pain Preference Questionnaire

Medication Performance Assessment 30 Minutes After-treatment

Medication Performance Assessment 60 Minutes After-treatment

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)

Pain Flare Treatment Satisfaction (PFTS) Questionnaire - Question 21 at the End of the First Double-blind Treatment Period (Visit 5)

Pain Flare Treatment Satisfaction (PFTS) Questionnaire - Question 21 at the End of the Second Double-blind Treatment Period (Visit 6)

Pain Intensity Difference (PID 10) at 10 Minutes

Pain Intensity Difference (PID 30) at 30 Minutes

Pain Intensity Difference (PID 45) at 45 Minutes

Pain Intensity Difference (PID 5) at 5 Minutes

Pain Intensity Difference (PID 60) at 60 Minutes

Pain Relief (PR) Score at 5 Minutes

Pain Relief Score (PR) at 10 Minutes

Pain Relief Score (PR) at 15 Minutes

Pain Relief Score (PR) at 30 Minutes

Pain Relief Score (PR) at 45 Minutes

Pain Relief Score (PR) at 60 Minutes

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

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

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

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

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

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

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

Standard Rescue Medication Usage

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Total Pain Relief (TOTPAR60) at 60 Minutes