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

Study Overview
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Brief Summary
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Evaluate the efficacy of treatment with the fentanyl buccal tablet (FBT) compared with immediate release oxycodone treatment in alleviating breakthrough pain (BTP) in opioid tolerant patients with chronic pain.

Official Title
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A Double Blind, Active Controlled Crossover Study to Evaluate the Efficacy and Safety of Fentanyl Buccal Tablets Versus Immediate Release Oxycodone for the Management of Breakthrough Pain in Opioid Tolerant Patients With Chronic Pain

Conditions
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Chronic Pain

Intervention / Treatment
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* Drug: Fentanyl Buccal Tablet
* Drug: Immediate release oxycodone


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: The patient has chronic pain of at least 3 months duration associated with any of the following conditions: diabetic peripheral neuropathy, postherpetic neuralgia, traumatic injury, complex regional pain syndrome, back pain, neck pain, fibromyalgia, chronic pancreatitis, osteoarthritis, rheumatoid arthritis, or cancer. Other chronic painful conditions may be evaluated for possible inclusion. The patient is currently using at least one 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 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, including a written opioid agreement form, to participate in this study. 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 PI score, over the 24 hours prior to screening, 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, at least 1 and less than 5 BTP episodes per day while taking ATC opioid therapy, and on average, the duration of each BTP episode is less than 4 hours during the screening period. 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. Key Exclusion Criteria: The patient has uncontrolled or rapidly escalating pain as determined by the investigator 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 a diagnosis of chronic headache or migraine as the primary painful condition with associated BTP. 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 the patient's safety or collected data. The patient has suicidal ideation at screening or has a history of suicidal ideation within 1 year or history of suicide attempt within 2 years before screening, or a diagnosis of bipolar disorder or history of schizophrenia 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 FBT or oral transmucosal fentanyl citrate for BTP. The patient is currently using 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 (e.g., 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 UDS for an illicit drug or a medication not prescribed for him/her or which is not medically explainable (i.e., active metabolites). The investigator feels that the patient is not suitable for the study for any reason (e.g., the patient's social history indicates an increased risk of drug diversion) Additional exclusion criteria will apply for patients who decide to participate in the pharmacokinetics assessment to be performed at designated study sites.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fentanyl buccal tablet first then immediate release oxycodone<br>This crossover study includes a screening period, two titration periods, two double-blind treatment periods during which subjects will be randomized to receive fentanyl buccal tablet (FBT) plus placebo during the first treatment period and then immediate release oxycodone plus placebo during the second treatment period or vice versa, then followed by a 12-week open-label treatment period with FBT or an alternative short acting opioid. | Drug: Fentanyl Buccal Tablet<br>* FBT dose strengths = 200, 400, 600, or 800 mcg (1, 2, 3, or 4 tablets) taken prn (as needed) in the event of breakthrough pain. The maximum dose of FBT permitted during the titration and double-blind periods in this study is 800 mcg (4 tablets). For the subsequent 12-week open-label treatment period, patients will either continue with FBT treatment or begin treatment with an alternative short-acting opioid deemed appropriate for each patient by the clinician.<br>* Other names: CEP-25608;Drug: Immediate release oxycodone<br>* Immediate release oxycodone dosage strength: 15, 30, 45, and 60 mg doses (1, 2, 3 or 4 capsules) to be taken prn (as needed) for breakthrough pain. The maximum single dose would be 60 mg (4 capsules).<br>|
| Experimental: Immediate Release Oxycodone first then FBT<br>This crossover study includes a screening period, two titration periods, two double-blind treatment periods during which subjects will be randomized to receive fentanyl buccal tablet (FBT) plus placebo during the first treatment period and then immediate release oxycodone plus placebo during the second treatment period or vice versa, then followed by a 12-week open-label treatment period with FBT or an alternative short acting opioid. | Drug: Fentanyl Buccal Tablet<br>* FBT dose strengths = 200, 400, 600, or 800 mcg (1, 2, 3, or 4 tablets) taken prn (as needed) in the event of breakthrough pain. The maximum dose of FBT permitted during the titration and double-blind periods in this study is 800 mcg (4 tablets). For the subsequent 12-week open-label treatment period, patients will either continue with FBT treatment or begin treatment with an alternative short-acting opioid deemed appropriate for each patient by the clinician.<br>* Other names: CEP-25608;Drug: Immediate release oxycodone<br>* Immediate release oxycodone dosage strength: 15, 30, 45, and 60 mg doses (1, 2, 3 or 4 capsules) to be taken prn (as needed) for breakthrough pain. The maximum single dose would be 60 mg (4 capsules).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain Intensity Difference (PID) at 15 Minutes Post-treatment (PID15) | 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. | Immediately pre-dose and 15 minutes after dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 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. | Immediately pre-dose and 5 minutes after dosing | 
| 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 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. | Immediately pre-dose and 10 minutes after dosing | 
| 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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). | 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). | 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). | 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). | 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). | 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). | 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. | 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. | 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. | 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. | 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. | 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 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 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 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. | 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 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 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 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. | 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 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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). | 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. | 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). | End of open-label extension period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breakthrough Pain, Opioid-tolerant, Chronic Pain