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

Chronic Pain Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00463047
• Other study ID #: C25608/3055/BP/MN
• Status: Completed
• Phase: Phase 3
• First received: February 8, 2007
• Last updated: May 22, 2012
• Start date: July 2007
• Est. completion date: February 2009

Study information

• Verified date: May 2012
• Source: Teva Pharmaceutical Industries
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 323
• Est. completion date: February 2009
• Est. primary completion date: February 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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.

Study Design

Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breakthrough Pain
• Chronic Pain

Intervention

Drug:
• Fentanyl 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.

Locations

Country	Name	City	State
United States	Lovelace Scientific Resources, Inc.	Albuquerque	New Mexico
United States	Allegheny Pain Management	Altoona	Pennsylvania
United States	Center for Prospective Outcome Studies, Inc.	Atlanta	Georgia
United States	The Rehabilitation Team West	Baltimore	Maryland
United States	Northwest Clinical Research Center	Bellevue	Washington
United States	Lovelace Scientific Resources, Inc.	Beverly Hills	California
United States	Alabama Clinical Therapeutics	Birmingham	Alabama
United States	Birmingham Pain Center	Birmingham	Alabama
United States	The Center for Pain Relief	Charleston	West Virginia
United States	Columbus Clinical Research	Columbus	Ohio
United States	North Georgia Premier Research	Dawnsonville	Georgia
United States	City of Hope National Medical Center	Duarte	California
United States	Altoona Center for Clinical Research	Duncansville	Pennsylvania
United States	Duke University Medical Center	Durham	North Carolina
United States	Englewood Hospital and Medical Center	Englewood	New Jersey
United States	Tristate Arthritis & Rheumatology Center, LLC	Evansville	Indiana
United States	PharmQuest	Greensboro	North Carolina
United States	Greenville Pharmaceutical	Greenville	South Carolina
United States	Comprehensive Pain Specialists, PLLC	Hendersonville	Tennessee
United States	Peters Medical Research	High Point	North Carolina
United States	Rehabilitation Associates of Indiana	Indianapolis	Indiana
United States	Jacksonville Center for Clinical Research	Jacksonville	Florida
United States	Samaritan Center for Medical Research, Med. Group	Los Gatos	California
United States	DrugStudies America	Marietta	Georgia
United States	Taylor Research, LLC	Marietta	Georgia
United States	Advanced Diagnostic Pain Treatment Center, PC	New Haven	Connecticut
United States	Metropolitan Hospital Center	New York	New York
United States	Mount Sinai School of Medicine	New York	New York
United States	Compass Research	Orlando	Florida
United States	International Clinical Research Institute, Inc.	Overland Park	Kansas
United States	Kansas City Bone & Joint Clinic, Inc.	Overland Park	Kansas
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Arizona Research Center	Phoenix	Arizona
United States	Desert Pain & Rehab Specialists/Redpoint Research	Phoenix	Arizona
United States	Hope Research Institute	Phoenix	Arizona
United States	Mid Atlantic Pain Medicine Center	Pikesville	Maryland
United States	AvivoClin Clinical Services	Port Orange	Florida
United States	Raleigh Neurology Associate	Raleigh	North Carolina
United States	Consultants in Pain Research	San Antonio	Texas
United States	InVisions Consultants, LLC	San Antonio	Texas
United States	Lovelace Scientific Resources, Inc.	Sarasota	Florida
United States	Willis-Knighton Pain Management Center	Shreveport	Louisiana
United States	Clinical Research of Tampa Bay, Inc.	Spring Hill	Florida
United States	Stedman Clinical Trials, LLC	Tampa	Florida
United States	Integrated Clinical Trial Services, Inc.	West Des Moines	Iowa

Sponsors (1)

Lead Sponsor	Collaborator
Cephalon

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	Immediately pre-dose and fifteen minutes after administration of study drug	No
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.	Immediately before and 5 minutes after study drug administration	No
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.	Immediately before and 10 minutes after administration of study drug	No
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.	Immediately before and 10 minutes after study drug administration	No
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.	Immediately before and 45 minutes after study drug administration	No
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.	Immediately before and 60 minutes after administration of study drug	No
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.	Immediately before and 5 minutes after administration of study drug	No
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.	Immediately before and 10 minutes after study drug administration	No
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.	Immediately before and 15 minutes after administration of study drug	No
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.	Immediately before and 30 minutes after study drug administration	No
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.	Immediately before and 45 minutes after study drug administration	No
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.	Immediately before and 60 minutes after study drug administration	No
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 = (? x PID5) + (? x PID10) + (? 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	No
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.	From 5 minutes after dosing through 60 minutes after dosing	No
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).	Five minutes after administration of study drug	No
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).	10 minutes after treatment with study drug	No
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).	15 minutes after treatment with study drug	No
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).	30 minutes after treatment with study drug	No
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).	45 minutes after treatment with study drug	No
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).	60 minutes after treatment with study drug	No
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 =(? x PR5)+ (? x PR10) +(? 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	No
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.	From 5 minutes through 60 minutes after study drug treatment	No
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.	From time was administered to 5 minutes after treatment	No
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.	From study drug treatment until 10 minutes after treatment	No
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.	From study drug administration to 15 minutes after treatment	No
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 of study drug administration till 30 minutes after treatment	No
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 of study drug treatment until 45 minutes after treatment	No
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 of study drug treatment until 60 minutes after treatment	No
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.	From time study drug was taken until 5 minutes after treatment	No
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 of study drug treatment until 10 minutes after treatment	No
Secondary	Time to Meaningful Pain Relief (MPR) by Treatment, <=15 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 15 minutes was compared.	Time of study drug administration until 15 minutes after treatment	No
Secondary	Time to Meaningful Pain Relief (MPR) by Treatment, <=30 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 30 minutes was compared.	Time of study drug administration until 30 minutes after treatment	No
Secondary	Time to Meaningful Pain Relief (MPR) by Treatment, <=45 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 45 minutes was compared.	From study drug administration until 45 minutes after treatment	No
Secondary	Time to Meaningful Pain Relief (MPR) by Treatment, <=60 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 60 minutes was compared.	Time of study drug administration until 60 minutes after treatment	No
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.	During the administration of study drug during the double blind treatment periods.	No
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.	30 minutes post-treatment	No
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.	60 minutes post-treatment	No
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.	After completion of both double-blind treatment periods or early termination	No
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.	The end of the first double-blind treatment period.	No
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.	At the end of the second double-blind treatment period (Visit 6)	No
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.	Endpoint (End of second double-blind treatment period or last observation after start of treatment period)	No