Clinical trial NCT00813488: Fentanyl Buccal Tablets Versus Immediate Release Oxycodone for Breakthrough Pain in Patients With Chronic Pain
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Pain
Keywords: Breakthrough Pain
Opioid-tolerant
Chronic Pain
Lead sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
Sponsor class: INDUSTRY
First posted: 2008-12-23
Enrollment: 213
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Pain Intensity Difference (PID) at 15 Minutes Post-treatment (PID15)
timeFrame: Immediately pre-dose and 15 minutes after dosing
Secondary outcomes:
measure: Pain Intensity Difference (PID) at 5 Minutes Post-treatment
timeFrame: Immediately pre-dose and 5 minutes after dosing
measure: Pain Intensity Difference (PID) at 10 Minutes Post-treatment
timeFrame: Immediately pre-dose and 10 minutes after dosing
measure: Pain Intensity Difference (PID) at 30 Minutes Post-treatment
timeFrame: Immediately pre-dose and 30 minutes after dosing
measure: Pain Intensity Difference (PID) at 45 Minutes Post-treatment
timeFrame: Immediately pre-dose and 45 minutes after dosing
measure: Pain Intensity Difference (PID) at 60 Minutes Post-treatment
timeFrame: Immediately pre-dose and 60 minutes after dosing
measure: Percentage Change in Pain Intensity Difference (% PID) at 5 Minutes Post-treatment
timeFrame: Immediately pre-dose and 5 minutes after dosing
measure: Percentage Change in Pain Intensity Difference (% PID) at 10 Minutes Post-treatment
timeFrame: Immediately before treatment and 10 minutes after treatment.
measure: Percentage Change in Pain Intensity Difference (% PID) at 15 Minutes Post-treatment
timeFrame: Baseline (immediately pre-dose) and 15 minutes after dosing
measure: Percentage Change in Pain Intensity Difference (% PID) at 30 Minutes Post-treatment
timeFrame: Pre-dose and 30 minutes after dosing
measure: Percentage Change in Pain Intensity Difference (% PID) at 45 Minutes Post-treatment
timeFrame: Immediately pre-dose and 45 minutes after dosing
measure: Percentage Change in Pain Intensity Difference (% PID) at 60 Minutes Post-treatment
timeFrame: Immediately pre-dose and 60 minutes after dosing
measure: Sum of Pain Intensity Difference at 30 Minutes Post-treatment (SPID30)
timeFrame: From 5 minutes after dosing through 30 minutes after dosing
measure: Sum of Pain Intensity Difference at 60 Minutes Post-treatment (SPID60)
timeFrame: From 5 minutes after dosing through 60 minutes after dosing
measure: Pain Relief (PR) Score at 5 Minutes Post-treatment
timeFrame: 5 minutes after treatment
measure: Pain Relief Score at 10 Minutes Post-treatment
timeFrame: 10 minutes after treatment with study drug
measure: Pain Relief Score at 15 Minutes Post-treatment
timeFrame: 15 minutes after treatment with study drug
measure: Pain Relief Score at 30 Minutes Post-treatment
timeFrame: 30 minutes after treatment with study drug
measure: Pain Relief Score at 45 Minutes Post-treatment
timeFrame: 45 minutes after treatment with study drug
measure: Pain Relief Score at 60 Minutes Post-treatment
timeFrame: 60 minutes after treatment with study drug
measure: Total Pain Relief at 60 Minutes (TOTPAR60)
timeFrame: From 5 minutes to 60 minutes after dosing
measure: Percent Total Pain Relief at 60 Minutes Posttreatment (%TOTPAR)
timeFrame: From 5 minutes through 60 minutes after study drug treatment
measure: Time to Any Pain Relief (APR) by Treatment - <= 5 Minutes
timeFrame: From time study drug was taken until 5 minutes after treatment
measure: Time to Any Pain Relief (APR) by Treatment <=10 Minutes
timeFrame: From study drug treatment until 10 minutes after treatment
measure: Time to Any Pain Relief (APR) by Treatment <=15 Minutes
timeFrame: From study drug administration to 15 minutes after treatment
measure: Time to Any Pain Relief (APR) by Treatment <=30 Minutes
timeFrame: Time of study drug administration till 30 minutes after treatment
measure: Time to Any Pain Relief (APR) by Treatment <=45 Minutes
timeFrame: Time of study drug treatment until 45 minutes after treatment
measure: Time to Any Pain Relief (APR) by Treatment <=60 Minutes
timeFrame: Time of study drug treatment until 60 minutes after treatment
measure: Time to Meaningful Pain Relief (MPR) by Treatment - <= 5 Minutes
timeFrame: From time study drug was taken until 5 minutes after treatment
measure: Time to Meaningful Pain Relief (MPR) by Treatment <=10 Minutes
timeFrame: Time of study drug treatment until 10 minutes after treatment
measure: Time to Meaningful Pain Relief (MPR) by Treatment <=15 Minutes
timeFrame: Time of study drug administration until 15 minutes after treatment
measure: Time to Meaningful Pain Relief (MPR) by Treatment <=30 Minutes
timeFrame: Time of study drug administration until 30 minutes after treatment
measure: Time to Meaningful Pain Relief (MPR) by Treatment <=45 Minutes
timeFrame: From study drug administration until 45 minutes after treatment
measure: Time to Meaningful Pain Relief (MPR) by Treatment <=60 Minutes
timeFrame: Time of study drug administration until 60 minutes after treatment
measure: Use of Standard Rescue Medication
timeFrame: Throughout the double-blind treatment period
measure: Medication Performance Assessment 30 Minutes Post-treatment
timeFrame: 30 minutes post-treatment
measure: Medication Performance Assessment 60 Minutes Post-treatment
timeFrame: 60 minutes post-treatment
measure: Breakthrough Pain Preference Questionnaire
timeFrame: 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.
measure: Patient Global Impression of Change (PGIC) at Visit 7- 1 Month After Open Label Treatment
timeFrame: One month after start of open-label treatment
measure: Patient Global Impression of Change (PGIC) at Visit 8- 2 Months After Open Label Treatment
timeFrame: 2 months after start of open-label extension period
measure: Patient Global Impression of Change (PGIC) at Visit 9- 3 Months After Open Label Treatment
timeFrame: 3 months after start of open-label extension period
measure: Patient Global Impression of Change (PGIC) Endpoint
timeFrame: At conclusion of open-label extension period
measure: Clinician Global Impression of Change at Visit 7- 1 Month After Open Label Treatment
timeFrame: One month after start of open-label extension
measure: Clinician Global Impression of Change (CGIC) at Visit 8- 2 Months After Open Label Treatment
timeFrame: Two months after start of open-label extension period
measure: Clinician Global Impression of Change (CGIC) at Visit 9- 3 Months After Open Label Treatment
timeFrame: 3 months after start of open-label extension period
measure: Clinician Global Impression of Change (CGIC)Endpoint
timeFrame: End of open-label extension period
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Parkway Medical Center
state: Alabama
city: Mobile
country: United States
facility: Horizon Research Group, Inc
state: Alabama
city: Beverly Hills
country: United States
facility: Robert Karns, MD a Medical Corporation
state: California
city: Chino
country: United States
facility: Catalina Research Institute, LLC
state: California
city: Laguna Hills
country: United States
facility: Pacific Coast Pain Management
state: California
city: Loma Linda
country: United States
facility: Loma Linda University Health
state: California
city: Mather
country: United States
facility: VA Northern California Health
state: California
city: Trumbull
country: United States
facility: New England Research Associates
state: Connecticut
city: Delray Beach
country: United States
facility: Delray Research Associates
state: Florida
city: Marianna
country: United States
facility: Emerald Coast Research Group Inc
state: Florida
city: Orlando
country: United States
facility: Compass Research, LLC
state: Florida
city: Plantation
country: United States
facility: Gold Coast Research
state: Florida
city: Sarasota
country: United States
facility: Sarasota Pain Medicine Research
state: Florida
city: St. Petersburg
country: United States
facility: Suncoast Neuroscience Associates
state: Florida
city: Tampa
country: United States
facility: Clinical Research of West Florida
state: Florida
city: Marietta
country: United States
facility: Taylor Research
state: Georgia
city: Marietta
country: United States
facility: Drug Studies America
state: Georgia
city: Newman
country: United States
facility: Georgia Pain Care
state: Georgia
city: Savannah
country: United States
facility: South Coast Medical Group
state: Georgia
city: Bloomington
country: United States
facility: Millennium Pain Center
state: Illinois
city: Bolingbrook
country: United States
facility: Suburban Clinical Research
state: Illinois
city: Peoria
country: United States
facility: Knight Center for Integrated Health
state: Illinois
city: Elkhart
country: United States
facility: Indiana Medical Research
state: Indiana
city: Indianapolis
country: United States
facility: Rehabilitation Associates of Indiana
state: Indiana
city: South Bend
country: United States
facility: Indiana Pain & Spine Clinic
state: Indiana
city: Overland Park
country: United States
facility: ICRI Inc.
state: Kansas
city: Lexington
country: United States
facility: The Pain Treatment Center of the Bluegrass
state: Kentucky
city: Baton Rouge
country: United States
facility: Gulf Coast Research Associates, Inc
state: Louisiana
city: Columbia
country: United States
facility: Columbia Medical Practice
state: Maryland
city: Pikesville
country: United States
facility: MidAtlantic Pain Medicine Center
state: Maryland
city: Clinton Township
country: United States
facility: Michigan Neurology Associates PC
state: Michigan
city: Jackson
country: United States
facility: CRC of Jackson
state: Mississippi
city: Florissant
country: United States
facility: Healthcare Research
state: Missouri
city: Las Vegas
country: United States
facility: Clinical Research Center of Nevada
state: Nevada
city: Cedarhurst
country: United States
facility: Five Towns Neuroscience Research
state: New York
city: Williamsville
country: United States
facility: Upstate Clinical Research Associates
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
city: Perrysburg
country: United States
facility: Clinical Research Source Inc
state: Ohio
city: Eugene
country: United States
facility: Pain Research of Oregon
state: Oregon
city: Altoona
country: United States
facility: Allegheny Pain Management
state: Pennsylvania
city: Jenkintown
country: United States
facility: The Clinical Trial Center, LLC
state: Pennsylvania
city: Philadelphia
country: United States
facility: CRI Worldwide
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: West Reading
country: United States
facility: Clinical Research Center
state: Pennsylvania
city: Greenville
country: United States
facility: Greenville Pharmaceutical Research
state: South Carolina
city: North Charleston
country: United States
facility: Trident Institute of Medical Research, LLC
state: South Carolina
city: Spartanburg
country: United States
facility: South Carolina Pharmaceutical Research
state: South Carolina
city: Austin
country: United States
facility: Lovelace Scientific
state: Texas
city: San Antonio
country: United States
facility: Sun Research Institute
state: Texas
city: Orem
country: United States
facility: Aspen Clinical Research
state: Utah
Study officials:
affiliation: Cephalon
name: Sponsor's Medical Expert, MD
role: STUDY_DIRECTOR
References:
citation: Webster LR, Slevin KA, Narayana A, Earl CQ, Yang R. Fentanyl buccal tablet compared with immediate-release oxycodone for the management of breakthrough pain in opioid-tolerant patients with chronic cancer and noncancer pain: a randomized, double-blind, crossover study followed by a 12-week open-label phase to evaluate patient outcomes. Pain Med. 2013 Sep;14(9):1332-45. doi: 10.1111/pme.12184. Epub 2013 Jul 15.