NCT00813488CompletedPhase 3
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
Cephalon50 sites in 1 country213 target enrollmentStarted: December 2008Last updated:
Conditions
Interventions
Drugs
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Enrollment
- 213
- Locations
- 50
- Primary Endpoint
- Pain Intensity Difference (PID) at 15 Minutes Post-treatment (PID15)
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 80 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
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.
Arms & Interventions
Fentanyl buccal tablet first then immediate release oxycodone
Experimental
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.
Intervention: Fentanyl Buccal Tablet (Drug)
Fentanyl buccal tablet first then immediate release oxycodone
Experimental
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.
Intervention: Immediate release oxycodone (Drug)
Immediate Release Oxycodone first then FBT
Experimental
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.
Intervention: Fentanyl Buccal Tablet (Drug)
Immediate Release Oxycodone first then FBT
Experimental
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.
Intervention: Immediate release oxycodone (Drug)
Outcomes
Primary Outcomes
Pain Intensity Difference (PID) at 15 Minutes Post-treatment (PID15)
Time Frame: Immediately pre-dose and 15 minutes after dosing
Pain intensity (PI) scores were assessed on an 11-point numerical rating scale from 0 = no pain to 10 = pain as bad as you can imagine after each episode of breakthrough pain during the double-blind treatment period. The PID15 is the difference between the PI scores from the episode baseline (immediately prior to study drug administration)and 15 minutes after the administration of the study drug. Least squared mean was from an analysis of variance (ANOVA) with treatment as randomized, phase, and sequence as fixed factors and patient as a random factor using compound symmetry.
Secondary Outcomes
- Pain Intensity Difference (PID) at 5 Minutes Post-treatment(Immediately pre-dose and 5 minutes after dosing)
- Pain Intensity Difference (PID) at 10 Minutes Post-treatment(Immediately pre-dose and 10 minutes after dosing)
- Pain Intensity Difference (PID) at 30 Minutes Post-treatment(Immediately pre-dose and 30 minutes after dosing)
- Pain Intensity Difference (PID) at 45 Minutes Post-treatment(Immediately pre-dose and 45 minutes after dosing)
- Pain Intensity Difference (PID) at 60 Minutes Post-treatment(Immediately pre-dose and 60 minutes after dosing)
- Percentage Change in Pain Intensity Difference (% PID) at 5 Minutes Post-treatment(Immediately pre-dose and 5 minutes after dosing)
- Percentage Change in Pain Intensity Difference (% PID) at 10 Minutes Post-treatment(Immediately before treatment and 10 minutes after treatment.)
- Percentage Change in Pain Intensity Difference (% PID) at 15 Minutes Post-treatment(Baseline (immediately pre-dose) and 15 minutes after dosing)
- Percentage Change in Pain Intensity Difference (% PID) at 30 Minutes Post-treatment(Pre-dose and 30 minutes after dosing)
- Percentage Change in Pain Intensity Difference (% PID) at 45 Minutes Post-treatment(Immediately pre-dose and 45 minutes after dosing)
- Percentage Change in Pain Intensity Difference (% PID) at 60 Minutes Post-treatment(Immediately pre-dose and 60 minutes after dosing)
- Sum of Pain Intensity Difference at 30 Minutes Post-treatment (SPID30)(From 5 minutes after dosing through 30 minutes after dosing)
- Sum of Pain Intensity Difference at 60 Minutes Post-treatment (SPID60)(From 5 minutes after dosing through 60 minutes after dosing)
- Pain Relief (PR) Score at 5 Minutes Post-treatment(5 minutes after treatment)
- Pain Relief Score at 10 Minutes Post-treatment(10 minutes after treatment with study drug)
- Pain Relief Score at 15 Minutes Post-treatment(15 minutes after treatment with study drug)
- Pain Relief Score at 30 Minutes Post-treatment(30 minutes after treatment with study drug)
- Pain Relief Score at 45 Minutes Post-treatment(45 minutes after treatment with study drug)
- Pain Relief Score at 60 Minutes Post-treatment(60 minutes after treatment with study drug)
- Total Pain Relief at 60 Minutes (TOTPAR60)(From 5 minutes to 60 minutes after dosing)
- Percent Total Pain Relief at 60 Minutes Posttreatment (%TOTPAR)(From 5 minutes through 60 minutes after study drug treatment)
- Time to Any Pain Relief (APR) by Treatment - <= 5 Minutes(From time study drug was taken until 5 minutes after treatment)
- Time to Any Pain Relief (APR) by Treatment <=10 Minutes(From study drug treatment until 10 minutes after treatment)
- Time to Any Pain Relief (APR) by Treatment <=15 Minutes(From study drug administration to 15 minutes after treatment)
- Time to Any Pain Relief (APR) by Treatment <=30 Minutes(Time of study drug administration till 30 minutes after treatment)
- Time to Any Pain Relief (APR) by Treatment <=45 Minutes(Time of study drug treatment until 45 minutes after treatment)
- Time to Any Pain Relief (APR) by Treatment <=60 Minutes(Time of study drug treatment until 60 minutes after treatment)
- Time to Meaningful Pain Relief (MPR) by Treatment - <= 5 Minutes(From time study drug was taken until 5 minutes after treatment)
- Time to Meaningful Pain Relief (MPR) by Treatment <=10 Minutes(Time of study drug treatment until 10 minutes after treatment)
- Time to Meaningful Pain Relief (MPR) by Treatment <=15 Minutes(Time of study drug administration until 15 minutes after treatment)
- Time to Meaningful Pain Relief (MPR) by Treatment <=30 Minutes(Time of study drug administration until 30 minutes after treatment)
- Time to Meaningful Pain Relief (MPR) by Treatment <=45 Minutes(From study drug administration until 45 minutes after treatment)
- Time to Meaningful Pain Relief (MPR) by Treatment <=60 Minutes(Time of study drug administration until 60 minutes after treatment)
- Use of Standard Rescue Medication(Throughout the double-blind treatment period)
- Medication Performance Assessment 30 Minutes Post-treatment(30 minutes post-treatment)
- Medication Performance Assessment 60 Minutes Post-treatment(60 minutes post-treatment)
- Breakthrough Pain Preference Questionnaire(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(One month after start of open-label treatment)
- Patient Global Impression of Change (PGIC) at Visit 8- 2 Months After Open Label Treatment(2 months after start of open-label extension period)
- Patient Global Impression of Change (PGIC) at Visit 9- 3 Months After Open Label Treatment(3 months after start of open-label extension period)
- Patient Global Impression of Change (PGIC) Endpoint(At conclusion of open-label extension period)
- Clinician Global Impression of Change at Visit 7- 1 Month After Open Label Treatment(One month after start of open-label extension)
- Clinician Global Impression of Change (CGIC) at Visit 8- 2 Months After Open Label Treatment(Two months after start of open-label extension period)
- Clinician Global Impression of Change (CGIC) at Visit 9- 3 Months After Open Label Treatment(3 months after start of open-label extension period)
- Clinician Global Impression of Change (CGIC)Endpoint(End of open-label extension period)
Investigators
Study Sites (50)
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