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”

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.

Intervention(s) in this Clinical Trial

• Drug: Fentanyl Buccal Tablet
  • 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.
• Drug: Immediate release oxycodone
  • 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).

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Fentanyl buccal tablet first then immediate release oxycodone
  • 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.
• Experimental: Immediate Release Oxycodone first then FBT
  • 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.

Primary Measures

• Pain Intensity Difference (PID) at 15 Minutes Post-treatment (PID15)
  • Time Frame: Immediately pre-dose and 15 minutes after dosing
    Safety Issue?: No

Secondary Measures

• Pain Intensity Difference (PID) at 5 Minutes Post-treatment
  • Time Frame: Immediately pre-dose and 5 minutes after dosing
    Safety Issue?: No
• Pain Intensity Difference (PID) at 10 Minutes Post-treatment
  • Time Frame: Immediately pre-dose and 10 minutes after dosing
    Safety Issue?: No
• Pain Intensity Difference (PID) at 30 Minutes Post-treatment
  • Time Frame: Immediately pre-dose and 30 minutes after dosing
    Safety Issue?: No
• Pain Intensity Difference (PID) at 45 Minutes Post-treatment
  • Time Frame: Immediately pre-dose and 45 minutes after dosing
    Safety Issue?: No
• Pain Intensity Difference (PID) at 60 Minutes Post-treatment
  • Time Frame: Immediately pre-dose and 60 minutes after dosing
    Safety Issue?: No
• Percentage Change in Pain Intensity Difference (% PID) at 5 Minutes Post-treatment
  • Time Frame: Immediately pre-dose and 5 minutes after dosing
    Safety Issue?: No
• Percentage Change in Pain Intensity Difference (% PID) at 10 Minutes Post-treatment
  • Time Frame: Immediately before treatment and 10 minutes after treatment.
    Safety Issue?: No
• Percentage Change in Pain Intensity Difference (% PID) at 15 Minutes Post-treatment
  • Time Frame: Baseline (immediately pre-dose) and 15 minutes after dosing
    Safety Issue?: No
• Percentage Change in Pain Intensity Difference (% PID) at 30 Minutes Post-treatment
  • Time Frame: Pre-dose and 30 minutes after dosing
    Safety Issue?: No
• Percentage Change in Pain Intensity Difference (% PID) at 45 Minutes Post-treatment
  • Time Frame: Immediately pre-dose and 45 minutes after dosing
    Safety Issue?: No
• Percentage Change in Pain Intensity Difference (% PID) at 60 Minutes Post-treatment
  • Time Frame: Immediately pre-dose and 60 minutes after dosing
    Safety Issue?: No
• Sum of Pain Intensity Difference at 30 Minutes Post-treatment (SPID30)
  • Time Frame: From 5 minutes after dosing through 30 minutes after dosing
    Safety Issue?: No
• Sum of Pain Intensity Difference at 60 Minutes Post-treatment (SPID60)
  • Time Frame: From 5 minutes after dosing through 60 minutes after dosing
    Safety Issue?: No
• Pain Relief (PR) Score at 5 Minutes Post-treatment
  • Time Frame: 5 minutes after treatment
    Safety Issue?: No
• Pain Relief Score at 10 Minutes Post-treatment
  • Time Frame: 10 minutes after treatment with study drug
    Safety Issue?: No
• Pain Relief Score at 15 Minutes Post-treatment
  • Time Frame: 15 minutes after treatment with study drug
    Safety Issue?: No
• Pain Relief Score at 30 Minutes Post-treatment
  • Time Frame: 30 minutes after treatment with study drug
    Safety Issue?: No
• Pain Relief Score at 45 Minutes Post-treatment
  • Time Frame: 45 minutes after treatment with study drug
    Safety Issue?: No
• Pain Relief Score at 60 Minutes Post-treatment
  • Time Frame: 60 minutes after treatment with study drug
    Safety Issue?: No
• Total Pain Relief at 60 Minutes (TOTPAR60)
  • Time Frame: From 5 minutes to 60 minutes after dosing
    Safety Issue?: No
• Percent Total Pain Relief at 60 Minutes Posttreatment (%TOTPAR)
  • Time Frame: From 5 minutes through 60 minutes after study drug treatment
    Safety Issue?: No
• Time to Any Pain Relief (APR) by Treatment - <= 5 Minutes
  • Time Frame: From time study drug was taken until 5 minutes after treatment
    Safety Issue?: No
• Time to Any Pain Relief (APR) by Treatment <=10 Minutes
  • Time Frame: From study drug treatment until 10 minutes after treatment
    Safety Issue?: No
• Time to Any Pain Relief (APR) by Treatment <=15 Minutes
  • Time Frame: From study drug administration to 15 minutes after treatment
    Safety Issue?: No
• Time to Any Pain Relief (APR) by Treatment <=30 Minutes
  • Time Frame: Time of study drug administration till 30 minutes after treatment
    Safety Issue?: No
• Time to Any Pain Relief (APR) by Treatment <=45 Minutes
  • Time Frame: Time of study drug treatment until 45 minutes after treatment
    Safety Issue?: No
• Time to Any Pain Relief (APR) by Treatment <=60 Minutes
  • Time Frame: Time of study drug treatment until 60 minutes after treatment
    Safety Issue?: No
• Time to Meaningful Pain Relief (MPR) by Treatment - <= 5 Minutes
  • Time Frame: From time study drug was taken until 5 minutes after treatment
    Safety Issue?: No
• Time to Meaningful Pain Relief (MPR) by Treatment <=10 Minutes
  • Time Frame: Time of study drug treatment until 10 minutes after treatment
    Safety Issue?: No
• Time to Meaningful Pain Relief (MPR) by Treatment <=15 Minutes
  • Time Frame: Time of study drug administration until 15 minutes after treatment
    Safety Issue?: No
• Time to Meaningful Pain Relief (MPR) by Treatment <=30 Minutes
  • Time Frame: Time of study drug administration until 30 minutes after treatment
    Safety Issue?: No
• Time to Meaningful Pain Relief (MPR) by Treatment <=45 Minutes
  • Time Frame: From study drug administration until 45 minutes after treatment
    Safety Issue?: No
• Time to Meaningful Pain Relief (MPR) by Treatment <=60 Minutes
  • Time Frame: Time of study drug administration until 60 minutes after treatment
    Safety Issue?: No
• Use of Standard Rescue Medication
  • Time Frame: Throughout the double-blind treatment period
    Safety Issue?: No
• Medication Performance Assessment 30 Minutes Post-treatment
  • Time Frame: 30 minutes post-treatment
    Safety Issue?: No
• Medication Performance Assessment 60 Minutes Post-treatment
  • Time Frame: 60 minutes post-treatment
    Safety Issue?: No
• Breakthrough Pain Preference Questionnaire
  • Time Frame: 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.
    Safety Issue?: No
• Patient Global Impression of Change (PGIC) at Visit 7- 1 Month After Open Label Treatment
  • Time Frame: One month after start of open-label treatment
    Safety Issue?: No
• Patient Global Impression of Change (PGIC) at Visit 8- 2 Months After Open Label Treatment
  • Time Frame: 2 months after start of open-label extension period
    Safety Issue?: No
• Patient Global Impression of Change (PGIC) at Visit 9- 3 Months After Open Label Treatment
  • Time Frame: 3 months after start of open-label extension period
    Safety Issue?: No
• Patient Global Impression of Change (PGIC) Endpoint
  • Time Frame: At conclusion of open-label extension period
    Safety Issue?: No
• Clinician Global Impression of Change at Visit 7- 1 Month After Open Label Treatment
  • Time Frame: One month after start of open-label extension
    Safety Issue?: No
• Clinician Global Impression of Change (CGIC) at Visit 8- 2 Months After Open Label Treatment
  • Time Frame: Two months after start of open-label extension period
    Safety Issue?: No
• Clinician Global Impression of Change (CGIC) at Visit 9- 3 Months After Open Label Treatment
  • Time Frame: 3 months after start of open-label extension period
    Safety Issue?: No
• Clinician Global Impression of Change (CGIC)Endpoint
  • Time Frame: End of open-label extension period
    Safety Issue?: No

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.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 80 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Cephalon Industry

Overall Clinical Trial Officials and Contacts

Sponsor's Medical Expert, MD Study Director Cephalon  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00813488

Study ID Number: C25608/3056/BP/US

ClinicalTrials.gov Identifier: NCT00813488

Health Authority: United States: Food and Drug Administration