Open-Label Study to Evaluate the Effect of Treatment With Fentanyl Buccal Tablets on Pain Anxiety Symptoms When Used for the Management of Breakthrough Pain

Study Overview
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Brief Summary
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The primary purpose of the study is to evaluate the impact of treatment with fentanyl buccal tablets on the anxiety symptoms commonly associated with chronic pain in patients with breakthrough pain (BTP). Other purposes are to assess the management of BTP, to evaluate patient functioning, and to determine any influences on the successful dose achieved.

Official Title
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A 4-week Open-Label Study to Evaluate the Effect of Treatment With Fentanyl Buccal Tablets on Pain Anxiety Symptoms When Used for the Management of Breakthrough Pain in Opioid-Tolerant Patients With Chronic Pain

Conditions
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Pain, Chronic Pain, Breakthrough Pain

Intervention / Treatment
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* Drug: Fentanyl Buccal Tablets


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 (i.e., barrier method with spermicide, steroidal contraceptive [oral, transdermal, implanted, and injected contraceptives must be used in conjunction with the barrier method], or intrauterine device [IUD]) and agree to continued use of this method for the duration of the study. The patient has chronic pain of at least 3 months duration associated with any of the following conditions: cancer, diabetic peripheral neuropathy, postherpetic neuralgia, traumatic injury, complex regional pain syndrome, back pain, neck pain, fibromyalgia (patient has met diagnostic criteria), chronic pancreatitis, or osteoarthritis. Other chronic painful conditions may be evaluated for entry upon discussion with and written approval from the Cephalon medical expert. 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 a stable dose of around-the-clock (ATC) therapy for at least 7 days prior to enrollment in the study. The patient reports an average pain intensity score, over the prior 24 hours, of 6 or less (0=no pain through 10=worst pain) for the chronic pain. The patient experiences, on average, 1 to 4 BTP episodes per day while taking around-the-clock (ATC) opioid therapy, and on average, the duration of each breakthrough pain (BTP) episode is less than 3 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, and return to the clinic for scheduled study visits and a follow-up evaluation as specified in this protocol. Exclusion Criteria: The patient has uncontrolled or rapidly escalating pain as determined by the investigator (ie, the 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 known or suspected hypersensitivities, allergies, or other contraindications to any ingredient in the study drug. The patient has a recent history (within 5 years) or current evidence of alcohol or other substance abuse. The patient has cardiopulmonary disease that, in the opinion of the investigator, would 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's primary painful condition is headache, including migraine. The patient is expected to have surgery during the study, and it is anticipated that the surgery will alleviate the patient's pain. 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 fentanyl buccal tablets. The patient has participated in a study involving an investigational drug in the previous 30 days. 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, in the opinion of the investigator, would 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 chronic pain currently being treated. The patient has a positive urine drug screen (UDS) for an illicit substance or a medication not legitimately prescribed to the patient.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: fentanyl buccal tablets<br>Successful dose strength for each participant was determined during a titration period of no more than 10 days. Participants used the successful dose of 100, 200, 400, 600, or 800 mcg during the four week open-label treatment period. | Drug: Fentanyl Buccal Tablets<br>* Fentanyl buccal tablets (FBT) placed in the buccal cavity above a rear molar until disintegrated, approximately 14-25 minutes. Dose titration: Participants self-administered FBT, starting at 100, 200 or 400 mcg (depending on analgesic used pre-study) and titrated to 600 and 800 mcg as needed. For each breakthrough pain (BTP) episode, participants took a dose, and did not take further study drug if adequate pain relief was achieved. If pain was not controlled within 30 minutes, the same dose level was repeated. If pain relief was inadequate 30 minutes after the second dose, usual rescue medication was taken for that BTP episode. Doses were adjusted until pain relief was adequate and side effects were tolerated. Open-label: Once the successful dose of FBT was identified (100, 200, 400, 600, or 800 mcg), participants were dispensed a 4-week supply at the successful dose. Participants were not to use FBT for more than 6 BTP episodes or take more than 8 FBT daily.<br>* Other names: Fentanyl citrate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Pain Anxiety Symptoms Scale (PASS) Total Score at Approximately Week 5 | The change from baseline to approximately week 5 in the PASS total score. PASS asks participants to indicate how often they engage in each of the 40 thoughts or activities that represent anxiety symptoms on a scale of 0=never to 5=always. The total score has a range of 0-200. | Day 0 (baseline), approximately week 5 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Pain Anxiety Symptoms Scale (PASS) Subscale Scores at Approximately Week 5 | The change from baseline to approximately week 5 in the PASS subscale scores. PASS asks participants to indicate how often they engage in each of the 40 thoughts or activities that represent anxiety symptoms on a scale of 0=never to 5=always. Those 40 questions are organized into four subscales: fear, cognitive anxiety, somatic anxiety, and escape/avoidance. Each subscale score is obtained by summing the answers to the ten items in the subscore resulting in a range of 0-50. | Day 0 (baseline), approximately week 5 | 
| Change From Baseline in the Beck Depression Inventory at Approximately Week 5 | Change from baseline to endpoint (week 4 of Treatment period or last post baseline visit) in the Beck Depression Inventory (BDI). The BDI is a self-reporting instrument that asks 21 questions regarding how the participant felt in the past few days. Answers are in sentence form, and offer a scale where the first answer (worth 0 points) indicates no depression and the fourth answer (worth 3 points) indicates significant depression. Totals (0-63) are grouped so that totals of 1-10 are interpreted as 'These ups and downs are considered normal' and scores >40 indicate extreme depression. | Day 0 (baseline), approximately week 5 | 
| Change From Baseline in the West Haven-Yale Multidimensional Pain Inventory Subscales at Approximately Week 5 | Change from baseline to endpoint (week 4 of Treatment period or last post baseline visit) in the Multidimensional Pain Inventory Subscales. Answers to questions in the MPI are captured on a 7-point scale, with 0=most positive answer and 6= least positive answer. Twenty questions focus on pain, fourteen on a significant other's response when participant is in pain, and eighteen questions about daily activities. There are a total of 13 subscales with variable ranges. Subscales and corresponding ranges are listed in the results table. The General Activity category combines the Household Chores, Outdoor Work, Activities Away from Home, and Social Activities categories. | Day 0 (baseline), approximately week 5 | 
| Medication Preference From the Pain Flare Treatment Satisfaction Questionnaire at Approximately Week 5 | The summary question from the Pain Flare Treatment Satisfaction Questionnaire asked participants which medication they preferred to use for their break-through pain. Options were 1) Prior medication 2) Study medication 3) no preference | approximately week 5 | 
| Patient Assessment of Ability to Go to Work at Approximately Week 5 | At the endpoint of the study (week 4 of Treatment period or last post baseline visit) participants completed the Patient Assessment of Function Scale which asks 7 questions about the effect of study treatment on the patient's ability to function. This question asks about the ability to go to work. | approximately week 5 | 
| Patient Assessment of Ability to Perform at Work at Approximately Week 5 | At the endpoint of the study (week 4 of Treatment period or last post baseline visit) participants completed the Patient Assessment of Function Scale which asks 7 questions about the effect of study treatment on the patient's ability to function. This question asks about the ability to perform at work and includes both work outside the home and housework. | approximately week 5 | 
| Patient Assessment of Ability to Walk at Approximately Week 5 | At the endpoint of the study (week 4 of Treatment period or last post baseline visit) participants completed the Patient Assessment of Function Scale which asks 7 questions about the effect of study treatment on the patient's ability to function. This question asks about the ability to walk. | approximately week 5 | 
| Patient Assessment of Ability to Exercise at Approximately Week 5 | At the endpoint of the study (week 4 of Treatment period or last post baseline visit) participants completed the Patient Assessment of Function Scale which asks 7 questions about the effect of study treatment on the patient's ability to function. This question asks about the ability to exercise. | approximately week 5 | 
| Patient Assessment of Ability to Participate in Social Events at Approximately Week 5 | At the endpoint of the study (week 4 of Treatment period or last post baseline visit) participants completed the Patient Assessment of Function Scale which asks 7 questions about the effect of study treatment on the patient's ability to function. This question asks about the ability to participate in social events. | approximately week 5 | 
| Patient Assessment of Ability to Have Sex at Approximately Week 5 | At the endpoint of the study (week 4 of Treatment period or last post baseline visit) participants completed the Patient Assessment of Function Scale which asks 7 questions about the effect of study treatment on the patient's ability to function. This question asks about the ability to have sex. | approximately week 5 | 
| Patient Assessment of Ability to Enjoy Life at Approximately Week 5 | At the endpoint of the study (week 4 of Treatment period or last post baseline visit) participants completed the Patient Assessment of Function Scale which asks 7 questions about the effect of study treatment on the patient's ability to function. This question asks about the ability to enjoy life. | approximately week 5 | 
| Clinical Assessment of Patient Function - General Activities - at Approximately Week 5 | At the endpoint of the study (week 4 of Treatment period or last post baseline visit) investigators completed the Clinical Assessment of Patient Function Scale which asks 5 questions about the effect of study treatment on the patient's ability to function. This question asks about the patient's general activities. | approximately week 5 | 
| Clinical Assessment of Patient Function - Patient's Walking Ability - at Approximately Week 5 | At the endpoint of the study (week 4 of Treatment period or last post baseline visit) investigators completed the Clinical Assessment of Patient Function Scale which asks 5 questions about the effect of study treatment on the patient's ability to function. This question asks about the patient's walking ability. | approximately week 5 | 
| Clinical Assessment of Patient Function - Patient's Ability to Work/Perform Activities of Daily Living - at Approximately Week 5 | At the endpoint of the study (week 4 of Treatment period or last post baseline visit) investigators completed the Clinical Assessment of Patient Function Scale which asks 5 questions about the effect of study treatment on the patient's ability to function. This question asks about the patient's ability to work and perform activities of daily living. | approximately week 5 | 
| Clinical Assessment of Patient Function - Patient's Relationship With Others - at Approximately Week 5 | At the endpoint of the study (week 4 of Treatment period or last post baseline visit) investigators completed the Clinical Assessment of Patient Function Scale which asks 5 questions about the effect of study treatment on the patient's ability to function. This question asks about the patient's relationship with others. | approximately week 5 | 
| Clinical Assessment of Patient Function - Patient's Enjoyment of Life - at Approximately Week 5 | At the endpoint of the study (week 4 of Treatment period or last post baseline visit) investigators completed the Clinical Assessment of Patient Function Scale which asks 5 questions about the effect of study treatment on the patient's ability to function. This question asks about the patient's enjoyment of life. | approximately week 5 | 
| Summary of Participants' Successful Dosing Levels of Fentanyl Buccal Tablets to Control Episodes of Breakthrough Pain (BTP) | During the dose titration period, participants self-administered FBT, starting at 100, 200 or 400 mcg (depending on analgesic used pre-study) and titrated to 600 and 800 mcg if needed. For each breakthrough pain (BTP) episode, participants took a dose, and did not take further study drug if adequate pain relief was achieved. If pain was not controlled within 30 minutes, the same dose level was repeated. If pain relief was inadequate 30 minutes after the second dose, usual rescue medication was taken for that BTP episode. Doses were adjusted until pain relief was adequate and side effects were tolerated. This outcome summarizes the successful dose levels identified during the titration period. | up to 10 days |