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

Pain Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00387010
• Other study ID #: C25608/3054/BP/US
• Status: Terminated
• Phase: Phase 3
• First received: October 10, 2006
• Last updated: September 19, 2012
• Start date: December 2006
• Est. completion date: October 2007

Study information

• Verified date: September 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

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 218
• Est. completion date: October 2007
• Est. primary completion date: October 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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.

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breakthrough Pain
• Chronic Pain
• Pain

Intervention

Drug:
• Fentanyl Buccal Tablets
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.

Locations

Country	Name	City	State
United States	Allegheny Pain Management, PC	Altoona	Pennsylvania
United States	Orange County Clinical Trials	Anaheim	California
United States	Vertex Clinical Research	Bakersfield	California
United States	Lovelace Scientific Resources, Inc.	Beverly Hills	California
United States	Birmingham Pain Center	Birmingham	Alabama
United States	Millennium Pain Center	Bloomington	Illinois
United States	Pain and Rehabilitation Clinic of Chicago	Chicago	Illinois
United States	Alliance Medical Research Group	Clearwater	Florida
United States	Dawsonville Family Medicine	Dawsonville	Georgia
United States	Altoona Center for Clinical Research	Duncansville	Pennsylvania
United States	Elkhart Clinic, LLC	Elkhart	Indiana
United States	Pain Consultants of Oregon	Eugene	Oregon
United States	DeGarmo Institute of Medical Research	Greer	South Carolina
United States	Lovelace Scientific Resources Center	Henderson	Nevada
United States	Comprehensive Pain Specialists, PLLC	Hendersonville	Tennessee
United States	Rehabilitation Associates of Indiana	Indianapolis	Indiana
United States	Innovative Research of West Florida	Largo	Florida
United States	Clinical Research Center of Nevada	Las Vegas	Nevada
United States	Montana Cancer Specialists	Missoula	Montana
United States	Synergy Clinical Research Center	National City	California
United States	Advanced Diagnostic Pain Treatment Center	New Haven	Connecticut
United States	ICRI, Inc.	Overland Park	Kansas
United States	Arizona Research Center	Phoenix	Arizona
United States	BeXar Clinical Trials, LLC	Richardson	Texas
United States	KRK Medical Research	Richardson	Texas
United States	Lifetree Clinical Research	Salt Lake City	Utah
United States	Pain Institute of Santa Monica	Santa Monica	California
United States	Lovelace Scientific Resources, Inc.	Sarasota	Florida
United States	Willis-Knighton Pain Management Center	Shreveport	Louisiana
United States	SUNY - Stonybrook	Stony Brook	New York
United States	Stedman Clinical Trials	Tampa	Florida
United States	Northwest Indiana Center for Clinical Research, PC	Valparaiso	Indiana
United States	Integrative Pain Manage Centers	Westminster	Colorado

Sponsors (1)

Lead Sponsor	Collaborator
Cephalon

Country where clinical trial is conducted

United States, 

References & Publications (1)

Webster LR, Messina J, Xie F, Nalamachu S. Effect of fentanyl buccal tablet on pain-related anxiety: a 4-week open-label study among opioid-tolerant patients with chronic and breakthrough pain. J Opioid Manag. 2011 Jul-Aug;7(4):297-308. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No