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

• Sponsor: Cephalon (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00387010
• Collaborator: (none)
• Enrollment: 218
• Locations: 33
• Arm: 1
• Duration (Months): 10
• Patients Per Site: 6.6
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Pain; Chronic Pain; Breakthrough Pain	Drug: Fentanyl Buccal Tablets	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 218 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Study Start Date: Dec 1, 2006
• Actual Primary Completion Date: Oct 1, 2007
• Actual Study Completion Date: Oct 1, 2007

Arms and Interventions

Arm

Intervention/Treatment

Experimental: fentanyl buccal tablets 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; 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.; Other Names: Fentora CEP-25608 Fentanyl citrate

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in the Pain Anxiety Symptoms Scale (PASS) Total Score at Approximately Week 5 [Day 0 (baseline), 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.

Secondary Outcome Measures

1. Change From Baseline in the Pain Anxiety Symptoms Scale (PASS) Subscale Scores at Approximately Week 5 [Day 0 (baseline), 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.

2. Change From Baseline in the Beck Depression Inventory at Approximately Week 5 [Day 0 (baseline), 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.

3. Change From Baseline in the West Haven-Yale Multidimensional Pain Inventory Subscales at Approximately Week 5 [Day 0 (baseline), 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.

4. Medication Preference From the Pain Flare Treatment Satisfaction Questionnaire at Approximately Week 5 [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

5. Patient Assessment of Ability to Go to Work at Approximately Week 5 [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.

6. Patient Assessment of Ability to Perform at Work at Approximately Week 5 [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.

7. Patient Assessment of Ability to Walk at Approximately Week 5 [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.

8. Patient Assessment of Ability to Exercise at Approximately Week 5 [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.

9. Patient Assessment of Ability to Participate in Social Events at Approximately Week 5 [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.

10. Patient Assessment of Ability to Have Sex at Approximately Week 5 [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.

11. Patient Assessment of Ability to Enjoy Life at Approximately Week 5 [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.

12. Clinical Assessment of Patient Function - General Activities - at Approximately Week 5 [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.

13. Clinical Assessment of Patient Function - Patient's Walking Ability - at Approximately Week 5 [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.

14. Clinical Assessment of Patient Function - Patient's Ability to Work/Perform Activities of Daily Living - at Approximately Week 5 [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.

15. Clinical Assessment of Patient Function - Patient's Relationship With Others - at Approximately Week 5 [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.

16. Clinical Assessment of Patient Function - Patient's Enjoyment of Life - at Approximately Week 5 [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.

17. Summary of Participants' Successful Dosing Levels of Fentanyl Buccal Tablets to Control Episodes of Breakthrough Pain (BTP) [up to 10 days]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Birmingham Pain Center	Birmingham	Alabama	United States	35244
2	Arizona Research Center	Phoenix	Arizona	United States	85023
3	Orange County Clinical Trials	Anaheim	California	United States	92801
4	Vertex Clinical Research	Bakersfield	California	United States	93311
5	Lovelace Scientific Resources, Inc.	Beverly Hills	California	United States	90211
6	Synergy Clinical Research Center	National City	California	United States	91950
7	Pain Institute of Santa Monica	Santa Monica	California	United States	90404
8	Integrative Pain Manage Centers	Westminster	Colorado	United States	80021
9	Advanced Diagnostic Pain Treatment Center	New Haven	Connecticut	United States	06511
10	Alliance Medical Research Group	Clearwater	Florida	United States	33761
11	Innovative Research of West Florida	Largo	Florida	United States	33770
12	Lovelace Scientific Resources, Inc.	Sarasota	Florida	United States	34233
13	Stedman Clinical Trials	Tampa	Florida	United States	33647
14	Dawsonville Family Medicine	Dawsonville	Georgia	United States	30534
15	Millennium Pain Center	Bloomington	Illinois	United States	61701
16	Pain and Rehabilitation Clinic of Chicago	Chicago	Illinois	United States	60610
17	Elkhart Clinic, LLC	Elkhart	Indiana	United States	46514
18	Rehabilitation Associates of Indiana	Indianapolis	Indiana	United States	46250
19	Northwest Indiana Center for Clinical Research, PC	Valparaiso	Indiana	United States	46383
20	ICRI, Inc.	Overland Park	Kansas	United States	66211
21	Willis-Knighton Pain Management Center	Shreveport	Louisiana	United States	71103
22	Montana Cancer Specialists	Missoula	Montana	United States	59802
23	Lovelace Scientific Resources Center	Henderson	Nevada	United States	89014
24	Clinical Research Center of Nevada	Las Vegas	Nevada	United States	89104
25	SUNY - Stonybrook	Stony Brook	New York	United States	11794
26	Pain Consultants of Oregon	Eugene	Oregon	United States	97401
27	Allegheny Pain Management, PC	Altoona	Pennsylvania	United States	16602
28	Altoona Center for Clinical Research	Duncansville	Pennsylvania	United States	16635
29	DeGarmo Institute of Medical Research	Greer	South Carolina	United States	29651
30	Comprehensive Pain Specialists, PLLC	Hendersonville	Tennessee	United States	37075
31	KRK Medical Research	Richardson	Texas	United States	75080
32	BeXar Clinical Trials, LLC	Richardson	Texas	United States	75082
33	Lifetree Clinical Research	Salt Lake City	Utah	United States	84106

Sponsors and Collaborators

• Cephalon

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Cephalon
• ClinicalTrials.gov Identifier: NCT00387010
• Other Study ID Numbers: C25608/3054/BP/US
• First Posted: Oct 12, 2006
• Last Update Posted: Oct 22, 2012
• Last Verified: Sep 1, 2012

• Additional relevant MeSH terms: Chronic Pain; Breakthrough Pain; Fentanyl

Study Results

Participant Flow

Recruitment Details	A total of 327 patients with chronic pain and breakthrough pain (BTP) were screened for enrollment into this study. Of the 327 patients screened, 218 patients at 31 centers in the US met entry criteria and were considered eligible for enrollment into the study.

Arm/Group Title	Fentanyl Buccal Tablets
Arm/Group Description	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.
Period Title: Dose Titration Period
STARTED	218
COMPLETED	180
NOT COMPLETED	38
Period Title: Dose Titration Period
STARTED	180
Full Analysis Set	175
COMPLETED	169
NOT COMPLETED	11

Baseline Characteristics

Arm/Group Title	Fentanyl Buccal Tablets
Arm/Group Description	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.
Overall Participants	218
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	49.9 (11.03)
Sex: Female, Male (Count of Participants)
Female	124 56.9%
Male	94 43.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	4 1.8%
Not Hispanic or Latino	203 93.1%
Unknown or Not Reported	11 5%
Race/Ethnicity, Customized (participants) [Number]
American Indian or Alaska Native	2 0.9%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	7 3.2%
White	208 95.4%
Unknown or Not Reported	1 0.5%
Primary chronic painful condition (participants) [Number]
Back pain	136 62.4%
Neck pain	14 6.4%
Fibromyalgia	13 6%
Traumatic injury	12 5.5%
Osteoarthritis	11 5%
Complex regional pain syndrome	9 4.1%
Diabetic peripheral neuropathy	3 1.4%
Cancer	3 1.4%
Chronic pancreatitis	2 0.9%
Other	15 6.9%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in the Pain Anxiety Symptoms Scale (PASS) Total Score at Approximately Week 5
Description	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.
Time Frame	Day 0 (baseline), approximately week 5

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Fentanyl Buccal Tablets
Arm/Group Description	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.
Measure Participants	175
Mean (Standard Deviation) [units on a scale]	-1.6 (20.71)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fentanyl Buccal Tablets
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3223
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.6
	Confidence Interval	(2-Sided) 95%; -4.64 to 1.54
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline in the Pain Anxiety Symptoms Scale (PASS) Subscale Scores at Approximately Week 5
Description	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.
Time Frame	Day 0 (baseline), approximately week 5

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Fentanyl Buccal Tablets
Arm/Group Description	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.
Measure Participants	175
Fear	-0.5 (6.14)
Cognitive anxiety	-1.1 (7.20)
Somatic anxiety	0.4 (7.39)
Escape/avoidance	-0.4 (5.87)

3. Secondary Outcome

Title	Change From Baseline in the Beck Depression Inventory at Approximately Week 5
Description	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.
Time Frame	Day 0 (baseline), approximately week 5

Outcome Measure Data

Analysis Population Description

Full analysis set of participants who answered the questions.

Arm/Group Title	Fentanyl Buccal Tablets
Arm/Group Description	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.
Measure Participants	169
Mean (Standard Deviation) [units on a scale]	-1.1 (6.98)

4. Secondary Outcome

Title	Change From Baseline in the West Haven-Yale Multidimensional Pain Inventory Subscales at Approximately Week 5
Description	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.
Time Frame	Day 0 (baseline), approximately week 5

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Fentanyl Buccal Tablets
Arm/Group Description	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.
Measure Participants	175
Interference (0-54)	-0.2 (0.90)
Support (0-18)	-0.0 (1.02)
Pain Severity (0-18)	-0.3 (0.97)
Life-Control (0-12)	0.1 (1.25)
Affective Distress (0-18)	-0.1 (1.24)
Negative Responses (0-24)	-0.1 (1.01)
Solicitous Responses (0-24)	0.1 (1.03)
Distracting Responses (0-36)	0.2 (1.02)
Household Chores (0-30)	0.1 (1.05)
Outdoor Work (0-30)	-0.0 (0.74)
Activities Away from Home (0-24)	0.1 (0.87)
Social Activities (0-24)	0.0 (0.86)
General Activity (0-108)	0.0 (0.67)

5. Secondary Outcome

Title	Medication Preference From the Pain Flare Treatment Satisfaction Questionnaire at Approximately Week 5
Description	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
Time Frame	approximately week 5

Outcome Measure Data

Analysis Population Description

Full analysis set of participants who answered the questions.

Arm/Group Title	Fentanyl Buccal Tablets
Arm/Group Description	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.
Measure Participants	174
Prior medication	38 17.4%
Study medication	115 52.8%
No preference	21 9.6%

6. Secondary Outcome

Title	Patient Assessment of Ability to Go to Work at Approximately Week 5
Description	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.
Time Frame	approximately week 5

Outcome Measure Data

Analysis Population Description

Full analysis set of participants who answered the question

Arm/Group Title	Fentanyl Buccal Tablets
Arm/Group Description	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.
Measure Participants	88
Very much worsened	2 0.9%
Much worsened	0 0%
Slightly worsened	2 0.9%
Unchanged	51 23.4%
Slightly improved	14 6.4%
Much improved	13 6%
Very much improved	6 2.8%

7. Secondary Outcome

Title	Patient Assessment of Ability to Perform at Work at Approximately Week 5
Description	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.
Time Frame	approximately week 5

Outcome Measure Data

Analysis Population Description

Full analysis set of participants who answered the question

Arm/Group Title	Fentanyl Buccal Tablets
Arm/Group Description	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.
Measure Participants	175
Very much worsened	4 1.8%
Much worsened	1 0.5%
Slightly worsened	6 2.8%
Unchanged	69 31.7%
Slightly improved	41 18.8%
Much improved	45 20.6%
Very much improved	9 4.1%

8. Secondary Outcome

Title	Patient Assessment of Ability to Walk at Approximately Week 5
Description	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.
Time Frame	approximately week 5

Outcome Measure Data

Analysis Population Description

Full analysis set of participants who answered the question

Arm/Group Title	Fentanyl Buccal Tablets
Arm/Group Description	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.
Measure Participants	174
Very much worsened	3 1.4%
Much worsened	1 0.5%
Slightly worsened	5 2.3%
Unchanged	76 34.9%
Slightly improved	42 19.3%
Much improved	36 16.5%
Very much improved	11 5%

9. Secondary Outcome

Title	Patient Assessment of Ability to Exercise at Approximately Week 5
Description	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.
Time Frame	approximately week 5

Outcome Measure Data

Analysis Population Description

Full analysis set of participants who answered the question

Arm/Group Title	Fentanyl Buccal Tablets
Arm/Group Description	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.
Measure Participants	175
Very much worsened	3 1.4%
Much worsened	1 0.5%
Slightly worsened	5 2.3%
Unchanged	90 41.3%
Slightly improved	46 21.1%
Much improved	21 9.6%
Very much improved	9 4.1%

10. Secondary Outcome

Title	Patient Assessment of Ability to Participate in Social Events at Approximately Week 5
Description	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.
Time Frame	approximately week 5

Outcome Measure Data

Analysis Population Description

Full analysis set of participants who answered the question

Arm/Group Title	Fentanyl Buccal Tablets
Arm/Group Description	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.
Measure Participants	175
Very much worsened	1 0.5%
Much worsened	3 1.4%
Slightly worsened	6 2.8%
Unchanged	80 36.7%
Slightly improved	46 21.1%
Much improved	34 15.6%
Very much improved	5 2.3%

11. Secondary Outcome

Title	Patient Assessment of Ability to Have Sex at Approximately Week 5
Description	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.
Time Frame	approximately week 5

Outcome Measure Data

Analysis Population Description

Full analysis set of participants who answered the question

Arm/Group Title	Fentanyl Buccal Tablets
Arm/Group Description	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.
Measure Participants	173
Very much worsened	4 1.8%
Much worsened	2 0.9%
Slightly worsened	3 1.4%
Unchanged	129 59.2%
Slightly improved	18 8.3%
Much improved	12 5.5%
Very much improved	5 2.3%

12. Secondary Outcome

Title	Patient Assessment of Ability to Enjoy Life at Approximately Week 5
Description	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.
Time Frame	approximately week 5

Outcome Measure Data

Analysis Population Description

Full analysis set of participants who answered the question

Arm/Group Title	Fentanyl Buccal Tablets
Arm/Group Description	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.
Measure Participants	175
Very much worsened	2 0.9%
Much worsened	1 0.5%
Slightly worsened	6 2.8%
Unchanged	66 30.3%
Slightly improved	48 22%
Much improved	38 17.4%
Very much improved	14 6.4%

13. Secondary Outcome

Title	Clinical Assessment of Patient Function - General Activities - at Approximately Week 5
Description	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.
Time Frame	approximately week 5

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Fentanyl Buccal Tablets
Arm/Group Description	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.
Measure Participants	175
Very much worsened	0 0%
Much worsened	1 0.5%
Slightly worsened	4 1.8%
Unchanged	58 26.6%
Slightly improved	57 26.1%
Much improved	46 21.1%
Very much improved	9 4.1%

14. Secondary Outcome

Title	Clinical Assessment of Patient Function - Patient's Walking Ability - at Approximately Week 5
Description	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.
Time Frame	approximately week 5

Outcome Measure Data

Analysis Population Description

Full analysis set. One participant was not assessed by the investigator.

Arm/Group Title	Fentanyl Buccal Tablets
Arm/Group Description	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.
Measure Participants	174
Very much worsened	0 0%
Much worsened	0 0%
Slightly worsened	4 1.8%
Unchanged	81 37.2%
Slightly improved	48 22%
Much improved	31 14.2%
Very much improved	10 4.6%

15. Secondary Outcome

Title	Clinical Assessment of Patient Function - Patient's Ability to Work/Perform Activities of Daily Living - at Approximately Week 5
Description	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.
Time Frame	approximately week 5

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Fentanyl Buccal Tablets
Arm/Group Description	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.
Measure Participants	175
Very much worsened	0 0%
Much worsened	1 0.5%
Slightly worsened	5 2.3%
Unchanged	63 28.9%
Slightly improved	55 25.2%
Much improved	39 17.9%
Very much improved	12 5.5%

16. Secondary Outcome

Title	Clinical Assessment of Patient Function - Patient's Relationship With Others - at Approximately Week 5
Description	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.
Time Frame	approximately week 5

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Fentanyl Buccal Tablets
Arm/Group Description	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.
Measure Participants	175
Very much worsened	0 0%
Much worsened	0 0%
Slightly worsened	1 0.5%
Unchanged	98 45%
Slightly improved	35 16.1%
Much improved	32 14.7%
Very much improved	9 4.1%

17. Secondary Outcome

Title	Clinical Assessment of Patient Function - Patient's Enjoyment of Life - at Approximately Week 5
Description	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.
Time Frame	approximately week 5

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Fentanyl Buccal Tablets
Arm/Group Description	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.
Measure Participants	175
Very much worsened	0 0%
Much worsened	2 0.9%
Slightly worsened	1 0.5%
Unchanged	69 31.7%
Slightly improved	45 20.6%
Much improved	43 19.7%
Very much improved	15 6.9%

18. Secondary Outcome

Title	Summary of Participants' Successful Dosing Levels of Fentanyl Buccal Tablets to Control Episodes of Breakthrough Pain (BTP)
Description	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.
Time Frame	up to 10 days

Outcome Measure Data

Analysis Population Description

Safety analysis set

Arm/Group Title	Fentanyl Buccal Tablets
Arm/Group Description	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.
Measure Participants	218
100 mcg	18 8.3%
200 mcg	49 22.5%
400 mcg	41 18.8%
600 mcg	31 14.2%
800 mcg	41 18.8%
None (no successful dose)	38 17.4%

Adverse Events

Time Frame	Treatment emergent adverse events: Day 1 to approximately 5 weeks.
Arm/Group Title	Fentanyl Buccal Tablets
Arm/Group Description	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.
All Cause Mortality
	Fentanyl Buccal Tablets
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Fentanyl Buccal Tablets
	Affected / at Risk (%)	# Events
Total	4/218 (1.8%)
Infections and infestations
Bronchitis	1/218 (0.5%)
Injury, poisoning and procedural complications
Radius fracture	1/218 (0.5%)
Metabolism and nutrition disorders
Diabetic ketoacidosis	1/218 (0.5%)
Psychiatric disorders
Suicide attempt	1/218 (0.5%)
Other (Not Including Serious) Adverse Events
	Fentanyl Buccal Tablets
	Affected / at Risk (%)	# Events
Total	21/218 (9.6%)
Gastrointestinal disorders
Nausea	21/218 (9.6%)

Limitations/Caveats

This study was terminated early. Additional research is recommended to develop a valid measure of anxiety, specifically related to breakthrough pain.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Sponsor has the right 60 days before submission for publication to review/provide comments. If the Sponsor's review shows that potentially patentable subject matter would be disclosed, publication or public disclosure shall be delayed for up to 90 additional days in order for the Sponsor, or Sponsor's designees, to file the necessary patent applications. In multicenter trials, each PI will postpone single center publications until after disclosure or publication of multicenter data.