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Fentanyl Buccal Tablets Versus Immediate Release Oxycodone for Breakthrough Pain in Patients With Chronic Pain

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Teva Pharmaceutical Industries ( Cephalon )
ClinicalTrials.gov Identifier:
NCT00813488
First received: December 19, 2008
Last updated: May 22, 2012
Last verified: May 2012
History of Changes
Results First Received: August 31, 2010  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Crossover Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Chronic Pain
Interventions: Drug: Fentanyl Buccal Tablet
Drug: Immediate release oxycodone

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Subjects with chronic pain who had been receiving opioid therapy for the previous 7 days and reported on average 1 to 5 breakthrough pain episodes per day were recruited from 50 different study sites throughout the United States beginning December 2008 and completing in November 2009.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Prior to the double-blind treatment period, subjects participated in two titration periods to identify a "successful" and tolerated dose of FBT and immediate-release oxycodone. Subjects who did not titrate to a successful and tolerated dose were excluded from further participation in the study.

Reporting Groups
  Description
FBT First Immediate Release Oxycodone Second Subjects in this treatment group were assigned 200 mcg FBT during the first titration period and then 15 mg oxycodone during the second titration period. Standard rescue medication could be taken if pain relief was unsuccessful. If more than one dose was required for at least 1 of 3 breakthrough pain episodes in one day, the next day the dose was increased (in 200 mcg increments for FBT and 15 mg increments for oxycodone). The maximum allowable dose was 800 mcg for FBT (4 tablets) and 60 mg (4 capsules) for oxycodone. If a dose was not tolerated the dose was lowered to the previous tolerated dose. Titration completed when successful analgesia was achieved with a tolerated dose or maximum dose was reached. If unsuccessful at maximum dose subject was discontinued from proceeding further in the study. Subjects who successfully titrated were randomized.
Immediate-Release Oxycodone First FBT Second Subjects in this treatment group were assigned 15 mg oxycodone during the first titration period and then 200 mcg FBT during the second titration period. Standard rescue medication could be taken if pain relief was unsuccessful. If more than one dose was required for at least 1 of 3 breakthrough pain episodes in one day, the next day the dose was increased (in 200 mcg increments for FBT and 15 mg increments for oxycodone). The maximum allowable dose was 800 mcg for FBT (4 tablets) and 60 mg (4 capsules) for oxycodone. If a dose was not tolerated the dose was lowered to the previous tolerated dose. Titration completed when successful analgesia was achieved with a tolerated dose or maximum dose was reached. If unsuccessful at maximum dose subject was discontinued from proceeding further in the study. Subjects who successfully titrated were randomized.

Participant Flow for 5 periods

 Period 1:   Titration Period 1
    FBT First Immediate Release Oxycodone Second     Immediate-Release Oxycodone First FBT Second  
STARTED     107     106  
COMPLETED     80     89  
NOT COMPLETED     27     17  
Adverse Event                 6                 1  
Lack of Efficacy                 9                 7  
Withdrawal by Subject                 2                 2  
Protocol Violation                 4                 3  
Non-compliance to study medication                 4                 1  
Non-compliance to study procedures                 2                 2  
Technical Difficulties                 0                 1  

Period 2:   Titration Period 2
    FBT First Immediate Release Oxycodone Second     Immediate-Release Oxycodone First FBT Second  
STARTED     80     89  
COMPLETED     64     79  
NOT COMPLETED     16     10  
Adverse Event                 2                 3  
Lack of Efficacy                 8                 4  
Protocol Violation                 3                 2  
Lost to Follow-up                 1                 0  
Non-compliance with study procedures                 2                 1  

Period 3:   Double-blind Treatment Period 1
    FBT First Immediate Release Oxycodone Second     Immediate-Release Oxycodone First FBT Second  
STARTED     72 [1]   71 [1]
COMPLETED     71     66  
NOT COMPLETED     1     5  
Adverse Event                 1                 1  
Withdrawal by Subject                 0                 1  
Protocol Violation                 0                 2  
Lost to Follow-up                 0                 1  
[1] After titration subjects were re-randomized to these two treatment arms

Period 4:   Double-blind Treatment Period 2
    FBT First Immediate Release Oxycodone Second     Immediate-Release Oxycodone First FBT Second  
STARTED     71     66  
COMPLETED     66     65  
NOT COMPLETED     5     1  
Adverse Event                 1                 0  
Withdrawal by Subject                 1                 1  
Protocol Violation                 2                 0  
Not Specified                 1                 0  

Period 5:   Open-label Extension
    FBT First Immediate Release Oxycodone Second     Immediate-Release Oxycodone First FBT Second  
STARTED     65 [1]   66 [1]
COMPLETED     53 [2]   59 [3]
NOT COMPLETED     12     7  
Adverse Event                 1                 2  
Lack of Efficacy                 3                 0  
Withdrawal by Subject                 0                 2  
Protocol Violation                 1                 2  
Non-compliance study medication                 4                 0  
Non-compliance study procedures                 2                 1  
Not specified                 1                 0  
[1] Patients completing double-blind periods were randomized to FBT or standard of care for open-label
[2] This group received FBT open--label
[3] This group received standard of care (including immediate-release oxycodone)



  Baseline Characteristics
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Reporting Groups
  Description
Total Number of Patients No text entered.

Baseline Measures
    Total Number of Patients  
Number of Participants  
[units: participants]
 		  213  
Age  
[units: years]
Mean ± Standard Deviation 		  51.0  ± 9.97  
Gender  
[units: participants]
 		 
Female     120  
Male     93  
Ethnicity (NIH/OMB)  
[units: Participants]
 		 
Hispanic or Latino     10  
Not Hispanic or Latino     195  
Unknown or Not Reported     8  
Race (NIH/OMB)  
[units: Participants]
 		 
American Indian or Alaska Native     1  
Asian     1  
Native Hawaiian or Other Pacific Islander     0  
Black or African American     19  
White     191  
More than one race     0  
Unknown or Not Reported     1  
Region of Enrollment  
[units: participants]
 		 
United States     213  
Body Mass Index (BMI)  
[units: kg/m^2]
Mean ± Standard Deviation 		  30.1  ± 7.25  



  Outcome Measures
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1.  Primary:   Pain Intensity Difference (PID) at 15 Minutes Post-treatment (PID15)   [ Time Frame: Immediately pre-dose and 15 minutes after dosing ]
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2.  Secondary:   Pain Intensity Difference (PID) at 5 Minutes Post-treatment   [ Time Frame: Immediately pre-dose and 5 minutes after dosing ]
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3.  Secondary:   Pain Intensity Difference (PID) at 10 Minutes Post-treatment   [ Time Frame: Immediately pre-dose and 10 minutes after dosing ]
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4.  Secondary:   Pain Intensity Difference (PID) at 30 Minutes Post-treatment   [ Time Frame: Immediately pre-dose and 30 minutes after dosing ]
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5.  Secondary:   Pain Intensity Difference (PID) at 45 Minutes Post-treatment   [ Time Frame: Immediately pre-dose and 45 minutes after dosing ]
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6.  Secondary:   Pain Intensity Difference (PID) at 60 Minutes Post-treatment   [ Time Frame: Immediately pre-dose and 60 minutes after dosing ]
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7.  Secondary:   Percentage Change in Pain Intensity Difference (% PID) at 5 Minutes Post-treatment   [ Time Frame: Immediately pre-dose and 5 minutes after dosing ]
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8.  Secondary:   Percentage Change in Pain Intensity Difference (% PID) at 10 Minutes Post-treatment   [ Time Frame: Immediately before treatment and 10 minutes after treatment. ]
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9.  Secondary:   Percentage Change in Pain Intensity Difference (% PID) at 15 Minutes Post-treatment   [ Time Frame: Baseline (immediately pre-dose) and 15 minutes after dosing ]
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10.  Secondary:   Percentage Change in Pain Intensity Difference (% PID) at 30 Minutes Post-treatment   [ Time Frame: Pre-dose and 30 minutes after dosing ]
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11.  Secondary:   Percentage Change in Pain Intensity Difference (% PID) at 45 Minutes Post-treatment   [ Time Frame: Immediately pre-dose and 45 minutes after dosing ]
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12.  Secondary:   Percentage Change in Pain Intensity Difference (% PID) at 60 Minutes Post-treatment   [ Time Frame: Immediately pre-dose and 60 minutes after dosing ]
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13.  Secondary:   Sum of Pain Intensity Difference at 30 Minutes Post-treatment (SPID30)   [ Time Frame: From 5 minutes after dosing through 30 minutes after dosing ]
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14.  Secondary:   Sum of Pain Intensity Difference at 60 Minutes Post-treatment (SPID60)   [ Time Frame: From 5 minutes after dosing through 60 minutes after dosing ]
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15.  Secondary:   Pain Relief (PR) Score at 5 Minutes Post-treatment   [ Time Frame: 5 minutes after treatment ]
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16.  Secondary:   Pain Relief Score at 10 Minutes Post-treatment   [ Time Frame: 10 minutes after treatment with study drug ]
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17.  Secondary:   Pain Relief Score at 15 Minutes Post-treatment   [ Time Frame: 15 minutes after treatment with study drug ]
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18.  Secondary:   Pain Relief Score at 30 Minutes Post-treatment   [ Time Frame: 30 minutes after treatment with study drug ]
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19.  Secondary:   Pain Relief Score at 45 Minutes Post-treatment   [ Time Frame: 45 minutes after treatment with study drug ]
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20.  Secondary:   Pain Relief Score at 60 Minutes Post-treatment   [ Time Frame: 60 minutes after treatment with study drug ]
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21.  Secondary:   Total Pain Relief at 60 Minutes (TOTPAR60)   [ Time Frame: From 5 minutes to 60 minutes after dosing ]
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22.  Secondary:   Percent Total Pain Relief at 60 Minutes Posttreatment (%TOTPAR)   [ Time Frame: From 5 minutes through 60 minutes after study drug treatment ]
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23.  Secondary:   Time to Any Pain Relief (APR) by Treatment - <= 5 Minutes   [ Time Frame: From time study drug was taken until 5 minutes after treatment ]
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24.  Secondary:   Time to Any Pain Relief (APR) by Treatment <=10 Minutes   [ Time Frame: From study drug treatment until 10 minutes after treatment ]
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25.  Secondary:   Time to Any Pain Relief (APR) by Treatment <=15 Minutes   [ Time Frame: From study drug administration to 15 minutes after treatment ]
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26.  Secondary:   Time to Any Pain Relief (APR) by Treatment <=30 Minutes   [ Time Frame: Time of study drug administration till 30 minutes after treatment ]
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27.  Secondary:   Time to Any Pain Relief (APR) by Treatment <=45 Minutes   [ Time Frame: Time of study drug treatment until 45 minutes after treatment ]
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28.  Secondary:   Time to Any Pain Relief (APR) by Treatment <=60 Minutes   [ Time Frame: Time of study drug treatment until 60 minutes after treatment ]
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29.  Secondary:   Time to Meaningful Pain Relief (MPR) by Treatment - <= 5 Minutes   [ Time Frame: From time study drug was taken until 5 minutes after treatment ]
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30.  Secondary:   Time to Meaningful Pain Relief (MPR) by Treatment <=10 Minutes   [ Time Frame: Time of study drug treatment until 10 minutes after treatment ]
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31.  Secondary:   Time to Meaningful Pain Relief (MPR) by Treatment <=15 Minutes   [ Time Frame: Time of study drug administration until 15 minutes after treatment ]
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32.  Secondary:   Time to Meaningful Pain Relief (MPR) by Treatment <=30 Minutes   [ Time Frame: Time of study drug administration until 30 minutes after treatment ]
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33.  Secondary:   Time to Meaningful Pain Relief (MPR) by Treatment <=45 Minutes   [ Time Frame: From study drug administration until 45 minutes after treatment ]
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34.  Secondary:   Time to Meaningful Pain Relief (MPR) by Treatment <=60 Minutes   [ Time Frame: Time of study drug administration until 60 minutes after treatment ]
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35.  Secondary:   Use of Standard Rescue Medication   [ Time Frame: Throughout the double-blind treatment period ]
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36.  Secondary:   Medication Performance Assessment 30 Minutes Post-treatment   [ Time Frame: 30 minutes post-treatment ]
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37.  Secondary:   Medication Performance Assessment 60 Minutes Post-treatment   [ Time Frame: 60 minutes post-treatment ]
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38.  Secondary:   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. ]
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39.  Secondary:   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 ]
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40.  Secondary:   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 ]
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41.  Secondary:   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 ]
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42.  Secondary:   Patient Global Impression of Change (PGIC) Endpoint   [ Time Frame: At conclusion of open-label extension period ]
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43.  Secondary:   Clinician Global Impression of Change at Visit 7- 1 Month After Open Label Treatment   [ Time Frame: One month after start of open-label extension ]
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44.  Secondary:   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 ]
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45.  Secondary:   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 ]
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46.  Secondary:   Clinician Global Impression of Change (CGIC)Endpoint   [ Time Frame: End of open-label extension period ]
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  Serious Adverse Events
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  Other Adverse Events
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.  


Results Point of Contact:  
Name/Title: Sponsor's Medical Expert, Clinical Research
Organization: Cephalon, Inc.
phone: 1-800-896-5855


No publications provided


Responsible Party: Teva Pharmaceutical Industries ( Cephalon )
ClinicalTrials.gov Identifier: NCT00813488     History of Changes
Other Study ID Numbers: C25608/3056/BP/US
Study First Received: December 19, 2008
Results First Received: August 31, 2010
Last Updated: May 22, 2012
Health Authority: United States: Food and Drug Administration