Study of BEMA™ Fentanyl in the Treatment of Breakthrough Pain in Cancer Subjects

Pain Clinical Trial

Official title:

A Double-blind, Placebo Controlled Evaluation of the Efficacy, Safety and Tolerability of BEMA™ Fentanyl in the Treatment of Breakthrough Pain in Cancer Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00293033
• Other study ID #: FEN-201
• Status: Completed
• Phase: Phase 3
• Start date: February 2006
• Est. completion date: April 2007

Study information

• Verified date: November 2019
• Source: BioDelivery Sciences International
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the efficacy of BEMA Fentanyl (Onsolis) at any dose in the management of breakthrough pain in cancer subjects on background opioid therapy. The standard of care for these breakthrough pain episodes is a rapid onset, short acting analgesic with minimal associated sleepiness. Oral morphine, oxycodone and hydromorphone are routinely used, but because of slow and variable oral absorption, the pain control is not the best with these products. Oral transmucosal fentanyl citrate (OTFC) has been used successfully in treating breakthrough pain episodes associated with cancer. OTFC is a lozenge of fentanyl on a stick and is administered by continuously swabbing the interior of the subject's mouth until the product is dissolved (approximately 15 to 30 minutes). The buccal route of administration avoids the delay and variability associated with oral absorption.

Description:

This is a randomized, double-blind, placebo controlled, multiple cross-over study. Eligible subjects will be treated with open label BEMA fentanyl over a period of up to two weeks. Doses will be titrated upward, starting at 200 μg, until a dose is identified that produces satisfactory pain relief for at least 2 episodes. Those subjects who identify a dose of BEMA fentanyl that produces satisfactory relief of breakthrough pain episodes will enter the double-blind, placebo controlled period of the trial. They will receive 3 placebo doses and 6 BEMA fentanyl doses in a random sequence per randomization schedule.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 152
• Est. completion date: April 2007
• Est. primary completion date: April 2007
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Male or non-pregnant and non-lactating female. A female of child-bearing potential is eligible to participate in this study if she is using an acceptable method of birth control.

• 18 years or older

• Patient must have pain associated with cancer or cancer treatment.

• Patient must be on a stable current regimen of oral opioids equivalent to 60 - 1000 mg/day of oral morphine or 50 - 300 µg/hr of transdermal fentanyl (e.g. oxycodone 30 mg, methadone 20 mg, and hydromorphone 7.5 mg).

• Regularly experiences 1 - 4 breakthrough pain episodes per day that require additional opioids for pain control

• At least partial relief of breakthrough pain by use of opioid therapy

• Subject must be able to self-administer the study medication correctly.

• Subject must be willing and able to complete the electronic diary card with each pain episode.

• Signed consent must be obtained at screening prior to any procedures being performed.

Exclusion Criteria:

• Psychiatric/cognitive or neurological impairment that would limit the subject's ability to understand or complete the diary

• Cardiopulmonary disease that, in the opinion of the investigator, would significantly increase the risk of respiratory depression

• Recent history or current evidence of alcohol or other drug substance (licit or illicit) abuse

• Rapidly escalating pain that the investigator believes may require an increase in the dosage of background pain medication during the study

• Moderate (Grade 3) to severe (Grade 4) mucositis (Subjects with less than moderate mucositis are permitted and must be instructed to not apply the BEMA disc at a site of inflammation.)

• Strontium 89 therapy within the previous 6 months

• Any other therapy prior to the study that the investigator considers could alter pain or the response to pain medication.

• Use of an investigational drug within 4 weeks preceding this study

• History of hypersensitivity or intolerance to fentanyl

• Regularly more than 4 episodes per day

• Eastern Cooperative Oncology Group (ECOG) performance status of 4 or 5

• Subject is pregnant, actively trying to become pregnant, breast feeding or not using adequate contraceptive measures

Related Conditions & MeSH terms

• Breakthrough Pain
• Cancer
• Pain

Intervention

Drug:
• BEMA™
BioDelivery Sciences International, Inc. (BDSI) has developed BioErodible MucoAdhesive (BEMA) Fentanyl, an alternative product to OTFC that does not require the subject to continuously paint the inside of the mouth with the dosage form. The BDSI product is a small soluble film that is placed against the mucosal membrane inside the mouth. The mucoadhesive polymers in the film readily adhere to the mucosal membrane (within 5 seconds) when moistened. The components of the film are water soluble, so the entire dosage form dissolves within 30 minutes of application.
• Placebo

Locations

Country	Name	City	State
United States	PPD Development	Wilmington	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
BioDelivery Sciences International

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	SPID in Neuropathic Pain Subpopulation	Pain intensity (using an 11-point [0 = no pain to 10 = worst pain] numeric scale) was recorded at 0, 5, 10, 15, 30, 45, and 60 minutes after dosing. Pain intensity difference (PID) was defined as the baseline pain score minus the pain score of each time point. The primary endpoint was the Summary of Pain Intensity Differences at 30 minutes after dosing (SPID 30) in ITT population for Onsolis versus placebo during double-blind period of study. SPID was calculated as a weighted sum of the PID of all time points at or before time point of interest.Range of possible SPID values is -10X time point (minutes) to 10X time point (minutes). Higher value indicates a better outcome. SPID was calculated as a weighted sum of the pain intensity difference of all time points at or before the time point of interest for the Neuropathic pain subpopulation for relevant time points (15, 30, 45, 60 minutes). Neuropathic pain subpopulation is a subset of ITT population who have neuropathic pain at baseline.	15 minutes
Other	SPID in Neuropathic Pain Subpopulation	Pain intensity (using an 11-point [0 = no pain to 10 = worst pain] numeric scale) was recorded at 0, 5, 10, 15, 30, 45, and 60 minutes after dosing. Pain intensity difference (PID) was defined as the baseline pain score minus the pain score of each time point. The primary endpoint was the Summary of Pain Intensity Differences at 30 minutes after dosing (SPID 30) in ITT population for Onsolis versus placebo during double-blind period of study. SPID was calculated as a weighted sum of the PID of all time points at or before time point of interest.Range of possible SPID values is -10X time point (minutes) to 10X time point (minutes). Higher value indicates a better outcome. SPID was calculated as a weighted sum of the pain intensity difference of all time points at or before the time point of interest for the Neuropathic pain subpopulation for relevant time points (15, 30, 45, 60 minutes). Neuropathic pain subpopulation is a subset of ITT population who have neuropathic pain at baseline.	30 minutes
Other	SPID in Neuropathic Pain Subpopulation	Pain intensity (using an 11-point [0 = no pain to 10 = worst pain] numeric scale) was recorded at 0, 5, 10, 15, 30, 45, and 60 minutes after dosing. Pain intensity difference (PID) was defined as the baseline pain score minus the pain score of each time point. The primary endpoint was the Summary of Pain Intensity Differences at 30 minutes after dosing (SPID 30) in ITT population for Onsolis versus placebo during double-blind period of study. SPID was calculated as a weighted sum of the PID of all time points at or before time point of interest.Range of possible SPID values is -10X time point (minutes) to 10X time point (minutes). Higher value indicates a better outcome. SPID was calculated as a weighted sum of the pain intensity difference of all time points at or before the time point of interest for the Neuropathic pain subpopulation for relevant time points (15, 30, 45, 60 minutes). Neuropathic pain subpopulation is a subset of ITT population who have neuropathic pain at baseline.	45 minutes
Other	SPID in Neuropathic Pain Subpopulation	Pain intensity (using an 11-point [0 = no pain to 10 = worst pain] numeric scale) was recorded at 0, 5, 10, 15, 30, 45, and 60 minutes after dosing. Pain intensity difference (PID) was defined as the baseline pain score minus the pain score of each time point. The primary endpoint was the Summary of Pain Intensity Differences at 30 minutes after dosing (SPID 30) in ITT population for Onsolis versus placebo during double-blind period of study. SPID was calculated as a weighted sum of the PID of all time points at or before time point of interest.Range of possible SPID values is -10X time point (minutes) to 10X time point (minutes). Higher value indicates a better outcome. SPID was calculated as a weighted sum of the pain intensity difference of all time points at or before the time point of interest for the Neuropathic pain subpopulation for relevant time points (15, 30, 45, 60 minutes). Neuropathic pain subpopulation is a subset of ITT population who have neuropathic pain at baseline.	60 minutes
Primary	Summary of Pain Intensity Differences (SPID)	Pain intensity (using an 11-point [0 = no pain to 10 = worst pain] numeric scale) was recorded at 0, 5, 10, 15, 30, 45, and 60 minutes after dosing. Pain intensity difference (PID) was defined as the baseline pain score minus the pain score of each time point. The primary endpoint was the Summary of Pain Intensity Differences at 30 minutes after dosing (SPID 30) in ITT population for Onsolis versus placebo during double-blind period of study. SPID was calculated as a weighted sum of the PID of all time points at or before time point of interest.Range of possible SPID values is; -10X time point (minutes) to 10X time point (minutes). Higher value indicates a better outcome.	0-30 minutes
Secondary	SPID	Pain intensity (using an 11-point [0 = no pain to 10 = worst pain] numeric scale) was recorded at 0, 5, 10, 15, 30, 45, and 60 minutes after dosing. Pain intensity difference (PID) was defined as the baseline pain score minus the pain score of each time point. The primary endpoint was the Summary of Pain Intensity Differences at 30 minutes after dosing (SPID 30) in ITT population for Onsolis versus placebo during double-blind period of study. SPID was calculated as a weighted sum of the PID of all time points at or before time point of interest.Range of possible SPID values is -10X time point (minutes) to 10X time point (minutes). Higher value indicates a better outcome.SPID was calculated as a weighted sum of the pain intensity difference of all time points at or before the time point of interest.	0-5 minutes
Secondary	SPID	Pain intensity (using an 11-point [0 = no pain to 10 = worst pain] numeric scale) was recorded at 0, 5, 10, 15, 30, 45, and 60 minutes after dosing. Pain intensity difference (PID) was defined as the baseline pain score minus the pain score of each time point. The primary endpoint was the Summary of Pain Intensity Differences at 30 minutes after dosing (SPID 30) in ITT population for Onsolis versus placebo during double-blind period of study. SPID was calculated as a weighted sum of the PID of all time points at or before time point of interest.Range of possible SPID values is -10X time point (minutes) to 10X time point (minutes). Higher value indicates a better outcome.SPID was calculated as a weighted sum of the pain intensity difference of all time points at or before the time point of interest.	0-10 minutes
Secondary	SPID	Pain intensity (using an 11-point [0 = no pain to 10 = worst pain] numeric scale) was recorded at 0, 5, 10, 15, 30, 45, and 60 minutes after dosing. Pain intensity difference (PID) was defined as the baseline pain score minus the pain score of each time point. The primary endpoint was the Summary of Pain Intensity Differences at 30 minutes after dosing (SPID 30) in ITT population for Onsolis versus placebo during double-blind period of study. SPID was calculated as a weighted sum of the PID of all time points at or before time point of interest.Range of possible SPID values is -10X time point (minutes) to 10X time point (minutes). Higher value indicates a better outcome.SPID was calculated as a weighted sum of the pain intensity difference of all time points at or before the time point of interest.	0-15 minutes
Secondary	SPID	Pain intensity (using an 11-point [0 = no pain to 10 = worst pain] numeric scale) was recorded at 0, 5, 10, 15, 30, 45, and 60 minutes after dosing. Pain intensity difference (PID) was defined as the baseline pain score minus the pain score of each time point. The primary endpoint was the Summary of Pain Intensity Differences at 30 minutes after dosing (SPID 30) in ITT population for Onsolis versus placebo during double-blind period of study. SPID was calculated as a weighted sum of the PID of all time points at or before time point of interest.Range of possible SPID values is -10X time point (minutes) to 10X time point (minutes). Higher value indicates a better outcome.SPID was calculated as a weighted sum of the pain intensity difference of all time points at or before the time point of interest.	0-45 minutes
Secondary	SPID	Pain intensity (using an 11-point [0 = no pain to 10 = worst pain] numeric scale) was recorded at 0, 5, 10, 15, 30, 45, and 60 minutes after dosing. Pain intensity difference (PID) was defined as the baseline pain score minus the pain score of each time point. The primary endpoint was the Summary of Pain Intensity Differences at 30 minutes after dosing (SPID 30) in ITT population for Onsolis versus placebo during double-blind period of study. SPID was calculated as a weighted sum of the PID of all time points at or before time point of interest.Range of possible SPID values is -10X time point (minutes) to 10X time point (minutes). Higher value indicates a better outcome.SPID was calculated as a weighted sum of the pain intensity difference of all time points at or before the time point of interest.	0-60 minutes
Secondary	PID	Pain intensity (using an 11-point [0 = no pain to 10 = worst pain] numeric scale) was recorded at 0, 5, 10, 15, 30, 45, and 60 minutes after dosing. Pain intensity difference (PID) was defined as the baseline pain score minus the pain score of each time point.	5 minutes after dosing
Secondary	PID	Pain intensity (using an 11-point [0 = no pain to 10 = worst pain] numeric scale) was recorded at 0, 5, 10, 15, 30, 45, and 60 minutes after dosing. Pain intensity difference (PID) was defined as the baseline pain score minus the pain score of each time point.	10 minutes after dosing
Secondary	PID	Pain intensity (using an 11-point [0 = no pain to 10 = worst pain] numeric scale) was recorded at 0, 5, 10, 15, 30, 45, and 60 minutes after dosing. Pain intensity difference (PID) was defined as the baseline pain score minus the pain score of each time point.	15 minutes after dosing
Secondary	PID	Pain intensity (using an 11-point [0 = no pain to 10 = worst pain] numeric scale) was recorded at 0, 5, 10, 15, 30, 45, and 60 minutes after dosing. Pain intensity difference (PID) was defined as the baseline pain score minus the pain score of each time point.	30 minutes after dosing
Secondary	PID	Pain intensity (using an 11-point [0 = no pain to 10 = worst pain] numeric scale) was recorded at 0, 5, 10, 15, 30, 45, and 60 minutes after dosing. Pain intensity difference (PID) was defined as the baseline pain score minus the pain score of each time point.	45 minutes after dosing
Secondary	PID	Pain intensity (using an 11-point [0 = no pain to 10 = worst pain] numeric scale) was recorded at 0, 5, 10, 15, 30, 45, and 60 minutes after dosing. Pain intensity difference (PID) was defined as the baseline pain score minus the pain score of each time point.	60 minutes after dosing
Secondary	Pain Relief	Pain relief (PR) is measured using a 5-point categorical scale (0=no relief to 4=complete relief) at 5, 10, 15, 30, 45, and 60 minutes after taking the study medication or until rescue.	5 minutes after dosing
Secondary	Pain Relief	Pain relief (PR) is measured using a 5-point categorical scale (0=no relief to 4=complete relief) at 5, 10, 15, 30, 45, and 60 minutes after taking the study medication or until rescue.	10 minutes after dosing
Secondary	Pain Relief	Pain relief (PR) is measured using a 5-point categorical scale (0=no relief to 4=complete relief) at 5, 10, 15, 30, 45, and 60 minutes after taking the study medication or until rescue.	15 minutes after dosing
Secondary	Pain Relief	Pain relief (PR) is measured using a 5-point categorical scale (0=no relief to 4=complete relief) at 5, 10, 15, 30, 45, and 60 minutes after taking the study medication or until rescue.	30 minutes after dosing
Secondary	Pain Relief	Pain relief (PR) is measured using a 5-point categorical scale (0=no relief to 4=complete relief) at 5, 10, 15, 30, 45, and 60 minutes after taking the study medication or until rescue.	45 minutes after dosing
Secondary	Pain Relief	Pain relief (PR) is measured using a 5-point categorical scale (0=no relief to 4=complete relief) at 5, 10, 15, 30, 45, and 60 minutes after taking the study medication or until rescue.	60 minutes after dosing
Secondary	Total Pain Relief	Total Pain Relief (TOTPAR) is calculated as the weighted sum of the pain relief (PR) of all time points at or prior to the time point of interest.Pain relief (PR) is measured using a 5-point categorical scale (0=no relief to 4=complete relief)compared to baseline (pre-dose)	5 minutes
Secondary	Total Pain Relief	Total Pain Relief (TOTPAR) is calculated as the weighted sum of the pain relief (PR) of all time points at or prior to the time point of interest. Pain relief (PR) is measured using a 5-point categorical scale (0=no relief to 4=complete relief)compared to baseline (pre-dose)	10 minutes
Secondary	Total Pain Relief	Total Pain Relief (TOTPAR) is calculated as the weighted sum of the pain relief (PR) of all time points at or prior to the time point of interest. Pain relief (PR) is measured using a 5-point categorical scale (0=no relief to 4=complete relief)compared to baseline (pre-dose)	15 minutes
Secondary	Total Pain Relief	Total Pain Relief (TOTPAR) is calculated as the weighted sum of the pain relief (PR) of all time points at or prior to the time point of interest. Pain relief (PR) is measured using a 5-point categorical scale (0=no relief to 4=complete relief)compared to baseline (pre-dose)	30 minutes
Secondary	Total Pain Relief	Total Pain Relief (TOTPAR) is calculated as the weighted sum of the pain relief (PR) of all time points at or prior to the time point of interest. Pain relief (PR) is measured using a 5-point categorical scale (0=no relief to 4=complete relief)compared to baseline (pre-dose)	45 minutes
Secondary	Total Pain Relief	Total Pain Relief (TOTPAR) is calculated as the weighted sum of the pain relief (PR) of all time points at or prior to the time point of interest. Pain relief (PR) is measured using a 5-point categorical scale (0=no relief to 4=complete relief)compared to baseline (pre-dose)	60 minutes
Secondary	Subject Overall Satisfaction With Study Drug	Subjects evaluated their overall satisfaction with study drug at the time rescue medication was consumed or at the 60-minute time point using a 5-point categorical scale (0 = poor, 1 = fair, 2 = good, 3 = very good, and 4 = excellent).	60 minutes or at time of rescue medication use
Secondary	Percentage of Pain Free Episodes	A pain free episode is one with 0 pain intensity at the specified time point. Percentage of episodes that are pain-free per subject is analyzed.	5 minutes
Secondary	Percentage of Pain Free Episodes	A pain free episode is one with 0 pain intensity at the specified time point. Percentage of episodes that are pain-free per subject is analyzed.	10 minutes
Secondary	Percentage of Pain Free Episodes	A pain free episode is one with 0 pain intensity at the specified time point. Percentage of episodes that are pain-free per subject is analyzed.	15 minutes
Secondary	Percentage of Pain Free Episodes	A pain free episode is one with 0 pain intensity at the specified time point. Percentage of episodes that are pain-free per subject is analyzed.	30 minutes
Secondary	Percentage of Pain Free Episodes	A pain free episode is one with 0 pain intensity at the specified time point. Percentage of episodes that are pain-free per subject is analyzed.	45 minutes
Secondary	Percentage of Pain Free Episodes	A pain free episode is one with 0 pain intensity at the specified time point. Percentage of episodes that are pain-free per subject is analyzed.	60 minutes
Secondary	Episodes With at Least 50% Decreases in Pain	Number of episodes where the total pain score has at least a 50% reduction from baseline.	15 minutes
Secondary	Episodes With at Least 50% Decreases in Pain	Number of episodes where the total pain score has at least a 50% reduction from baseline.	30 minutes
Secondary	Episodes With at Least 50% Decreases in Pain	Number of episodes where the total pain score has at least a 50% reduction from baseline.	45 minutes
Secondary	Episodes With at Least 50% Decreases in Pain	Number of episodes where the total pain score has at least a 50% reduction from baseline.	60 minutes
Secondary	Episodes With at Least 33% Decreases in Pain	Number of episodes where the total pain score has at least a 33% reduction from baseline.	15 minutes
Secondary	Episodes With at Least 33% Decreases in Pain	Number of episodes where the total pain score has at least a 33% reduction from baseline.	30 minutes
Secondary	Episodes With at Least 33% Decreases in Pain	Number of episodes where the total pain score has at least a 33% reduction from baseline.	45 minutes
Secondary	Episodes With at Least 33% Decreases in Pain	Number of episodes where the total pain score has at least a 50% reduction from baseline.	60 minutes
Secondary	Episodes With Complete Pain Relief	Pain relief (PR) is measured using a 5-point categorical scale (0=no relief to 4=complete relief). Percentage of episodes with complete relief per subject is analyzed where a complete pain relief episode is defined as pain relief of value 4 at the specified time point.	5 minutes
Secondary	Episodes With Complete Pain Relief	Pain relief (PR) is measured using a 5-point categorical scale (0=no relief to 4=complete relief).Percentage of episodes with complete relief per subject is analyzed where a complete pain relief episode is defined as pain relief of value 4 at the specified time point.	10 minutes
Secondary	Episodes With Complete Pain Relief	Pain relief (PR) is measured using a 5-point categorical scale (0=no relief to 4=complete relief).Percentage of episodes with complete relief per subject is analyzed where a complete pain relief episode is defined as pain relief of value 4 at the specified time point.	15 minutes
Secondary	Episodes With Complete Pain Relief	Pain relief (PR) is measured using a 5-point categorical scale (0=no relief to 4=complete relief). Percentage of episodes with complete relief per subject is analyzed where a complete pain relief episode is defined as pain relief of value 4 at the specified time point.	30 minutes
Secondary	Episodes With Complete Pain Relief	Pain relief (PR) is measured using a 5-point categorical scale (0=no relief to 4=complete relief). Percentage of episodes with complete relief per subject is analyzed where a complete pain relief episode is defined as pain relief of value 4 at the specified time point.	45 minutes
Secondary	Episodes With Complete Pain Relief	Pain relief (PR) is measured using a 5-point categorical scale (0=no relief to 4=complete relief). Percentage of episodes with complete relief per subject is analyzed where a complete pain relief episode is defined as pain relief of value 4 at the specified time point.	60 minutes
Secondary	Rescue Medication Usage	Rescue medication is medication taken if adequate pain relief is not realized within 30 minutes following application of the study drug. Percentage of episodes when rescue medication was used per subject is analyzed.	28 Days