Cancer, Pain
Conditions
Keywords
Breakthrough Pain in Cancer Patients
Brief summary
The purpose of this study is to evaluate the safety of BEMA fentanyl 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. BioDelivery Sciences International, Inc. (BDSI) has developed BEMA (BioErodible MucoAdhesive) 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 disc that is placed against the mucosal membrane inside the mouth. The mucoadhesive polymers in the disc readily adhere to the mucosal membrane (within 5 seconds) when moistened. The components of the disc are water soluble, so the entire dosage form dissolves within 30 minutes of application.
Interventions
DRUGBEMA Fentanyl
buccal soluble film; 200, 400, 600, 800, 1200 mcg fentanyl; up to 4 times daily
Sponsors
BioDelivery Sciences International
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 experience 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 * ECOG performance status of 4 or 5 * Subject is pregnant, actively trying to become pregnant, breast feeding or not using adequate contraceptive measures
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Adverse Events. | Participants were followed for the duration of the study, an average of 126 days | After the first dose of BEMA Fentanyl, all adverse events were recorded and summarized. |
Countries
United States
Participant flow
Recruitment details
The enrollment period was 3/14/06 - 6/13/08. Subjects were recruited from academic & private clinics in the US. Two groups of subjects were eligible for enrollment in this study. Subjects were eligible to enter this study following completion of the placebo-controlled study, FEN-201 or they were enrolled directly into this study.
Participants by arm
| Arm | Count |
|---|---|
| Open Label Fentanyl Treatment BioErodible Muco Adhesive(BEMA) Fentanyl | 243 |
| Total | 243 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 30 |
| Overall Study | Death | 32 |
| Overall Study | Lack of Efficacy | 12 |
| Overall Study | Lost to Follow-up | 4 |
| Overall Study | No dose taken | 1 |
| Overall Study | Other Reason | 22 |
| Overall Study | Physician Decision | 21 |
| Overall Study | Protocol Violation | 6 |
| Overall Study | Withdrawal by Subject | 34 |
Baseline characteristics
| Characteristic | Open Label Fentanyl Treatment |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 75 Participants |
| Age, Categorical Between 18 and 65 years | 168 Participants |
| Age Continuous | 58.0 years STANDARD_DEVIATION 12.12 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 23 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 9 Participants |
| Race (NIH/OMB) White | 209 Participants |
| Region of Enrollment United States | 243 participants |
| Sex: Female, Male Female | 128 Participants |
| Sex: Female, Male Male | 115 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 215 / 243 |
| serious Total, serious adverse events | 121 / 243 |
Outcome results
Primary
Percentage of Participants With Adverse Events.
After the first dose of BEMA Fentanyl, all adverse events were recorded and summarized.
Time frame: Participants were followed for the duration of the study, an average of 126 days
Population: All subjects that received at least 1 dose of study drug were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Open Label Fentanyl Treatment | Percentage of Participants With Adverse Events. | 88.5 percentage of participants |