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

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

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.

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.

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