Long-term Safety and Efficacy Study of Fentanyl Sublingual Spray for the Treatment of Breakthrough Cancer Pain

This was an open-label multi-center study of the safety of fentanyl sublingual spray as a treatment for breakthrough cancer pain. The study medication was administered under the tongue as a simple spray and could be self-administered by patients or assisted by their caregivers. In addition to safety, there was a questionnaire to assess satisfaction with the study medication.

Subjects could enter this study by 1 of 2 routes:

• De novo subjects who meet the inclusion criteria and none of the exclusion criteria at the Screening Visit were enrolled into the Open-label Titration Period of the study. Upon successful completion of the titration period, patients entered the Open-label Maintenance Period.
• All patients who successfully completed the Double-blind Randomization Period and the Final Visit of study INS-05-001 (NCT00538850) were eligible to enter the Open-label Maintenance Period of this study.

Inclusion criteria

All subjects who have completed the Double-blind Period and Final Visit of protocol INS-05-001(NCT00538850), Multicenter Randomized Double-blind Trial of Fentanyl Sublingual Spray for the Treatment of Breakthrough Cancer Pain are eligible for participation in this open-label extension study.

All de novo subjects must meet all of the following criteria to be eligible for participation in the study:

• Male or female, > 18 years of age.
• Diagnosis of cancer.
• Opioid treatment. Patients who are treated with opioids are defined as those patients who are taking at least 60 mg of oral morphine/day, at least 25 µg of transdermal fentanyl/hour, at least 30 mg of oxycodone/day, at least 8 mg of oral hydromorphone/day or an equianalgesic dose of another opioid for > 7 days for cancer-related pain.
• Experience persistent pain related to the cancer or its treatment of moderate or lesser intensity in the 24 hours prior to assessment by a verbal rating scale at the Screening Visit.
• Experience on average 1 to 4 breakthrough cancer pain episodes per day usually at least partially controlled by supplemental medication of at least 5 mg immediate-release morphine or an equivalent short-acting opioid (eg, oxycodone, hydrocodone, or codeine with acetaminophen).
• Able to evaluate pain relief, assess medication performance, report adverse events (AEs), report use of the study drug or supplemental medication (a caregiver may provide the subject the medication).
• Able and willing to give informed consent.
• Women of childbearing potential must have a) a negative urine pregnancy test, b) not be breast feeding and c) agree to practice a reliable form of contraception.

Exclusion criteria

• Intolerable side effects to opioids or fentanyl.
• Rapidly increasing/uncontrolled pain.
• A history of major organ system impairment or disease, that in the Investigator's or his/her designee's opinion could increase the risk associated with the use of opioids.
• Uncontrolled hypertension (systolic blood pressure [BP] > 180 mm Hg or diastolic BP > 90 mm Hg on 2 occasions at least 6 hours apart) despite antihypertensive therapy, or has a history of hypertensive crisis within the past 2 years.
• A recent history (within the past 2 years) of transient ischemic attacks, neural vascular disease, stroke, or cerebral aneurysms.
• Serum creatinine, ALT or AST that is greater than 3 times the upper limit of normal.
• Diagnosis of sleep apnea.
• Brain metastases with signs or symptoms of increased intracranial pressure.
• Inability to assess pain or response to pain medications for any reason, including psychiatric disorder, concurrent medical disorder, or concomitant therapy.
• Has used methadone within 14 days of the Screening Visit.
• Received an investigational study product(s) within 30 days of the Screening Visit.
• Use of monoamine oxidase (MAO) inhibitors within 14 days of the Screening Visit.