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

Open-label Multi-center Safety Trial of Fentanyl Sublingual Spray (Fentanyl SL Spray) for the Treatment of Breakthrough Cancer Pain

The purpose of this study was to assess the 90-day safety of fentanyl sublingual spray for the treatment of breakthrough cancer pain in subjects on around-the-clock opioids for their persistent 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:

1. Male or female, > 18 years of age.
2. Diagnosis of cancer.
3. 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.
4. 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.
5. 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).
6. 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).
7. Able and willing to give informed consent.
8. 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:

1. Intolerable side effects to opioids or fentanyl.
2. Rapidly increasing/uncontrolled pain.
3. 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.
4. 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.
5. A recent history (within the past 2 years) of transient ischemic attacks, neural vascular disease, stroke, or cerebral aneurysms.
6. Serum creatinine, ALT or AST that is greater than 3 times the upper limit of normal.
7. Diagnosis of sleep apnea.
8. Brain metastases with signs or symptoms of increased intracranial pressure.
9. Inability to assess pain or response to pain medications for any reason, including psychiatric disorder, concurrent medical disorder, or concomitant therapy.
10. Has used methadone within 14 days of the Screening Visit.
11. Received an investigational study product(s) within 30 days of the Screening Visit.
12. Use of monoamine oxidase (MAO) inhibitors within 14 days of the Screening Visit.