• Pain relief by 30 minutes after dosing [ Designated as safety issue: No ]
  

• Pain relief at various time points [ Designated as safety issue: No ]
  
• Safety, tolerability, and acceptability [ Designated as safety issue: Yes ]
  

OBJECTIVES:

Primary

• Determine the efficacy and safety of fentanyl sublingual (SL) spray for the treatment of breakthrough cancer pain in patients on around-the-clock opioids for their persistent cancer pain.

Secondary

• Evaluate the safety of fentanyl SL spray in these opioid-tolerant patients.
• Assess the patient's satisfaction with treatment medication.

OUTLINE: This is a phase III, randomized, double-blind, placebo-controlled, multicenter study of the clinical response to fentanyl sublingual (SL) spray as a treatment for breakthrough cancer pain.

The study medication is administered under the tongue as a simple spray and can be self-administered by patients or assisted by their caregivers. In addition, there is a questionnaire assessing satisfaction with the treatment. Patients are titrated to an effective-dose of fentanyl SL spray in the open-label titration period and then proceed to the double-blind randomized period. Patients are treated for up to a total of 6-7 weeks (including both the open-label titration and the double-blind randomized periods).

DISEASE CHARACTERISTICS:

• Diagnosis of cancer

• Opioid-tolerant, defined as undergoing opioid treatment for cancer-related pain for ≥ 7 days and meeting 1 of the following criteria:

  • Receiving at least 60 mg of oral morphine/day
  • Receiving at least 25 mcg of transdermal fentanyl/hour
  • Receiving at least 30 mg of oxycodone/day
  • Receiving at least 8 mg of oral hydromorphone/day
  • Receiving an equianalgesic dose of another opioid
• Experiences 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
• Experiences on average one to four 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 (e.g., oxycodone, hydrocodone, or codeine with acetaminophen)
• Brain metastases allowed provided the patient has no signs or symptoms of increased intracranial pressure

PATIENT CHARACTERISTICS:

• Able to evaluate pain relief, assess medication performance, convey adverse events, and record each use of the study drug or supplemental medication in an electronic diary (a caregiver may provide the patient the medication and help with the electronic diary but cannot enter information)
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No intolerable side effects to opioids or fentanyl
• No 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
• No uncontrolled hypertension (systolic blood pressure [BP] > 180 mm Hg or diastolic BP > 90 mm Hg on two occasions at least six hours apart) despite antihypertensive therapy
• No hypertensive crisis within the past two years
• No recent history (within the past two years) of transient ischemic attacks, neural vascular disease, stroke, or cerebral aneurysms
• No clinically uncontrolled sleep apnea
• No inability to assess pain or response to pain medications for any reason, including psychiatric disorder, concurrent medical disorder, or concomitant therapy
• No painful erythema, edema, or ulcers under the tongue

PRIOR CONCURRENT THERAPY:

• At least 30 days since prior investigational study product(s)
• At least 14 days since prior monoamine oxidase inhibitors
• Medications or therapies that have been and continue to be used for a chronic disease condition may be continued throughout the study provided the medication or therapy is stable in dose and frequency for at least one week prior to the screening visit
• Medications used to help manage pain (e.g., bisphosphonates, steroids, or gabapentin) allowed provided the medication is stable in dose and frequency for at least one week prior to the screening visit of the study and the dose/frequency are not anticipated to change during the study
• Short-acting commercially available fentanyl medications used to help manage breakthrough pain (e.g., buccal fentanyl [Fentora®] or transmucosal fentanyl [Actiq®]) allowed for up to one-week prior to study entry onto the open-label titration period, but are not allowed during the open-label titration period or double-blind randomization period of the study
• Patients who complete the double-blind period and final visit of this study are eligible to proceed to INSYS-INS-06-007