This was an open-label, single-dose study to assess the safety, tolerability, and absorption/distribution kinetics of a single 100 µg dose of fentanyl sublingual spray in opioid-tolerant cancer subjects, with or without oral mucositis.

RATIONALE: One dose of fentanyl sublingual spray may be effective in relieving pain in opioid-tolerant cancer patients.

PURPOSE: This phase III trial is studying the side effects of fentanyl sublingual spray and to see how well it works in treating opioid-tolerant cancer patients with or without oral mucositis.

OBJECTIVES:

Primary

• To compare the absorption/distribution kinetics of a single dose of fentanyl sublingual spray in opioid-tolerant cancer patients with or without oral mucositis.
• To evaluate the safety and tolerability of this regimen.

OUTLINE: This is a multicenter study.

Patients fast for at least 8 hours before and at least 4 hours after and no water is allowed for at least 1 hour before and at least 1 hour after study drug administration. Patients receive a single dose of fentanyl sublingual spray while in an upright position in clinical care recliners or beds, and remain in an upright posture for at least 4 hours after administration. Patients are instructed not to swallow for at least 5 minutes after administration and not to expectorate the drug.

After study drug administration, 10 blood samples are collected over a 12-hour period for pharmacokinetic and other analyses.

DISEASE CHARACTERISTICS:

• Diagnosis of cancer and meets 1 of the following criteria:

  • Mild mucositis, defined as grade 1 (erythema of the mucosa) or 2 (patchy ulcerations or pseudomembranes) on the day of study drug administration.
  • No mucositis, defined as normal oral cavity upon examination on the day of study drug administration.

• Opioid-tolerant, defined as patients who are taking ≥ 60 mg of oral morphine/day, ≥ 30 mg of oxycodone/day, ≥ 8 mg of oral hydromorphone/day, or an equianalgesic dose of another opioid for ≥ 7 days for cancer-related pain.

• Persistent pain related to cancer or its treatment over the past 7 days.

• No brain metastases with signs or symptoms of increased intracranial pressure.

PATIENT CHARACTERISTICS:

• Negative pregnancy test.
• Agree to be confined to study site for approximately 12 hours, to eat only the food served by the study unit during the study confinement period, and to consume all food provided at the designated meal or snack times.
• 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 despite antihypertensive therapy or history of hypertensive crisis within the past 2 years.
• No recent history (within the past 2 years) of transient ischemic attacks, neural vascular disease, stroke, or cerebral aneurysms.
• No intolerable side effects to opioids or fentanyl.

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics.

• More than 30 days since prior investigational agents.

• More than 14 days since prior monoamine oxidase inhibitors.

• No prior participation in either Insys Fentanyl Sublingual Spray Phase III study INSYS-INS-05-001 or INSYS-INS-06-007.

• No other concurrent use of any fentanyl product.

  • Patients who have received Actiq®, Fentora®, or Duragesic® are eligible after a 7-day washout.

• No concurrent medications (prescription, over-the-counter, vitamin, or herbal substances) except for hormonal contraceptives and/or ≤ 3 doses of acetaminophen at ≤ 1 g each.

Safety population: All subjects who received study drug.

Safety population: All subjects who received study drug.