Study of Breakthrough Cancer Pain: Assessment of Fentanyl Buccal Tablets Titration and Treatment in Opioid-Tolerant Patients

• Kaplan-Meier Estimates for Time to Meaningful Pain Relief As Assessed by Participants During the Treatment Period For Overall Breakthrough Pain (BTP) Episodes [ Time Frame: approximately Day 8-15 ] [ Designated as safety issue: No ]
  Overall episode data analyzed all values of time to meaningful pain relief taken over all BTP episodes during the treatment period. If meaningful pain relief was not achieved within 60 minutes of FBT intake, or if rescue medication was taken, the event was censored. Meaningful pain relief was left to the judgment of participants, who used a stopwatch and recorded the time from treatment until pain relief in a patient diary.
• Number of Participants Reaching An Effective Dose As Assessed by the Participant During the Titration Period [ Time Frame: Day 1 up to Day 7 ] [ Designated as safety issue: No ]
  Number of participants for which an effective dose of FBT was reached as judged by each participant. The effective dose was the dose that, for 2 consecutive break-through pain (BTP) episodes, provided adequate analgesia within the first 30 minutes after administration of study drug and that minimized undesirable effects. The assessment was performed by the participant and was reported in the titration-period diary. The next BTP episode was used to confirm the effective dose, and if confirmed, the effective dose was used for all following BTP episodes.
• Breakthrough Pain (BTP) Episodes Requiring the Use of Rescue Medication During the Titration Period and the Treatment Period [ Time Frame: Days 1 to up to Day 7 (Titration Period); approximately Day 8 up to Day 15 (Treatment Period) ] [ Designated as safety issue: No ]
  The number of breakthrough pain (BTP) episodes in which the participant did not obtain effective pain relief from study medication and took a rescue medication.
• Participant Assessment of Medication Performance During the Treatment Period [ Time Frame: approximately Day 8-15 ] [ Designated as safety issue: No ]
  Participants assessed the performance of FBT at 30 minutes and 60 minutes after dosing each episode during the treatment period. For each episode, the participant answered the question 'How well did your study medication perform in controlling the breakthrough pain episode?' on a 5-point Likert-type scale (poor=0, fair=1, good=2, very good=3, and excellent=4).
• Change From Baseline to End of Treatment Period (Approximately Day 15) in the Brief Pain Inventory 7-item (BPI-7S) Questionnaire Subscale: General Activity [ Time Frame: Day 0 (baseline), approximately Day 15 (end of Treatment Period) ] [ Designated as safety issue: No ]

  Participants completed the BPI-7S questionnaire to indicate their quality of life and functional status between study time points. For each subscale, the participant rated their responses from 0=Does not interfere through to 10=Completely interferes. A negative change from baseline represents an improvement.

  This subscale assesses general activity.

• Change From Baseline to End of Treatment Period (Approximately Day 15) in the Brief Pain Inventory 7-item (BPI-7S) Questionnaire Subscale: Mood [ Time Frame: Day 0 (baseline), approximately Day 15 (end of Treatment Period) ] [ Designated as safety issue: No ]

  Participants completed the BPI-7S questionnaire to indicate their quality of life and functional status between study time points. For each subscale, the participant rated their responses from 0=Does not interfere through to 10=Completely interferes. A negative change from baseline represents an improvement.

  This subscale assesses mood.

• Change From Baseline to End of Treatment Period (Approximately Day 15) in the Brief Pain Inventory 7-item (BPI-7S) Questionnaire Subscale: Walking Ability [ Time Frame: Day 0 (baseline), approximately Day 15 (end of Treatment Period) ] [ Designated as safety issue: No ]

  Participants completed the BPI-7S questionnaire to indicate their quality of life and functional status between study time points. For each subscale, the participant rated their responses from 0=Does not interfere through to 10=Completely interferes. A negative change from baseline represents an improvement.

  This subscale assesses walking ability.

• Change From Baseline to End of Treatment Period (Approximately Day 15) in the Brief Pain Inventory 7-item (BPI-7S) Questionnaire Subscale: Normal Work [ Time Frame: Day 0 (baseline), approximately Day 15 (end of Treatment Period) ] [ Designated as safety issue: No ]

  Participants completed the BPI-7S questionnaire to indicate their quality of life and functional status between study time points. For each subscale, the participant rated their responses from 0=Does not interfere through to 10=Completely interferes. A negative change from baseline represents an improvement.

  This subscale assesses normal work.

• Change From Baseline to End of Treatment Period (Approximately Day 15) in the Brief Pain Inventory 7-item (BPI-7S) Questionnaire Subscale: Relations With Other People [ Time Frame: Day 0 (baseline), approximately Day 15 (end of Treatment Period) ] [ Designated as safety issue: No ]

  Participants completed the BPI-7S questionnaire to indicate their quality of life and functional status between study time points. For each subscale, the participant rated their responses from 0=Does not interfere through to 10=Completely interferes. A negative change from baseline represents an improvement.

  This subscale assesses relations with other people.

• Change From Baseline to End of Treatment Period (Approximately Day 15) in the Brief Pain Inventory 7-item (BPI-7S) Questionnaire Subscale: Sleep [ Time Frame: Day 0 (baseline), approximately Day 15 (end of Treatment Period) ] [ Designated as safety issue: No ]

  Participants completed the BPI-7S questionnaire to indicate their quality of life and functional status between study time points. For each subscale, the participant rated their responses from 0=Does not interfere through to 10=Completely interferes. A negative change from baseline represents an improvement.

  This subscale assesses sleep.

• Change From Baseline to End of Treatment Period (Approximately Day 15) in the Brief Pain Inventory 7-item (BPI-7S) Questionnaire Subscale: Enjoyment of Life [ Time Frame: Day 0 (baseline), approximately Day 15 (end of Treatment Period) ] [ Designated as safety issue: No ]

  Participants completed the BPI-7S questionnaire to indicate their quality of life and functional status between study time points. For each subscale, the participant rated their responses from 0=Does not interfere through to 10=Completely interferes. A negative change from baseline represents an improvement.

  This subscale assesses enjoyment of life.

• Change From Baseline to End of Treatment Period (Approximately Day 15) in the Brief Pain Inventory 7-item (BPI-7S) Questionnaire: Global Score [ Time Frame: Day 0 (baseline), approximately Day 15 (end of Treatment Period) ] [ Designated as safety issue: No ]
  Participants completed the BPI-7S questionnaire to indicate their quality of life and functional status between study time points. For each subscale, the participant rated their responses from 0=Does not interfere through to 10=Completely interferes. The Global Score is the sum of the subscales (total scale is 0-70). A negative change from baseline represents an improvement.
• Participant's Global Assessment of Satisfaction (Satisfied With BTP Treatment?) at the End of the Treatment Period [ Time Frame: approximately Day 15 (end of Treatment Period) ] [ Designated as safety issue: No ]
  Responses to the Patient Satisfaction questionnaire question, "Satisfied with the BTP Treatment?", were captured on a five-point scale from 0=not at all to 4=very much.
• Participant's Global Assessment of Satisfaction (Does This BTP Medication Relieve Your Pain Quickly so You Can Get Back to Sleep?) at the End of the Treatment Period [ Time Frame: approximately Day 15 (end of Treatment Period) ] [ Designated as safety issue: No ]
  Responses to the Patient Satisfaction questionnaire question, "Does this BTP medication relieve your pain quickly so you can get back to sleep?", were captured on a five-point scale from 0=not at all to 4=very much.
• Participant's Global Assessment of Satisfaction (Does This Medication Work Fast?) at the End of the Treatment Period [ Time Frame: approximately Day 15 (end of Treatment Period) ] [ Designated as safety issue: No ]
  Responses to the Patient Satisfaction questionnaire question, "Does this medication work fast?", were captured on a five-point scale from 0=not at all to 4=very much.
• Participant's Global Assessment of Satisfaction (Does This Medication Provide Adequate Relief?) at the End of the Treatment Period [ Time Frame: approximately Day 15 (end of Treatment Period) ] [ Designated as safety issue: No ]
  Responses to the Patient Satisfaction questionnaire question, "Does this medication provide adequate relief?", were captured on a five-point scale from 0=not at all to 4=very much.
• Participant's Global Assessment of Satisfaction (Is This Medication Easy to Take?) at the End of the Treatment Period [ Time Frame: approximately Day 15 (end of Treatment Period) ] [ Designated as safety issue: No ]
  Responses to the Patient Satisfaction questionnaire question, "Is this medication easy to take?", were captured on a five-point scale from 0=not at all to 4=very much.
• Participant's Global Assessment of Satisfaction (Do You Find This Medication Comfortable to Take in Public?) at the End of the Treatment Period [ Time Frame: approximately Day 15 (end of Treatment Period) ] [ Designated as safety issue: No ]
  Responses to the Patient Satisfaction questionnaire question, "Do you find this medication comfortable to take in public?", were captured on a five-point scale from 0=not at all to 4=very much.
• Participant's Global Assessment of Satisfaction (Do You Feel Safe Taking This Medication?) at the End of the Treatment Period [ Time Frame: approximately Day 15 (end of Treatment Period) ] [ Designated as safety issue: No ]
  Responses to the Patient Satisfaction questionnaire question, "Do you feel safe taking this medication?", were captured on a five-point scale from 0=not at all to 4=very much.
• Participant's Global Assessment of Satisfaction (Do You Understand the Instructions?) at the End of the Treatment Period [ Time Frame: approximately Day 15 (end of Treatment Period) ] [ Designated as safety issue: No ]
  Responses to the Patient Satisfaction questionnaire question, "Do you understand the instructions?", were captured on a five-point scale from 0=not at all to 4=very much.
• Participant's Global Assessment of Ease of Use at the End of the Treatment Period [ Time Frame: approximately Day 15 (end of Treatment Period) ] [ Designated as safety issue: No ]
  Ease of use was assessed using the question 'Did you find this treatment easy/convenient to use for treatment of your breakthrough pain episodes?'. The answer was based on a 4-point numerical scale (0=Poor, 1=Fair, 2=Easy, 3=Very Easy). This assessment was performed at the end of the Treatment Period (or early termination).
• Participant's Global Impression of Change at the End of the Treatment Period [ Time Frame: approximately Day 15 (end of Treatment Period) ] [ Designated as safety issue: No ]
  Global impression of change was assessed using the question 'Since the start of the study, my overall status is?'. The answer was based on a 7-point scale (1=Very much improved, 2=Much improved, 3=Minimally improved, 4=No change, 5=Minimally worse, 6=Much worse, and 7=Very much worse). This assessment was performed at the end of the Treatment Period (or early termination).
• Participants With Adverse Events (AE) Summarized by Treatment Period [ Time Frame: Day 1-7 (Titration Period). Day 8-15 (Treatment Period), Days 16-688 (Continuation Period) ] [ Designated as safety issue: No ]
  Participants with treatment-emergent adverse events are summarized by each treatment period. Relation to study drug was assessed by the investigator. The 'Any AE' category below includes serious adverse events.

Breakthrough cancer pain (BTcP) is a common problem in patients with cancer. Fentanyl Buccal Tablet (FBT) is used for the treatment of BTP in adults with cancer who are already receiving maintenance opioid therapy for chronic cancer pain. FBT treatment should be individually titrated to an effective dose that provides adequate analgesia and minimizes undesirable effects. To reach the safest effective dose for the individual patient as soon as possible, the dose titration process is critical. The aim of this study, conducted under pragmatic conditions in a large-scale population of cancer patients is to compare the proportion of patients reaching an effective FBT dose after titration starting with either a 100 mcg dose or a 200 mcg dose.

• Cancer Pain
• Breakthrough Pain

• Experimental: FBT 100 mcg
  During the Titration Period, participants took fentanyl buccal tables (FBT) with a starting dose of 100 mcg until they reached an effective dose, with a maximum dose of 800 mcg and a maximum timeframe of 7 days. Participants who reached an effective dose entered the Open-label Treatment Period, whose length depended on how long was needed to treat up to 8 episodes of breakthrough pain (BTP) with FBT (maximum of 8 days). The length of the Continuation Period (when applicable) varied from country to country, up to until FBT was commercially available in that country.
  Intervention: Drug: Fentanyl Buccal Tablet (FBT)
• Active Comparator: FBT 200 mcg
  During the Titration Period, participants took fentanyl buccal tables (FBT) with a starting dose of 200 mcg until they reached an effective dose, with a maximum dose of 800 mcg and a maximum timeframe of 7 days. Participants who reached an effective dose entered the Open-label Treatment Period, whose length depended on how long was needed to treat up to 8 episodes of breakthrough pain (BTP) with FBT (maximum of 8 days). The length of the Continuation Period (when applicable) varied from country to country, up to until FBT was commercially available in that country.
  Intervention: Drug: Fentanyl Buccal Tablet (FBT)

Inclusion Criteria:

• The patient is willing to provide written informed consent to participate in this study.
• The patient can be either an out-patient or an in-patient.
• The patient has a histologically documented diagnosis of cancer.
• The patient has stable background pain due to cancer.
• The patient experiences up to 4 BTcP episodes per 24 hours.
• As maintenance opioid therapy, the patient is currently taking 1 of the following: at least 60 mg of oral morphine/day, at least 25 mcg of transdermal fentanyl/hour, at least 30 mg of oxycodone/day, at least 8 mg of hydromorphone/day, of an equianalgesic dose of another opioid for a week or longer before administration of the first dose of study drug.
• Women of childbearing potential, using a medically accepted, highly effective method of birth control and agree to continued use of this method for the duration of the study.
• The patient must be willing and able to successfully self-administer the study drug and to fill in study documents.

Exclusion Criteria:

• The patient is without maintenance opioid therapy.
• The patient has uncontrolled or rapidly escalating pain as determined by the investigator.
• The patient has known or suspected hypersensitivities, allergies, or other contraindications to the active drug or to any of the excipients of the study drug.
• The patient has respiratory depression or chronic obstructive pulmonary disease, or any other medical condition predisposing to respiratory depression.
• The patient has medical or psychiatric disease that, in the opinion of the investigator, would compromise collected data.
• The patient is expected to have surgery during the study.
• The patient is pregnant or lactating.
• The patient has participated in a study involving an investigational drug in the prior 30 days.
• The patient has received a monoamine oxidase inhibitor (MAOI) within 14 days before the first treatment with study drug.
• The patient has any other medical condition or is receiving concomitant medication/therapy (e.g., regional nerve block) that could, in the opinion of the investigator, compromise the patient's safety or compliance with the study protocol, or compromise collected data.