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

Phase 4TerminatedNCT00842829

Cephalon330 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Masking

NONE

Enrollment

330

Conditions

Cancer Pain Breakthrough Pain

Interventions

FBTs were self-administered by participants via the oral mucosa. During the open-label dose titration period, participants used 1 to 4 tablets of the 100 mcg or 200 mcg strength to individually titrate upwards to an effective dose through the range of available strengths (i.e. 100, 200, 400, 600, or 800 mcg). For the open-label treatment and continuation periods, single dose tablets at the effective dose identified during the titration period were used. The maximum dose allowed per breakthrough pain (BTP) episode was 800 mcg. On any single day, participants were not to use FBT for more than 4 BTP episodes.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (123)

Investigational Site

Bayonne, France

Investigational Site

Bordeaux, France

Investigational Site

Caen, France

Investigational Site

Clichy, France

Investigational Site

Grenoble, France

Investigational Site

Le Chesnay, France

Outcomes

Primary Outcomes

Percentage of Participants Reaching an Effective Fentanyl Buccal Tablet (FBT) Dose As Assessed by the Participant During the Titration Period

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.

Time frame: Day 1 up to Day 7

Secondary Outcomes

Kaplan-Meier Estimates for Time to Meaningful Pain Relief As Assessed by Participants During the Treatment Period For Overall Breakthrough Pain (BTP) Episodes

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.

Time frame: approximately Day 8-15

Number of Participants Reaching An Effective Dose As Assessed by the Participant During the Titration Period

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.

Time frame: Day 1 up to Day 7

Breakthrough Pain (BTP) Episodes Requiring the Use of Rescue Medication During the Titration Period and the Treatment Period

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.

Time frame: Days 1 to up to Day 7 (Titration Period); approximately Day 8 up to Day 15 (Treatment Period)

Participant Assessment of Medication Performance During the Treatment Period

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).

Time frame: approximately Day 8-15

Change From Baseline to End of Treatment Period (Approximately Day 15) in the Brief Pain Inventory 7-item (BPI-7S) Questionnaire Subscale: General Activity

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.

Time frame: Day 0 (baseline), approximately Day 15 (end of Treatment Period)

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)

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)

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)

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)

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)

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)

Change From Baseline to End of Treatment Period (Approximately Day 15) in the Brief Pain Inventory 7-item (BPI-7S) Questionnaire: Global Score

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.

Time frame: Day 0 (baseline), approximately Day 15 (end of Treatment Period)

Participant's Global Assessment of Satisfaction (Satisfied With BTP Treatment?) at the End of the Treatment Period

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.