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

NCT00842829 | Terminated Phase 4 Results

• 2 other identifiers: C25608/4027/BP/EU2008-001841-24
• Study Type: interventional
• Target: 330
• Locations: 7 countries
• Sites: 123

Brief Summary

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.

Conditions

Cancer Pain; Breakthrough Pain

Keywords

Breakthrough Cancer Pain

Outcome Measures

Primary Outcomes (1)

• 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.

  Day 1 up to Day 7

Secondary Outcomes (23)

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

  approximately Day 8-15

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

  Day 1 up to Day 7

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

  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

  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

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

Study Arms (2)

FBT 100 mcg

EXPERIMENTAL

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.

Drug: Fentanyl Buccal Tablet (FBT)

FBT 200 mcg

ACTIVE COMPARATOR

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.

Drug: Fentanyl Buccal Tablet (FBT)

Interventions

Fentanyl Buccal Tablet (FBT) DRUG

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.

Also known as: Fentora, CEP-25608, Fentanyl citrate, Effentora

FBT 100 mcg; FBT 200 mcg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Cephalon: lead

Study Sites (123)

Investigational Site

Bayonne, 64100, France

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Bordeaux, 33075, France

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Caen, 14033, France

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Clichy, 92110, France

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Grenoble, 38043, France

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Le Chesnay, 78157, France

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Le Kremlin-Bicêtre, 94275, France

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Le Mans, 72018, France

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Lorient, 58107, France

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Montpellier, 34298, France

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Nevers, 58033, France

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Orléans, 45032, France

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Paris, 75010, France

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Paris, 75013, France

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Paris, 75730, France

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Pierre-Bénite, 69495, France

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Poitiers, 86021, France

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Rouen, 76031, France

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Saint-Herblain, 44805, France

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Tarbes, 65000, France

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Toulouse, 31059, France

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Villejuif, 94800, France

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Bad Honnef, 53604, Germany

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Bad Lippspringe, 33175, Germany

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Berlin, 10435, Germany

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Berlin, 13353, Germany

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Berlin, 13585, Germany

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Berlin, 14089, Germany

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Bonn, 53111, Germany

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Böhlen, 04564, Germany

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Dresden, 01307, Germany

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Duisburg, 47055, Germany

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Duisburg, 47166, Germany

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Erfurt, 99084, Germany

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Freiburg im Breisgau, 79108, Germany

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Geesthacht, 21502, Germany

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Greifenstein, 35753, Germany

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Hanover, 30625, Germany

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Herne, 44623, Germany

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Hildesheim, 31135, Germany

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Jena, 07747, Germany

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Kassel, 34117, Germany

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Leipzig, 04107, Germany

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Lohsa, 02999, Germany

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Lünen, 44534, Germany

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Mainz, 55131, Germany

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Munich, 80637, Germany

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Munich, 81377, Germany

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Mülhausen, 99974, Germany

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Neustadt, 01844, Germany

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Rostock, 18059, Germany

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Weiden, 92637, Germany

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Würselen, 52146, Germany

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Dublin, Ireland

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Aviano, 33081, Italy

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Bari, 70120, Italy

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Brescia, 25123, Italy

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Cagliari, 9121, Italy

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Candiolo, 10060, Italy

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Caserta, 81100, Italy

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Cosenza, 87100, Italy

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Florence, 50100, Italy

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Garbagnate Milanese, 20024, Italy

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Genova, 16128, Italy

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Lugo, 48022, Italy

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L’Aquila, 67100, Italy

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Milan, 20142, Italy

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Modena, 41100, Italy

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Napoli, 80131, Italy

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Palermo, 90146, Italy

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Piacenza, 29100, Italy

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Pisa, 56100, Italy

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Roma, 133, Italy

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Roma, 144, Italy

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Roma, 161, Italy

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Torino, 10126, Italy

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Torino, 10153, Italy

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Verona, 37024, Italy

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Bielsko-Biala, 43300, Poland

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Bydgoszcz, 85796, Poland

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Elblag, 82300, Poland

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Gdansk, 80208, Poland

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Gdansk, 80952, Poland

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Gliwice, 44101, Poland

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Lodz, 90251, Poland

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Poznan, 60245, Poland

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Poznan, 61866, Poland

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Puszczykowo, 62041, Poland

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Szczecin, 71730, Poland

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Szczecin, 71740, Poland

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Tychy, 43100, Poland

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Warsaw, 02781, Poland

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Wroclaw, 53413, Poland

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Włocławek, 87800, Poland

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A Coruña, 15006, Spain

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A Coruña, 15009, Spain

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Barcelona, 08025, Spain

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Barcelona, 08907, Spain

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Bilbao, 48013, Spain

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Cadiz, 11009, Spain

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Córdoba, 14002, Spain

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Granada, 18012, Spain

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Lleida, 28195, Spain

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Madrid, 28006, Spain

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Madrid, 28035, Spain

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Madrid, 28046, Spain

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Palma de Mallorca, 07012, Spain

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Pamplona, 31008, Spain

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Salamanca, 37007, Spain

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San Cristóbal de La Laguna, 38320, Spain

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Santander, 39008, Spain

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Santiago de Compostela, 15706, Spain

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Seville, 41009, Spain

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Seville, 41013, Spain

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Valencia, 46014, Spain

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Valencia, 46015, Spain

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Bath, BA15 2LG, United Kingdom

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Dumfries, DG1 4AP, United Kingdom

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London, SW3 6JJ, United Kingdom

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Nottingham, NG5 1PB, United Kingdom

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Plymouth, PL68DH, United Kingdom

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Surrey, KT10 8NA, United Kingdom

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Sutton, SM2 5PT, United Kingdom

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MeSH Terms

Conditions

Cancer Pain; Breakthrough Pain

Interventions

Fentanyl

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Director, Clinical Research
• Organization: Teva Branded Pharmaceutical Products, R&D Inc.

ustevatrials@tevapharm.com

215-591-3000

Study Officials

• Sponsor's Medical Expert

  Cephalon Europe

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 29, 2009
• First Posted: February 12, 2009
• Study Start: January 1, 2009
• Primary Completion: May 1, 2011
• Study Completion: May 1, 2011
• Last Updated: October 1, 2012
• Results First Posted: September 20, 2012

Record last verified: 2012-09

Locations

DE (31); FR (22); GB (7); IT (24); IE (1); PL (16); ES (22)