A Dose Titration Study of Fentanyl Buccal Soluble Film for Breakthrough Cancer Pain in Taiwan

Fentanyl Buccal Soluble Films Feasible Dose Range Study for Breakthrough Pain in Taiwanese Cancer Patients

Primary Objective:

To determine the feasible dose range of Painkyl® required for Taiwanese population.

Secondary Objectives:

To evaluate the efficacy of Painkyl® by calculating squared mean of pain intensity difference at 30 minutes after taking Painkyl® (SPID30, an 11-point scale).

To evaluate subjects' satisfaction by conducting global evaluation of medication performance (a 5-point categorical scale).

To identify percentage of episodes requiring rescue medication during maintenance treatment period.

To evaluate the safety data of Painkyl® for breakthrough pain.

Study Overview

• Status: Completed
• Conditions: Breakthrough Cancer Pain
• Intervention / Treatment: Drug: Fentanyl buccal soluble film (FBSF)

Detailed Description

The primary endpoint was the feasible range of FBSF required for Taiwanese population. The secondary endpoints were the difference in pain intensity at 30 minutes (PID30) after FBSF administration, subjects' satisfaction, and the percentage of episodes requiring rescue medications.

Pain intensity was determined using an 11-point numeric scale from 0="no pain" to 10="worst pain." Patients were assessed with baseline pain as well as pain intensity at 30 minutes after dosing. The PID30 was obtained by baseline pain score minus score rated 30 minutes after dosing.

Patient's satisfaction was assessed using a 5-point (poor, fair, good, very good, and excellent) categorical scale at 30 minutes after taking FBSF with the following question: "What was your overall satisfaction with the medication?" At each episode of BTP, subjects recorded whether a rescue medication was taken after administration of FBSF.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Taiwan
  • Keelung, Taiwan
    • Chang Gung Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• a. a stable current regimen of oral opioids equivalent to 60-1000 mg/day of oral morphine or 20-120 mg/day of iv morphine or 25-300 mcg/hr of transdermal fentanyl for one week or longer;
• b. regularly experienced 1 to 3 breakthrough pain episodes per day that required additional opioids from pain control;
• c. at least partial relief of breakthrough pain by use of opioid therapy;
• d. 20 years of age or older;
• e. ability to understand and willingness to sign a written informed consent document;
• f. able to self-administer the study medication correctly or has the availability of a responsible adult caregiver available to administer the study medication correctly;
• g. willing and able to complete patient diary with each pain episode

Exclusion Criteria:

• a. rapidly escalating pain (e.g., regularly more than 3 breakthrough pain episodes per day) that are hard to be controlled by analgesics;
• b. history of hypersensitivity or intolerance to fentanyl;
• c. cardiopulmonary disease that, in the opinion of the investigator, would significantly increase the risk of respiratory depression;
• d. psychiatric/cognitive or neurological impairment that would limit the subject's ability to understand or complete the diary;
• e. moderate (Grade 3) to severe (Grade 4) mucositis (subjects with less than moderate mucositis are permitted and must be instructed to not apply the Painkyl® film at a site of inflammation);
• f. abnormal oral mucosa which will impede drug absorption;
• g. currently under other treatments that may alter effect of pain control based on investigator's judgment;
• h. recent history or current evidence of alcohol or other drug substance (licit or illicit) abuse;
• i. use of an investigational drug within 4 weeks preceding this study;
• j. pregnant women or nursing mothers, or positive pregnancy test for women of childbearing potential;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Fentanyl buccal soluble film (FBSF); Single arm

Drug: Fentanyl buccal soluble film (FBSF); After screening, eligible subjects were individually titrated to an adequate dose of FBSF (titration period) and continued on this dose as required to control their BTP throughout the maintenance period of the study. During the dose titration period, subjects were administered with FBSF in a dose escalation manner until a treatment dose was identified (defined as an adequate relief of BTP observed for at least two consecutive episodes). All patient started with a dose of 200 μg and increased by 200 μg in each subsequent episode until an adequate pain relief with tolerable side effects was achieved. Doses above 1200 μg were not allowed.; Other Names: Painkyl, fentanyl buccal soluble film (FBSF)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Optimal dose calculation of Painkyl®	Time to "optimal" dose of an open-label study medication in the titration phase. During the dose titration period, subjects were administered with FBSF (Painkyl®) in a dose escalation manner until a treatment dose was identified (defined as an adequate relief of BTP observed for at least two consecutive episodes). All patient started with a dose of 200 μg and increased by 200 μg in each subsequent episode until an adequate pain relief with tolerable side effects was achieved.	Within 2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy Phase : Pain intensity difference at 30 minutes (PID30) after treatment	During the efficacy phase participants assessed their pain intensity at each breakthrough pain (BTP) episode at 0 and 30 minutes after taking dose using the 11-point Numerical Rating Scale (NRS) on a scale from 0 to 10, where 0 represents the absence of pain and 10 is "worst possible pain". PID30 is calculated as the difference in pain intensity from time 0 to 30 minutes. A positive value is a decrease (improvement) of the pain; a ≥ 3-point difference is considered as clinically important.	During the efficacy phase, at each episode of breakthrough pain, 30 minutes after taking dose of study drug, at 0 and 10 minutes after taking dose of study drug
Efficacy Phase : Subjects' satisfaction score at 30 minutes after treatment	Participants assessed their subjects' satisfaction of treatment efficacy for treated BTP episodes at 30 minutes after taking dose of study drug. The validated, categorical 5-point Verbal Rating Scale (VRS) was used for this assessment and scored as follows: poor; fair; good; very good; excellent.	During the efficacy phase, at each episode of breakthrough pain, 30 minutes after taking dose of study drug
The percentage of episodes requiring rescue medications.	• Percentage of episodes requiring rescue medications: subjects will record whether rescue medication was taken after study medication administration for each episode of BTP, by answering "yes" or "no."	Within 2 weeks
Incidence of adverse events (AEs), serious adverse events (SAEs) [Safety and Tolerability]	Assessed by the NCI-CTCAE (Common Toxicity Criteria for Adverse Effects) v4.0 and within some subgroups of patients	From the date of study entry until 30 days after the last dose of study treatment

Collaborators and Investigators

• Sponsor: Chang Gung Memorial Hospital
• Collaborators: TTY Biopharm
• Investigators: Study Chair: Cheng-Hsu Wang, Chang Gung Memorial Hospital, Linkou, Taiwan

Publications and helpful links

General Publications

• Greco MT, Corli O, Montanari M, Deandrea S, Zagonel V, Apolone G; Writing Protocol Committee; Cancer Pain Outcome Research Study Group (CPOR SG) Investigators. Epidemiology and pattern of care of breakthrough cancer pain in a longitudinal sample of cancer patients: results from the Cancer Pain Outcome Research Study Group. Clin J Pain. 2011 Jan;27(1):9-18. doi: 10.1097/AJP.0b013e3181edc250.
• Rhiner MI, von Gunten CF. Cancer breakthrough pain in the presence of cancer-related chronic pain: fact versus perceptions of health-care providers and patients. J Support Oncol. 2010 Nov-Dec;8(6):232-8. doi: 10.1016/j.suponc.2010.10.006.
• Mercadante S. The use of rapid onset opioids for breakthrough cancer pain: the challenge of its dosing. Crit Rev Oncol Hematol. 2011 Dec;80(3):460-5. doi: 10.1016/j.critrevonc.2010.12.002. Epub 2011 Jan 6.
• Rauck R, North J, Gever LN, Tagarro I, Finn AL. Fentanyl buccal soluble film (FBSF) for breakthrough pain in patients with cancer: a randomized, double-blind, placebo-controlled study. Ann Oncol. 2010 Jun;21(6):1308-1314. doi: 10.1093/annonc/mdp541. Epub 2009 Nov 25.
• Chiou TJ, Chao TC, Chao TY, Huang JS, Chang YF, Wang CH. A dose titration study of fentanyl buccal soluble film for breakthrough cancer pain in Taiwan. Cancer Rep (Hoboken). 2019 Oct;2(5):e1179. doi: 10.1002/cnr2.1179. Epub 2019 Apr 23.

Study record dates

Study Major Dates

• Study Start (Actual): November 25, 2014
• Primary Completion (Actual): June 23, 2016
• Study Completion (Actual): July 1, 2016

Study Registration Dates

• First Submitted: August 17, 2018
• First Submitted That Met QC Criteria: September 11, 2018
• First Posted (Actual): September 13, 2018

Study Record Updates

• Last Update Posted (Actual): September 13, 2018
• Last Update Submitted That Met QC Criteria: September 11, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: Painkyl®; fentanyl buccal soluble film; dose titration
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Cancer Pain; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Analgesics, Opioid; Narcotics; Adjuvants, Anesthesia; Fentanyl
• Other Study ID Numbers: PK1302

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No