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

Breakthrough Cancer Pain Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03669263
• Other study ID #: PK1302
• Status: Completed
• Phase: N/A
• Start date: November 25, 2014
• Est. completion date: July 1, 2016

Study information

• Verified date: August 2018
• Source: Chang Gung Memorial Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: July 1, 2016
• Est. primary completion date: June 23, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

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;

Related Conditions & MeSH terms

• Breakthrough Cancer Pain
• Breakthrough Pain
• Cancer Pain

Intervention

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.

Locations

Country	Name	City	State
Taiwan	Chang Gung Memorial Hospital	Keelung

Sponsors (2)

Lead Sponsor	Collaborator
Chang Gung Memorial Hospital	TTY Biopharm

Country where clinical trial is conducted

Taiwan, 

References & Publications (4)

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. — View Citation

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. Review. — View Citation

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):1308-14. doi: 10.1093/annonc/mdp541. Epub 2009 Nov 25. — View Citation

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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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