Fentanyl Sublingual Spray in Treating Patients With Breakthrough Cancer Pain

A Randomized, Double-blind, Placebo-controlled Multi-center Study to Evaluate the Safety and Efficacy of Fentanyl Sublingual Spray (Fentanyl SL Spray) for the Treatment of Breakthrough Cancer Pain

Sponsors

Lead Sponsor: INSYS Therapeutics Inc

Collaborator: National Cancer Institute (NCI)

Source INSYS Therapeutics Inc
Brief Summary

This is a phase III, randomized, double-blind, placebo-controlled, multicenter study of the clinical response to fentanyl sublingual spray as a treatment for breakthrough cancer pain. The study medication is administered under the tongue as a simple spray and can be self-administered by patients or assisted by their caregivers. Patients are titrated to an effective-dose of fentanyl sublingual spray in the open-label titration period and then proceed to the double-blind randomized period where they randomly receive 7 treatments with fentanyl sublingual spray and 3 treatments with placebo. Patients are treated for up to a total of 6-7 weeks (including both the open-label titration and the double-blind randomized periods).

Detailed Description

RATIONALE Fentanyl sublingual spray may help relieve breakthrough pain in patients receiving opioids for cancer pain. OBJECTIVES Primary - Determine the efficacy and safety of fentanyl sublingual spray for the treatment of breakthrough cancer pain in patients on around-the-clock opioids for their persistent cancer pain. Secondary - Evaluate the safety of fentanyl sublingual spray in these opioid-tolerant patients. - Assess the patient's satisfaction with treatment medication.

Overall Status Completed
Start Date October 2007
Completion Date October 2010
Primary Completion Date February 2010
Phase Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
Summed Pain Intensity Differences (SPID) at 30 Minutes After Dosing (SPID30) Baseline (time 0, beginning of each pain episode) through 30 minutes after dosing for each pain episode
Secondary Outcome
Measure Time Frame
Summed Pain Intensity Differences (SPID) at 5, 10, 15, 45, and 60 Minutes After Dosing Baseline (time 0, beginning of each pain episode) through 60 minutes after dosing for each pain episode
Total Pain Relief (TOTPAR) at 5, 10, 15, 30, 45, and 60 Minutes After Dosing 5 through 60 minutes after dosing for each pain episode
Global Evaluation of the Study Medication at 30 and 60 Minutes After Dosing 30 through 60 minutes after dosing for each pain episode
Enrollment 130
Condition
Intervention

Intervention Type: Drug

Intervention Name: Fentanyl sublingual spray

Description: In the open-label titration period of the study, participants started at a dose of 100, 200, or 400 µg and titrated upward to a maximum dose of 1600 µg. Titration was stopped when the dose administered provided adequate analgesia for breakthrough pain without unacceptable side effects or the maximum titration period of 21±5 days was reached. In the double-blind period of the study, participants received fentanyl sublingual spray in doses of 100, 200, 400, 600, 800, 1200, or 1600 µg determined in the open-label titration period of the study.

Arm Group Label: Fentanyl sublingual spray

Other Name: SUBSYS

Intervention Type: Drug

Intervention Name: Placebo

Description: Matching placebo to fentanyl sublingual spray.

Arm Group Label: Fentanyl sublingual spray

Eligibility

Criteria:

Inclusion Criteria: - Male or female, ≥ 18 years of age. - Diagnosis of cancer. - Opioid-tolerant. Subjects who were opioid tolerant were those taking ≥ 60 mg of oral morphine/day, at least 25 μg of transdermal fentanyl/hour, at least 30 mg of oxycodone daily, at least 8 mg of oral hydromorphone daily or an equianalgesic dose of another opioid for a week or longer for cancer-related pain. - Experienced persistent pain related to the cancer or its treatment of moderate or lesser intensity in the 24 hours prior to assessment by a verbal rating scale at the Screening Visit. - Over the previous 7 days, subject experienced, on average, 1 to 4 breakthrough cancer pain episodes per day usually at least partially controlled by supplemental medication of at least 5 mg immediate-release morphine or an equivalent short-acting opioid (eg, oxycodone, hydrocodone, or codeine with acetaminophen). - Able to evaluate and record pain relief, assess medication performance at set times after dosing, record AEs, record each use of the study drug or supplemental medication in an electronic diary (a caregiver may have provided the subject the medication, help with the mechanics of handling the electronic diary but was not permitted to record any information in the electronic diary). - Able and willing to give informed consent. - Women of childbearing potential were to have a) a negative serum pregnancy test, b) not be breastfeeding and c) agree to practice a reliable form of contraception. Exclusion Criteria: - Intolerance to opioids or fentanyl. - Current use of commercially available oral short-acting fentanyl for breakthrough pain. Subjects previously on Actiq or Fentora were permitted to be enrolled if they had a 7 day washout. - Rapidly increasing/uncontrolled pain. - A history of major organ system impairment or disease, that in the Investigator's or his/her designee's opinion could increase the risk associated with the use of opioids. - Uncontrolled hypertension (systolic blood pressure {SBP} > 180 mmHg or diastolic blood pressure [DBP] > 90 mmHg on 2 occasions ≥ 6 hours apart) despite antihypertensive therapy, or a history of hypertensive crisis within the past 2 years. - A recent history (≤ 2 years prior) of transient ischemic attacks, neural vascular disease, stroke, or cerebral aneurysms. - Clinically uncontrolled sleep apnea. - Brain metastases with signs or symptoms of increased intracranial pressure. - Inability to assess pain or response to pain medications for any reason, including psychiatric disorder, concurrent medical disorder, or concomitant therapy. - Received investigational study product(s) ≤ 30 days prior to the Screening Visit. - Painful erythema, oedema or ulcers under the tongue. - Use of monoamine oxidase (MAO) inhibitors within 14 days of the Screening Visit.

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Larry Dillaha, MD Study Chair INSYS Therapeutics Inc
Location
Facility: InSys Therapeutics, Incorporated
Location Countries

United States

Verification Date

January 2014

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 1
Arm Group

Label: Fentanyl sublingual spray

Type: Experimental

Description: Participants received fentanyl sublingual spray 7 times or placebo 3 times in random order to treat up to a maximum of 2 breakthrough pain episodes per day with a minimum separation of 2 hours between treatments. Patients received a dose of 100 to 1600 µg determined in the open-label dose titration period of the current study.

Study Design Info

Intervention Model: Crossover Assignment

Primary Purpose: Treatment

Masking: Triple (Participant, Investigator, Outcomes Assessor)

Source: ClinicalTrials.gov

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