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
Overview
- Phase
- Phase 3
- Intervention
- Fentanyl sublingual spray
- Conditions
- Cancer
- Sponsor
- INSYS Therapeutics Inc
- Enrollment
- 130
- Locations
- 1
- Primary Endpoint
- Summed Pain Intensity Differences (SPID) at 30 Minutes After Dosing (SPID30)
- Status
- Completed
- Last Updated
- 12 years ago
Overview
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.
Investigators
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.
Arms & Interventions
Fentanyl sublingual spray
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.
Intervention: Fentanyl sublingual spray
Fentanyl sublingual spray
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.
Intervention: Placebo
Outcomes
Primary Outcomes
Summed Pain Intensity Differences (SPID) at 30 Minutes After Dosing (SPID30)
Time Frame: Baseline (time 0, beginning of each pain episode) through 30 minutes after dosing for each pain episode
Pain intensity was assessed by the participant using a 0-100 mm visual analog scale where 0 represented "no pain" and 100 represented "worst possible pain" at 0 (baseline, beginning of the pain episode), 5, 10, 15, and 30 minutes after each dose of study medication during each breakthrough pain episode. The pain intensity difference was defined as the difference in pain intensity at the various time points versus time 0 (baseline). SPID30 was calculated as the time-weighted sum of the PID scores using the following formula: SPID30=(5\*PID5)+(5\*PID10)+(5\*PID15)+(15\*PID30). The minimum and maximum SPID30 scores were -3000 and 3000. A higher score indicates less pain.
Secondary Outcomes
- 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)