Fentanyl Sublingual Spray for the Treatment of Moderate to Severe Post-Operative Pain

A Phase 2 Multicenter, Randomized, Double-Blind, Multiple-Dose, Parallel-Group, Placebo-Controlled Study of Fentanyl Sublingual Spray for the Treatment of Moderate to Severe Post-Operative Pain

The primary objective of this trial is to evaluate analgesic efficacy of Fentanyl Sublingual Spray compared with placebo in participants with postoperative pain after a bunionectomy.

Study Overview

• Status: Completed
• Conditions: Pain
• Intervention / Treatment: Drug: Fentanyl; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85023
      • Arizona Research Center
  • California
    • Anaheim, California, United States, 92801
      • Anaheim Clinical Trials

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Meets protocol-specified criteria for qualification and contraception
• Willing and able to remain confined in the study unit for the entire duration of each treatment period and comply with restrictions related to food, drink and medications
• Voluntarily consents to participate and provides written informed consent prior to any protocol-specific procedures

Exclusion Criteria:

• History or current use of over-the-counter medications, dietary supplements, or drugs (including nicotine and alcohol) outside protocol-specified parameters

• Signs, symptoms or history of any condition that, per protocol or in the opinion of the investigator, might compromise:

  1. the safety or well-being of the participant or study staff;
  2. the safety or well-being of the participant's offspring (such as through pregnancy or breast-feeding);
  3. the analysis of results

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lower Dose Fentanyl; Lower dose Fentanyl delivered via sublingual spray every 4 hours.	Drug: Fentanyl; Fentanyl delivered via sublingual spray
Experimental: Higher Dose Fentanyl Sublingual Spray; Higher dose Fentanyl delivered via sublingual spray every 4 hours.	Drug: Fentanyl; Fentanyl delivered via sublingual spray
Placebo Comparator: Placebo; Placebo (matching Fentanyl) delivered via sublingual spray every 4 hours.	Drug: Placebo; Matching placebo delivered via sublingual spray

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Numeric Rating Scale (NRS) Summed Pain Intensity Difference (SPID) Over 0 to 48 Hours (NRS SPID-48) After Time 0	Pain intensity was assessed by the participant using an 11-point NRS from 0=no pain to 10=worst possible pain. Pain intensity scores were collected at Baseline (prior to study drug) and at multiple time points up to 48 hours after Time 0 (administration of first dose of study drug). Pain intensity difference is calculated by subtracting the pain intensity at each time point from the pain intensity at Time 0. The SPID scores are the sum of the differences at each time point multiplied by the duration in hours since the previous time point. Positive numbers indicate a reduction in pain [maximum(max)=10 at each time point], and negative numbers indicate an increase in pain [minimum(min)=-10 at each time point]. The overall min and max are -10 and 10 times the number of hours specified; SPID-48 range is -480 to 480. The NRS SPID-48 was analyzed using an analysis of covariance (ANCOVA) model, which included treatment and site as main effects and Baseline pain intensity as the covariate.	Over 0 to 48 hours after Time 0

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
NRS Pain Intensity Difference (NRS PID) at Each Categorical Time Point After Time 0	Pain intensity was assessed by the participant using an 11-point NRS from 0=no pain to 10=worst possible pain. Pain intensity scores were collected at Baseline (prior to study drug administration) and at multiple time points after Time 0 (time of administration of the first dose of study drug). NRS PID is defined as the difference in pain at each scheduled time point relative to Baseline (PID=pain intensity at baseline - pain intensity at time point). A higher value of NRS PID score indicates a higher decrease in pain from Baseline. NRS PID is reported as the least squares mean difference.	Baseline, 1, 16, and 24 hours
NRS Pain Intensity Score at Each Scheduled Time Point After Time 0	Pain intensity was assessed by the participant using an 11-point NRS from 0=no pain to 10=worst possible pain. Pain intensity scores were collected at Baseline (prior to study drug administration) and at multiple time points after Time 0 (time of administration of the first dose of study drug). A lower value indicates improvement in pain.	Baseline, 1, 16, and 24 hours
NRS SPID After Time 0	Pain intensity was assessed by the participant using an 11-point NRS from 0=no pain to 10=worst possible pain. Pain intensity scores were collected at Baseline (prior to study drug) and at multiple time points after Time 0 (administration of first dose of study drug). Pain intensity difference is calculated by subtracting the pain intensity at each time point from the pain intensity at Time 0. The SPID scores are the sum of the differences at each time point multiplied by the duration in hours since the previous time point. Positive numbers indicate a reduction in pain [maximum(max)=10 at each timepoint], and negative numbers indicate an increase in pain [minimum(min)=-10 at each timepoint]. The overall min and max are -10 and 10 times the number of hours specified: SPID-4=(-40 to 40), SPID-8=(-80 to 80) and SPID-24=(-240 to 240). The NRS SPID-4, 8 and 24 were analyzed using an ANCOVA model which included treatment and site as main effects and Baseline pain intensity as the covariate.	Over 0 to 4 hours (NRS SPID-4), over 0 to 8 hours (NRS SPID-8), and over 0 to 24 hours (NRS SPID-24)
Total Pain Relief (TOTPAR) After Time 0	TOTPAR was assessed by the participant using a 5-point NRS (0=no relief, 1=a little, 2=some, 3=a lot, 4=complete relief). TOTPAR scores were collected at Baseline (prior to study drug) and at multiple time points up to 48 hours after Time 0 (first dose of study drug). The TOTPAR scores are the sum of the pain relief at each time point multiplied by the duration in hours since the previous time point. Larger positive numbers indicate more pain relief (maximum=4 at each time point) and smaller positive numbers indicate less pain relief (minimum=0 at each time point). The overall minimum is 0 for each variable and the overall maximum is 4 times the number of hours specified for the variable: TOTPAR-4=(0 to 16), TOTPAR-8=(0 to 32), TOTPAR-24=(0 to 96) and TOTPAR-48=(0 to 192). TOTPAR-4, TOTPAR-8, TOTPAR-24 and TOTPAR-48 were analyzed using an ANCOVA model with factors for treatment, site and baseline pain intensity.	Over 0 to 4 hours (TOTPAR-4), over 0 to 8 hours (TOTPAR-8), over 0 to 24 hours (TOTPAR-24), and over 0 to 48 hours (TOTPAR-48)
Time to Onset of Analgesia	Measured as time to perceptible pain relief confirmed by meaningful pain relief using the 2-stopwatch method (2 stopwatches will be started as soon as the first dose of study drug is administered. Each participant will be instructed to stop the first stopwatch when he or she experiences any perceptible pain relief and the second stopwatch when he or she experiences pain relief that is meaningful to them.)	Within 48 hours
Pain Relief at Each Scheduled Time Point After Time 0 (First Dose of Study Medication)	Pain relief is determined on a 5-point categorical scale where 0=none, 1=a little, 2=some, 3=a lot, 4=complete.	2.5, 5, 15, 30, and 45 minutes, and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 32, 40, and 48 hours, as well as immediately before each use of rescue analgesia
Peak Pain Relief From Time 0 (First Dose of Study Medication)	The highest level of pain relief achieved on a 5-point categorical scale where 0=none, 1=a little, 2=some, 3=a lot, 4=complete.	Within 48 hours after Time 0
Time (Minutes) to Peak Pain Relief From Time 0 (First Dose of Study Medication)		Within 48 hours after Time 0
Time (Minutes) to First Perceptible Pain Relief From Time 0 (First Dose of Study Medication)	Time to perceptible and meaningful pain relief will be evaluated using the 2-stopwatch method (after the first dose only) (2 stopwatches will be started as soon as the first dose of study drug is administered. Each participant will be instructed to stop the first stopwatch when he or she experiences any perceptible pain relief and the second stopwatch when he or she experiences pain relief that is meaningful to them.)	Within 48 hours after Time 0
Time (Minutes) to Meaningful Pain Relief From Time 0 (First Dose of Study Medication)	Time to perceptible and meaningful pain relief will be evaluated using the 2-stopwatch method (after the first dose only) (2 stopwatches will be started as soon as the first dose of study drug is administered. Each participant will be instructed to stop the first stopwatch when he or she experiences any perceptible pain relief and the second stopwatch when he or she experiences pain relief that is meaningful to them.)	Within 48 hours after Time 0
Number of Participants Using Rescue Medication		Within 48 hours
Time (Minutes) to First Use of Rescue Medication (Duration of Analgesia) Following Each Dose of the Investigational Product (IP)		Within 48 hours
Number of Participants Using Rescue Analgesia Over 0 to 24 Hours and Over 0 to 48 Hours		Over 0 to 24 hours; Over 0 to 48 hours
Participant Global Evaluation of Study Drug	Participants provide a global evaluation of study drug on a 5-point categorical scale where 0=poor, 1=fair, 2=good, 3=very good, and 4=excellent.	Within 48 hours

Collaborators and Investigators

• Sponsor: INSYS Therapeutics Inc

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2016
• Primary Completion (Actual): February 10, 2017
• Study Completion (Actual): February 10, 2017

Study Registration Dates

• First Submitted: September 23, 2016
• First Submitted That Met QC Criteria: September 26, 2016
• First Posted (Estimate): September 27, 2016

Study Record Updates

• Last Update Posted (Actual): February 14, 2018
• Last Update Submitted That Met QC Criteria: January 19, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; 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: INS002-16-092