Study to Evaluate the Overall Performance of the Zalviso System™ (Sufentanil Sublingual Tablet System) 15 mcg

A Multicenter, Open-Label Trial to Evaluate the Overall Performance of the Zalviso System™ (Sufentanil Sublingual Tablet System) 15 mcg

Study to evaluate the overall performance of the Zalviso System™ (sufentanil sublingual tablet system) 15 mcg

Study Overview

• Status: Completed
• Conditions: Moderate-to-severe Acute Pain
• Intervention / Treatment: Drug: Zalviso™ 15 mcg

Detailed Description

320 adult postoperative in-patients, who met all study entry requirements, and were expected to require opioid analgesia for at least 24 hours, and up to 72 hours, after surgery were enrolled. Patients used the Zalviso™ (sufentanil sublingual tablet system) 15 mcg to self-administer a tablet of study drug as needed for pain. The System was evaluated for usability and functionality for up to 72 hours.

• Study Type: Interventional
• Enrollment (Actual): 320
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Florence, Alabama, United States, 35630
      • Eliza Coffee Memorial Hospital
    • Sheffield, Alabama, United States, 35660
      • Shoals Medical Trials
  • Arizona
    • Phoenix, Arizona, United States, 85023
      • Arizona Research Center
  • Florida
    • Sarasota, Florida, United States, 34232
      • Gulfcoast Research Associates
    • Vero Beach, Florida, United States, 32960
      • Orthopedic Center of Vero Beach
    • Vero Beach, Florida, United States, 32960
      • G&G Research
    • Wellington, Florida, United States, 33414
      • Visions Clinical Research
  • Georgia
    • Decatur, Georgia, United States, 30333
      • Southeastern Center for Clinical Trials
  • Texas
    • Houston, Texas, United States, 77027
      • Westside Surgical Hospital
    • Houston, Texas, United States, 77089
      • Hermann Drive Surgical Hospital
  • Utah
    • Salt Lake City, Utah, United States, 84124
      • Jean Brown Research

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Male or female patients who were 18 years of age or older.
2. Patients who were scheduled to undergo surgery under general or spinal anesthesia that does not include intrathecal opioids during the operation.
3. Patients classified as American Society of Anesthesiologists (ASA) class I - III (Appendix I).
4. Female patients of childbearing potential must have been using an effective method of birth control at the time of screening visit and for 30 days following the end of the study period. Acceptable methods of birth control included oral or transdermal contraceptives, condom, spermicidal foam, intrauterine device (IUD), progestin implant or injection, abstinence, vaginal ring, or sterilization of partner. The reason for non-child bearing potential, such as bilateral tubal ligation, bilateral oophorectomy, hysterectomy, or postmenopausal for > 1 year, was specified. Patients using hormonal forms of contraception were also willing to use a barrier method of contraception from screening through 30 days following the study period.
5. Post-surgical patients who had been admitted to the PACU, and were expected to have acute pain requiring opioids for 24 - 72 hours after surgery.

Exclusion Criteria:

1. Patients who had taken an opioid for more than 30 consecutive days, at a daily dose of 15 mg or more of morphine (or equivalent), within the past 3 months prior to surgery (e.g. more than 3 doses per day of Vicodin®, Norco®, Lortab® with 5 mg hydrocodone per tablet).
2. Patients who were currently taking monoamine oxidase inhibitors (MAOIs) or had taken MAOIs within 14 days of the first dose of study drug.
3. Patients with current sleep apnea that had been documented by a sleep laboratory study or were on home continuous positive airway pressure (CPAP).
4. Patients with an allergy or hypersensitivity to opioids.
5. Patients who were currently taking monoamine oxidase inhibitors (MAOIs) or had taken MAOIs within 14 days of the first dose of study drug.
6. Patients with current sleep apnea that had been documented by a sleep laboratory study or were on home continuous positive airway pressure (CPAP).
7. Patients who were receiving oxygen therapy at the time of screening.

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: Zalviso™ 15 mcg; Zalviso™(sufentanil sublingual tablet system) 15 mcg	Drug: Zalviso™ 15 mcg; Zalviso™ (sufentanil sublingual tablet system) 15 mcg. Tablets to be self-administered by the patient as needed for pain, no more than every 20 minutes, for 24 hours and up to 72 hours; Other Names: Zalviso™ (sufentanil sublingual tablet system) 15 mcg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Patients Who Experienced at Least One System-generated Error Based on the Controller Data While Using the Zalviso System		Up to 72 hours
Percentage of Patients, if Any, With Tablets Dispensed But Not Requested		Up to 72 hours
Percentage of Patients, if Any, With Tablet Dispensed When the Zalviso System Was in Lockout		Up to 72 hours
Percentage of Patients With Misplaced Tablet(s)		Up to 72 hours
Number of Misplaced Tablets (i.e., Tablet Found Outside the Patient's Mouth)		Up to 24 hours
Percentage of Patients Who Experienced Either a System-generated Error or a Misplaced Tablet (i.e., a Dispense Failure)		Up to 72 hours
Number of Zalviso System Notifications to the Nurse to Retrain Patient to Not Pull Down on the Controller While Dosing		Up to 72 hours
Percentage of Patients Who Experienced Either a System-generated Error or a Misplaced Tablet That Caused an Analgesic Gap		Up to 72 hours
Percentage of Patients Who Rate the Patient Global Assessment (PGA) of Method of Pain Control Over 24 Hours as "Good" or "Excellent"		Up to 24 hours
Percentage of Patients Who Rate the Patient Global Assessment (PGA) of Method of Pain Control Over 48 Hours as "Good" or "Excellent"		Up to 48 hours
Percentage of Patients Who Rate the Patient Global Assessment (PGA) of Method of Pain Control Over 72 Hours as "Good" or "Excellent"		Up to 72 hours
Percentage of Patients Who Responded to the Patient Global Assessment (PGA) as "Poor" at 24 Hours		Up to 24 hours
Percentage of Patients Who Responded to the Patient Global Assessment (PGA) as "Fair" at 24 Hours		Up to 24 hours
Percentage of Patients Who Responded to the Patient Global Assessment (PGA) as "Good" at 24 Hours		Up to 24 hours
Percentage of Patients Who Responded to the Patient Global Assessment (PGA) as "Excellent" at 24 Hours		Up to 24 hours
Percentage of Patients Who Responded to the Patient Global Assessment (PGA) at 48 Hours as "Poor"		Up to 48 hours
Percentage of Patients Who Responded to the Patient Global Assessment (PGA) at 48 Hours as "Fair"		Up to 48 hours
Percentage of Patients Who Responded to the Patient Global Assessment (PGA) at 48 Hours as "Good"		Up to 48 hours
Percentage of Patients Who Responded to the Patient Global Assessment (PGA) at 48 Hours as "Excellent"		Up to 48 hours
Percentage of Patients Who Responded to the Patient Global Assessment (PGA) at 72 Hours as "Poor"		Up to 72 hours
Percentage of Patients Who Responded to the Patient Global Assessment (PGA) at 72 Hours as "Fair"		Up to 72 hours
Percentage of Patients Who Responded to the Patient Global Assessment (PGA) at 72 Hours as "Good"		Up to 72 hours
Percentage of Patients Who Responded to the Patient Global Assessment (PGA) at 72 Hours as "Excellent"		Up to 72 hours
Percentage of Healthcare Professionals (HCPs) Who Rated the Healthcare Professional Global Assessment (HPGA) of Method of Pain Control Over 24 Hours as "Good" or "Excellent"		Up to 24 hours
Percentage of Healthcare Professionals (HCPs) Who Rate the Healthcare Professional Global Assessment (HPGA) of Method of Pain Control Over 48 Hours as "Good" or "Excellent"		Up to 48 hours
Percentage of Healthcare Professionals (HCPs) Who Rated the Healthcare Professional Global Assessment (HPGA) of Method of Pain Control Over 72 Hours as "Good" or "Excellent"		Up to 72 hours
Percentage of Healthcare Professional (HCPs) Who Responded to the Healthcare Professional Global Assessment (HPGA) as "Poor" at 24 Hours		Up to 24 hours
Percentage of Healthcare Professional Global Assessment (HCPs) Who Responded to the Healthcare Professional Global Assessment (HPGA) as "Fair" at 24 Hours		Up to 24 hours
Percentage of Healthcare Professionals (HCPs) Who Responded to the Healthcare Professional Global Assessment (HPGA) as "Good" at 24 Hours		Up to 24 hours
Percentage of Healthcare Professional (HCPs) Who Responded to the Healthcare Professional Global Assessment (HPGA) as "Excellent" at 24 Hours		Up to 24 hours
Percentage of Healthcare Professionals (HCPs) Who Responded to the Healthcare Professional Global Assessment (HPGA) at 48 Hours as "Poor"		Up to 48 hours
Percentage of Healthcare Professionals (HCPs) Who Responded to the Healthcare Professional Global Assessment (HPGA) at 48 Hours as "Fair"		Up to 48 hours
Percentage of Healthcare Professionals (HCPs) Who Responded to the Healthcare Professional Global Assessment (HPGA )at 48 Hours as "Good"		Up to 48 hours
Percentage of Healthcare Professionals (HCPs) Who Responded to the Healthcare Professional Global Assessment (HPGA) at 48 Hours as "Excellent"		Up to 48 hours
Percentage of Healthcare Professionals (HCPs) Who Responded to the Healthcare Professional Global Assessment (HPGA) at 72 Hours as "Poor"		Up to 72 hours
Percentage of Healthcare Professionals (HCPs) Who Responded to the Healthcare Professional Global Assessment (HPGA) at 72 Hours as "Fair"		Up to 72 hours
Percentage of Healthcare Professionals (HCPs) Who Responded to the Healthcare Professional Global Assessment (HPGA) at 72 Hours as "Good"		Up to 72 hours
Percentage of Healthcare Professionals (HCPs) Who Responded to the Healthcare Professional Global Assessment (HPGA) at 72 Hours as "Excellent"		Up to 72 hours
Percentage of Patients Who Terminated From the Study Due to Inadequate Analgesia Over the 24-hour Study Period		Up to 24 hours
Percentage of Patients Who Terminated From the Study Due to Inadequate Analgesia After the 24-hour Study Period and Prior to or During the 48 Hour Study Period		Up to 48 hours
Percentage of Patients Who Terminated From the Study Due to Inadequate Analgesia Prior to or During the 72 Hour Study Period		Up to 72 hours
Time-weighted Summed Pain Intensity Difference (SPID) Over the 24-hour Study Period (SPID24)	The pain intensity difference (PID) at each evaluation time point after the dose of study drug is the difference in pain intensity at the specific evaluation time point and baseline pain intensity [PID(evaluation time after the first dose) = PI(baseline) - PI(evaluation time after the first dose)]. A pain intensity score ranging from 0 (no pain) to 10 (worst possible pain) is obtained at baseline and at protocol-specified time points throughout the 24 hour period. The time-weighted SPID24 is the time-weighted summed PID over the 24-hour study period. A negative score indicates an increase in pain intensity and a higher score indicates a greater decrease in pain intensity.The scores ranged from - 72 to 204.	Up to 24 hours
Time-weighted Summed Pain Intensity Difference (SPID) Over the 48-hour Study Period (SPID-48) Study Period	The pain intensity difference (PID) at each evaluation time point after the dose of study drug is the difference in pain intensity at the specific evaluation time point and baseline pain intensity [PID(evaluation time after the first dose) = PI(baseline) - PI(evaluation time after the first dose)]. A pain intensity score ranging from 0 (no pain) to 10 (worst possible pain) is obtained at baseline and at protocol-specified time points and throughout the 48 hour period. The time-weighted SPID48 is the time-weighted summed PID over the 48-hour study period. A negative score indicates an increase in pain intensity and a higher score indicates a greater decrease in pain intensity.The scores ranged from -144 to 408.	Up to 48 hours
Time-weighted Summed Pain Intensity Difference (SPID) Over the 72-hour Study Period (SPID-72) Study Period	The pain intensity difference (PID) at each evaluation time point after the dose of study drug is the difference in pain intensity at the specific evaluation time point and baseline pain intensity [PID(evaluation time after the first dose) = PI(baseline) - PI(evaluation time after the first dose)]. A pain intensity score ranging from 0 (no pain) to 10 (worst possible pain) is obtained at baseline and at protocol-specified time points throughout the 72 hour period. The time-weighted SPID72 is the time-weighted summed PID over the 72-hour study period. A negative score indicates an increase in pain intensity and a higher score indicates a greater decrease in pain intensity. The scores ranged from -239 to 624.	Up to 72 hours
Total Pain Relief (TOTPAR) Over the 24-hour Study Period (TOTPAR24)	Total pain relief over the 24-hour study period. A higher TOTPAR score means a greater relief in pain. Range of scores was from 0.00 to 96.00.	Up to 24 hours
Total Pain Relief (TOTPAR) Over the 48-hour Study Period (TOTPAR48)	Total pain relief over the 48-hour study period. A higher TOTPAR score means a greater relief in pain. Range of scores was from 0.00 to 192.00.	Up to 48 hours
Total Pain Relief (TOTPAR) Over the 72-hour Study Period (TOTPAR72)	Total pain relief over the 72-hour study period. A higher TOTPAR means a greater relief in pain. Range of scores was from 0.00 to 288.00.	Up to 72 hours
Pain Intensity (PI) at Each Evaluation Time Point	At protocol-specified time points, the patient is asked to self-record his/her current level of pain on an 11-point numerical rating scale where 0 equals no pain and 10 equals the worst possible pain.	Up to 72 hours
Pain Intensity Difference (PID) at Each Evaluation Time Point	The PID at each evaluation time point after the dose of study drug is the difference in pain intensity at the specific evaluation time point and baseline pain intensity [PID(evaluation time after the first dose) = PI(baseline) - PI(evaluation time after the first dose)]. The higher the PID score, the lower the pain intensity. The scores ranged from - 239 to 624.	Up to 72 hours
Pain Relief (PR) at Each Evaluation Time Point	At protocol-specified time points, the patient is asked to self-record his/her current level of pain relief on 5-point numerical rating scale where 0 equaled no pain relief and 4 equaled complete pain relief. The baseline score references the baseline pain intensity score and the following timepoints reference pain relief scores.	Up to 72 hours
Patient Usability Questionnaire (PUQ)	Questionnaire completed by patients at the end of his/her participation in the study regarding the usability of Zalviso.	Up to 72 hours
Nurse Usability Questionnaire (NUQ)	Questionnaire regarding the usability of Zalviso completed by HCPs who had set up at least 5 Zalviso Systems for patients	Up to 72 hours
Number of Study Drug Doses Used		Up to 72 hours
Average Hourly Use of Study Drug	Average number of study drug doses used per hour, adjusting by treatment exposure time and study period	Up to 72 hours
Average Inter-dosing Interval (in Minutes)		Up to 72 hours
Total Amount of Supplemental Morphine (mg) Utilized	Supplemental opioid medication (2 mg IV morphine) was allowed in the first 30 minutes after the first on-demand dose of study drug had been administered, if necessary, to keep a patient comfortable. Otherwise, supplemental opioid medication (2 mg IV morphine, no more frequently than hourly) was allowed for pain due to ambulation or with the initiation of passive range of motion therapy throughout the remainder of the study.	Up to 72 hours

Collaborators and Investigators

• Sponsor: AcelRx Pharmaceuticals, Inc.
• Investigators: Study Director: Pamela Palmer, MD, PhD, AcelRx Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): September 28, 2016
• Primary Completion (Actual): April 14, 2017
• Study Completion (Actual): May 5, 2017

Study Registration Dates

• First Submitted: January 20, 2016
• First Submitted That Met QC Criteria: January 21, 2016
• First Posted (Estimate): January 26, 2016

Study Record Updates

• Last Update Posted (Actual): August 8, 2018
• Last Update Submitted That Met QC Criteria: August 6, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Acute 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; Sufentanil; Dsuvia
• Other Study ID Numbers: IAP312

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes