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

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

Detailed Description
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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.

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

Conditions
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Moderate-to-severe Acute Pain

Intervention / Treatment
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* Drug: Zalviso™ 15 mcg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients who were 18 years of age or older. Patients who were scheduled to undergo surgery under general or spinal anesthesia that does not include intrathecal opioids during the operation. Patients classified as American Society of Anesthesiologists (ASA) class I - III (Appendix I). 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. 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: 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). Patients who were currently taking monoamine oxidase inhibitors (MAOIs) or had taken MAOIs within 14 days of the first dose of study drug. Patients with current sleep apnea that had been documented by a sleep laboratory study or were on home continuous positive airway pressure (CPAP). Patients with an allergy or hypersensitivity to opioids. Patients who were currently taking monoamine oxidase inhibitors (MAOIs) or had taken MAOIs within 14 days of the first dose of study drug. Patients with current sleep apnea that had been documented by a sleep laboratory study or were on home continuous positive airway pressure (CPAP). Patients who were receiving oxygen therapy at the time of screening.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Zalviso™ 15 mcg<br>Zalviso™(sufentanil sublingual tablet system) 15 mcg | Drug: Zalviso™ 15 mcg<br>* 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<br>* Other names: Zalviso™ (sufentanil sublingual tablet system) 15 mcg;|

What is the study measuring?
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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 |