Post Operative Pain
Conditions
Brief summary
The purpose of this study is to compare the efficacy and safety of the Sufentanil NanoTab PCA System/15 mcg to the Placebo Sufentanil NanoTab PCA System for the management of acute moderate to severe post-operative pain after total unilateral knee or total unilateral hip replacement surgery.
Interventions
15 mcg Sufentanil NanoTab dosed sublingually every 20 minutes as needed for pain for at least 48 hours. Patients may elect to remain in study for up to 72 hours.
Placebo NanoTab dosed sublingually every 20 minutes as needed for pain for at least 48 hours. Patients may elect to remain in study for up to 72 hours.
Sponsors
Talphera, Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female patients who are 18 years of age or older * Patients who are scheduled for an elective cemented or uncemented total unilateral knee replacement or total unilateral hip replacement, under general or spinal anesthesia that does not include use of an intrathecal opioid * Post-surgical patients who have been admitted to the PACU and are expected to remain hospitalized and to have acute post-operative pain requiring parenteral opioids for at least 48 hours after surgery
Exclusion criteria
* Patients who have undergone a replacement of the same knee or hip * Patients who have taken an opioid for more than 30 consecutive days, at a daily dose of more than 15 mg 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 with an allergy or hypersensitivity to opioids
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time-weighted Summed Pain Intensity Difference (SPID) Over the 48-hour Study Period (SPID48). | 48 hours | SPID-48 is the sum of the pain intensity difference (PID) over the 48 hour time period. A pain intensity score of 0 (no pain) to 10 (worse possible pain) is obtained before starting the study and throughout the 48 time period. The pain score at each assessment time is subtracted from the baseline pain score to provide the total sum score or SPID-48. A higher SPID-48 is better and indicates a reduction in pain intensity compared to the baseline score. Range of SPID48 scores were -239 to 417. Time-weighted SPID48 = ∑ \[T(i) - T(i-1)\] x PID(i), where T(0) = Time 0 (baseline), T(i) is the scheduled or unscheduled assessment time, and PID(i) is the PID score at time i for i=0 to 48 hours |
Countries
United States
Participant flow
Recruitment details
Recruitment period of 9 months - August 2012 through April 2013
Pre-assignment details
Patients were excluded per protocol exclusion criteria at Screening as well as post surgery for certain conditions including the following: 1. Patients who were not awake or stable 2. Patients with arterial oxygen saturation that couldn't be maintained at 95% or greater 3. Patients with uncontrollable vomiting
Participants by arm
| Arm | Count |
|---|---|
| Sufentanil NanoTab PCA System/15 mcg Sufentanil NanoTab PCA System/15 mcg : 15 mcg Sufentanil NanoTab dosed sublingually q 20 minutes as needed for pain for at least 48 hours. Patient may elect to remain in study for up to 72 hours | 315 |
| Placebo Sufentanil NanoTab PCA System Placebo Sufentanil NanoTab PCA System : Placebo NanoTab dosed sublingually q 20 minutes as needed for pain for at least 48 hours. Patient may elect to remain in study for up to 72 hours | 104 |
| Total | 419 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 22 | 7 |
| Overall Study | Lack of Efficacy | 45 | 50 |
| Overall Study | Patient ready for early discharge | 28 | 4 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Withdrawal by Subject | 4 | 0 |
Baseline characteristics
| Characteristic | Placebo Sufentanil NanoTab PCA System | Sufentanil NanoTab PCA System/15 mcg | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 54 Participants | 186 Participants | 240 Participants |
| Age, Categorical Between 18 and 65 years | 50 Participants | 129 Participants | 179 Participants |
| Age, Continuous | 65.0 years STANDARD_DEVIATION 10.5 | 66.6 years STANDARD_DEVIATION 10.8 | 66.2 years STANDARD_DEVIATION 10.7 |
| Region of Enrollment United States | 104 participants | 315 participants | 419 participants |
| Sex: Female, Male Female | 66 Participants | 188 Participants | 254 Participants |
| Sex: Female, Male Male | 38 Participants | 127 Participants | 165 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 171 / 315 | 35 / 104 |
| serious Total, serious adverse events | 8 / 315 | 4 / 104 |
Outcome results
Primary
Time-weighted Summed Pain Intensity Difference (SPID) Over the 48-hour Study Period (SPID48).
SPID-48 is the sum of the pain intensity difference (PID) over the 48 hour time period. A pain intensity score of 0 (no pain) to 10 (worse possible pain) is obtained before starting the study and throughout the 48 time period. The pain score at each assessment time is subtracted from the baseline pain score to provide the total sum score or SPID-48. A higher SPID-48 is better and indicates a reduction in pain intensity compared to the baseline score. Range of SPID48 scores were -239 to 417. Time-weighted SPID48 = ∑ \[T(i) - T(i-1)\] x PID(i), where T(0) = Time 0 (baseline), T(i) is the scheduled or unscheduled assessment time, and PID(i) is the PID score at time i for i=0 to 48 hours
Time frame: 48 hours
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Sufentanil NanoTab PCA System/15 mcg | Time-weighted Summed Pain Intensity Difference (SPID) Over the 48-hour Study Period (SPID48). | 76.24 Units on a scale | Standard Error 7.02 |
| Placebo Sufentanil NanoTab PCA System | Time-weighted Summed Pain Intensity Difference (SPID) Over the 48-hour Study Period (SPID48). | -11.35 Units on a scale | Standard Error 10.55 |
p-value: <0.00195% CI: [66.2, 108.98]ANCOVA