Moderate-to-severe Acute Pain
Conditions
Brief summary
To evaluate the safety and efficacy of sufentanil tablet (ST) 30 mcg in the management of moderate-to-severe acute pain in patients in an emergency room (ER) setting.
Detailed description
The study is a multicenter, open-label trial, in patients 18 years and older, who present to the ER with moderate-to-severe acute pain due to obvious trauma or injury evident on physical examination. Upon meeting all entrance criteria, patients will be administered up to four doses of sufentanil 30 mcg and remain in the study for 5 hours for safety and efficacy measurements. Safety will be monitored via periodic measurement of vital signs and continuous monitoring of oxygen saturation, as well as assessment of adverse events (AEs) and the use of concomitant medications. Efficacy will be assessed by patient reports of pain intensity (PI) and pain relief. A Six-Item Screener (SIS) will be administered before and 1 hour after study drug administration to measure cognitive impairment. The Patient Global Assessment (PGA) and the Healthcare Professional Global Assessment (HPGA) will assess global satisfaction with the method of pain control.
Interventions
Sponsors
U.S. Army Medical Research and Development Command
Talphera, Inc
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients who present to the ER with moderate-to-severe pain due to obvious trauma or injury evident on physical examination. * Patients classified as American Society of Anesthesiologists (ASA) class I-III * Patients who are willing and capable of understanding and cooperating with the requirements of the study. * Patients able to understand and communicate in English. * Patients who have provided written informed consent and signed the IRB approved consent form.
Exclusion criteria
* 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 (e.g. more than 3 doses per day of Vicodin®, Norco®, Lortab® with 5 mg hydrocodone per tablet). * Patients who have used any illicit drugs of abuse, abused prescription medication or alcohol (4 or more drinks per day) within one year before the start of the study. * Patients with an allergy or hypersensitivity to opioids. * Patients who are currently taking monoamine oxidase inhibitors (MAOIs) or have taken MAOIs within 14 days of the dose of study drug. * Patients with current sleep apnea that has been documented by a sleep laboratory study or are on home continuous positive airway pressure (CPAP). * Female patients who are pregnant (positive pregnancy test) or breastfeeding. * Patients with a medical condition that, in the Investigator's opinion, could adversely impact the patient's participation or safety, conduct of the study, or interfere with the pain assessments, including chronic pain or active infection. * Patients who present to the ER using supplemental oxygen. * Patients who have participated in a clinical trial of an investigational drug or device within 30 days of enrollment. * Patients who are active or reserve duty with the US military.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time-weighted Summed Pain Intensity Difference (SPID) Over the 1-hour (SPID1). | One hour | The primary efficacy endpoint is the time-weighted SPID1 evaluated from the patient questionnaire data. Pain intensity (PI) will be measured using an 11-point numerical rating scale (NRS) with 0 (no pain) and 10 (worst possible pain). The patient's rating of PI will be measured at baseline and at 0.25 (15 min), 0.5 (30 min), 0.75 (45 min), 1, 2, 3, 4, and 5 hours following the first dose of study drug. The PID at each evaluation time point after the initiation of the first dose is the difference in PI 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 time-weighted SPID1 is the time-weighted summed PID over the 1-hour study period. The observed SPID scores ranged from -.70 to 8.00. A negative score indicates an increase in pain intensity and a positive score indicates a decrease in pain intensity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| TOTPAR1 (Time-weighted) | 1-hour | The total pain relief (TOTPAR) is the time-weighted sum of the pain relief scores over the first hour (15 minutes, 30 minutes, 45 minutes and 1-hour after the first dose of study drug is taken) of the study period. The minimum score is 0.00 and the maximum score is 4.00. A higher score indicates greater pain relief. |
| PI at Each Evaluation Time Point | 5 hours | Pain intensity at each evaluation time point after the first dose of study drug up through 5 hours is evaluated using an 11-point NRS where 0 equals no pain and 10 equals worst possible pain. The score was obtained at Baseline, 15- , 30-, 45- minutes, 1-hour, and 2-hours after the first dose for all patients, and at hours 3, 4, and 5 for cohort 2 (patients 41-76). Scores ranged from 0 -10 for the first two hours, and 2 - 10 for hours three to five. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sufentanil Sublingual Tablet 30 mcg Patients may be administered one tablet every 60 minutes as needed during the study period | 76 |
| Total | 76 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lack of Efficacy | 4 |
| Overall Study | Patient discharged | 3 |
| Overall Study | Withdrawal by Subject | 4 |
Baseline characteristics
| Characteristic | Sufentanil Sublingual Tablet 30 mcg |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 9 Participants |
| Age, Categorical Between 18 and 65 years | 67 Participants |
| Sex: Female, Male Female | 30 Participants |
| Sex: Female, Male Male | 46 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 12 / 76 |
| serious Total, serious adverse events | 1 / 76 |
Outcome results
Primary
Time-weighted Summed Pain Intensity Difference (SPID) Over the 1-hour (SPID1).
The primary efficacy endpoint is the time-weighted SPID1 evaluated from the patient questionnaire data. Pain intensity (PI) will be measured using an 11-point numerical rating scale (NRS) with 0 (no pain) and 10 (worst possible pain). The patient's rating of PI will be measured at baseline and at 0.25 (15 min), 0.5 (30 min), 0.75 (45 min), 1, 2, 3, 4, and 5 hours following the first dose of study drug. The PID at each evaluation time point after the initiation of the first dose is the difference in PI 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 time-weighted SPID1 is the time-weighted summed PID over the 1-hour study period. The observed SPID scores ranged from -.70 to 8.00. A negative score indicates an increase in pain intensity and a positive score indicates a decrease in pain intensity.
Time frame: One hour
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sufentanil Sublingual Tablet 30 mcg | Time-weighted Summed Pain Intensity Difference (SPID) Over the 1-hour (SPID1). | 2.11 units on a scale | Standard Error 0.24 |
Secondary
PI at Each Evaluation Time Point
Pain intensity at each evaluation time point after the first dose of study drug up through 5 hours is evaluated using an 11-point NRS where 0 equals no pain and 10 equals worst possible pain. The score was obtained at Baseline, 15- , 30-, 45- minutes, 1-hour, and 2-hours after the first dose for all patients, and at hours 3, 4, and 5 for cohort 2 (patients 41-76). Scores ranged from 0 -10 for the first two hours, and 2 - 10 for hours three to five.
Time frame: 5 hours
Population: The first cohort of patients (N=40) received one dose of study drug and the study was completed at two hours. The second cohort of patients (N=36) had the option of remaining in the study through five hours; most patients discontinued the study at 2 hours.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sufentanil Sublingual Tablet 30 mcg | PI at Each Evaluation Time Point | Baseline | 8.08 units on a scale | Standard Error 0.2 |
| Sufentanil Sublingual Tablet 30 mcg | PI at Each Evaluation Time Point | 15-minutes | 6.00 units on a scale | Standard Error 0.27 |
| Sufentanil Sublingual Tablet 30 mcg | PI at Each Evaluation Time Point | 30-minutes | 6.23 units on a scale | Standard Error 0.3 |
| Sufentanil Sublingual Tablet 30 mcg | PI at Each Evaluation Time Point | 45-minutes | 5.51 units on a scale | Standard Error 0.35 |
| Sufentanil Sublingual Tablet 30 mcg | PI at Each Evaluation Time Point | 1-hour | 5.2 units on a scale | Standard Error 0.36 |
| Sufentanil Sublingual Tablet 30 mcg | PI at Each Evaluation Time Point | 2-hours | 5.49 units on a scale | Standard Error 0.37 |
| Sufentanil Sublingual Tablet 30 mcg | PI at Each Evaluation Time Point | 3-hours | 6.83 units on a scale | Standard Error 1.17 |
| Sufentanil Sublingual Tablet 30 mcg | PI at Each Evaluation Time Point | 4-hours | 4.67 units on a scale | Standard Error 1.2 |
| Sufentanil Sublingual Tablet 30 mcg | PI at Each Evaluation Time Point | 5-hours | 2 units on a scale | — |
Secondary
TOTPAR1 (Time-weighted)
The total pain relief (TOTPAR) is the time-weighted sum of the pain relief scores over the first hour (15 minutes, 30 minutes, 45 minutes and 1-hour after the first dose of study drug is taken) of the study period. The minimum score is 0.00 and the maximum score is 4.00. A higher score indicates greater pain relief.
Time frame: 1-hour
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sufentanil Sublingual Tablet 30 mcg | TOTPAR1 (Time-weighted) | 1.37 units on a scale | Standard Error 0.12 |