Major Upper or Lower Abdominal Surgery
Conditions
Brief summary
The purpose of this study is to evaluate dosages of ARX-F01 (opioid pain medication) versus a placebo (or sugar pill) for the treatment of post-operative pain in subjects following abdominal surgery. We hypothesize that subjects receiving placebo will have poor pain relief and will drop out of the study sooner and more often than the ARX-F01 treated subjects.
Interventions
DRUGOral sufentanil
Oral dosage of sufentanil
DRUGPlacebo
Oral dosage of placebo
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 80 Years
Healthy volunteers
Yes
Inclusion criteria
at Screening: 1. Male or female patients between 18 to 80 years of age. 2. Patient is scheduled to undergo an upper or lower abdominal surgery under general anesthesia. 3. Patient must be classified as American Society of Anesthesiologists (ASA) class I - III. 4. Patient must have Body Mass Index \[BMI = weight (kg)/height (m2)\] between 18 and 39, inclusively. 5. Female patients of childbearing potential must be using an effective method of birth control from the screening visit through the end of study. Acceptable methods of birth control include 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-childbearing potential, such as bilateral tubal ligation, bilateral oophorectomy, hysterectomy, or postmenopausal for ≥1 year, must be specified in the patient's case report form (CRF). 6. The patient must be willing and able to understand the study procedures and the use of pain scales, and to communicate meaningfully with the study personnel. 7. The patient must provide written informed consent and sign the Informed Consent
Exclusion criteria
at Screening: 1. Patient is scheduled to undergo a laparoscopically-assisted abdominal surgery. 2. Patient has previously not responded to opioid analgesics for treatment of pain. 3. Patient is currently taking or has taken an opioid for more than 30 consecutive days of daily use at a daily dose equivalent to greater than 15 mg morphine 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). 4. Patient has an allergy or hypersensitivity to opioids. 5. Patient currently has sleep apnea that has been documented by a sleep laboratory study. 6. Patient has any screening laboratory test value outside the laboratory normal range which is considered clinically significant by the Investigator. 7. Patient is a woman who is pregnant or lactating. 8. Patient has psychiatric disease or encephalopathy severe enough to prevent patient from providing reliable study documentation. 9. Patient, in the Investigator's judgment, does not have adequate ability to read and understand English. 10. Patient has 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 abdominal pain or active infection. 11. Patient has clinically significant renal or liver impairment which could affect metabolism or clearance of sufentanil. 12. Patient has a painful physical condition other than acute abdominal pain that, in the opinion of the Investigator, may confound post-operative pain assessments. 13. Patient has a history of drug, prescription medicine, or alcohol abuse within the past 2 years or a positive drug screen test for cocaine, amphetamines, barbiturates, phencyclidine, or methadone at screening. 14. Patient is receiving oxygen therapy at the time of screening. 15. Patient has participated in a clinical trial of an investigational drug or device within 30 days of screening visit or is scheduled to receive an investigational product other than ARX-F01 while participating in this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| SPID-12 | 12 hours after surgery | The primary outcome measure is the summed pain intensity difference over the 12-hour study period (SPID-12). A pain intensity score ranging from 0 (no pain) to 10 (worst possible pain) is obtained at baseline and throughout the 12 hour study period. The SPID-12 is calculated by summing the difference between baseline pain score and pain score at each assessment time point. The scores after summing could range from -122 to +122. A higher SPID-12 score is better. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients Who Responded Very Good or Excellent in Patient Global Evaluation of Pain Relief | Up to 12 hours after surgery | At the end of the 12-hour study period each patient rated their overall pain relief since starting study drug on a 5-point scale: poor, fair, good, very good or excellent. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sufentanil NanoTab 10 mcg | 29 |
| Sufentanil NanoTab 15 mcg | 29 |
| Placebo NanoTab | 30 |
| Total | 88 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 |
| Overall Study | Lack of Efficacy | 7 | 3 | 21 |
Baseline characteristics
| Characteristic | Sufentanil NanoTab 15 mcg | Placebo NanoTab | Sufentanil NanoTab 10 mcg | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 2 Participants | 3 Participants | 8 Participants |
| Age, Categorical Between 18 and 65 years | 26 Participants | 28 Participants | 26 Participants | 80 Participants |
| Age, Continuous | 45.3 years STANDARD_DEVIATION 11.3 | 46.8 years STANDARD_DEVIATION 10.1 | 46.4 years STANDARD_DEVIATION 9.7 | 46.2 years STANDARD_DEVIATION 10.3 |
| Region of Enrollment United States | 29 participants | 30 participants | 29 participants | 88 participants |
| Sex: Female, Male Female | 28 Participants | 28 Participants | 28 Participants | 84 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 1 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 15 / 29 | 17 / 29 | 15 / 30 |
| serious Total, serious adverse events | 0 / 29 | 0 / 29 | 0 / 30 |
Outcome results
Primary
SPID-12
The primary outcome measure is the summed pain intensity difference over the 12-hour study period (SPID-12). A pain intensity score ranging from 0 (no pain) to 10 (worst possible pain) is obtained at baseline and throughout the 12 hour study period. The SPID-12 is calculated by summing the difference between baseline pain score and pain score at each assessment time point. The scores after summing could range from -122 to +122. A higher SPID-12 score is better.
Time frame: 12 hours after surgery
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Sufentanil NanoTab 10 mcg | SPID-12 | 22.41 units on a scale | Standard Error 3.61 |
| Sufentanil NanoTab 15 mcg | SPID-12 | 27.56 units on a scale | Standard Error 3.5 |
| Placebo NanoTab | SPID-12 | 2.93 units on a scale | Standard Error 3.46 |
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
Secondary
Proportion of Patients Who Responded Very Good or Excellent in Patient Global Evaluation of Pain Relief
At the end of the 12-hour study period each patient rated their overall pain relief since starting study drug on a 5-point scale: poor, fair, good, very good or excellent.
Time frame: Up to 12 hours after surgery
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sufentanil NanoTab 10 mcg | Proportion of Patients Who Responded Very Good or Excellent in Patient Global Evaluation of Pain Relief | 38 percentage of patients |
| Sufentanil NanoTab 15 mcg | Proportion of Patients Who Responded Very Good or Excellent in Patient Global Evaluation of Pain Relief | 55 percentage of patients |
| Placebo NanoTab | Proportion of Patients Who Responded Very Good or Excellent in Patient Global Evaluation of Pain Relief | 10 percentage of patients |