A Multicenter, Randomized, Placebo-Controlled Phase 2 Study to Evaluate the Clinical Efficacy, Safety, and Tolerability of ARX-F01 Sublingual Sufentanil in Patients Undergoing Major Abdominal Surgery

Study Overview
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Brief Summary
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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.

Official Title
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A Multicenter, Randomized, Placebo-Controlled Phase 2 Study to Evaluate the Clinical Efficacy, Safety, and Tolerability of ARX-F01 Sublingual Sufentanil in Patients Undergoing Major Abdominal Surgery

Conditions
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Major Upper or Lower Abdominal Surgery

Intervention / Treatment
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* Drug: Oral sufentanil
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria at Screening: Male or female patients between 18 to 80 years of age. Patient is scheduled to undergo an upper or lower abdominal surgery under general anesthesia. Patient must be classified as American Society of Anesthesiologists (ASA) class I - III. Patient must have Body Mass Index [BMI = weight (kg)/height (m2)] between 18 and 39, inclusively. 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). 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. The patient must provide written informed consent and sign the Informed Consent Exclusion Criteria at Screening: Patient is scheduled to undergo a laparoscopically-assisted abdominal surgery. Patient has previously not responded to opioid analgesics for treatment of pain. 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). Patient has an allergy or hypersensitivity to opioids. Patient currently has sleep apnea that has been documented by a sleep laboratory study. Patient has any screening laboratory test value outside the laboratory normal range which is considered clinically significant by the Investigator. Patient is a woman who is pregnant or lactating. Patient has psychiatric disease or encephalopathy severe enough to prevent patient from providing reliable study documentation. Patient, in the Investigator's judgment, does not have adequate ability to read and understand English. 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. Patient has clinically significant renal or liver impairment which could affect metabolism or clearance of sufentanil. Patient has a painful physical condition other than acute abdominal pain that, in the opinion of the Investigator, may confound post-operative pain assessments. 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. Patient is receiving oxygen therapy at the time of screening. 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. Exclusion Criteria at Randomization (during early PACU time period): Patient has a respiratory rate that is less than 8 breaths per minute or greater than 24 breaths per minute. Patient has arterial oxygen saturation by pulse oximetry (SpO2) of less than 90% with supplemental oxygen. Patient is not able to answer questions and follow commands. Patient has vomiting that is not responsive to standard treatment. The surgical procedure from incision to closure was longer than 4 hours. There have been any deviations from the surgical or anesthetic protocols as specified in Section 6.1.2.1. approved by the Institutional Review Board (IRB).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Oral Sufentanil | Drug: Oral sufentanil<br>* Oral dosage of sufentanil<br>|
| Experimental: 2<br>Oral sufentanil | Drug: Oral sufentanil<br>* Oral dosage of sufentanil<br>|
| Placebo Comparator: 3<br>Oral dosage of placebo | Drug: Placebo<br>* Oral dosage of placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 12 hours after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Up to 12 hours after surgery |