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
total knee replacement 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
- Male or female patients between 45 to 75 years of age.
- Patient is scheduled for an elective unilateral, tri-compartmental, cemented total
knee replacement under general anesthesia.
- Patient must be classified as American Society of Anesthesiologists (ASA) class I -
- Patient must have Body Mass Index [BMI = weight (kg)/height (m2)] between 18 and 35,
- 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
approved by the Institutional Review Board (IRB).
- Patient is scheduled to undergo the surgical procedure without cement.
- Patient has previously undergone a knee replacement of the same knee.
- A passive range-of-motion (PRM) will be used before the 12-hour study period is
- 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
- Patient has any screening laboratory test value outside the laboratory normal range
which is considered clinically significant by the Investigator.
- Patient has a contraindication to the use of general anesthesia.
- 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
- 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 fracture 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 knee arthritis 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 test for drugs of abuse at screening.
- Patient is receiving oxygen therapy at the time of screening.
- Patient 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
- 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 3 hours.
- There have been any deviations from the surgical or anesthetic protocols as specified
in Section 18.104.22.168.