ENA-001 for Post Operative Respiratory Depression (PORD)

Inclusion Criteria

• •1. Willing to give written informed consent for the trial and willing/able to adhere to study procedures.
• •2. Scheduled to undergo a major elective surgery, including abdominal, laparoscopic, nephrology, thoracic (non-cardiac), orthopedic (e.g., shoulder and ankle surgery), where the subject will be transferred to recover in the general postanesthesia recover unit (PACU) and extubation will be performed in the operating room or PACU.
• •3. Undergoing surgical procedure with a intraoperative requirement of ≥ 250 µg of fentanyl; Enrolled base on expected pain management to necessitate ≥ 250 µg of fentanyl intraoperatively.
• •4. Male and female, ≥18 years of age.
• •5. American Society of Anesthesiologists (ASA) physical status classification 1-3.
• •6. Have no clinical or electrocardiographic signs of ischemic heart disease as determined by the Investigator. The Screening 12 lead ECG conduction intervals must be within gender specific normal range (e.g., QTcF female \< 450 msec QTcF males \< 430 msec, PR interval ≤ 220 msec). ECGs are to be judged by the investigator or sub-investigator as per standardized procedures.
• •7. Clinical laboratory tests (blood hematology, blood chemistry, coagulation and urinalysis) must not include any significant clinical abnormalities.
• •8. Vital sign measurements must be within the following ranges during screening and on the day of dosing:
• •1. body temperature, ≥35.5°C to ≤37.5°C
• •2. systolic blood pressure, ≥90 to ≤150 mm Hg
• •3. diastolic blood pressure, ≥50 to ≤95 mm Hg
• •4. pulse rate, ≥40 to ≤100 bpm
• •9. Non-vasectomized men must agree to use a condom with spermicide, double-barrier contraception, abstain from heterosexual intercourse, or have a sole-sexual partner of non childbearing potential during the trial and for 3 months after stopping the medication. Male subjects must agree not to donate sperm from the time of dosing until 90 days after dosing.
• •10. Women of childbearing potential (defined as all women who are not surgically sterile or postmenopausal for at least 1 year prior to informed consent) must have a negative pregnancy test prior to enrolment and must agree to the following contraception requirements from screening through 3 months after dosing of the study drug:
• •1. Be sexually inactive (abstinent)
• •2. Intrauterine device in place for at least three months prior to dosing with a barrier method (condom or diaphragm) and spermicide throughout the study.
• •3. Double barrier methods (e.g., condom and diaphragm) with spermicide for at least 14 days prior to dosing and throughout the study.
• •4. Surgical sterilization of the partner (vasectomy at least six months prior to dosing) with a barrier method (e.g., condom or diaphragm) and spermicide throughout the study.
• •5. Female subjects who claim to be sexually inactive but become sexually active during the course of the study must agree to use a double barrier method (e.g., condom and diaphragm) with spermicide from the time of the start of sexual activity through completion of the study. In addition, female subjects of childbearing potential must be advised to remain sexually inactive or to keep the same birth control method for at least 14 days following study medication administration. Females of non-childbearing potential must have undergone one of the following sterilization procedures at least 6 months prior to dosing:
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• •1. Hysteroscopic sterilization and be using a barrier method (e.g., condom or diaphragm) and spermicide throughout the study.
• •2. Bilateral tubal ligation or bilateral salpingectomy and be using a barrier method (e.g., condom or diaphragm) and spermicide throughout the study.
• •3. Hysterectomy.
• •4. Bilateral oophorectomy. Women with amenorrhea for at least 1 year prior to dosing and who have follicle-stimulating hormone (FSH) serum levels consistent with postmenopausal status, are considered post menopausal and therefore of non-childbearing potential.
• •11. Subjects must be free of any clinically significant disease that would interfere with the study evaluations.