| Eligibility |
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 post-anesthesia
recover unit (PACU) and extubation will be performed in the operating room or PACU.
3. Undergoing surgical procedure with an intraoperative requirement of = 250 µg of
fentanyl.
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 with normal cardiac intervals appropriate for their gender. 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 and liver enzymes
must be in normal range.
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:
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
5. Postmenopausal (amenorrhea for at least 1 year prior to dosing)
11. Subjects must be free of any clinically significant disease that would interfere with
the study evaluations.
Exclusion Criteria:
1. Ongoing treatment for a pre-existing chronic pain condition
2. Use of an epidural / spinal block / major nerve block for the surgical procedure
3. Surgical procedure that may interfere with the collection of data under the study
protocol, such as craniofacial surgery which may impact the placement of a face mask
for pulmonary function measurements.
4. Current diagnosis of psychiatric disease requiring daily medication, including
controlled or uncontrolled schizophrenia, current or recently treated depressive
disorders.
5. Past history of anxiety disorder including panic attack, depression, obsessive
compulsive disorder, phobias restricting normal daily function, social anxiety, and
paranoia.
6. History of alcohol abuse (more than an average of 2-drinks per day) within the past 2
years.
7. History of drug abuse within the past 2 years.
8. History of regular smoking within the past year (>5 per week means exclusion).
9. Positive for HIV, or Hepatitis B or C at screening.
10. Blood donation or blood loss within 60 days of screening or plasma donation within 7
days of screening.
11. History of dyspnea, asthma, tuberculosis, chronic obstructive pulmonary disease, sleep
apnea (central or obstructive) or any other ventilatory / lung disease.
12. Treatment with another investigational drug within 3 months prior to screening or
having participated in more than four investigational drug studies within 1 year prior
to screening.
13. History of moderate to severe motion sickness.
14. Subjects who are unwilling to remove excessive facial hair preventing sealing of the
occlusive face mask.
15. Subjects who, in the opinion of the investigator, will not be able to participate
optimally in the study.
16. Any surgical or medical condition which might significantly alter the distribution,
metabolism or excretion of any drug. The investigator should be guided by evidence of
any of the following, and be discussed with the sponsor prior to enrollment into the
trial:
1. history of pancreatic injury or pancreatitis;
2. history or presence of liver disease or liver injury;
3. history or presence of impaired renal function as indicated by clinically
significant elevation in creatinine, BUN/urea, urinary albumin, or clinically
significant urinary cellular constituents; or
4. history of urinary obstruction or difficulty in voiding.
17. Subject who has a history of any infectious disease within 4 weeks prior to drug
administration that in the opinion of the investigator, affects the subject's ability
to participate in the trial.
18. Subjects who are part of the study staff personnel or family members of the study
staff personnel.
19. Subjects who have demonstrated allergic reactions (e.g., food, drug, atopic reactions
or asthmatic episodes) which, in the opinion of the investigator and sponsor,
interfere with their ability to participate in the trial.
20. Subjects who have a history of malignancy and are in remission <5 years.
21. Personal or family history of malignant hyperthermia.
22. History of arrhythmias or ECG conductance abnormalities.
23. Subjects with a history of daily consumption of caffeine greater than 6 servings (40
mL each) from beverages (e.g., coffee, tea, soft drinks) and food stuffs (e.g.,
chocolate, ice cream, cookies) (45 gm each) in the month prior to screening.
24. Subjects with history of known difficult airway access and presence of a
"non-reassuring" airway exam (as determined by the investigator), gastroesophageal
reflex disease, gastric motility disorders, or delayed gastric emptying, or any
condition that may lead to delayed gastric emptying such as diabetes.
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