Clinical trial NCT06137638: ENA-001 for Post Operative Respiratory Depression (PORD)
Official title: A Placebo-controlled, Double-blind, Randomized Trial to Evaluate the Efficacy of ENA-001 in Preventing Postoperative Respiratory Depression
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Respiratory Depression
Lead sponsor: Enalare Therapeutics Inc.
Sponsor class: INDUSTRY
First posted: 2023-11-18
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This study is a Phase II, randomized, placebo-controlled, double-blind trial in 200 subjects having general anesthesia for major elective surgery with postoperative pain management to evaluate the efficacy, safety and tolerability of ENA-001 as a therapy to prevent post operative respiratory depression.


Eligibility criteria: 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 \&amp;amp;amp;lt; 450 msec QTcF males \&amp;amp;amp;lt; 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.

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, including anxiety disorder, that is uncontrolled and/or restricting normal daily function.
5. History of alcohol abuse (more than an average of 2-drinks per day) within the past 2 years.
6. History of drug abuse within the past 2 years.
7. History of regular smoking within the past year (\&amp;gt;5 per week means exclusion).
8. Positive for HIV, or Hepatitis B or C at screening.
9. Blood donation or blood loss within 60 days of screening or plasma donation within 7 days of screening.
10. Current or recent presentation of clinically significant of dyspnea, asthma, tuberculosis, chronic obstructive pulmonary disease, sleep apnea (central or obstructive) or any other ventilatory / lung disease.
11. 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.
12. History of moderate to severe motion sickness.
13. Subjects who are unwilling to remove excessive facial hair preventing sealing of the occlusive face mask.
14. Subjects who, in the opinion of the investigator, will not be able to participate optimally in the study.
15. 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.
16. 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.
17. Subjects who are part of the study staff personnel or family members of the study staff personnel.
18. 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.
19. Subjects who have a history of malignancy and are in remission \&lt;5 years.
20. Personal or family history of malignant hyperthermia.
21. History of arrhythmias or ECG conductance abnormalities.
22. 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.

Primary outcomes:
measure: To evaluate the effects of ENA-001 on pulmonary ventilation when administered to 100 subjects via continuous infusion of a loading dose of 2.0 mg/kg/hr for 20 minutes followed by a maintenance dose of 1.1 mg/kg/hr
timeFrame: 2 hours
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
References: