A Double Blinded, Placebo Controlled, Crossover Infusion Study of Respiratory Pharmacodynamics of ENA-001 in Conjunction with Propofol, Hypoxia, and Hypercapnia
- Conditions
- Breathing problemsRespiratory impairment10038716
- Registration Number
- NL-OMON50050
- Lead Sponsor
- Enalare Therapeutics Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 12
The subject must meet ALL the criteria listed below for entry at baseline:
1. Subjects must be willing to give written informed consent for the trial and
able to adhere to dose and visit schedules.
2. Male and female, >18 to *55 years of age.
3. Subject must weigh *50 to *100 kg.
4. Subjects must have Body Mass Index [weight/height2 (kg/m2)] between 18 to 30
kg/m2 (inclusive).
5. 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 * 470 msec QTcF males * 450
msec, PR interval * 220 msec). ECGs are to be judged by the investigator or
sub-investigator as per standardized procedures.
6. Subjects* clinical laboratory tests (blood hematology, blood chemistry,
coagulation and urinalysis) must not include any clinically significant
abnormalities.
7. Vital sign measurements must be within the following ranges during screening
and on Day -1: (Individuals with values outside (or indicate lower or higher)
of these ranges may be enrolled if clinically acceptable to the investigator
and sponsor.
a. body temperature, >35.5*C to *37.5*C
b. systolic blood pressure, >90 to *150 mm Hg
c. diastolic blood pressure, >40 to *95 mm Hg
d. pulse rate, >40 to *100 bpm
8. Non-vasectomized men must agree to use a condom with spermicide (when
marketed in the country), 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.
9. 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 requirement from screening through at least 3 months
after the last dose of study drug:
a. Be sexually inactive (abstinent)
b. Intrauterine device in place for at least three months prior to dosing with
a barrier method (condom or diaphragm) and spermicide throughout the study.
c. Double barrier methods (e.g., condom and diaphragm) with spermicide for at
least 14 days prior to dosing and throughout the study.
d. 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.
e. 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:
f. Hysteroscopic sterilization and be using a barrier method (e.g., c
The subject will be excluded from entry if ANY of the criteria listed below are
met at baseline:
1. Current diagnosis of psychiatric disease requiring daily medication,
including controlled or uncontrolled schizophrenia, current or recently treated
depressive disorders, or Columbia-Suicide Severity Rating Scale (C-SSRS)
indicative of suicidal ideation or behavior at screening and day -1.
2. Past history of the anxiety disorder including panic attack, depression,
obsessive compulsive disorder, phobias restricting normal daily function,
social anxiety, and paranoia.
3. History of alcohol abuse (more than an average of 2-drinks per day) within
the past 2 years.
4. History of drug abuse within the past 2 years.
5. History of regular smoking within the past year (>5 per week means
exclusion).
6. Failure to take or test positive of the drug of abuse tests at screening or
check-in.
7. Positive for HIV, or Hepatitis B or C at screening.
8. Blood donation or blood loss within 60 days of screening or plasma donation
within 7 days of screening.
9. Subjects with a history of bleeding disorders or coagulopathies.
10. History of dyspnea, asthma, tuberculosis, chronic obstructive pulmonary
disease, sleep apnea 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:
a. history of pancreatic injury or pancreatitis;
b. history or presence of liver disease or liver injury;
c. 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
d. 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 >2 years.
20. Personal or family history of malignant hyperthermia.
21. Personal or family history of arrhythmias or ECG conductance abnormalities.
22. 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 th
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Tolerability / safety endpoints<br /><br>Safety will be evaluated based on reported adverse events, physical<br /><br>examinations, vital signs, 12-lead ECGs, clinical laboratory test results and<br /><br>Columbia-Suicide Severity Rating Scale (C-SSRS) responses.<br /><br>Other parameters may be collected or derived with equipment used by the study<br /><br>center but will not be captured in the CRF. Values will be listed with<br /><br>descriptive statistics.<br /><br><br /><br>Pharmacodynamic endpoints<br /><br>Included will be Hypoxic sensitivity (*Ventilation/*Saturation), tidal volume<br /><br>(VT), respiratory rate (breaths/min), minute ventilation (VE), end-tidal CO2<br /><br>(mmHg), and transcutaneous hemoglobin saturation (SpO2 in %), arterial blood<br /><br>gases, BIS, and hemodynamic parameters from arterial line monitoring.</p><br>
- Secondary Outcome Measures
Name Time Method