Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase II/III, Open-Label, Multicenter, Safety, Efficacy and Pharmacokinetic Study of Dexmedetomidine in Neonates Ages ≥28 Weeks to ≤44 Weeks Gestational Age
Brief Summary: The purpose of this study is to investigate the safety, efficacy and pharmacokinetics (PK) of dexmedetomidine (DEX) at 3 different dose levels in infants, ages ≥28 weeks to ≤44 weeks gestational age, administered as a loading dose followed by a continuous infusion for a minimum of 6 hours and up to 24 hours in the neonatal intensive care unit (NICU), cardiac intensive care unit (CICU), or pediatric intensive care unit (PICU).


Options:
A: Inclusion Criteria:

1. Subject is ≥18 years of age.
2. If female, subject is non-lactating, and is either:

   1. Not of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile due to bilateral tubal ligation, bilateral oophorectomy, or hysterectomy.
   2. Of childbearing potential but is not pregnant as confirmed by negative serum pregnancy test at time of screening, and is practicing one of the following methods of birth control: oral or parenteral contraceptives for three months prior to study drug administration, a vasectomized partner, or abstinence from sexual intercourse.
3. Subject is initially intubated and mechanically ventilated, or is planned for imminent intubation and mechanical ventilation, sedation is anticipated to be required during mechanical ventilation, and mechanical ventilation is anticipated to continue for at least 72 hours.
4. Subject or subject's legally authorized representative has voluntarily signed and dated an informed consent form, approved by the applicable Institutional Review Board (IRB), after the nature of the study has been explained and the subject or subject's legally authorized representative has had the opportunity to ask questions. The informed consent must be signed before any study specific procedures are performed.
5. Subject is sedated within a Richmond Agitation-Sedation Scale (RASS) range of -2 to +1 at the time of initiation of study drug

Exclusion Criteria:

1. Subject has been intubated for greater than 96 hours prior to the initiation of study drug (thus, the attainment of consent, screening evaluations, and randomization must all have been completed by the 96th hour post-intubation, so that the actual initiation of the study drug infusion may start by the end of the 96 hour window).
2. Subject has serious central nervous system pathology/trauma that, per clinical judgment of the Investigator, precludes responsiveness or survival.
3. Subject for whom opiates, benzodiazepines, or dexmedetomidine are contraindicated, or who has known or suspected serious allergy to any drug that might be administered during the course of the study.
4. Subject for whom alpha-2 agonists are contraindicated.
5. Subject requires neuromuscular blocking agents during the study for use other than intubation.
6. Subject requires epidural or spinal analgesia during the study.
7. Subject meets any of the following cardiovascular criteria:

   * Acute unstable angina (defined during current hospital stay).
   * Suspicion of acute myocardial infarction.
   * Considered to have a left ventricular ejection fraction of less than 30%. Decision to exclude is predicated on the Investigator's opinion, and may be based on any combination of acute presentations, recently performed diagnostic studies, or a history that suggests poor cardiac function. Pulmonary congestion of a non-cardiac origin or mild congestive failure primarily attributable to etiologies other than poor ventricular function are not exclusion criteria.
   * Heart rate \<50 bpm prior to infusion start.
   * Systolic blood pressure \<90 mmHg prior to infusion start.
   * Conduction abnormalities except 1st degree AV block and rate-controlled atrial fibrillation; subjects with functional pacemaker capacity may be enrolled.
8. Subject is hospitalized primarily due to trauma and/or burns, has received general anaesthesia within the 24 hours prior to the start of study drug infusion, or is anticipated to require general anaesthesia within 24 hours after the start of the infusion.
9. Subject has participated in a trial with any experimental drug within 30 days prior to enrollment in the study, or has ever been enrolled in this study.
10. Subject is unable to undergo any procedure required by the protocol.
11. Subject has laboratory results indicating the presence of liver disease consistent with a Child-Pugh score \>9 (Grade C).
12. Subject has acute hepatitis, history or presence of chronic hepatitis, and/or has had a positive result for Hepatitis B Surface Antigen Test.
13. Subject requires dialysis (eg, hemodialysis, peritoneal dialysis, Continuous Venovenous Hemodialysis \[CVVHD\]).
14. Subject has a known, uncontrolled seizure disorder.
15. Subject has, per the Investigator's judgment, a known or suspected physical or psychological dependence on an abused drug, other than alcohol.
16. Subject has a known psychiatric illness that could confound a normal response to sedative treatment.
17. Subject is incarcerated.
18. Subject is terminally ill with a life duration expectancy of ≤60 days.
19. Subject has any other condition or factor which, in the Investigator's opinion, might increase the risk to the subject.
B: Inclusion Criteria:

1. Initially intubated and mechanically ventilated pediatric subjects in an intensive care setting anticipated to require a minimum of 6 hours of continuous IV sedation.
2. The ability to complete all PK sampling blood draws.
3. Age: subjects must fit into 1 of the following age ranges at screening:

   * Preterm neonates ≥28 weeks through \<36 weeks, gestational age; this would constitute treatment Group I.
   * Term neonates born at ≥36 weeks through ≤44 weeks gestational age; this would constitute treatment Group II.
4. Weight: subject's weight at the time of enrollment must be \>1000 g.
5. Subject's parent(s) or legal guardian(s) has/have voluntarily signed and dated the informed consent document approved by the Institutional Review Board (IRB)/Independent Ethics Committee (IEC).

Exclusion Criteria:

1. Neonate subjects with neurological conditions that prohibit an evaluation of sedation such as:

   * Diminished consciousness from increased intracranial pressure.
   * The presence of catastrophic brain injury or other severe mental disorders that would make responses to sedatives unpredictable and/or measurement of the N-PASS unreliable.
   * Subjects with immobility from neuromuscular disease or continuous infusion of neuromuscular blocking (NMB) agents.
2. Subjects with second degree or third degree heart block unless subject has a pacemaker or pacing wires are in situ.
3. Heart rate \<120 bpm prior to the initiation of study drug.
4. Exposure to any investigational drug within 30 days prior to study drug administration.
5. Previous exposure to Dexmedetomidine (DEX) as part of an investigational study.
6. Maternal history of poly-substance drug abuse, based upon the presence of 1) an abnormal urine drug screen for cocaine, opiates and/or benzodiazepines; or 2) Investigator's judgment.
7. At the discretion of the Investigator, subjects in whom the risk of DEX treatment is expected to exceed its benefits.
8. Subjects who have a known allergy or contraindication to fentanyl, morphine, Midazolam, DEX, or other α-2 agonists.
9. Requirement for medications other than DEX, Midazolam, morphine, or fentanyl for sedation and pain control.
10. Screening alanine aminotransferase (ALT) levels \>115 U/L.
C: Inclusion Criteria:

* Age 18 years and over
* Clinical need for sedation of an initially intubated (or tracheotomised) and ventilated (with inspiratory assistance) patient
* Prescribed light to moderate sedation (target RASS = 0 to -3) using midazolam infusion
* Patients should be randomised within 72 hours from ICU admission and within 48 hours of commencing continuous sedation in the ICU
* Patients should have an expected requirement for sedation of at least 24 hours from time of randomisation
* Written informed consent must be obtained according to local regulations before starting any study procedures other than pre-screening.

Exclusion Criteria:

* Acute severe intracranial or spinal neurological disorder due to vascular causes, infection, intracranial expansion or injury
* Uncompensated acute circulatory failure at time of randomisation (severe hypotension with MAP \< 55 mmHg despite volume and pressors)
* Severe bradycardia (HR \< 50 beats/min)
* AV-conduction block II-III (unless pacemaker installed)
* Severe hepatic impairment (bilirubin \> 101 µmol/L)
* Need for muscle relaxation at the time of randomisation (may only be used for intubation and initial stabilization)
* Loss of hearing or vision, or any other condition which would significantly interfere with the collection of study data
* Burn injuries requiring regular anaesthesia or surgery
* Use of centrally acting α2 agonists or antagonists at the time of randomisation, notably clonidine (see section 5.7 for prior and concomitant treatments)
* Known allergy to any of the study drugs or any excipients of the study drugs
* Patients who have or are expected to have treatment withdrawn or withheld due to poor prognosis
* Patients receiving sedation for therapeutic indications rather than to tolerate the ventilator (e.g. epilepsy)
* Patients unlikely to require continuous sedation during mechanical ventilation (e.g. Guillain-Barré syndrome)
* Patients who are unlikely to be weaned from mechanical ventilation; e.g. diseases/injuries primarily affecting the neuromuscular function of the respiratory apparatus such as clearly irreversible disease requiring prolonged ventilatory support (e.g. high spinal cord injury or advanced amyotrophic lateral sclerosis)
* Distal paraplegia
* Positive pregnancy test or currently lactating
* Received any investigational drug within the preceding 30 days
* Concurrent participation in any other interventional study (any study in which patients are allocated to different treatment groups and/or non-routine diagnostic or monitoring procedures are performed)
* Previous participation in this study
* Any other condition which, in the investigator's opinion, would make it detrimental for the subject to participate in the study
D: Inclusion Criteria:

1. Initially intubated and mechanically ventilated pediatric subjects in an intensive care setting anticipated to require at least 6 hours of continuous IV sedation.
2. Age: subjects must fit the following age range at screening:

   Preterm subjects ≥28 weeks through \<36 weeks, gestational age;

   Note: Gestational age (in weeks) will be calculated as follows: the time elapsed between the first day of the last menstrual period and the day of enrollment.
3. Weight: subject's weight at the time of enrollment must be \>1000 g.
4. Subject's parent(s) or legal guardian(s) has/have voluntarily signed and dated the informed consent document approved by the Institutional Review Board (IRB)/Independent Ethics Committee (IEC).

Exclusion Criteria:

1. Neonate subjects with neurological conditions that prohibit an evaluation of sedation such as:

   * Diminished consciousness from increased intracranial pressure.
   * The presence of catastrophic brain injury or other severe mental disorders that would make responses to sedatives unpredictable and/or measurement of the N-PASS unreliable.
   * Subjects with immobility from neuromuscular disease or continuous infusion of neuromuscular blocking (NMB) agents.
2. Subjects with second degree or third degree heart block unless subject has a pacemaker or pacing wires are in situ.

   Note: If subject's status-post Cardio Pulmonary Bypass (CPB) was managed without pacing wires in situ, the subject must not be suspected to be in second degree or third degree heart block at the time of DEX administration.
3. HR \< 120 bpm prior to the initiation of DEX.
4. Exposure to any investigational drug within 30 days prior to DEX administration.
5. Previous exposure to DEX as part of an investigational study.
6. In subjects that are ex-utero for less than 72 hours, a maternal history of poly-substance drug abuse, based upon the Investigator's clinical judgment.
7. At the discretion of the Investigator, subjects in whom the risk of DEX treatment is expected to exceed its benefits.
8. Subjects who have a known allergy or contraindication to fentanyl, morphine, MDZ, DEX, or other α-2 agonists.
9. Requirement for medications other than DEX, MDZ, morphine, or fentanyl for sedation and pain control.
10. Screening ALT levels \>115 U/L.

Answer: B