E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Initially intubated and mechanically ventilated pediatric subjects in ICU setting |
|
E.1.1.1 | Medical condition in easily understood language |
Initially intubated and mechanically ventilated pediatric subjects in ICU setting |
|
E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Anesthesia and Analgesia [E03] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
to characterize the loading and maintenance dosing of DEX by age group and overall medical condition of pediatric subjects, to evaluate the safety an efficacy of loading and maintenance infusions for sedation on initially intubated and mechanically ventilated pediatric intensive care unit subjects and to explore the exposure-response relationship between dose of DEX and clinical neasures of sedation and safety |
|
E.2.2 | Secondary objectives of the trial |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Initially intubated and mechanically ventilated pediatric subjects (≥1 month (birth age corrected for
prematurity) to <17 years of age) in an intensive care setting. The means by which the subject
was intubated could include nasotracheal, endotracheal or via tracheotomy. The subject must
have been mechanically ventilated prior to and during the commencement of study drug.
2. Anticipated to require a minimum of 6 hours of continuous intravenous (IV) sedation.
3. American Association of Anesthesiologists (ASA) classification of 1, 2, 3, or 4.
4. A UMSS score of 1, 2, 3, or 4 at the start of infusion of study drug.
5. A dose had been established for this subject's age based upon Table 1.
6. If female, subject was non-lactating and was either:
a. Not of childbearing potential, defined as pre-menarche, or surgically sterile due to
bilateral tubal ligation, bilateral oophorectomy, or hysterectomy.
b. Of childbearing potential but was not pregnant at time of baseline.
7. Subject's parent(s) or legally acceptable representative had/have voluntarily signed and dated the
informed consent document approved by the Institutional Review Board (IRB). Assent was
obtained where age-appropriate and according to state regulations. |
|
E.4 | Principal exclusion criteria |
Pediatric subjects with neurological conditions that prohibited an evaluation of sedation in the
opinion of the Investigator (e.g., increased intracranial pressure or extensive brain surgery).
2. The infusion pump minimal capacity could not accommodate the lowest possible maintenance
infusion rate of study drug based on subject's weight.
3. Subjects with second degree or third degree heart block unless subject had a pacemaker or
pacing wires.
4. Hypotension that persisted beyond a 15-minute period of re-assessment prior to starting study
drug:12
• Age 1 month to ≤6 months old: systolic BP (SBP) <60 mmHg
• Age >6 months to <2 years old: SBP <70 mmHg
• Age >2 to <12 years old: SBP <80 mmHg
• Age >12 to <17 years old: SBP <90 mmHg
5. Pre-existing bradycardia that persisted beyond a 15-minute period of re-assessment prior to
starting study drug:
• Age 1 month to <2 months old: HR <90 beats per minute (bpm)
• Age ≥2 months to <12 months old: HR <80 bpm
• Age ≥12 months to <2 years old: HR <70 bpm
• Age ≥2 to <12 years old: HR <60 bpm
Age ≥12 to <17 yrs old: HR <50 bpm
6. Alanine aminotransferase (ALT/ serum glutamic-pyruvic transaminase [SGPT]):
• 1 month to 12 months old: >165 units/liter (U/L)
• >12 months to <17 years old: ≥100U/L
Note: Subjects could be re-screened up to 6 hours prior to study drug infusion (not including
subjects undergoing cardiac surgery with CPB).
7. Subjects had a known allergy to DEX, MDZ, morphine, or fentanyl.
8. Requirement for medications other than DEX, MDZ, morphine, or fentanyl for sedation and pain
control.Subjects with immobility from neuromuscular disease, paralysis from administration of
neuromuscular blocking (NMB) agents, spinal cord injury above T5 or subjects with muscle |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The percent of subjects that do not require rescue MDZ for
sedation based on achieving and maintaining a target UMSS score of 1 to 3 while intubated |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
continuous infusion of DEX must be at least 6 hours |
|
E.5.2 | Secondary end point(s) |
Secondary endpoints included the absolute time and percentage of time on study drug that the subject
is in a UMSS score range of 1 to 3 while intubated; absolute time and percentage of time on study drug
that the subject was out of the target sedation range while intubated (UMSS score of 0 or 4); total amount
of rescue medication required for sedation and analgesia; time to first dose of rescue medication for
sedation and analgesia; and time to extubation. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
|
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
different dosage of the investigational product |
|
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
|
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |