E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Critically Ill Premature Neonates between 23 and 32 weeks of gestation who are receiving morphine as part of their routine medical management of pain or other medically indicated condition for which the drug is prescribed. |
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E.1.1.1 | Medical condition in easily understood language |
Zieke te vroeg geboren kinderen tussen de 23 en 32 weken zwangerschap geboren waarbij morfine als pijnmedicatie volgens standaard protocol wordt voorgeschreven. |
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E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Anesthesia and Analgesia [E03] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10056350 |
E.1.2 | Term | Pain management |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
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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 improve dosing of morphine in critically ill premature neonates, leading to improved pain control and decreased adverse drug reactions. More immediately, we will develop a PK/PD model for morphine dosing based on relevant developmental and genetic characteristics |
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E.2.2 | Secondary objectives of the trial |
To evaluate the relationship of developmental stage (defined by both gestational and postnatal age) to UGT2B7 activity (as determined by CLf,M3G and CLf,M6G).
To evaluate the relationship of UGT2B7 genetic variability to UGT2B7 activity (as determined by CLf,M3G and CLf,M6G).
To evaluate the relationship of glomerular filtration rate to the elimination clearances of morphine, M3G and M6G (CLother, CLM3G, and CLM6G ) and morphine concentrations in both blood and urine.
To evaluate the relationship of µ-opioid receptor and COMT genetic variability to clinical response following administration of morphine.
To develop a population PK/PD model of morphine dosing based on gestational age, postnatal age, glomerular filtration rate, and variability in UGT2B7, µ-opioid receptor and COMT genes |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Preterm neonates of both genders and all races
postnatal age less than 30 days
an indwelling (peripheral or umbilical) arterial line, and
a clinical indication for intravenous morphine administration
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E.4 | Principal exclusion criteria |
Neonates with severe asphyxia, grade III or IV intraventricular hemorrhage, major congenital malformations/facial malformations, neurological disorders, and those receiving continuous or intermittent neuromuscular blockers.
clinical or biochemical evidence of hepatic and renal compromise (including systemic hypoperfusion) or
received drugs that are UGT2B7 substrates (including Lorazepam, ibuprofen, valproic acid, naloxone and other morphine derivatives or propanolol)
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E.5 End points |
E.5.1 | Primary end point(s) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
TIMELINE
PK/PD model (year 03 - 05)
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E.5.2 | Secondary end point(s) |
Year 01-Year 05
I. Patient enrollment in clinical study and morphine assay
II. UGT2B7 SNP discovery and genotyping
III. Patient enrollment in clinical study and inulin assay
IV. COMT and µ-opioid receptor SNP discovery and genotyping
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
TIMELINE
Year 01-Year 05
I. Patient enrollment in clinical study and morphine assay (year 01 -04)
II. UGT2B7 SNP discovery and genotyping (year 01 - 05)
III. Patient enrollment in clinical study and inulin assay (year 01 -04)
IV. COMT and µ-opioid receptor SNP discovery and genotyping (year 01 -05)
V. PK/PD model (year 03 - 05)
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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 | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
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 | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
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 |