E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Spinal muscular atrophy type II (SMA II)
Cerebral palsy (CP) |
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E.1.1.1 | Medical condition in easily understood language |
SMA II is a neuromuscular disorder, causing muscular wasting and low skeletal muscle mass. CP is a disease caused by a brain damage occured in perinatal period. The patients has low muscle mass. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To investigate the safety and toxicity related to paracetamol treatment in children and adults with respectively SMA and CP.
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Patients: Men, women and children diagnosed with/biochemically verified SMA and CP - Patients admitted to the ICU: Men, women, children diagnosed with/biochemically verified SMA and CP - Healthy controls: Need to be healthy, evaluated by the investigator. - Age: o Children: 6-18 years o Adult patients: 18-45 years o Healthy controls: 18-45 years o ICU-admitted patients: 6-45 years - Signed informed consent to participation in the trial
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E.4 | Principal exclusion criteria |
- Inability to understand the purpose of the trial or cooperate in the conduction of the experiments. o For the children this will concern of course the parents or the guardians of the child. - Competing conditions at risk for compromising the results of the study. - Participation in other trials that may interfere with the results. - Intake of medications that may interfere with the results, evaluated by investigator. - Pregnancy and breastfeeding. - BMI >30
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E.5 End points |
E.5.1 | Primary end point(s) |
- Clearance (total, glucuronidation, sulphation, CYP2E1 oxidation and unchanged) of paracetamol in patients with SMA, CP and ICU-admitted patients with either SMA or CP. - Volume of distribution of paracetamol in patients with SMA, CP and ICU-admitted patients with SMA or CP, in comparison with healthy controls.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Before, during and after treatment of paracetamol in three consecutive days. |
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E.5.2 | Secondary end point(s) |
- Liver function tests in patients with SMA, CP and ICU-admitted patients with SMA or CP. - Concentration-time data on plasma paracetamol, paracetamol-sulphate, paracetamol-glucuronide, paracetamol-cysteine and paracetamol-mercapturate (oxidative metabolites), plasma-glutathione and liver biomarkers (ALAT, PP, bilirubin, MicroRNA-122 (miR-122)).
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Before, during and after treatment of paracetamol in three consecutive days. |
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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 | No |
E.6.8 | Bioequivalence | Yes |
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) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
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E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
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 | Yes |
E.8.2.3.1 | Comparator description |
Matched healthy controls for adult patients and data from litterature for child patients |
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E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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 | 6 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |