E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acquired methemoglobinemia |
|
E.1.1.1 | Medical condition in easily understood language |
abnormal increase in blood concentration of an altered form of haemoglobin |
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E.1.1.2 | Therapeutic area | Diseases [C] - Injuries, poisonings, and occupational diseases [C21] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10054290 |
E.1.2 | Term | Acquired methemoglobinemia |
E.1.2 | System Organ Class | 100000012871 |
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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 confirm that methylene blue after a single administration is efficacious in patients with acquired methemoglobinemia. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of a single dose of 1 mg/kg of methylene blue
· To evaluate the efficacy of a second dose of 1 mg/kg of methylene blue to further reduce metHb levels when metHb is not fully reduced by a single dose;
· To evaluate the normalisation of the respiratory rate, heart rate and blood pressure of patients who achieve a reduction in metHb level within 2 hours of receiving the first dose of methylene blue
· To confirm the safety and tolerability of methylene blue injection in patients with acquired methemoglobinemia. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Paediatric or adult patients (males and females of all ages are included) diagnosed with acquired methemoglobinemia and receiving treatment with methylene blue as per the treating physician’s diagnosis and hospital standard of care.
Acquired methemoglobinemia is defined as a level of methemoglobinemia >30% or ≤30% with associated clinical symptoms (e.g. sleepiness, cyanosis, dizziness, etc.).
2. Written informed consent obtained prior to any data collection (retrospective and prospective) for this study and study specific assessments. |
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E.4 | Principal exclusion criteria |
1. Known severe hypersensitivity reactions to methylene blue or any other thiazine dye;
2. Known deficiency in glucose-6-phosphate dehydrogenase (G6PD) due to the risk of haemolytic anaemia as well as lack of therapeutic effect. |
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E.5 End points |
E.5.1 | Primary end point(s) |
A 50% reduction in metHb level for treatment of acquired methemoglobinemia. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
within 1 hour of the first dose of ProvayBlue |
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E.5.2 | Secondary end point(s) |
1) Concomitant normalisation of the respiratory rate, heart rate and blood pressure
2) Evaluation of the patients who achieve a 50% reduction in metHb level after a single
dose of methylene blue in addition to normalisation of the respiratory rate, heart rate and blood pressure;
3a) Evaluation of the number of patients who achieve a 50% reduction in metHb level in addition to 3b) normalisation of the respiratory rate, heart rate and blood pressure·
4) Evaluation of the patients who achieve a 50% reduction in metHb level after a second dose of methylene blue, in addition to normalisation of the respiratory rate, heart rate and blood pressure, in cases where a single dose did not completely normalise metHb level; |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
for 1), within 2 hours of the first dose of methylene blue;
for 3a) within one hour after treatment with methylene blue
for 3b) within 2 hours of receiving the first dose of methylene blue |
|
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 | Yes |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
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 | 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
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 15 |
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 |
|
E.8.7 | Trial has a data monitoring committee | No |
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 | 3 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 12 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 12 |