E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Nephrogenic diabetes insipidus |
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E.1.1.1 | Medical condition in easily understood language |
A genetic disease where the ability to retain water in the kidney is impaired (Nephrogenic Diabetes Insipidus) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10012600 |
E.1.2 | Term | Diabetes insipidus nephrogenic |
E.1.2 | System Organ Class | 100000004857 |
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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 |
The overall aim is to improve quality of life and relieve of the severe impairment associated with NDI in patients. This is achieved by testing if the antifungal drug fluconazole can reduce diuresis and improve the urinary concentration ability in patients with nephrogenic diabetes insipidus due to an AVPR2 gene mutation. |
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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 |
- Male
- Age > 18 year
- Mentally capable of understanding the test
- Nephrogenic diabetes insipidus diagnosed by genetic defect in AVPR2
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E.4 | Principal exclusion criteria |
- Other known relevant disease including malignity
- Contraindications to fluconazole
- Prolonged QT interval on baseline ECG
- Concurrent treatment with drugs metabolized by CYP3A4, CYP2C19 or CYP2C9
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Diuresis (mL/day): Evaluated weekly by 24hour urine samples
2. Urinary concentration ability evaluated by a water deprivation test before and after the intervention
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Weekly throughout the intervention
2. Before and after the intervention |
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E.5.2 | Secondary end point(s) |
Secondary outcomes:
1. Urinary osmolality
2. Plasma osmolality (mmol/kg): Evaluated by weekly blood samples
3. Plasma electrolytes
4. Micturition frequency
5. Abundance of AQP2 in urinary exosomes: Spot urine samples before and after the intervention
6. Plasma vasopressin and copeptin concentrations |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Weekly throughout the intervention
2. Weekly throughout the intervention
3. Weekly throughout the intervention
4. Daily throughout the intervention
5. Before and after the intervention
6. Weekly throughout the intervention |
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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 | 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) | 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 | 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
| 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 | 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 | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |