E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Distal renal tubular acidosis |
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E.1.1.1 | Medical condition in easily understood language |
Genetic disease resulting in too low blood pH |
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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 | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10038535 |
E.1.2 | Term | Renal tubular acidosis |
E.1.2 | System Organ Class | 10038359 - Renal and urinary disorders |
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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 |
To evaluate the safety and tolerability as measured by adverse events of ADV7103 at long term. |
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E.2.2 | Secondary objectives of the trial |
- To evaluate the efficacy on correcting metabolic acidosis as measured by bicarbonataemia of ADV7103 at long-term. - To evaluate the effects on hypocitraturia of ADV7103 at long term. - To evaluate the effects on hypercalciuria of ADV7103 at long term. - To evaluate the effects on crystalluria of ADV7103 at long term. - To evaluate the paraclinical and biological safety of ADV7103 at long term. - To evaluate the compliance to ADV7103 at long term.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subject who has participated to and completed the previous Advicenne clinical Study B21CS. |
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E.4 | Principal exclusion criteria |
Subject who has not participated to Advicenne clinical Study B21CS Subject for whom any safety issue could contraindicate her/his participation to the extension study.
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety and tolerability endpoint: Number/proportion of subjects presenting adverse events during the course of the study, including the incidence and severity of the adverse events |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
During the all study period |
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E.5.2 | Secondary end point(s) |
1. Efficacy endpoints - Number/proportion of subjects presenting a bicarbonataemia in the normal ranges - Mean and change from baseline of values of bicarbonate blood level at each study visit (with baseline defined at the inclusion in the B21CS Study) - Number/proportion of subjects presenting a citraturia in the normal ranges, at each study visit including the incidence and severity of the hypocitraturia - Mean and change from baseline (with baseline defined at the inclusion in the B21CS Study) of values of citrate/creatinine urine ratio (UCi/Cr) at each study visit - Number/proportion of subjects presenting a calciuria in the normal ranges, at each study visit including the incidence and severity of the hypercalciuria - Mean and change from baseline of urine calcium/citrate ratio (UCa/Ci) at each study visit (with baseline defined at the inclusion in the B21CS Study) - Number/proportion of subjects presenting a crystalluria (mainly with hydroxyapaptite) at each study visit - Mean and change from baseline of crystalluria (mainly with hydroxyapatite) at each study visit (with baseline defined at the inclusion in the B21CS Study)
2. Safety and tolerability endpoints • Number/proportion of subjects presenting abnormal values after treatment, at each study visit including the incidence and severity of these abnormal values and the change from baseline (with baseline defined at the inclusion in the B21CS Study when applicable) - Vital signs (SBP, DBP, HR, RR) - ECG parameters (PR, QRS, QT interval, Bazett and Fridericia QTc intervals) - Liver function tests (transaminases ASAT, ALAT) - Urinalysis including urine pH and specific gravity, with microscopic examination if required
3. Compliance endpoint • Compliance to the treatment by counting of the empty pillboxes returned by the patient, including the incidence of events of non-compliance at M3, M6, M12, M18 and M24 presented as number/proportion of subjects compliant at least 50%, at least 75% or at least 90% of the time |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | 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 | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 22 |
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 |
France |
Serbia |
Slovakia |
Spain |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 6 |