| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated | | Ongoing hyponatraemia in euvolemic and hypervolemic states | |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 7 | | E.1.2 | Level | 1.1 | | E.1.2 | Classification code | 10021036 | |
| 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 assess the safety of long-term tolvaptan use in patients previously enrolled in shorter-term Phase 3 studies and gather information on the natural history of hyponatraemia in the context of tolvaptan therapy and underlying disease states. | |
| E.2.2 | Secondary objectives of the trial | | The efficay of tolvaptan will be measured. Study drug compliance, dosage adminsitered, serum levels and clinical laboratory measurements will be monitored and summarised. | |
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria | 1. Age greater than or equal to 18 years.
2. Ability to provide informed consent or assesnt.
3. Prior successful participation up to completion of planned Amendment 3 trial termination with evidence of continued need or desire for therapy. | |
| E.4 | Principal exclusion criteria | 1. A current medical condition where long-term treatment with an aquaretic agent may present an undue risk to the patient.
2. Hyponatraemia which is acute, reversible, artifactual or due to conditions not associated with vasopressin excess or likely to repond to aquaretic therapy.
3. Hyponatraemia due to reversible medical condition or therapy.
4. Conditions associated with an independent imminent risk of morbidity and mortality.
5. Conditions which confound the assessment of end points.
| |
| E.5 End points |
| E.5.1 | Primary end point(s) | | Safety and long-term tolvaptan therapy will be assessed qualitatively and quantitavely using descriptive statistics of adverse events, vital signs (weight, HR and BP), and local electrocardiograms (baseline, post dose 8 hours, Day 1, Day 14, W58, W106, W154, W214/ET and at the Post-W214 Follow-up visit) and local clinical lab testing of critical electrolytes (sodium, chloride, potassium), glucose, renal function (serum creatinine, BUN/Blood nitrogen), liver functions (AST, ALT, total bilirubin). cell counts (RBC or hemoglobin/hematocrit, WBC, platelet) and coagulation parameters (PTT, PT and/or INR) | |
| 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 | Yes |
| 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 | Information not present in EudraCT |
| 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 | 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 | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 10 |
| 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 | Information not present in EudraCT |
| 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 | |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 4 |
| E.8.9.1 | In the Member State concerned months | 3 |
| 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 | 3 |
