E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10029446 |
E.1.2 | Term | Nocturia |
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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 determine the pharmacodynamic profile of VA106483 including urinary volume, urinary osmolality, blood pressure, pulse rate, serum electrolytes and blood coagulation factors in elderly male subjects.
To determine the pharmacokinetic profile of VA106483 in elderly male subjects.
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E.2.2 | Secondary objectives of the trial |
To assess the safety and tolerability of VA106483 given as single and repeated oral doses compared to placebo in elderly male subjects. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Age: 65 years and above 2. Gender: Male 3. Weight: 55–95 kg 4. BMI: 18–32 kg/m2 5. Medical history without clinically relevant pathologies 6. A history of nocturia 7. Physical examination parameters without signs of serious disease 8. Electrocardiogram recording without signs of clinically relevant pathology, in particular QTc (Bazett) <450 ms 9. Values for haematology and for biochemistry tests of blood and urine within the normal range or showing no clinically relevant deviation as judged by the medical investigator (in particular serum electrolytes) 10. Having given written informed consent before any study-related activities are carried out
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E.4 | Principal exclusion criteria |
1. Female 2. Males aged under 65 years 3. Evidence of serious pathology or disease 4. Cardiac insufficiency; signs or symptoms suggestive of heart failure or requiring treatment with diuretics 5. Supine arterial blood pressure higher than 170/100 mmHg or less than 105/60 mmHg 6. Presence of poorly controlled endocrine disorders 7. Renal insufficiency. Subjects with impaired renal function defined as calculated creatinine clearance < 40 mL/min based upon the value derived at screening using the Cockcroft and Gault equation ((140−age)*(weight in kg)/(72*serum creatinine in mg/dl). 8. Active hepatic and/or biliary disease. AST or ALT should not be >10% above maximum of normal range. Total bilirubin should not be > 1.5 mg/dl (or equivalent). 9. Hyponatraemia. Plasma sodium level must be within normal limits 10. Syndrome of Inappropriate ADH secretion 11. Symptoms suggestive of psychogenic or habitual polydipsia or of diabetes insipidus 12. Mental handicap 13. Legal incapacity 14. Any history of clinically important emotional and/or psychiatric illness or of any clinically important neurological disorders and/or epilepsy 15. Chronic diarrhoea or other chronic gastrointestinal disorders 16. Known hypersensitivity to the study drug or constituent of the study drug 17. History of any relevant allergy, especially drug and/or food allergies 18. Strict vegetarian 19. Intake of diuretics 20. Intake of non-prescription medication or vitamin preparations within 14 days of drug administration 21. Use of St. John’s Wort or Ginkgo Biloba (also known as Ginkgo Bilbao) within 48 hours prior to randomization 22. Participation in a clinical study within 30 days prior to randomization 23. Donation of blood within 60 days prior to randomization 24. Receipt of blood, blood products or plasma derivates one year prior to randomization 25. Any history of alcohol abuse or drug addiction 26. Positive results at screen for drugs of abuse (cocaine, amphetamine / methamphetamine, tetrahydrocannabiol, opiates) or alcohol (breath test) at screening or on admission 27. Positive screen results for HBsAg, anti-HCV, or anti-HIV1&2 28. Any disease which in the Investigator’s opinion would exclude the subject from the study 29. Intake of any concomitant medication known to be a cytochrome 3A4 substrate or inhibitor with the exception of simvastatin, atorvastatin, lovastatin and cerivastatin* *The statins listed above are amongst the most common concomitant medications in the population under study. The highest exposure to VA106483 in the current study is Cmax of 71.1ng/ml at a dose of 4mg. Since the Ki of VA106483 for cytochrome P450 3A4 is 7500ng/ml the [I]/Ki is <0.01 rendering any interaction with other 3A4 substrates remote even at doses of VA106483 up to 16mg. Similarly, since the listed statins are also substrates, any effect on the pharmacokinetics of VA106483 is remote |
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E.5 End points |
E.5.1 | Primary end point(s) |
Pharmacokinetic parameters measured in plasma: AUC0-t, AUC0-∞, AUC0-τ, Cmax, Cmaxss, Ctrough, tmax, tmaxss, λz, t½, MRT
Pharmacodynamic parameters measured in plasma: Serum electrolytes sodium and potassium, hematocrit, serum osmolality, circulating FVIII and vWF levels
Pharmacodynamic parameters measured in urine: Urinary volume and urine osmolality, AUC urine osmolality, total volume voided, urinary output rate, duration of antidiuretic action, number and frequency of nocturnal voids during non-water loading periods
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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 | Yes |
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 | Information not present in EudraCT |
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 | 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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
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 | Yes |
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 | Information not present in EudraCT |
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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The study will terminate once the last subject has been discharged. |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 14 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 14 |