A double-blind, placebo-controlled dose response study to investigate pharmacodynamics and pharmacokinetics of single and repeated oral doses of VA106483 in elderly male subjects

• Conditions: octuria.; MedDRA version: 9.1Level: LLTClassification code 10029446Term: Nocturia

• Registration Number: EUCTR2008-003774-17-GB
• Lead Sponsor: Vantia Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-06-27
• Last Update Posted: 24 July 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Male
• Target Recruitment: 27

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

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified