VA106483 Dose Response Study in Elderly Males

Study Overview
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Brief Summary
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The main purpose of the study is to evaluate the way VA106483 enters and leaves the blood and tissues over time and how the drug acts on and in the body at various dose levels compared to placebo in the same volunteer.

Detailed Description
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VA106483 is intended to be used as a treatment for patients suffering from nocturia (defined as waking to urinate at least once per night between periods of sleep). Nocturia is a condition that often worsens as sufferers get older. This may be due to an over-active bladder muscle, the bladder being able to hold less urine at night-time or over production of urine in the bladder at night. The only antidiuretic approved for the treatment (in some countries) of nocturia is the peptide drug, desmopressin. However, as it can cause hyponatraemia in a proportion of patients above the age of 65 years it is contra-indicated in the elderly. This side-effect has not been observed with VA106483, making it potentially suitable for treating the elderly. The purpose of this study is to confirm that duration of action of VA106483 can be effectively controlled by dose and therefore that satisfactory clinical outcome in the treatment of nocturia can be achieved by individual dose titration. Subjects will be water-loaded, dosed with either VA106483 or placebo and then urine production will be monitored to assess any anti-diuretic effect.

Official Title
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An Open Label, Escalation Study to Assess Intra-Subject Dose Response to VA106483 in Elderly Male Subjects

Conditions
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Nocturia

Intervention / Treatment
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* Drug: VA106483
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male, Age: 65 years and above Using adequate contraception Medical history without clinically significant pathologies; no evidence of serious pathology or disease Physical examination parameters without signs of serious disease No clinically significant ECG and lab safety tests (sodium must be within normal range) Willing and able to participate and provides written informed consent Exclusion Criteria: Cardiac insufficiency; signs or symptoms suggestive of heart failure or requiring treatment with diuretics Supine arterial blood pressure higher than 170/100 mmHg or less than 105/60 mm Hg Presence of poorly controlled endocrine disorders Renal insufficiency, active hepatic and/or biliary disease Hyponatraemia. Serum sodium level must be within normal limits Syndrome of inappropriate antidiuretic hormone (ADH) secretion Symptoms suggestive of psychogenic or habitual polydipsia or of diabetes insipidus Known hypersensitivity to the IP or any constituent of the IP Use of any non-prescription preparation within 72 hours prior to study entry, with the exception of defined pain killers A history of alcohol abuse or drug addiction within the last 2 years Positive screen for HIV, hepatitis B or C Currently taking any diuretics or any concomitant medication known to be a cytochrome 3A4 inhibitor Other protocol defined eligibility criteria may apply.

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Sugar pill<br> | Drug: Placebo<br>* Placebo on Day 1, 1 mg VA106483 on Day 3, 2 mg VA106483 on Day 5 and 4 mg VA106483 on Day 7<br>|
| Experimental: VA106483 1 mg<br> | Drug: VA106483<br>* Placebo on Day 1, 1 mg VA106483 on Day 3, 2 mg VA106483 on Day 5 and 4 mg VA106483 on Day 7<br>|
| Experimental: VA106483 2 mg<br> | Drug: VA106483<br>* Placebo on Day 1, 1 mg VA106483 on Day 3, 2 mg VA106483 on Day 5 and 4 mg VA106483 on Day 7<br>|
| Experimental: VA106483 4 mg<br> | Drug: VA106483<br>* Placebo on Day 1, 1 mg VA106483 on Day 3, 2 mg VA106483 on Day 5 and 4 mg VA106483 on Day 7<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urine volume and osmolality and plasma PK assessments |  | 24 Hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nocturia, Pharmacokinetics, Pharmacodynamics, Water-loading, Elderly, Males