Dose Response Study of VA106483 in Males With Nocturia and Benign Prostatic Hypertrophy (BPH)

Study Overview
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Brief Summary
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The purpose of this study is to establish the dose response relationship of VA106483 and nocturnal urine volumes in a population of elderly male subjects with Benign Prostatic Hypertrophy (BPH) who are likely to present with nocturia.

Detailed Description
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VA106483 is a selective vasopressin V2-receptor (V2-receptor) agonist that is being developed for the treatment of nocturia. The antidiuretic effect of V2-receptor stimulation in the kidneys is well established through the use of the peptide agonist, desmopressin, which shows clinical benefit in diabetes insipidus, primary nocturnal enuresis and nocturia. Nocturia, defined as waking to void at least once per night between periods of sleep, is a common complaint and shows an age-dependent increase in both prevalence and severity (number of nocturnal voids). It is the most bothersome symptom of benign prostatic hypertrophy and has been linked to an age-dependent loss in circadian release of endogenous nocturnal vasopressin and consequent over production of urine at night (nocturnal polyuria). Correlation between nocturnal urine volume and nocturnal void frequency has been demonstrated in previous studies of V2-receptor agonists. The purpose of this study is to determine the dose response relationship of VA106483 and nocturnal urine volumes.

Official Title
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A Randomised, Double-blind, Placebo-controlled, Five-way Cross-over Dose Response Study to Determine the Effect of VA106483 on Nocturnal Urine Volume in Elderly Male Subjects With Nocturia and Benign Prostatic Hypertrophy (BPH)

Conditions
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Nocturia, Benign Prostatic Hypertrophy (BPH)

Intervention / Treatment
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* Drug: VA106483


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males aged 65 years old and above with history of nocturia and benign prostatic hypertrophy (BPH) Exclusion Criteria: Administration of any Investigational Medicinal Product (IMP) within 10 weeks before entry to the study Any clinically significant concomitant medical disease, condition or abnormal laboratory test result 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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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VA106483 0.5 mg<br> | Drug: VA106483<br>* Once daily oral dose of placebo for 2 nights Once daily oral dose of 0.5 mg VA106483 for 2 nights Once daily oral dose of 1 mg VA106483 for 2 nights Once daily oral dose of 2 mg VA106483 for 2 nights Once daily oral dose of 4 mg VA106483 for 2 nights Placebo: as above<br>|
| Experimental: VA106483 1 mg<br> | Drug: VA106483<br>* Once daily oral dose of placebo for 2 nights Once daily oral dose of 0.5 mg VA106483 for 2 nights Once daily oral dose of 1 mg VA106483 for 2 nights Once daily oral dose of 2 mg VA106483 for 2 nights Once daily oral dose of 4 mg VA106483 for 2 nights Placebo: as above<br>|
| Experimental: VA106483 2 mg<br> | Drug: VA106483<br>* Once daily oral dose of placebo for 2 nights Once daily oral dose of 0.5 mg VA106483 for 2 nights Once daily oral dose of 1 mg VA106483 for 2 nights Once daily oral dose of 2 mg VA106483 for 2 nights Once daily oral dose of 4 mg VA106483 for 2 nights Placebo: as above<br>|
| Experimental: VA106483 4 mg<br> | Drug: VA106483<br>* Once daily oral dose of placebo for 2 nights Once daily oral dose of 0.5 mg VA106483 for 2 nights Once daily oral dose of 1 mg VA106483 for 2 nights Once daily oral dose of 2 mg VA106483 for 2 nights Once daily oral dose of 4 mg VA106483 for 2 nights Placebo: as above<br>|
| Placebo Comparator: Sugar pill<br> | Drug: VA106483<br>* Once daily oral dose of placebo for 2 nights Once daily oral dose of 0.5 mg VA106483 for 2 nights Once daily oral dose of 1 mg VA106483 for 2 nights Once daily oral dose of 2 mg VA106483 for 2 nights Once daily oral dose of 4 mg VA106483 for 2 nights Placebo: as above<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the mean nocturnal urine volumes |  | 20 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the mean nocturnal void frequency |  | 20 days | 
| Change in mean time to first void |  | 20 days | 
| Change in frequency of daytime voids |  | 20 days | 
| Change in mean volume of daytime voids |  | 20 days | 
| Change in mean nocturnal urine osmolality |  | 20 days | 
| Change in mean daytime urine osmolality |  | 20 days | 
| Change in mean voided volumes |  | 20 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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VA106483, Nocturia, Benign Prostatic Hypertrophy, BPH, Elderly, Males, Nocturnal voids, Anti-diuretic