Hypothesis / aims of study
Nocturia is a highly prevalent, under-recognized condition associated with disrupted sleep, reduced productivity, and negative impacts on overall health and health-related quality of life. Oftentimes, it is unclear whether a therapy is effective for nocturia given the lengthy time to confirm responsiveness, if at all. Hence, the rapidity of effect on nocturia is of keen interest. ≥2 nocturic voids (NOVs) is associated with decreased quality of life. Achieving a reduction of 0.5 NOVs is clinically significant. First uninterrupted sleep period (FUSP) is defined as the time from bedtime to first nocturic void or awakening if no void occurred. The first 3-4 hours of sleep includes deep, slow wave, restorative sleep, which is correlated with improved productivity. AV002 is an emulsified microdose vasopressin analog nasal spray approved for the treatment of nocturia due to nocturnal polyuria. The effect of the first dose of AV002 on the number of NOV and FUSP were assessed in patients in two Phase 3 randomized, double-blind pivotal studies.
Study design, materials and methods
Patients ≥50 years old with a history of ≥2 NOVs per night for ≥6 months (n=1333) were randomized to AV002 1.66mcg, AV002 0.83mcg, or placebo and treated for 12 weeks. After first dose, number of NOV and FUSP were measured. Safety evaluations included adverse events (AEs) and incidence of hyponatremia (moderate: 126-129 mmol/L; severe: ≤125 mmol/L).
Interpretation of results
After first dose, patients treated with AV002 demonstrated significant reduction of nocturic voids and improvement in duration of first uninterrupted sleep period. These results suggest AV002 has rapid efficacy with a favorable safety profile in patients with nocturia due to nocturnal polyuria.