Introduction & Objective : 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. It is often unclear whether a therapy is effective for nocturia given the lengthy time to confirm responsiveness. Hence, the rapidity of effect on nocturia is of keen interest. First uninterrupted sleep period (FUSP) is defined as elapsed 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 desmopressin nasal spray approved for the treatment of nocturia due to nocturnal polyuria (NP). The efficacy of the first dose of AV002 on FUSP and safety were assessed in two Phase 3 randomized, double-blind pivotal studies. Patients’ difficulty getting enough sleep was assessed in one study.
Methods : Patients ≥50 years old with NP at screening and a history of ≥2 nocturic voids per night for ≥6 months (n=1,045) were randomized to AV002 1.66mcg, 0.83mcg, or placebo and treated for 12 weeks. After first dose, FUSP was measured. Patients’ level of difficulty getting enough sleep was reported via the Impact of Nighttime Urination (INTU) health-related quality of life instrument. Safety evaluations included adverse events (AEs) and incidence of hyponatremia. Safety and INTU were evaluated throughout the study period.
Results : On first dose, increase in FUSP was significant compared to baseline in both AV002-treated groups (Table 1A). Patients on AV002 were 3 times more likely to not have any difficulty getting enough sleep. Throughout the two studies, incidence and severity of AEs in AV002-treated groups were similar to placebo. No patients treated with 0.83 mcg experienced severe hyponatremia (Table 1B).
Conclusions : Patients treated with AV002 experienced significant improvement in duration of FUSP on first dose and their difficulty getting enough sleep. The incidence of hyponatremia was low for both doses. These results suggest AV002 has rapid efficacy with a favorable safety profile in patients with nocturia due to NP. Rapidly reducing nocturia on first dose enables clinicians and patients to quickly confirm responsiveness while providing confidence in ongoing therapy.