AUA 2018: Extended First Uninterrupted Sleep Period in Elderly Patients Following Treatment with AV002, an Emulsified Low Dose Vasopressin Analog for Nocturia

San Francisco, CA ( Nocturia, characterized by the need to wake at night to urinate, has gained increasing exposure in the urologic community due to its high prevalence and negative impact on quality of life. It often is associated with disrupted sleep, resulting in decreased productivity, poorer overall and mental health, increased risk of falls and fractures, and increased mortality. Studies have also shown it leads to decreased concentration and cognitive function, poorer moods, and reduced energy, as well as increased susceptibility to disease. Unfortunately, treatment options for nocturia remain limited and/or associated with adverse side effects.

AV002, an emulsified low dose vasopressin analog delivered by a nasal spray, is a new medication approved for the treatment of nocturia due to nocturnal polyuria (NP). Compared to DDAVP, however, AV002 has an immediate effect, with 4-6 hour duration, and a lower risk of hyponatremia, according to recent studies. Microdoses of desmopressin are administered, due to a new formulation of the medication, which allows for administration of lower doses, high consistency, high bioavailability, and increased absorption. 

Benjamin Brucker, MD of NYU presented the results of two Phase 3 randomized, double-blind pivotal studies involving AV002 during the late-breaking abstract session at the 2018 AUA meeting. The objective of the study was to assess the use of AV002 in older adults ≥65 years and ≥75 years and its effect on first uninterrupted sleep period (FUSP), defined as the elapsed time from bedtime to first nocturic void (NOV) or awakening if no void occurred. The study also evaluated whether AV002 impacted the percentage of nights with 0-1 nocturic voids, and whether it was safe in this age group. 

1333 patients greater than ≥50 years old with a history of 2+ NOV per night for 6 months were included. For a secondary efficacy and safety analysis, patients ≥65 years (n=727) and ≥75 years (n=292) were evaluated. Subjects were randomized to three treatment arms: 1.66mcg AV002, 0.83mcg AV002, or placebo for 12 weeks. FUSP and percentage of nights with ≤1 NOEP were evaluated. Safety evaluation included adverse events (AEs) and incidence of hyponatremia (moderate: 126-129 mmol/L; severe: ≤125 mmol/L).

AV002 was found to consistently extend FUSP across all age groups at the 1.66 mcg dose, increasing the amount of time to the first void from an average of 2.5 hours at baseline to over 4 hours of sleep. At the 0.83 mcg dose, a similar effect as seen compared to placebo, but the FUSP was not as high as the 1.66 mcg dose.  The percentage of nights with ≤1 NOEP was seen to increase significantly from baseline as well, with a greater effect seen at the higher dose. The rate of hyponatremia was low with both the 0.83 mcg and 1.66 mcg doses; 5/448 (1.1%) subjects in the 1.66mcg dose treatment arm developed severe hyponatremia, compared to 0/454 (0%) in the 0.83 mcg dose treatment arm and 1/454 (0.2%) in the placebo arm. Of note, none of the subject participants were instructed to undergo any dietary or fluid modifications, and patients with histories of either benign prostatic hyperplasia or overactive bladder were not excluded from analysis.

Based on the results of the study, AV002 demonstrated significant improvement in FUSP and proportion of nights with ≤1 NOEP with a low risk of severe hyponatremia. The current data suggest that AV002 is an effective therapy with a favorable safety profile for nocturia in older age groups.

Presented by: Benjamin M. Brucker, MD NYU, New York, NY
Co-Authors: Leo Francis, Alex Yang, Chesterfield, MO, Eric S. Rovner, Charleston, SC

Written by: Judy Choi, MD, Assistant Professor, Department of Urology, University of California, Irvine @judymchoi at the 2018 AUA Annual Meeting - May 18 - 21, 2018 – San Francisco, CA USA

Watch a Video on this Presentation by Benjamin Brucker, MD