Extended First Uninterrupted Sleep Period for Older Adults Following Treatment with AV002, an Emulsified Microdose Vasopressin Analog

Kobashi K1, Brucker B M2, Yang A3, Francis L3, Newman D K4

Research Type


Abstract Category


Abstract 7
Scientific Podium Short Oral Session 2
Wednesday 29th August 2018
08:35 - 08:42
Hall B
Nocturia Quality of Life (QoL) Gerontology Voiding Dysfunction Overactive Bladder
1. Virginia Mason Medical Center, 2. New York University Langone Health, 3. Avadel Specialty Pharmaceuticals, LLC., 4. Perelman School of Medicine, University of Pennsylvania

Kathleen Kobashi



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. The first uninterrupted sleep period (FUSP) is defined as the time from bedtime to first nocturic void (NOV) 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 the next day. AV002 is an emulsified microdose vasopressin analog nasal spray approved for the treatment of nocturia due to nocturnal polyuria (NP). The effect of AV002 on FUSP and percentage of nights with ≤1 NOV were assessed in patients (pts) ≥65 years (y) and ≥75y in two Phase 3 randomized, double-blind pivotal studies.
Study design, materials and methods
Patients 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. FUSP and the percentage of nights with ≤1 NOV were measured. Safety evaluations included adverse events (AEs) and incidence of hyponatremia (moderate hyponatremia is defined as serum sodium 126-129 mmol/L and severe hyponatremia as ≤125 mmol/L).
By end of study, in both age groups the increase in FUSP (Table 1A) and percentage of nights with ≤1 NOV (Table 1B) from baseline were statistically significant compared to placebo in both treatment groups. Incidence and severity of AEs in the AV002-treated groups were similar to placebo. The incidence of hyponatremia was low for both doses (Table 2).
Interpretation of results
Both ≥65y and ≥75y patients treated with AV002 demonstrated significant improvement in duration of first uninterrupted sleep period and percentage of nights with ≤1 nocturic void. For both age groups, the mean first uninterrupted sleep period after treatment was greater than 4 hours for 1.66mcg group and approximately 4 hours for 0.83mcg group. No patients treated with 0.83mcg (recommended starting dose for patients ≥65 years old) had severe hyponatremia. These results suggest AV002 is an effective therapy with a favorable safety profile in older adults with nocturia due to nocturnal polyuria.
Concluding message
Addressing nocturia in older adults may result in better quality of sleep, increased productivity during the day, and improved overall health and health-related quality of life.
Figure 1
Figure 2
  1. Bliwise DL, Foley DJ, Vitiello MV, Ansari FP, Ancoli-Israel S, Walsh JK. Nocturia and Disturbed Sleep in the Elderly. Sleep Med. 2009 May; 10(5):540-548.
  2. Stanley N. The Underestimated Impact of Nocturia on Quality of Life. Eur Urol Suppl. 2005;4(7):17-19.
  3. Bosch JLH, Weiss JP. The Prevalence and Causes of Nocturia. J Urol. 2010;184(2):440-446.
Funding Avadel Specialty Pharmaceuticals, LLC. Clinical Trial Yes Registration Number U.S. National Library of Medicine, NCT01357356 and NCT01900704 RCT Yes Subjects Human Ethics Committee Western Institutional Review Board Helsinki Yes Informed Consent Yes