SER120 (low dose desmopression) Shown Safe and Effective for Nocturia in Adults
San Diego, CA USA (UroToday.com) In findings from a Phase 3 clinical study, two doses of SER120 (low dose desmopressin) resulted in statistically significant efficacy vs. placebo, and were well tolerated by adult patients with nocturia. Patients in this large, phase 3, double-blind, randomized, placebo-controlled study also reported significant improvements in quality of life, based on a new, validated, quality of life questionnaire—INTU, Impact of Nighttime Urination.
Jed Kaminetsky, MD, from NYU Medical Center, presented these findings at the recent 2016 American Urological Association meeting in San Diego, for a multi-institutional group of researchers. The investigators sought to determine whether SER120 was a safe and effective option for the treatment of nocturia among adults.
This study, the investigators noted, addresses an unmet need for patients who endure this troublesome condition. There are currently no approved treatments for it in the U.S. Nocturia can be associated with benign prostatic hypertrophy (BPH) and overactive bladder (OAB) or occur independently of these conditions due to nocturnal polyuria or a combination of factors.
SER120 is a novel formulation of low dose desmopressin (peptide analogue of the human anti-diuretic hormone vasopressin) formulated as a nasal spray, and designed to achieve low blood concentrations, limiting its anti-diuretic effect to the hours of sleep, while also decreasing the risk of hyponatremia. (Marketed desmopressin drug products are most commonly used to treat bed-wetting in children age 6 years and older.)
SER120 is a novel formulation of low dose desmopressin formulated as a nasal spray. It is designed to achieve low blood concentrations, limiting its anti-diuretic effect to the hours of sleep.
For this study, after a 2-week screening period and a double-blind 2-week placebo lead-in (to identify placebo responders), patients 50 years and older with a history of 2 or more nocturic episodes per night were randomized to one of 2 doses of SER120—1.5 or 0.75 mcg—or placebo, and treated for 12 weeks. Serum sodium was monitored every 2 weeks. Each patient kept a 3-day voiding diary.
During screening and at weeks 6 and 12 of the study, patients also completed the INTU questionnaire, consisting of 10 questions categorized to daytime and nighttime domains.
The co-primary efficacy endpoints were the mean change in number of nocturic voids and the percentage of patients with greater than or equal to 50% decrease in the mean number of nocturic voids.
A total of 806 patients were randomized: 782 were included in the ITT population. The mITT population—with 586 patients—excluded placebo responders.
For the co-primary efficacy measures, the reduction in mean nocturic episodes was significantly greater with SER120 0.75 mcg and SER120 1.5 mcg compared with placebo in both the mITT and ITT populations . The percentage of patients who achieved a ≥50% reduction in mean nocturic episodes per night was significantly higher with both doses of SER120 compared with placebo in the mITT population, and significantly higher with SER120 1.5 mcg than placebo in the ITT population (Figure 1).
An exploratory analysis among SER120 responders showed a change of -2.1
nocturic episodes per night, compared with -1.0 and 0.8 nocturic episodes in nonresponders (Figure 2)
Clinical benefit (quality of life), as measured by the INTU questionnaire, showed statistical significance for the ITT population with the 1.5 mcg dose of SER120.
Adult subjects with nocturia experienced a statistically significant improvement in quality of life versus placebo with the 1.5 mcg dose of SER120
The treatment was safe and well tolerated.
Tomas L. Griebling, MD, MPH, Senior Associate Dean for Medical Education, the University of Kansas, reflected on the potential for desmopressin for this indication, saying that, “...research continues to explore changes in dosing and administration of desmopressin for possible treatment of nocturia and nocturnal polyuria. This may help to improve the overall safety and efficacy profiles for this medication.”
Kaminetsky J, Wein A, Dmochowski R, et al. A randomized, double-blind, placebo controlled study of 2 doses of SER120 (low dose desmopressin) nasal spray in patients with nocturia. AUA2016 Annual Meeting. Publication MP74-01. Available at: http://www.aua.org/abstracts/searchabstracts.cfm