Efficacy and Safety of Low Dose Desmopressin Orally Disintegrating Tablet in Men with Nocturia: Results of a Multicenter, Randomized, Double-Blind, Placebo Controlled, Parallel Group Study
Abstract
Purpose:
We investigated the efficacy and safety of 50 and 75 μg desmopressin orally disintegrating tablets in men with nocturia (2 or more nocturnal voids).
Materials and Methods:
In this 3-month, randomized, double-blind, parallel study 50 and 75 μg desmopressin were compared with placebo. The co-primary efficacy end points were changes from baseline in mean number of nocturnal voids and proportions of patients achieving at least a 33% reduction from baseline in nocturnal voids (33% responders) during a 3-month treatment period.
Results:
The full analysis set comprised 385 men (age range 20 to 87 years). The 50 and 75 μg doses significantly reduced the number of nocturnal voids (−0.37, p <0.0001 and −0.41, p = 0.0003, respectively) and increased the odds of a 33% or greater response (OR 1.98, p = 0.0009 and OR 2.04, p = 0.0004, respectively) compared with placebo during 3 months. Desmopressin 50 and 75 μg increased the time to first void from baseline by approximately 40 minutes compared to placebo (p = 0.006 and p = 0.003, respectively). The response to desmopressin was seen by 1 week of treatment and was sustained. Significant increases in health related quality of life and sleep quality were observed compared to placebo. Desmopressin was well tolerated as only 2 subjects (age 74 and 79 years) on 50 μg had a serum sodium level of less than 130 mmol/L (vs 9 subjects on 75 μg).
Conclusions:
Desmopressin (orally disintegrating tablet) is an effective and well tolerated treatment for men with nocturia. Treatment with 50 μg desmopressin, the minimum effective dose, provided sustained improvement of nocturia throughout the study and meaningful benefits to patients with an improved safety profile.
References
- 1 : The standardisation of terminology in nocturia: report from the Standardisation Sub-committee of the International Continence Society. Neurourol Urodyn2002; 21: 179. Google Scholar
- 2 : The prevalence and causes of nocturia. J Urol2010; 184: 440. Link, Google Scholar
- 3 : Nocturia and quality of life: results from the Boston area community health survey. Eur Urol2012; 61: 78. Google Scholar
- 4 : Association of nocturia and mortality: results from the Third National Health and Nutrition Examination Survey. J Urol2011; 185: 571. Link, Google Scholar
- 5 : Nocturia is associated with an increased risk of coronary heart disease and death. BJU Int2012; 110: 848. Google Scholar
- 6 : Impact of nocturia on bone fracture and mortality in older individuals: a Japanese longitudinal cohort study. J Urol2010; 184: 1413. Link, Google Scholar
- 7 : The effect of nocturia on sleep. Sleep Med Rev2011; 15: 91. Google Scholar
- 8 : Desmopressin orally disintegrating tablet effectively reduces nocturia: results of a randomized, double-blind, placebo-controlled trial. Neurourol Urodyn2012; 31: 441. Google Scholar
- 9 : Excessive nocturnal urine production is a major contributing factor to the etiology of nocturia. J Urol2011; 186: 1358. Link, Google Scholar
- 10 : Outcomes of pharmacological management of nocturia with non-antidiuretic agents: does statistically significant equal clinically significant?. BJU Int2011; 107: 1550. Google Scholar
- 11 : The evaluation and treatment of nocturia: a consensus statement. BJU Int2011; 108: 6. Google Scholar
- 12 : Thinking beyond the bladder: antidiuretic treatment of nocturia. Int J Clin Pract2010; 64: 807. Google Scholar
- 13 : Antidiuresis therapy: mechanism of action and clinical implications. Neurourol Urodyn2007; 26: 1008. Google Scholar
- 14 : Fourth International Consultation on Incontinence Recommendations of the International Scientific Committee: Evaluation and treatment of urinary incontinence, pelvic organ prolapse, and fecal incontinence. Neurourol Urodyn2010; 29: 213. Google Scholar
- 15 : EAU guidelines on urinary incontinence. Eur Urol2011; 59: 387. Google Scholar
- 16 : Guidelines on the Management of Male Lower Urinary Tract Symptoms (LUTS), incl. Benign Prostatic Obstruction (BPO). European Association of Urology. www.uroweb.org/gls/pdf/12_Male_LUTS_LR.pdf. Accessed October 2012. Google Scholar
- 17 : Desmopressin treatment in nocturia; an analysis of risk factors for hyponatremia. Neurourol Urodyn2006; 25: 105. Google Scholar
- 18 : Gender difference in antidiuretic response to desmopressin. Am J Physiol Renal Physiol2011; 300: F1116. Google Scholar
- 19 : Gender difference in efficacy and dose response in Japanese patients with nocturia treated with four different doses of desmopressin orally disintegrating tablet in a randomized, placebo-controlled trial. BJU Int2013; 111: 474. Google Scholar
- 20 : Long-term durability of the response to desmopressin in female and male nocturia patients. Neurourol Urodyn2013; 32: 363. Google Scholar
- 21 : A meta-analysis of the placebo response in antimuscarinic drug trials for overactive bladder. BMC Med Res Methodol2009; 9: 55. Google Scholar
- 22 : The placebo effect in overactive bladder syndrome. Nat Rev Urol2011; 8: 495. Google Scholar
- 23 : The placebo effect in the pharmacologic treatment of patients with lower urinary tract symptoms. Eur Urol2006; 50: 440. Google Scholar
- 24 : The validity and reproducibility of a work productivity and activity impairment instrument. Pharmacoeconomics1993; 4: 353. Google Scholar
- 25 : A review of self-report instruments measuring health-related work productivity: a patient-reported outcomes perspective. Pharmacoeconomics2004; 22: 225. Google Scholar
- 26 : Productivity, vitality and utility in a group of healthy professionally active individuals with nocturia. BJU Int2003; 91: 190. Google Scholar
- 27 : Efficacy of desmopressin in the treatment of nocturia: a double-blind placebo-controlled study in men. BJU Int2002; 89: 855. Google Scholar
- 28 : Clinical experiences with desmopressin for long-term treatment of nocturia. J Urol2004; 172: 1021. Link, Google Scholar
- 29 : Nocturia in the elderly in relation to thirst, dry mouth and dry eyes. Can J Urol2004; 11: 2322. Google Scholar