Efficacy and safety of desmopressin in nocturia and nocturnal polyuria control of neurological patients: A systematic review and meta-analysis.

PURPOSE: Evidence on the efficacy of desmopressin in nocturia in patients with neurological diseases is still very limited except for multiple sclerosis (MS). Our aim was to evaluate the efficacy and safety of desmopressin treatment on nocturia in patients with underlying neurological diseases. METHODS: Studies were identified by electronic search of PubMed, Embase, Cochrane, CINAHL, and Google Scholar databases. Studies were considered if they provided information on the effectiveness and safety of desmopressin (1-desamino-8-d-arginine vasopressin, or DDAVP) in the treatment of nocturia and their participants had acquired neurological pathology. Two researchers independently extracted the articles using specified datasets, such as quality-of-study indicators. Statistical meta-analysis was carried out using Review Manager (RevMan) 5.4 statistical software (Cochrane Collaboration). RESULTS: Of a total of 1042 articles in the initial search, 14 studies were included. Most of the published papers were related to MS (n = 7), two were on spinal cord injury, and other conditions were neural tube defect, myelodysplasia, Parkinson's disease, stroke, and multiple system atrophy. Overall, a total of 200 patients (mostly females) were enrolled. Thirteen studies evaluated the intranasal formulation of desmopressin and one study evaluated oral desmopressin. A significant decrease in nocturia episodes was reported in seven studies evaluating this topic. An increase in the maximum hours of uninterrupted sleep was reported in the three studies in which this outcome was assessed. A significant reduction in the volume of nocturnal incontinence was found in one study. Three studies were eligible to include in the meta-analysis. The results showed that desmopressin compared to placebo, significantly reduced nighttime urination (mean difference: -0.75, 95% CI: -1.10 to -0.41; p < 0.00001). The rate of adverse events ranged from 0% to 68.42%. The critical appraisal results for all trials showed that most of the studies had low or moderate quality. CONCLUSIONS: Our results emphasized desmopressin's safety and efficacy in reducing nocturia episodes, with transient adverse effects on neurological patients. However, the data were achieved from low or medium-quality trials, and further well-designed randomized controlled trials are needed.

Desmopressin Dose Requirements in Adults with Congenital and Acquired Central Diabetes Insipidus.

Central diabetes insipidus is a rare disorder characterized by a deficiency of vasopressin. The first line drug to treat this disorder is a synthetic analogue of vasopressin, desmopressin.The primary aim of this retrospective register study was to compare desmopressin dose requirements in patients with acquired and congenital DI, and secondly to assess the influence of BMI on dose requirement and risk of hyponatremia with different drug administrations. We included all patients with suspected DI attending the endocrine department at Rigshospitalet, Copenhagen, Denmark in 2022. We identified 222 patients who were included whereof 130/222 (58.6%) were females and median age was 53 years (IQR 35 to 63). The etiology included 7/222 (3.2%) congenital and 215/222 (96.8%) acquired. After converting nasal and sublingual doses to equivalent oral doses, the median daily dose requirement was 600 µg in patients with congenital etiology compared to 200 µg in patients with acquired etiology (p=0.005). We found no association between BMI and desmopressin dose requirements (p=0.6). During the past 12 months, 66/215 (30.7%) had sodium levels<136 mmol/l including 20/215 (9.3%) with sodium levels<131 mmol/l. No increased risk of hyponatremia was found, when nasal and oral were compared (p=0.9). Daily desmopressin dose requirements were higher in patients with congenital DI compared to patients with acquired DI. However, this result was associated with uncertainty due to the small congenital group. BMI did not influence daily dose requirements and nor did type of administration influence the risk of hyponatremia.

Investigation of Effect Predictors of Desmopressin in Nocturia Patients With Nocturnal Polyuria.

BACKGROUND/AIM: Effect predictors of desmopressin for nocturia associated with nocturnal polyuria are understudied. Herein, we investigated the effects of desmopressin on sleep and patient quality of life. We defined cases in which administration of desmopressin led to hours of undisturbed sleep (HUS) ≥3 hours as "marked response cases" and examined predictive factors of desmopressin treatment response. PATIENTS AND METHODS: Our study included 129 patients who were administered desmopressin 50 µg for nocturia associated with nocturnal polyuria at our hospital. Efficacy and safety of desmopressin were examined using bladder diaries, International Prostate Symptom Score, Overactive Bladder Symptom Score, Athens Insomnia Scale, Patient Global Impression of Improvement (PGI-I) score, physical examinations, blood tests, and body composition analyzers, and the predictors of desmopressin efficacy were investigated. RESULTS: Significant improvements in all endpoints were observed from the early stage onward after desmopressin treatment compared with before treatment. After treatment, HUS was significantly longer in patients with good PGI-I scores, which indicated patient satisfaction. Variation in nocturnal micturition frequency did not affect the improvement in patient satisfaction. Examination of cases defined as "marked response cases" showed that the mean night-time urine volume was an independent predictor of treatment response. CONCLUSION: Desmopressin can improve patients' quality of life and sleep by extending HUS. This suggests that desmopressin may be effective in patients with high mean night-time urine volumes based on their bladder diary.

Determining the optimal initial dose for Japanese patients with nocturnal polyuria using an initial dose of desmopressin 50 µg.

OBJECTIVE: There is no consistent opinion on the optimal initial dose of desmopressin for patients with nocturnal polyuria. Over a period of 12 weeks, we investigated the safety and efficacy of an initial dose of 50 µg of desmopressin for elderly men. METHODS: Eighty patients (mean age: 78.8 years) were started on an initial dose of 50 µg of desmopressin for nocturia associated with nocturnal polyuria. Safety and efficacy were evaluated after 1, 4, and 12 weeks using a frequency-volume chart, Athens Insomnia Scale, Patient Global Impression of Improvement scale, physical examination, blood tests, and a body composition analyzer. RESULTS: Along with reduction in the frequency and volume of night-time urination, improvements in hours of undisturbed sleep, nocturnal polyuria index, and International Prostate Symptom Score, and Overactive Bladder Symptom Scores on quality of life measures were also observed. Hyponatremia was observed in 15 patients (18.7%). However, only 5.0% of patients had hyponatremia after the dose was reduced to 25 µg, and the continuation rate at 12 weeks was high at 87.5%. Age and other physical factors, such as body mass index, body water content, body fat mass, and muscle mass were not significant predictors of adverse events. CONCLUSIONS: Our study suggests that an initial dose of 50 µg is more effective than a uniformly minimum dose based on factors such as age and physique. Furthermore, a high continuation rate can be achieved by appropriately reducing the dose, if adverse events occur.

Drugs Showing Real-world Efficacy for Nocturia in Patients With Bladder Storage Symptoms.

BACKGROUND/AIM: Nocturia is defined as the symptom that an individual has to disrupt their sleep at night, for one or several times, in order to void. Nocturia is a bothersome event that markedly reduces a patient's quality of life. The aim of the study was to elucidate which drugs, prescribed to reduce nocturia, show real-world efficacy in patients with bladder storage symptoms. PATIENTS AND METHODS: One hundred consecutive patients who visited the Fukuoka University Medical Center were evaluated between May and July 2022. Anticholinergic drugs, ß3 adrenoceptor agonists, α1 blockers, desmopressin, and other medicines were prescribed for relieving nocturia. Desmopressin was used as second-line treatment of nocturia only in males with nocturnal polyuria. The association between each drug and actual decrease in nocturia was investigated using multivariate analysis. RESULTS: The number of nocturia episodes was reduced in patients using anticholinergic drugs, ß3 adrenoceptor agonists, and desmopressin (-1.4±0.9, -1.3±0.9, -2.0 ±0.8 episodes/night, respectively). Multivariate analysis for the entire cohort showed that anticholinergic drugs and ß3 adrenoceptor agonists were associated with significantly decreased nocturia episodes (p=0.01 and p=0.04, respectively). In males, only desmopressin was associated with a significant decrease in nocturia (p=0.03), and combination therapy significantly decreased the number of nocturia episodes compared to monotherapy (p=0.001). CONCLUSION: In a real-world clinical setting, anticholinergic drugs and ß3 adrenoceptor agonists were similarly effective in reducing nocturia. Administration of desmopressin combined with anticholinergic drugs and/or ß3 adrenoceptor agonists is the most effective method for reducing nocturia in male patients with both storage symptoms and nocturnal polyuria.

Desmopressin therapy in children and adults: pharmacological considerations and clinical implications.

PURPOSE: This review aims to provide prescribing clinicians a deeper appreciation of desmopressin's clinical indications and formulation types, to better balance efficacy and safety through proper formulation selection. BACKGROUND: Since its discovery 50 years ago, desmopressin's antidiuretic properties have been used for central diabetes insipidus, primary monosymptomatic nocturnal enuresis and adult nocturnal polyuria, while its coagulant effects are useful for mild hemophilia A and von Willebrand Disease. During this time, newer formulations of desmopressin have also been introduced to the market raising questions on interchangeability, dose conversion and safety. The wide array of clinical indications and variable pharmacokinetic properties of different desmopressin preparations raises the possibility of medication error, especially the risk of hyponatraemia. METHODOLOGY: A narrative review to explore clinically relevant aspects of desmopressin therapy, synthesising information obtained from searches of published literature. RESULTS: We identified that the risk factors for developing hyponatremia include extremes of age, existing comorbidity, drug interaction, intranasal formulations and intercurrent illness. We describe the dose equivalence between all formulations to facilitate conversion. We highlight that in view of inter-subject variability, close monitoring is recommended when switching preparations. We found that paediatric data remains limited, leading to recent proposals for age- and weight-based dosing regimens. CONCLUSION: The risk of hyponatremia, albeit small, can be reduced by adhering to the indication-specific doses and taking steps to govern the safe prescription of the drug. Further paediatric clinical trials are awaited to expand the evidence base of childhood desmopressin therapy.

Desmopressin acetate the first sublingual tablet to treat nocturia due to nocturnal polyuria.

Introduction: Desmopressin was widely used to treat nocturnal polyuria in adults under the age of 65 due to the well-established risk of hyponatremia. Since the prevalence of nocturia increases with age, and with an aging population, those most affected were excluded from treatment. Recently, a new lower dose sublingual tablet formulation that optimizes the balance between efficacy and tolerability has been licensed for symptomatic treatment of nocturia due to idiopathic nocturnal polyuria in adults of any age, with the caveat of regular serum monitoring for those over 65. This newer formulation aims to achieve the same clinical outcomes as previous formulations while reducing the risk of hyponatremia.Areas covered: This review will look at the pharmacology of the newly formulated desmopressin and examine the results of the clinical trials that would support its treatment of adult nocturia with idiopathic nocturnal polyuria.Expert opinion: When reporting on the clinical efficacy of desmopressin on nocturia, it is important for clinical trials to publish their complete data on nocturnal and 24-hour urine voided volumes. Further research examining the physiological reasoning behind this gender-specific dosing for desmopressin and the optimal recommended treatment duration of desmopressin for those over 65 is needed.

Urinary reabsorption in the rat kidney by anticholinergics.

Anticholinergics, therapeutic agents for overactive bladder, are clinically suggested to reduce urine output. We investigated whether this effect is due to bladder or kidney urine reabsorption. Various solutions were injected into the bladder of urethane-anesthetized SD rats. The absorption rate for 2 h was examined following the intravenous administration of the anticholinergics imidafenacin (IM), atropine (AT), and tolterodine (TO). The bilateral ureter was then canulated and saline was administered to obtain a diuretic state. Anticholinergics or 1-deamino-[8-D-arginine]-vasopressin (dDAVP) were intravenously administered. After the IM and dDAVP administrations, the rat kidneys were immunostained with AQP2 antibody, and intracellular cAMP was measured. The absorption rate was ~ 10% of the saline injected into the bladder and constant even when anticholinergics were administered. The renal urine among peaked 2 h after the saline administration. Each of the anticholinergics significantly suppressed the urine production in a dose-dependent manner, as did dDAVP. IM and dDAVP increased the intracellular cAMP levels and caused the AQP2 molecule to localize to the collecting duct cells' luminal side. The urinary reabsorption mechanism through the bladder epithelium was not activated by anticholinergic administration. Thus, anticholinergics suppress urine production via an increase in urine reabsorption in the kidneys' collecting duct cells via AQP2.

Antidiabetic Therapy and Rate of Severe Hypoglycaemia in Patients with Type 2 Diabetes and Chronic Kidney Disease of Different Stages - A Follow-up Analysis of Health Insurance Data from Germany.

BACKGROUND: The presence of chronic kidney disease (CKD) influences the type of antiglycaemic therapy and the risk for hypoglycaemia. METHODS: In 2006, 2011 and 2016 health insurance data of people with diabetes type 2 were screened for CKD and the presence of severe hypoglycaemia (sHypo). The type of antihyperglycaemic therapy was recorded due to Anatomical Therapeutic Chemical (ATC) codes up to 3 months before suffering sHypo. RESULTS: The prevalence of CKD increased from 5.3% in 2006 to 7.3% in 2011 and 11.2% in 2016. Insulin-based therapies were used in 39.0, 39.1, and 37.9% of patients with, but only in 17.7, 17.4, and 18.8% of patients without CKD. Although the proportion of the CKD stages 1, 2 and 5 decreased, CKD stages 3 and 4 increased. The proportion of sHypo in CKD declined from 2006 (3.5%) to 2011 (3.0%) and 2016 (2.2%) but was still more than 10 times higher as compared to type 2 diabetic patients without CKD (0.3/0.2/0.2%) conferring a significantly higher probability of sHypo (OR 9.30, 95%CI 9.07-9.54) in CKD. The probability of sHypo was significantly lower in 2016 than in 2006 both in patients with (OR 0.58; CI 0.55-0.61) and without CKD (OR 0.70; CI 0.68-0.73). CONCLUSION: The prevalence of CKD increased from 2006 to 2016. Patients with CKD exhibited a 9-fold increased probability of sHypo, especially in patients treated with insulin plus oral anti-diabetic drugs. However, the rate and risk for sHypo decreased over time, probably as a consequence of new antidiabetic treatment options, better awareness of sHypo, and changed therapy goals.

Drug-induced cutaneous vasculitis and anticoagulant-related cutaneous adverse reactions: insights in pathogenesis, clinical presentation, and treatment.

Drug-induced vasculitis and anticoagulant-related skin reactions are commonly encountered in the inpatient and outpatient settings. The spectrum of clinical presentation is broad and ranges from focal, skin-limited disease, to more extensive cutaneous and soft tissue necrosis, to potentially fatal systemic involvement. The prompt recognition of these adverse events can have a significant impact on patient morbidity and mortality. We highlight the key features of the clinical presentation with an emphasis on primary lesion morphology, distribution, and epidemiology of purpuric drug reactions. The proposed pathophysiology, histologic findings, and therapeutic interventions of these potentially life-threatening diseases are discussed.

Comorbidities, Age, and Polypharmacy Limit the Use by US Older Adults with Nocturia of the Only FDA-approved Drugs for the Symptom.

PURPOSE: The goal of this study was to determine if the US adult population with nocturia (waking from sleep at night to void) can easily take medications (desmopressin acetate) approved by the US Food and Drug Administration for nocturia. The study examined: (1) the prevalence of comorbid conditions, laboratory abnormalities, and concomitant medications that increase risk of desmopressin use; and (2) whether these factors are associated with age or nocturia frequency. METHODS: Using a cross-sectional analysis of four US National Health and Nutrition Examination Survey (NHANES) waves (2005-2012), a total of 4111 participants aged ≥50 years who reported ≥2 nightly episodes of nocturia were identified. The main outcome was frequency of contraindications and drug interactions as described in US Food and Drug Administration-approved prescribing information. These prescribing concerns were matched to examination findings, medical conditions, concomitant medications, and laboratory results of NHANES participants. The associations between prescribing concerns and nocturia severity and age groups were examined. FINDINGS: The mean participant age was 65.7 years (95% CI, 65.3-66.1), and 45.5% were male. Desmopressin prescribing concerns were present in 80.5% (95% CI, 78.0-82.9) of those ≥50 years of age with nocturia; 50.0% (95% CI, 47.0-53.0) had contraindications, and 41.6% (95% CI, 39.3-44.0) took a concomitant drug that could increase risk of low serum sodium. Desmopressin contraindications were higher with older age (P < 0.001) and present in 73.2% (95% CI, 69.3-77.1) of those ≥80 years of age. IMPLICATIONS: Using NHANES data, this study showed that older US adults with nocturia have a high prevalence of medical conditions, concomitant medications, and baseline laboratory abnormalities that likely increase the risk of potentially severe adverse side effects from desmopressin use. A medication designed and approved for a clinical symptom that is most common in older adults could not be taken by most of the older adults with the symptom.

Vasopressin Administration Is Associated With Rising Serum Lactate Levels in Patients With Sepsis.

BACKGROUND: Vasopressin is used in conjunction with norepinephrine during treatment of patients with septic shock. Serum lactate is often used in monitoring of patients with sepsis; however, its importance as a therapeutic target is unclear. The objective of this study is to examine the relationship of vasopressin use on serum lactate levels in patients with sepsis. METHODS: This study uses electronic heath records available via the Medical Information Mart for Intensive Care III. Patients were required to have a serum lactate monitoring during the intensive care unit (ICU) stay. The treatment was the administration of vasopressin between hours 3 and 18 of the ICU stay. Analysis was performed using a matched design. RESULTS: Patients receiving vasopressin were more likely to have their serum lactate levels rise when compared to matched patients who did not receive vasopressin (odds ratio: 6.6; 95% confidence interval: 3.0-14.6, P < .001). Patients who received vasopressin had a median increase in serum lactate of 0.3 mmol/L, while patients who did not receive vasopressin had a median decrease in serum lactate of 0.7 mmol/L (P < .001). There was no statistically significant difference between the control and treated groups' lactate trajectories prior to possible administration of vasopressin (P = .15). The results did not change significantly when norepinephrine initiation was used as the index time. CONCLUSIONS: In patients with sepsis, the administration of vasopressin was associated with a statistically significant difference in lactate change over the course of 24 hours when compared to matched patients who did not receive vasopressin.

Meloxicam-desmopressin drug-drug interaction producing hyponatremia.

BACKGROUND: People with schizophrenia and medical comorbidities are often on multiple medications to manage their symptoms. Herein we present a case of drug-drug interaction (meloxicam and desmopressin), in a patient also on clozapine, that ultimately resulted in hyponatremia and seizure. METHODS: The patient provided consent to have his case published. We searched PubMed and after reviewing 321 articles, 11 were chosen for relevance. RESULTS: Meloxicam enhanced the adverse effect (hyponatremia) of desmopressin and was the likely culprit. CONCLUSIONS: In a patient with higher ADH levels, as in our patient taking desmopressin, the addition of an NSAID could further increase water retention and worsen hyponatremia; indeed, meloxicam was the only new medication added to the patient's regimen, and a drug interaction calculator supports the desmopressin-meloxicam drug-drug interaction as the culprit. We urge clinicians to avoid the use of desmopressin in patients with schizophrenia as this can lead to water intoxication. As meloxicam may worsen desmopressin-induced hyponatremia and could result in seizure, one should avoid using NSAIDs in patients with schizophrenia whom are also prescribed vasopressin/desmopressin. Serum sodium levels should be closely monitored in patients with schizophrenia whose regimen includes desmopressin.

Pharmacokinetic and Pharmacodynamic Properties of a Micro-Dose Nasal Spray Formulation of Desmopressin (AV002) in Healthy Water-Loaded Subjects.

PURPOSE: Antidiuretic therapy with desmopressin for nocturia has been hampered by formulations with high doses, low bioavailability and variable pharmacokinetics. AV002 (SER120), a novel, emulsified, microdose desmopressin nasal spray, with a permeation enhancer (cylcopentadecanolide), was developed to have pharmacokinetic characteristics suitable for nocturia treatment. METHODS: Twelve healthy subjects participated in an open-label, dose-escalating study. Water-loaded subjects were sequentially dosed every 48 h with AV002 0.5, 1.0, 2.0 µg and 0.12 µg desmopressin subcutaneous (SC) bolus injection. RESULTS: AV002 intranasal administration produced a time-to-maximum concentration (Tmax) between 15 and 30 min and a maximum concentration (Cmax) <10 pg/mL. Cmax and area under the curve showed dose proportionality. Coefficient of variation for AV002 was similar to that observed for the SC dose. Bioavailability of AV002 was approximately 8% compared to SC injection. AV002 demonstrated pharmacodynamic effects within 20 min of dosing and showed increasing magnitude and duration with escalating doses. AV002 2.0 µg had maximum median urine osmolality of 629 mOsm/kg and median urine output ≤2 mL/min for 5-6 h. CONCLUSIONS: AV002 demonstrated rapid absorption, high bioavailability, limited duration of action, and low coefficient of variation, suggesting it may be a suitable formulation for nocturia treatment. Trial registration not required (single-center, phase 1).

Pharmacokinetics and safety profile of desmopressin oral tablet formulations in healthy Chinese subjects under fasting and fed conditions.

OBJECTIVE: Desmopressin acetate (DDAVP®) is a synthetic analogue of the pituitary hormone vasopressin. Until now, few studies of desmopressin have focused on the pharmacokinetics (PK) or food effects in Asian populations. This study aimed to assess the effect of food intake on the PK of desmopressin and bioequivalence of two tablet formulations in Chinese subjects. MATERIALS AND METHODS: A single-center, single-dose, randomized, open-label, two-period crossover study was conducted in 104 healthy Chinese volunteers under fasted or fed conditions (52 volunteers for each condition). Blood samples were collected up to 14 hours after administration of oral desmopressin tablets (0.6 mg; 0.2 mg × 3) in each period. Plasma desmopressin concentrations were analyzed by validated liquid chromatography-tandem mass spectrometry (LC-MS/MS). PK and bioavailability parameters were calculated. Adverse events (AEs) were also recorded. RESULTS: No significant differences in mean (standard deviation, SD) PK parameters were observed between formulation 1 (F1) and formulation 2 (DDAVP®; F2) under both fasted and fed conditions. All AEs observed were mild and resolved quickly without treatment. The maximum concentration (Cmax) and area under the curve (AUC) were significantly decreased (p < 0.01) when the drug was taken with food, compared with fasted subjects. CONCLUSION: These findings suggest that both tablet formulations were well tolerated. Food can significantly decrease the exposure of desmopressin.
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[Desmopressin therapy of nocturia in elderly patients may contribute to severe hyponatraemia].

Hyponatraemia is a well-known side effect of desmopressin therapy. Nocturia in elderly patients can be treated with desmopressin, which usually induces mild and reversible hyponatraemia. This case report is about two patients, in which severe hyponatriaemia, at least partly induced by desmopressin, was observed. The patients were affected by nausea, vomiting and confusion. These symptoms are caused by brain swelling, which can result in coma and death. The case reports illustrate the importance in measuring baseline P-sodium concentration during therapy and examining current medication before prescribing desmopressin.

Pharmacotherapy for postural tachycardia syndrome.

Postural tachycardia syndrome (POTS) is a disorder characterized by the presence of orthostatic symptoms (including lightheadedness, palpitations, nausea, dyspnea, and tremulousness) as well as excessive upright tachycardia. POTS predominantly affects women of childbearing age. Treating POTS involves a multi-faceted approach using non-pharmacological and pharmacological interventions. There are no pharmacological treatments that are currently United States Food and Drug Administration (FDA) approved for POTS due to lack of randomized controlled trials. Yet, several medications can improve POTS symptoms and are supported by small prospective studies or retrospective case series. Drugs that are most commonly used for POTS target the following mechanisms 1) blood volume expansion, 2) reduction of heart rate, 3) peripheral vasoconstriction and 4) sympatholysis. Pharmacological approaches can also be used to target specific symptoms including "brain fog," fatigue, sleep, and depression. This review outlines pharmacological approaches for treating POTS and summarizes evidence supporting each treatment approach.

Efficacy and Safety of SER120 Nasal Spray in Patients with Nocturia: Pooled Analysis of 2 Randomized, Double-Blind, Placebo Controlled, Phase 3 Trials.

PURPOSE: SER120 desmopressin intranasal spray is the first U.S. Food and Drug Administration approved pharmacotherapy for nocturia. We evaluated its efficacy and safety in 2 randomized, double-blind, placebo controlled studies, DB3 and DB4. MATERIALS AND METHODS: A total of 1,333 intent to treat patients 50 years old or older with 2.16 or more nocturic voids per night during a 2-week screening period were randomized equally to SER120 intranasal spray 1.66 or 0.83 mcg, or placebo for a 12-week treatment. Co-primary end points were the mean change from baseline in nocturic episodes per night and the percent of patients with a 50% or greater reduction in mean nocturic episodes per night. Secondary end points were the validated INTU (Impact of Nighttime Urination) quality of life questionnaire in DB4, time to the first nocturic void and the percent of nights with 1 or fewer nocturic voids. RESULTS: Each SER120 dose showed statistical significance vs placebo for the 2 co-primary end points, including the mean nocturic episodes per night (-1.4 with 0.83 mcg and -1.5 with 1.66 mcg vs -1.2 with placebo, each p <0.0001), the percent of patients with a 50% or greater reduction in mean nocturic episodes per night (37.9% with 0.83 mcg and 48.7% with 1.66 mcg vs 30.3% with placebo, p = 0.0227 and <0.0001, respectively) as well as for all secondary end points in the pooled analyses. The 1.66 mcg dose demonstrated significant improvements in the INTU score (p = 0.0255). The incidence of hyponatremia, defined as serum sodium 125 mmol/l or less regardless of symptoms or less than 130 mmol/l with symptoms, was 1.1%, 0% and 0.2% in the 1.66 and 0.83 mcg, and placebo groups, respectively. Other adverse events were similar across treatment groups. CONCLUSIONS: SER120 demonstrated significant improvements over placebo for co-primary and secondary efficacy end points that corresponded with quality of life improvements. SER120 at each dose had an acceptable safety profile.