30th ESPU Congress - Lyon, France - 2019

S20: ENURESIS

Moderators: Simona Gerocarni Nappo (Italy), L García Aparicio (Spain)

ESPU Meeting on Saturday 27, April 2019, 09:20 - 09:46


09:20 - 09:25
S20-1 (LO)

★ A NEW DESMOPRESSIN ORAL SOLUTION: A RANDOMIZED, SINGLE-DOSE, OPEN-LABEL, 2-WAY CROSSOVER BIOEQUIVALENCE STUDY

Gemma GAMBUS 1, Rosa Maria SANAHUJA 2, Silvia GUERRERO 2, Carlos NIETO 3, Montserrat PUNTES 4, Maria Rosa BALLESTER 4, Juan MARTINEZ 4 and Rosa ANTONIJOAN 4
1) GP-Pharm, MEDICAL DEPARTMENT, L'Hospitalet De Llobregat ·, SPAIN - 2) GP-Pharm, L'Hospitalet De Llobregat ·, SPAIN - 3) Reig Jofre, Sant Joan Despi, SPAIN - 4) Institut de Recerca de l'HSCSP-IIB Sant Pau, CIM, Barcelona, SPAIN

PURPOSE

Desmopressin is available as oral tablet or lyophilisate for the first-line treatment of nocturnal enuresis in children. A new desmopressin formulation was developed as an oral solution to provide a series of advantages inherent to the nature of its pharmaceutical form: wider therapeutic dose range for dose titration and progressive withdrawal; easy swallowing in comparison to tablet and minimum fluid intake. Besides, desmopressin oral solution is odorless and tasteless, which are desirable for pediatric population.
The study evaluated this new desmopressin oral solution (Test) for bioequivalence versus the desmopressin tablet (Reference).

MATERIAL AND METHODS

This was a single-center, randomized, single-dose, open-label, 2-way crossover study in 69 healthy volunteers. Subjects received: 0.36 mg in 1 mL of Test (desmopressin base) and 0.4 mg as 2 tablets of 0.2 mg of Reference formulation (corresponding to 0.36mg of desmopressin base), separated by a minimum of 2-days washout period. AUC0t over 12 h in plasma and Cmax were compared by analysis of variance after log transformation.

RESULTS

All 69 subjects completed the study. Test to Reference drug mean ratios were within the bioequivalence boundaries with mean values of 109.84 (90% CI: 97.09-124.27) and 108.85 (90% CI: 97.03-122.13) for AUC0t and Cmax, respectively. Both Test and Reference formulations displayed similar PK profile over the course of the study and were well tolerated.

CONCLUSIONS

The new desmopressin formulation is bioequivalent to the Reference desmopressin tablets 0.2 mg, at equivalent dose. Desmopressin 360 mcg/mL oral solution provides an additional treatment option for enuretic children, which might enable an improved dose-dependent structured withdrawal regimen.


09:25 - 09:28
S20-2 (PP)

★ TOP-DOWN OR DOWN-TOP APPROACH WITH DESMOPRESSIN TREATMENT FOR PRIMARY MONOSYMPTOMATIC ENURESIS IN CHILDREN? A PROSPECTIVE NON-RANDOMIZED STUDY.

Anthony KALLAS-CHEMALY 1, Chebl MOURANI 2, Paul-Henri TORBEY 2, Fouad AOUN 3, Bassam EID 2 and Maroun MOUKARZEL 3
1) Hôtel-Dieu de France Hospital, Université Saint-Joseph, Faculté de Médecine, Paediatric Urology, Beirut, LEBANON - 2) Hôtel-Dieu de France Hospital, Université Saint-Joseph, Faculté de Médecine, Paediatrics, Beirut, LEBANON - 3) Hôtel-Dieu de France Hospital, Université Saint-Joseph, Faculté de Médecine, Urology, Beirut, LEBANON

PURPOSE

Desmopressin remains one of the first-line choice for the treatment of enuresis in children. We aimed to evaluate if increasing started dose of desmopressin may improve response rate with no added comorbidities in children with primary monosymptomatic enuresis (PME).

MATERIAL AND METHODS

Between 2015 and 2018, we prospectively enrolled 243 enuretic children. Patients with PME, nocturnal polyuria, normal bladder reservoir function and no treatment in the last three months were included. Children with comorbidities for enuresis such as constipation, ENT problems, diabetes insipidus, genito-urinary anomlies, urinary tract infection and abnormal psychological evaluation were excluded. Patients were divided into two groups: group A starting with 120 mcg of desmopressin and group B starting with the dose of 240 mcg. All children had general lifestyle advice. Dose change from 120 to 240 mcg or vice versa was done at the third week and continued to a total treatment duration of 3 months. Response rate was defined according to the ICCS guidelines. Response rate was evaluated at the third week and third month from treatment.

RESULTS

During this 3-year period, 79 patients were included (40 patients in group A and 39 in group B) with a follow-up of 3 months. The two groups were homogenous according to age, sex, weight and severity of enuresis. Complete, partial and non-responders were the same at 3 weeks (50% vs 69.2%, p= 0.31, 30% vs 20.5%, p=0.37 and 20% vs 10.3%, p= 0.25, in group A and B respectively) and 3 months from treatment (45% vs 54%, p=0.63, 30% vs 28%, p=0.83, 25% vs 18%, p=0.47, in group A and B respectively). Side effects such as headache, nausea and abdominal pain were higher in Group B (p=0.01).

CONCLUSIONS

Our study shows no advantages of the Top-Down approach with desmopressin for the treatment of enuresis in children. Physicians should be aware of more common side effects with this strategy.


09:28 - 09:31
S20-3 (PP)

PHARMACOKINETIC ASPECTS OF DESMOPRESSINE ORAL LYOPHILISATE ARE DIFFERENT IN YOUNG CHILDREN

Lien DOSSCHE 1, Anne-Françoise SPINOIT 2, Elke GASTHUYS 3 and Johan VANDE WALLE 1
1) Ghent University Hospital, Paediatric Nephrology, Gent, BELGIUM - 2) Ghent University Hospital, Paediatric Urology, Gent, BELGIUM - 3) Ghent University Hospital, Gent, BELGIUM

PURPOSE

Desmopressin (dDAVP) is indicated for primary enuresis, all start with a dose of 120 micrograms. Nowadays, desmopressin is also administered to younger children aging 5 to 8 years, despite the fact that  labelling in most countries begins only from 7-8 years. The aim of this study was to obtain pharmacokinetic data, in order to determine appropriate dosing regimens.

MATERIAL AND METHODS

An open label, non-randomized,  pilot study. 25 children were recruited (age 6 months – 8 years, mean age 4.8 years). All needed a urinary concentration test or had nocturnal polyuria with treatment failure on tablet. dDAVP was provided sublingual as one-time age-adapted dose (60 (6 months - 2 years), 120 (2- 4 years), or 240 micrograms (4- 8 years)). Plasma and urinary concentration of dDAVP were measured every 15 minutes during the first hour, and at 1h, 2h, 3h, 5h, 6h and 7h post-dosing. 

RESULTS

A double absorption peak was noted, especially in the plasma concentration-time curves of 60 µg and 120 µg. These observations are probably age/size dependency. 

CONCLUSIONS

The double absorption peak has never been demonstrated in the older children before, probably due to a lack of sampling during the absorption phase. In the current study, richer sampling were applied.
It is our hypothesis that younger children ingest a fraction of the dose will be ingested, followed by absorption in the gastro-intestinal tract. The influence of the double absorption peak on the efficacy and potential toxicity of the desmopressin lyophilisate still needs to be established.


09:31 - 09:34
S20-4 (PP)

SENS-U™: CONTINUOUS HOME MONITORING OF NOCTURAL BLADDER FILLING IN CHILDREN WITH ENURESIS - A FEASIBILITY STUDY

W.M.J. KWINTEN 1, P.G. VAN LEUTEREN 1, M. VAN DUREN - VAN IERSEL 2, P DIK 1 and P JIRA 2
1) Wilhelmina Children's Hospital UMC Utrecht, Pediatric Urology, Utrecht, NETHERLANDS - 2) Jeroen Bosch Hospital, Department of Pediatrics, 's-Hertogenbosch, NETHERLANDS

INTRODUCTION

Enuresis is a common problem in school-age children; 5-10% suffer from this condition. One of the treatment options is alarm therapy which uses a wetting alarm to teach pelvic floor contraction when incontinence occurs. However, a disadvantage of this approach is that the child is still awaken by wet sheets. Recently, a new, wearable ultrasonic bladder sensor became available, the SENS-U™ Bladder Sensor, which has the potential to prevent the enuretic event by waking up the child before the bladder is full. In this study, the aim is to perform a home-based evaluation of the SENS-U during the night in children with nocturnal enuresis.

PATIENTS AND METHODS

In this study, 15 children (6-12 years) with monosymptomatic nocturnal enuresis were included for a monitoring session at home for one night. Before bedtime, the SENS-U was positioned by the researcher. During the night, the SENS-U estimated the filling status (i.e. every 30 s), while notifications were deactivated.   In addition, urine volume was collected in a measurement cup (or diaper weight). The next morning, the SENS-U was removed by the researcher and SENS-U data was stored for off-line processing. The total number of measured nocturnal bladder filling cycles was analyzed by descriptive statistics.  

PRELIMINARY RESULTS

At this moment, 8 patients (boys/girls: 7/1) [mean age: 8.4 ± 1.3 years, range: 7 – 11 years] are included in the study. The first results show that the SENS-U is able to monitor the changes in bladder size overnight, due to the increase of bladder volume. Next, none of the patients experienced any difference in their sleep habit’s as result of wearing the SENS-U.

CONCLUSIONS

Based on the first results, the SENS-U™ Bladder Sensor is a feasible approach for monitoring the nocturnal bladder filling. Future research will focus on investigating the response to receiving a full-bladder notification during the night.


09:34 - 09:46
Discussion