Pharmacokinetics and Pharmacodynamics of Desmopressin Oral Lyophilisate Formulation in the Paediatric Population

Study Overview
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Brief Summary
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Patients suffering from nocturnal enuresis (starting from the age of 5 till adulthood) are all treated with the same dose of desmopressin, i.e. 120mcg once daily. In treatment resistant enuresis, this dose is doubled: those patients take 240mcg once daily. A pilot study performed at our department showed a correlation between weight and plasma concentration when a fixed dose of desmopressin oral lyophilisate formulation was given to the pediatric patient (older than 6 years). This study will investigate the pharmacokinetics (PK) and pharmacodynamics (PD) of desmopressin in young children, less than 8 years old. Additionally, the efficacy of desmopressin oral lyophilisate formulation in urinary concentration testing will be evaluated

Official Title
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Pharmacokinetics and Pharmacodynamics of Desmopressin Oral Lyophilisate Formulation in the Paediatric Population

Conditions
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Monosymptomatic Nocturnal Enuresis

Intervention / Treatment
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* Drug: desmopressin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children with an uro- and/or nephropathy who need an urinary concentration test OR Children with monosymptomatic nocturnal enuresis (based on nocturnal polyuria) with treatment failure on desmopressin tablet Otherwise healthy children (on medical history and physical examination) Parents or legal guardian of the child signed the informed consent form Age: between 6 months and 8 years Minimum weight: 8 kg Exclusion Criteria: Diabetes insipidus Renal failure (eGFR<60ml/min/1,73m²) Current urinary tract infection Syndrome of inappropriate antidiuretic hormone secretion Heart failure Clinical significant medical conditions (renal, hepatic, gastro-intestinal, pulmonary, cardiac, endocrinologic) that might interfere with the clinical endpoints Sensitivity to desmopressin or excipients of the oral lyophilisate formulation Use of antibiotics, diuretics or other drugs that can influence diuresis (tricyclic antidepressants, chlorpropamide, oxcarbazepine, selective serotonin reuptake inhibitors, chlorpromazine and carbamazepine). Use of drugs that influence intestinal motility (such as loperamide) Anomalies of the mouth that might interfere with the intake / absorption of the medication

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 8 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Patients needing an urinary concentration test<br>Patients who need a urinary concentration test because of uro- or nephropathy (age: 6 months - 8 year) | Drug: desmopressin<br>* One time dosing of desmopressin oral lyophilisate formulation. The dose is age-dependant: >6 months and < 2years: 60µg; ≥2 years and <4 years: 120µg PO and ≥4 years and <8 years: 240 µg PO. There will be blood sampling and urine sampling for PK and PD/safety<br>* Other names: dDAVP;|
| Experimental: Patients suffering from treatment resistant nocturnal enuresis<br>Patients suffering from treatment resistant nocturnal enuresis (age: 5 - 8 year) | Drug: desmopressin<br>* One time dosing of desmopressin oral lyophilisate formulation. The dose is age-dependant: >6 months and < 2years: 60µg; ≥2 years and <4 years: 120µg PO and ≥4 years and <8 years: 240 µg PO. There will be blood sampling and urine sampling for PK and PD/safety<br>* Other names: dDAVP;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Desmopressine concentrations | The assessed pharmacokinetic parameters are desmopressine concentrations at timepoints 0, 1/4, 1/2, 1, 2, 3, 5, 6 and 7h. | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy - urinary volume. | PD of desmopressin in children with nocturnal enuresis that is resistant to treatment with desmopressin tablet. First PD parameter is antidiuretic effect. This is urinary volume per hour. | 24 hours | 
| Efficacy - osmolality in urine. | PD of desmopressin in children with nocturnal enuresis that is resistant to treatment with desmopressin tablet. Second PD parameter is urinary concentration capacity. This is osmolality in urine. | 24 hours | 
| Urinary concentration test | Evaluation of the oral lyophilisate formulation of desmopressin for the urinary concentration test. Assessed parameter is urinary concentration capacity. | 24 hours | 
| Safety of desmopressin in children as assessed by registration of adverse events. | Registration of adverse events | 24 hours | 
| Safety of desmopressin in children as assessed by the measurement of natremia. | Measurement of natremia | 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Desmopressin, Paediatrics, urinary concentration test