Influence of Food-intake on Desmopressin Oral Tablets and MELT-formulation (TM)

Influence of Food-intake on Pharmacokinetic and Pharmacodynamic Parameters of Desmopressin Oral Tablet Formulation, in Comparison With Desmopressin MELT Formulation

Alarm-treatment as well as Desmopressin, a synthetic analogue of human vasopressin, are considered the only evidence-based medicine (EBM) IA treatments in monosymptomatic nocturnal enuresis (MNE). Desmopressin exists in three different formulations for ambulant use: nasal spray, tablet and lyophilisate (MELT) each with differences in bioavailability (spray 2%, tablet 0.2%, MELT 0.5%). There 's insufficient evidence to confirm the actually used bioequivalent doses ( 10µg spray = 120µg MELT= 0.2mg tablet).

Although so frequently used, very few pharmacokinetic and -dynamic data on desmopressin are available for children.

Due to prolonged half life, associated with waterintoxication,the nasal spray has a black box warning from the FDA and is no longer recommended . For some authors oral formulations appear to be a safer alternative. However, based on clinical experience of less response rate with oral formulations, lower biodisponibility is suspected. Adult research confirms low bioavailability of tablets but also show major influences by food-intake and changes in gastro-intestinal motility.

To achieve maximum efficacy, recommendations are to take desmopressin tablet 1 hour before bedtime and 2 hours after meal: this is unrealistic in schoolaged children since there never is 3 hours between evening meal and bedtime.

In 2005 a dose response study demonstrated superior pharmaco-kinetic and dynamic properties for desmopressin Lyophilisate MELT formula.

Since these results implicate superior action of MELT, often a change to MELT is recommended if there is a suboptimal response with tablet: sublingual absorption would eliminate the influence of food-intake.

However, for this statement there's no evidence, since these tests were all conducted in children in fasting condition. Only one clinical study demonstrates bioequivalence for MELT and tablet.

Hypothesis is that desmopressin MELT formulation has a better bioavailability when administered together with meal due to its sublingual absorption.

Study Overview

• Status: Completed
• Conditions: Enuresis; Polyuria
• Intervention / Treatment: Drug: desmopressin tablet; Drug: desmopressin MELT formulation

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 4

Contacts and Locations

Study Locations

• Belgium
  • Ghent, Belgium, 9000
    • University Hospital Ghent

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 16 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• children aged 6-16 years old
• with MNE and nocturnal polyuria
• treated with desmopressin tablet, non or partial responders, for whom change to MELT formulation is indicated according to the international standard guidelines.

Exclusion Criteria:

• history of urologic disease, diurnal urinary incontinence, diabetes insipidus, urinary tract infection, clinically significant disease
• No systemic use of antibiotics, diuretics, other medication that influences urinary concentrating mechanism
• abnormalities of oral mucosa which could influence drugrelease or absorption

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: desmopressin tablet	Drug: desmopressin tablet; Administration of desmopressine tablet
EXPERIMENTAL: desmopressin MELT-formulation	Drug: desmopressin MELT formulation; Administration of desmopressine MELT formulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Bioavailability of desmopressine MELT and tablet when taken with meal.	at 1h, 2h and 6h post adminstration

Secondary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetic and pharmacodynamic for desmopressine MELT and tablet.	at 1h, 2h, 3h, 6h and 8h post administration

Collaborators and Investigators

• Sponsor: University Hospital, Ghent
• Investigators: Principal Investigator: Johan Vande Walle, MD, PhD, University Hospital Ghent, department of pediatric nephrology

Publications and helpful links

Helpful Links

• Website of the University Hospital Ghent

Study record dates

Study Major Dates

• Study Start: December 1, 2009
• Primary Completion (ACTUAL): April 1, 2010
• Study Completion (ACTUAL): April 1, 2010

Study Registration Dates

• First Submitted: December 17, 2009
• First Submitted That Met QC Criteria: December 18, 2009
• First Posted (ESTIMATE): December 21, 2009

Study Record Updates

• Last Update Posted (ACTUAL): February 6, 2019
• Last Update Submitted That Met QC Criteria: February 4, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: MNE with nocturnal polyuria; monosymptomatic nocturnal enuresis with nocturnal polyuria
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Urologic Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Urination Disorders; Elimination Disorders; Urinary Incontinence; Enuresis; Nocturnal Enuresis; Polyuria; Physiological Effects of Drugs; Natriuretic Agents; Hemostatics; Coagulants; Antidiuretic Agents; Deamino Arginine Vasopressin
• Other Study ID Numbers: 2009/653