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CompletedNCT01036841TMUpdated Feb 6, 2019

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

A Phase 4 interventional study of desmopressin tablet and desmopressin MELT formulation in Enuresis and Polyuria, sponsored by University Hospital, Ghent. Completed at 1 site in Belgium. Open to participants aged 6 Years to 16 Years. Per ClinicalTrials.gov, last updated 2019-02-06.

Sponsored by University Hospital, Ghent · Phase 4, Interventional, and Treatment

Phase
Phase 4
Study type
Interventional
Enrollment
24
Allocation
Non-randomized
Ages
6 Years to 16 Years
Sex
All
01

Study summary

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.

02

Conditions studied

  • Enuresis
  • Polyuria

Keywords

  • MNE with nocturnal polyuria
  • monosymptomatic nocturnal enuresis with nocturnal polyuria
03

Who can participate

Ages eligible
6 Years to 16 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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
04

Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Crossover assignment
Masking
None (open label)
Enrollment
24 participants (actual)

Study arms

  • Active comparator
    desmopressin tablet

    Drug: desmopressin tablet

  • Experimental
    desmopressin MELT-formulation

    Drug: desmopressin MELT formulation

Interventions

  • Drugdesmopressin tablet

    Administration of desmopressine tablet

  • Drugdesmopressin MELT formulation

    Administration of desmopressine MELT formulation

05

What researchers measure

Primary outcomes

  1. Bioavailability of desmopressine MELT and tablet when taken with meal.

    Time frame: at 1h, 2h and 6h post adminstration

Secondary outcomes

  1. Pharmacokinetic and pharmacodynamic for desmopressine MELT and tablet.

    Time frame: at 1h, 2h, 3h, 6h and 8h post administration

06

Study locations

1 site
  • University Hospital Ghent
    Ghent, 9000, Belgium
07

References and documents

08

Registry details

Key details

Study ID
NCT01036841
Lead sponsor
University Hospital, Ghent
Responsible party
Sponsor
First posted
Dec 21, 2009
Start date
Dec 2009
Primary completion
Apr 2010
Completion
Apr 2010
Last update
Feb 6, 2019

Study contacts

Johan Vande Walle, MD, PhD
principal investigator · University Hospital Ghent, department of pediatric nephrology

Oversight

Data monitoring committee
No
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