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

This study has been completed.
Sponsor:
Information provided by:
University Hospital, Ghent
ClinicalTrials.gov Identifier:
NCT01036841
First received: December 17, 2009
Last updated: May 25, 2011
Last verified: May 2011
  Purpose

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.


Condition Intervention Phase
Enuresis
Polyuria
Drug: desmopressin tablet
Drug: desmopressin MELT formulation
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Influence of Food-intake on Pharmacokinetic and Pharmacodynamic Parameters of Desmopressin Oral Tablet Formulation, in Comparison With Desmopressin MELT Formulation

Resource links provided by NLM:


Further study details as provided by University Hospital, Ghent:

Primary Outcome Measures:
  • Bioavailability of desmopressine MELT and tablet when taken with meal. [ Time Frame: at 1h, 2h and 6h post adminstration ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Pharmacokinetic and pharmacodynamic for desmopressine MELT and tablet. [ Time Frame: at 1h, 2h, 3h, 6h and 8h post administration ] [ Designated as safety issue: No ]

Estimated Enrollment: 24
Study Start Date: December 2009
Study Completion Date: April 2010
Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: desmopressin tablet Drug: desmopressin tablet
Administration of desmopressine tablet
Experimental: desmopressin MELT-formulation Drug: desmopressin MELT formulation
Administration of desmopressine MELT formulation

  Eligibility

Ages Eligible for Study:   6 Years to 16 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01036841

Locations
Belgium
University Hospital Ghent
Ghent, Belgium, 9000
Sponsors and Collaborators
University Hospital, Ghent
Investigators
Principal Investigator: Johan Vande Walle, MD, PhD University Hospital Ghent, department of pediatric nephrology
  More Information

Additional Information:
No publications provided

Responsible Party: MD. PhD Vande Walle, University hospital Ghent
ClinicalTrials.gov Identifier: NCT01036841     History of Changes
Other Study ID Numbers: 2009/653
Study First Received: December 17, 2009
Last Updated: May 25, 2011
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products
Belgium: Institutional Review Board

Keywords provided by University Hospital, Ghent:
MNE with nocturnal polyuria
monosymptomatic nocturnal enuresis with nocturnal polyuria

Additional relevant MeSH terms:
Enuresis
Polyuria
Behavioral Symptoms
Elimination Disorders
Mental Disorders
Mental Disorders Diagnosed in Childhood
Signs and Symptoms
Urination Disorders
Urologic Diseases
Urological Manifestations
Deamino Arginine Vasopressin
Antidiuretic Agents
Cardiovascular Agents
Coagulants
Hematologic Agents
Hemostatics
Natriuretic Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014