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

NCT ID: NCT01036841

Last Updated: 2019-02-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-12-31
• Study Completion Date: 2010-04-30

Brief 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.

Conditions

Enuresis; Polyuria

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

desmopressin tablet

Group Type: ACTIVE_COMPARATOR

desmopressin tablet

Intervention Type: DRUG

Administration of desmopressine tablet

desmopressin MELT-formulation

Group Type: EXPERIMENTAL

desmopressin MELT formulation

Intervention Type: DRUG

Administration of desmopressine MELT formulation

Interventions

desmopressin tablet

Administration of desmopressine tablet

Intervention Type: DRUG

desmopressin MELT formulation

Administration of desmopressine MELT formulation

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 16 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Ghent

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Johan Vande Walle, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University Hospital Ghent, department of pediatric nephrology

Locations

University Hospital Ghent

Ghent, , Belgium

Countries

Belgium

Related Links

http://www.uzgent.be

Website of the University Hospital Ghent

Other Identifiers

2009/653

Identifier Type: -

Identifier Source: org_study_id