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

NCT01036841 | Completed Phase 4

• 1 other identifier: 2009/653
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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

Keywords

MNE with nocturnal polyuria; monosymptomatic nocturnal enuresis with nocturnal polyuria

Outcome Measures

Primary Outcomes (1)

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

  at 1h, 2h and 6h post adminstration

Secondary Outcomes (1)

• Pharmacokinetic and pharmacodynamic for desmopressine MELT and tablet.

  at 1h, 2h, 3h, 6h and 8h post administration

Study Arms (2)

desmopressin tablet

ACTIVE COMPARATOR

Drug: desmopressin tablet

desmopressin MELT-formulation

EXPERIMENTAL

Drug: desmopressin MELT formulation

Interventions

desmopressin tablet DRUG

Administration of desmopressine tablet

desmopressin tablet

desmopressin MELT formulation DRUG

Administration of desmopressine MELT formulation

desmopressin MELT-formulation

Eligibility Criteria

• Age: 6 Years - 16 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Ghent: lead

Study Sites (1)

University Hospital Ghent

Ghent, 9000, Belgium

Location

Related Links

• Website of the University Hospital Ghent

MeSH Terms

Conditions

Enuresis; Polyuria

Interventions

Deamino Arginine Vasopressin

Condition Hierarchy (Ancestors)

Urination Disorders; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Behavioral Symptoms; Behavior; Elimination Disorders; Mental Disorders; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Arginine Vasopressin; Vasopressins; Pituitary Hormones, Posterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Study Officials

• Johan Vande Walle, MD, PhD

  University Hospital Ghent, department of pediatric nephrology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 17, 2009
• First Posted: December 21, 2009
• Study Start: December 1, 2009
• Primary Completion: April 1, 2010
• Study Completion: April 1, 2010
• Last Updated: February 6, 2019

Record last verified: 2019-02

Locations

BE (1)