NCT01429090

Brief Summary

The primary objective of the study is:

  • To describe extent and rate of absorption of methantheline after single oral dose administration of Vagantin® coated tablets (Test) in comparison to a methantheline bromide solution (Reference) The secondary objectives of the study are:
  • To determine elimination the half-life of methantheline bromide
  • To describe the effects of Test and Reference on salivation, accommodation, pupil response, blood pressure and heart rate
  • to assess frequency and intensity of adverse drug reactions

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
12

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Oct 1999

Shorter than P25 for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

October 1, 1999

Completed
1 month until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 1999

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2000

Completed
11.7 years until next milestone

First Submitted

Initial submission to the registry

September 1, 2011

Completed
4 days until next milestone

First Posted

Study publicly available on registry

September 5, 2011

Completed
Last Updated

September 5, 2011

Status Verified

September 1, 2011

Enrollment Period

1 month

First QC Date

September 1, 2011

Last Update Submit

September 2, 2011

Conditions

Neurogenic Bladder

Keywords

PharmacokineticsAccommodation, OcularReflex, PupillarySalivation

Outcome Measures

Primary Outcomes (2)

  • area under the curve (AUC0-∞)

    AUC0-∞ was assessed by the trapezoidal formula up to the last sampling time with a concentration above the limit of quantitation (AUC0-), and was extrapolated to infinity using standard techniques

    0-16 h plasma concentration-time profile of methantheline after single oral administration

  • maximal plasma concentration (Cmax)

    Cmax was obtained directly from the measured concentration-time curves

    0-16 h plasma concentration-time profile of methantheline after single oral administration

Secondary Outcomes (5)

  • time of maximal plasma concentration (tmax)

    0-16 h plasma concentration-time profile of methantheline after single oral administration

  • terminal half-life (t½)

    0-16 h plasma concentration-time profile of methantheline after single oral administration

  • volume of salivary gland secretion

    before and 0, 0.5, 1, 2, 3, 4, 6, 8, 12 hours after administration of study medication

  • Measurement of accommodation

    before and 0, 1, 2, 3, 4, 6, 8, 12 hours after administration of study medication

  • Pupil function

    before and 0, 1, 2, 3, 4, 6, 8, 12 hours after administration of study medication

Study Arms (2)

Test

EXPERIMENTAL

Pharmacokinetics and -dynamics after single dose administration of 2 coated tablets Vagantin® (coated tablets of 50 mg methantheline bromide)

Procedure: blood samplingDrug: Vagantin®Procedure: Measurement of salivationProcedure: Measurement of accommodationProcedure: Pupillometry

Reference

ACTIVE COMPARATOR

Pharmacokinetics and -dynamics after single dose administration 100 ml methantheline solution (100 mg methantheline bromide)

Procedure: blood samplingDrug: methantheline solutionProcedure: Measurement of salivationProcedure: Measurement of accommodationProcedure: Pupillometry

Interventions

blood samplingPROCEDURE

blood sampling before and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 16 hours after administration of study medication

ReferenceTest
Vagantin®DRUG

administration of 2 coated tablets Vagantin® (coated tablets of 50 mg methantheline bromide)

Test
methantheline solutionDRUG

administration 100 ml methantheline solution (100 mg methantheline bromide)

Reference
Measurement of salivationPROCEDURE

Volume of salivary gland secretion was measured by chewing a 5 x 5 cm piece of PARAFILM "M"® (American Can Company, UK) for 5 min. Saliva was collected in glass tubes and the amount of the stimulated saliva was measured by weighing

ReferenceTest
Measurement of accommodationPROCEDURE

Accommodation was measured with the optometer according to Schober (Velhagen 1972)

ReferenceTest
PupillometryPROCEDURE

Pupil function was assessed with the pupillograph (Compact Integrated Pupillograph, AMTech, Weinheim, Germany). The following data were obtained: pupil diameter, response to defined flash stimuli

ReferenceTest

Eligibility Criteria

Age18 Years - 45 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • age: 18 - 45 years
  • sex: male and female
  • ethnic origin: Caucasian
  • body weight: ±20 % of normal weight (Broca)
  • good health as evidenced by the results of the clinical examination and the laboratory check-up which are judged by the clinical investigator not to differ in a clinical relevant way from the normal state
  • written informed consent

You may not qualify if:

  • known hypersensitivity to the investigational products or to their adjuvants
  • pollakisurie of cardial and renal reasons
  • megacolon
  • atonia of the gastrointestinal tract
  • atonia or hypotonia of the urinary bladder
  • tachycardiac arrhythmia
  • subvesical bladder obstruction, especially benign prostatic hypertrophy
  • narrow angle glaucoma
  • glasses or contact lenses
  • history of gastrointestinal diseases (except appendectomy)
  • history of renal and/or hepatic diseases
  • any disease known to modify absorption, metabolism or excretion of the drug under investigation
  • liability to orthostatic dysregulation, faintings, or blackouts
  • alcohol consumption more than 40 g/day
  • smokers of more than 10 cigarettes per day
  • +8 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Department of Clinical Pharmacology at the University of Greifswald

Greifswald, Mecklenburg-Vorpommern, 17487, Germany

Location

Related Publications (1)

  • Muller C, Lotsch J, Giessmann T, Franke G, Walter R, Zschiesche M, Siegmund W. Relative bioavailability and pharmacodynamic effects of methantheline compared with atropine in healthy subjects. Eur J Clin Pharmacol. 2012 Nov;68(11):1473-81. doi: 10.1007/s00228-012-1286-6. Epub 2012 Apr 21.

    PMID: 22527350DERIVED

MeSH Terms

Conditions

Urinary Bladder, NeurogenicSialorrhea

Interventions

Blood Specimen CollectionMethantheline

Condition Hierarchy (Ancestors)

Neurologic ManifestationsNervous System DiseasesUrinary Bladder DiseasesUrologic DiseasesFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesMale Urogenital DiseasesSigns and SymptomsPathological Conditions, Signs and SymptomsSalivary Gland DiseasesMouth DiseasesStomatognathic Diseases

Intervention Hierarchy (Ancestors)

Specimen HandlingClinical Laboratory TechniquesDiagnostic Techniques and ProceduresDiagnosisPuncturesSurgical Procedures, OperativeInvestigative TechniquesQuaternary Ammonium CompoundsAminesOrganic ChemicalsOnium Compounds

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
NONE
Purpose
BASIC SCIENCE
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 1, 2011

First Posted

September 5, 2011

Study Start

October 1, 1999

Primary Completion

November 1, 1999

Study Completion

January 1, 2000

Last Updated

September 5, 2011

Record last verified: 2011-09

Locations

DE(1)