Neurogenic BladderPhase 1NCT01429090
Bioavailability of Vagantin® Coated Tablets Relative to an Oral Methantheline Bromide Solution
A Phase 1 study testing blood sampling, Vagantin® and methantheline solution in people with Neurogenic Bladder, run by University Medicine Greifswald at 1 site in Germany.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Neurogenic Bladder
- What is being tested?
- blood sampling, Vagantin® and methantheline solution
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteGermany
- Study dates
- Oct 1999to Jan 2000
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 23Show fewer
- 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
- special or uniform nutritional habits, e.g. vegetarians or under-caloric diet
- less than 14 days after last acute disease
- less than 14 days after last systemic or local drug administration or 10 times the half life of the respective drug (except hormonal contraceptives)
- blood donation within the last two months
- blocking period due to another clinical study with investigational products; however at least 4 weeks after the end of the study or 10 times the half life of the respective drug
- lack of willingness or inability to co-operate adequately
- HIV and HBV and drug screening positive or not performed (in case of a positive HIV-test, the volunteers must be informed by a physician in a personal conversation)
- lactation and pregnancy test positive or not performed
Trial locations and contacts
1 site in 1 country.
Germany1 site
Department of Clinical Pharmacology at the University of Greifswald
Greifswald, Mecklenburg-Vorpommern, 17487
About this study
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
Read the detailed description
The quarternary anticholinergic compound methantheline bromide (diethyl-methyl [2-(9 xanthenyl carbonyloxy) ethyl] ammonium bromide) is marketed to treat neurogenic bladder instability. In comparison with atropine, it influences the parasympathetic nervous transmission more by ganglionic rather than peripheral muscarinic receptor blockade. Clinical effects after single therapeutic doses of 50-100 mg last for about 6 hours which is longer than after atropine. The drug relaxes smooth muscles of the gastrointestinal and urogenital tract. Furthermore, it inhibits bronchial, salivary and sweat glands secretion, lowers the production of gastric juice and disturbs accommodation.
There are no data available on the pharmacokinetic properties of methantheline in man. However, 25-50 mg intravenous methantheline seem to be equivalent to 50-100 mg p.o. with regard to the pharmacodynamic effects [Stille 1988].
Vagantin® is marketed as coated tablets containing 50 mg methantheline bromide. Because of the particular properties of methantheline (narrow therapeutic range, obviously erratic, incomplete and irregular absorption) and because of the national and international recommendations concerning the registration of drugs, Vagantin® must be evaluated with regard to its pharmacokinetic properties at least relative to a non-formulated form.
- Conditions
- Neurogenic Bladder
- Being tested
- blood sampling, Vagantin®, methantheline solution, Measurement of salivation, Measurement of accommodation
- Keywords
- Pharmacokinetics, Accommodation, Ocular, Reflex, Pupillary, Salivation
- Medical subject headings
- Urinary Bladder, Neurogenic, Sialorrhea
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
blood samplingProcedure or surgery
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
Vagantin®Drug
administration of 2 coated tablets Vagantin® (coated tablets of 50 mg methantheline bromide)
methantheline solutionDrug
administration 100 ml methantheline solution (100 mg methantheline bromide)
Measurement of salivationProcedure or surgery
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
Measurement of accommodationProcedure or surgery
Accommodation was measured with the optometer according to Schober (Velhagen 1972)
PupillometryProcedure or surgery
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
| Study group | Role | What they receive |
|---|---|---|
| Test | Experimental | Pharmacokinetics and -dynamics after single dose administration of 2 coated tablets Vagantin® (coated tablets of 50 mg methantheline bromide) Receives: Procedure: blood sampling; Drug: Vagantin®; Procedure: Measurement of salivation; Procedure: Measurement of accommodation; Procedure: Pupillometry |
| Reference | Active comparator | Pharmacokinetics and -dynamics after single dose administration 100 ml methantheline solution (100 mg methantheline bromide) Receives: Procedure: blood sampling; Drug: methantheline solution; Procedure: Measurement of salivation; Procedure: Measurement of accommodation; Procedure: Pupillometry |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 0-16 h plasma concentration-time profile of methantheline after single oral administration
Secondary outcomes (5)
time of maximal plasma concentration (tmax)
tmax was obtained directly from the measured concentration-time curves
Measured: 0-16 h plasma concentration-time profile of methantheline after single oral administration
terminal half-life (t½)
Half-life (t½) was evaluated by non-linear regression of the terminal slope
Measured: 0-16 h plasma concentration-time profile of methantheline after single oral administration
volume of salivary gland secretion
Volume of salivary gland secretion will be measured by chewing a 5 x 5 cm piece of PARAFILM "M"® (American Can Company, UK) for 5 min. Saliva will be collected in glass tubes the volume of which will be measured be weighing
Measured: before and 0, 0.5, 1, 2, 3, 4, 6, 8, 12 hours after administration of study medication
Measurement of accommodation
Accommodation will be measured with the optometer according to Schober (Velhagen 1972)
Measured: before and 0, 1, 2, 3, 4, 6, 8, 12 hours after administration of study medication
Pupil function
Pupil function will be assessed with the pupillograph (Compact Integrated Pupillograph, AMTech, Weinheim, Germany). The following data will be obtained: pupil diameter, response to defined flash stimuli
Measured: before and 0, 1, 2, 3, 4, 6, 8, 12 hours after administration of study medication
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Sep 2011 (estimated)
- Study startOct 1999
- Primary completionNov 1999
- Study completionJan 2000
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Neurogenic BladderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Medicine Greifswald
- Sponsor type
- University, hospital or other
- Collaborators
- RIEMSER Arzneimittel GmbH
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01429090
- Sponsor's protocol ID
- BAMB0199
- Status last verified
- Sep 2011
- First submitted
- 1 Sep 2011
- Last updated
- 5 Sep 2011
- Results posted
- No
Publications
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.
PubMed 22527350
Study at a glance
From the registry record, last updated by the sponsor on 5 Sep 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Bioavailability of Vagantin® Coated Tablets Relative to an Oral Methantheline Bromide Solution
- ClinicalTrials.gov ID
- NCT01429090
- Acronym / sponsor ID
- BAMB0199
- Conditions
- Neurogenic Bladder
- Keywords
- Pharmacokinetics, Accommodation, Ocular, Reflex, Pupillary, Salivation
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- University Medicine GreifswaldUniversity, hospital or other
- Collaborators
- RIEMSER Arzneimittel GmbH
- Study start
- Oct 1999
- Primary completion
- Nov 1999 (actual)
- Study completion
- Jan 2000 (actual)
- First posted
- 5 Sep 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed description
The quarternary anticholinergic compound methantheline bromide (diethyl-methyl [2-(9 xanthenyl carbonyloxy) ethyl] ammonium bromide) is marketed to treat neurogenic bladder instability. In comparison with atropine, it influences the parasympathetic nervous transmission more by ganglionic rather than peripheral muscarinic receptor blockade. Clinical effects after single therapeutic doses of 50-100 mg last for about 6 hours which is longer than after atropine. The drug relaxes smooth muscles of the gastrointestinal and urogenital tract. Furthermore, it inhibits bronchial, salivary and sweat glands secretion, lowers the production of gastric juice and disturbs accommodation.
There are no data available on the pharmacokinetic properties of methantheline in man. However, 25-50 mg intravenous methantheline seem to be equivalent to 50-100 mg p.o. with regard to the pharmacodynamic effects [Stille 1988].
Vagantin® is marketed as coated tablets containing 50 mg methantheline bromide. Because of the particular properties of methantheline (narrow therapeutic range, obviously erratic, incomplete and irregular absorption) and because of the national and international recommendations concerning the registration of drugs, Vagantin® must be evaluated with regard to its pharmacokinetic properties at least relative to a non-formulated form.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Test | Experimental | Procedure: blood sampling, Drug: Vagantin®, Procedure: Measurement of salivation, Procedure: Measurement of accommodation, Procedure: PupillometryPharmacokinetics and -dynamics after single dose administration of 2 coated tablets Vagantin® (coated tablets of 50 mg methantheline bromide) |
| Reference | Active comparator | Procedure: blood sampling, Drug: methantheline solution, Procedure: Measurement of salivation, Procedure: Measurement of accommodation, Procedure: PupillometryPharmacokinetics and -dynamics after single dose administration 100 ml methantheline solution (100 mg methantheline bromide) |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (23 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| blood samplingblood 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 | Procedure or surgery | Reference, Test |
| Vagantin®administration of 2 coated tablets Vagantin® (coated tablets of 50 mg methantheline bromide) | Drug | Test |
| methantheline solutionadministration 100 ml methantheline solution (100 mg methantheline bromide) | Drug | Reference |
| Measurement of salivationVolume 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 | Procedure or surgery | Reference, Test |
| Measurement of accommodationAccommodation was measured with the optometer according to Schober (Velhagen 1972) | Procedure or surgery | Reference, Test |
| PupillometryPupil function was assessed with the pupillograph (Compact Integrated Pupillograph, AMTech, Weinheim, Germany). The following data were obtained: pupil diameter, response to defined flash stimuli | Procedure or surgery | Reference, Test |
Primary outcome
area under the curve (AUC0-∞)
Time frame: 0-16 h plasma concentration-time profile of methantheline after single oral administration
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
maximal plasma concentration (Cmax)
Time frame: 0-16 h plasma concentration-time profile of methantheline after single oral administration
Cmax was obtained directly from the measured concentration-time curves
5 secondary outcomes
time of maximal plasma concentration (tmax)
Time frame: 0-16 h plasma concentration-time profile of methantheline after single oral administration
terminal half-life (t½)
Time frame: 0-16 h plasma concentration-time profile of methantheline after single oral administration
volume of salivary gland secretion
Time frame: before and 0, 0.5, 1, 2, 3, 4, 6, 8, 12 hours after administration of study medication
Measurement of accommodation
Time frame: before and 0, 1, 2, 3, 4, 6, 8, 12 hours after administration of study medication
Pupil function
Time frame: before and 0, 1, 2, 3, 4, 6, 8, 12 hours after administration of study medication
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Sep 2011.
- Derived from this study: PubMed 22527350Muller 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing blood sampling, Vagantin® and methantheline solution in people with Neurogenic Bladder, run by University Medicine Greifswald at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Sep 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
area under the curve (AUC0-∞) (time frame: 0-16 h plasma concentration-time profile of methantheline after single oral administration). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01429090, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Sep 2011.