Gastrointestinal Motility DisorderPhase 1NCT01635608
Absorption of Paracetamol, Talinolol and Amoxicillin After Oral Administration Using Non-caloric and Caloric Water
A Phase 1 study testing Acetaminophen, Talinolol and Amoxicillin in people with Gastrointestinal Motility Disorder, run by University Medicine Greifswald at 1 site in Germany.
Trial summary
To visualize the localization and to measure the volume of water in the small intestine by T2-weighted MRI imaging after oral administration of 240 ml water (non-caloric water) and after administration of 240 ml water containing 25.5 g sucrose (105 kcal, caloric water). Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Gastrointestinal Motility Disorder
- What is being tested?
- Acetaminophen, Talinolol and Amoxicillin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteGermany
- Study dates
- Apr 2011to Jul 2011
- 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: white
- body weight between 19 and 27 kg/m²
- good health as evidenced by the results of the clinical examination, ECG, 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
- weight less than 45 kg
- claustrophobia
- cardiac pacemakers, metallic implants or metal-containing tatoos
- known allergic reactions to the active ingredients used or to constituents of the study medication
- bronchial asthma (all stages)
- existing cardiac or hematological diseases and/or pathological findings, which might interfere with the drug's safety, tolerability and/or pharmacokinetics (e.g. tachycardia)
Show all 23Show fewer
- hepatic and renal diseases and/or pathological findings, which might interfere with pharmacokinetics and pharmacodynamics of the study medication
- gastrointestinal diseases and/or pathological findings, which might interfere with pharmacokinetics and pharmacodynamics of the study medication
- drug or alcohol dependence
- positive drug or alcohol screening
- smokers of 10 or more cigarettes per day
- positive results in HIV, HBV and HCV screenings
- subjects who are on a diet which could affect the pharmacokinetics of the drug
- heavy tea or coffee drinkers (more than 1L per day)
- lactation and pregnancy test positive or not performed
- subjects suspected or known not to follow instructions
- subjects who are unable to understand the written and verbal instructions, in particular regarding the risks and inconveniences they will be exposed to as a result of their participation in the study
- subjects liable to orthostatic dysregulation, fainting, or blackouts
- participation in a clinical trial during the last 3 months prior to the start of the study
- less than 14 days after last acute disease
- less than 3 months after last blood donation
- any systemically available medication within 2 weeks prior to the intended first administration unless because of the terminal elimination half-life complete elimination from the body can be assumed for the drug and/or its primary metabolites (except oral contraceptives)
- intake of grapefruit or poppy seeds containing products within 14 days prior to administration
Trial locations and contacts
1 site in 1 country.
Germany1 site
Department of Clinical Pharmacology, Ernst-Moritz-Arndt-University Greifswald
Greifswald, Meckleburg-Vorpommern, 17487
About this study
To visualize the localization and to measure the volume of water in the small intestine by T2-weighted MRI imaging after oral administration of 240 ml water (non-caloric water) and after administration of 240 ml water containing 25.5 g sucrose (105 kcal, caloric water).
To measure pharmacokinetics of the probe-drugs paracetamol, talinolol and amoxicillin after oral administration dissolved in 240 ml non-caloric and in 240 ml caloric water.
Read the detailed description
After swallowing, a drug first is deposited in the stomach together with the co-swallowed water. However, the stomach is not the major place of drug absorption. Therefore, the kinetics of gastric emptying plays a crucial role for the absorption process. In case of dissolved or finely suspended drug particles, gastric emptying of the drugs occurs together with gastric contents. The emptied liquid enters the small intestine where it is absorbed. Under fasting conditions, the emptied phase consists of the water that was co-swallowed with the drug (in clinical studies typically 240 ml) together with a small volume of gastric juice. Under fed conditions, the emptied liquid phase is a caloric suspension. It is known that both the gastric emptying and the intestinal absorption of pure water are rapid leading usually to rapid absorption of water soluble drugs that are taken under fasting conditions. In the contrary, delayed absorption under postprandial conditions is typically related to delayed gastric emptying. However, velocity and extent of intestinal filling and the absorption rate of the liquid phase from gut lumen are unknown.
Therefore, it is the primary objective of the study to determine the gastric emptying kinetics of 240 ml water (non-caloric water) and of 240 ml water containing 25.5 g sucrose (105 kcal, caloric water), the respective intestinal filling and the absorption rate of the intestinal liquid using water sensitive magnetic resonance imaging (MRI).
To evaluate the functional meaning of gastric emptying, intestinal filling and water uptake for oral drug absorption which are swallowed with non-caloric and caloric water, pharmacokinetics of paracetamol, talinolol and amoxicillin will be studied after administration with 240 ml non-caloric and 240 ml caloric water, respectively.
Paracetamol (acetaminophen) was chosen, because it is rapidly and completely absorbed from all parts of the gut. The time of its appearance in blood is expected to be a surrogate for the rate of gastric emptying. It is hypothesized that caloric content of the water for administration does not influence the extent of paracetamol absorption.
Talinolol represents a well established probe drug for the intestinal efflux transport protein ABCB1. Because expression of ABCB1 increases along the small intestine (duodenum<jejunum<ileum), we hypothesize, that administration of talinolol with caloric water leads to lower bioavailability and increase of the fecal excretion of the drug.
Amoxicillin acts as a probe drug for intestinal drug uptake via the dipeptide transporter PEPT1 which is predominately expressed in proximal parts of the small intestine ((duodenum>jejunum>ileum). Because of this region-specific expression, we hypothesize, that administration of amoxicillin with caloric water is associated with lower bioavailability.
- Conditions
- Gastrointestinal Motility Disorder
- Being tested
- Acetaminophen, Talinolol, Amoxicillin, non-caloric water, caloric water
- Keywords
- Pharmacokinetics, Talinolol, Amoxicillin, Acetaminophen, Magnetic Resonance Imaging
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AcetaminophenDrug
administration of 500 mg paracetamol
TalinololDrug
administration of 50 mg talinolol
AmoxicillinDrug
administration of 500 mg amoxicillin
non-caloric waterOther
administration of 240 ml water
caloric waterOther
administration of 240 ml caloric water (containing 25.5 g sucrose)
| Study group | Role | What they receive |
|---|---|---|
| non-caloric water | Active comparator | 500 mg paracetamol, 50 mg talinolol and 500 mg amoxicillin dissolved in 240 ml non-caloric water immediately before administration after overnight fasting Receives: Drug: Acetaminophen; Drug: Talinolol; Drug: Amoxicillin; Other: non-caloric water |
| caloric water | Active comparator | 500 mg paracetamol, 50 mg talinolol and 500 mg amoxicillin dissolved in 240 ml caloric water immediately before oral administration after overnight fasting Receives: Drug: Acetaminophen; Drug: Talinolol; Drug: Amoxicillin; Other: caloric water |
What is being measured
The primary outcome is the main question the study is designed to answer.
Correlation between volume of water in stomach and AUC of study medication
Measured: 0 to 48 h
Secondary outcomes (4)
area under the concentrations-time curve (AUC)
Measured: 0, 5, 10, 15, 20, 30, 40, 50, 60, 75, 90, 105 min and 2, 3, 4, 6, 8, 12, 24 and 48 h after drug administration
maximum concentration (Cmax)
Measured: 0, 5, 10, 15, 20, 30, 40, 50, 60, 75, 90, 105 min and 2, 3, 4, 6, 8, 12, 24 and 48 h after drug administration
volumen of water in stomach
Dynamic enhanced MR examination gradient-echo T2-weighted HASTE images (TR 1900 ms, TR 111 ms, flip-angle 0) will be acquired on a 1.5T MRI. A tube filled with 20 ml water will be fitted on the abdomen of the volunteers in order to have an internal reference for imaging.
Measured: before and 1.5, 6.5, 11.5, 16.5, 21.5, 26.5, 31.5, 36.5, 41.5, 46.5, 51.5, 56.5, 61.5, 66.5, 71.5, 76.5, 81.5, 86.5, 91.5, 96.5, 101.5, 106.5, 111.5, and 116.5 min after administration of the study medication
volumen of water in small intestine
Dynamic enhanced MR examination gradient-echo T2-weighted HASTE images (TR 1900 ms, TR 111 ms, flip-angle 0) will be acquired on a 1.5T MRI. A tube filled with 20 ml water will be fitted on the abdomen of the volunteers in order to have an internal reference for imaging.
Measured: before and 1.5, 6.5, 11.5, 16.5, 21.5, 26.5, 31.5, 36.5, 41.5, 46.5, 51.5, 56.5, 61.5, 66.5, 71.5, 76.5, 81.5, 86.5, 91.5, 96.5, 101.5, 106.5, 111.5, and 116.5 min after administration of the study medication
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jul 2012 (estimated)
- Study startApr 2011
- Primary completionJul 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Gastrointestinal Motility DisorderStudies 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
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01635608
- Sponsor's protocol ID
- MRI-probe drugs
- Other IDs
- 2011-000228-13
- Status last verified
- Jul 2012
- First submitted
- 4 Jul 2012
- Last updated
- 9 Jul 2012
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Jul 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Absorption of Paracetamol, Talinolol and Amoxicillin After Oral Administration Using Non-caloric and Caloric Water
- ClinicalTrials.gov ID
- NCT01635608
- Acronym / sponsor ID
- MRI-probe drugs
- Conditions
- Gastrointestinal Motility Disorder
- Keywords
- Pharmacokinetics, Talinolol, Amoxicillin, Acetaminophen, Magnetic Resonance Imaging
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- University Medicine GreifswaldUniversity, hospital or other
- Study start
- Apr 2011
- Primary completion
- Jul 2011 (actual)
- First posted
- 9 Jul 2012 (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.
To visualize the localization and to measure the volume of water in the small intestine by T2-weighted MRI imaging after oral administration of 240 ml water (non-caloric water) and after administration of 240 ml water containing 25.5 g sucrose (105 kcal, caloric water).
To measure pharmacokinetics of the probe-drugs paracetamol, talinolol and amoxicillin after oral administration dissolved in 240 ml non-caloric and in 240 ml caloric water.
Detailed description
After swallowing, a drug first is deposited in the stomach together with the co-swallowed water. However, the stomach is not the major place of drug absorption. Therefore, the kinetics of gastric emptying plays a crucial role for the absorption process. In case of dissolved or finely suspended drug particles, gastric emptying of the drugs occurs together with gastric contents. The emptied liquid enters the small intestine where it is absorbed. Under fasting conditions, the emptied phase consists of the water that was co-swallowed with the drug (in clinical studies typically 240 ml) together with a small volume of gastric juice. Under fed conditions, the emptied liquid phase is a caloric suspension. It is known that both the gastric emptying and the intestinal absorption of pure water are rapid leading usually to rapid absorption of water soluble drugs that are taken under fasting conditions. In the contrary, delayed absorption under postprandial conditions is typically related to delayed gastric emptying. However, velocity and extent of intestinal filling and the absorption rate of the liquid phase from gut lumen are unknown.
Therefore, it is the primary objective of the study to determine the gastric emptying kinetics of 240 ml water (non-caloric water) and of 240 ml water containing 25.5 g sucrose (105 kcal, caloric water), the respective intestinal filling and the absorption rate of the intestinal liquid using water sensitive magnetic resonance imaging (MRI).
To evaluate the functional meaning of gastric emptying, intestinal filling and water uptake for oral drug absorption which are swallowed with non-caloric and caloric water, pharmacokinetics of paracetamol, talinolol and amoxicillin will be studied after administration with 240 ml non-caloric and 240 ml caloric water, respectively.
Paracetamol (acetaminophen) was chosen, because it is rapidly and completely absorbed from all parts of the gut. The time of its appearance in blood is expected to be a surrogate for the rate of gastric emptying. It is hypothesized that caloric content of the water for administration does not influence the extent of paracetamol absorption.
Talinolol represents a well established probe drug for the intestinal efflux transport protein ABCB1. Because expression of ABCB1 increases along the small intestine (duodenum<jejunum<ileum), we hypothesize, that administration of talinolol with caloric water leads to lower bioavailability and increase of the fecal excretion of the drug.
Amoxicillin acts as a probe drug for intestinal drug uptake via the dipeptide transporter PEPT1 which is predominately expressed in proximal parts of the small intestine ((duodenum>jejunum>ileum). Because of this region-specific expression, we hypothesize, that administration of amoxicillin with caloric water is associated with lower bioavailability.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| non-caloric water | Active comparator | Drug: Acetaminophen, Drug: Talinolol, Drug: Amoxicillin, Other: non-caloric water500 mg paracetamol, 50 mg talinolol and 500 mg amoxicillin dissolved in 240 ml non-caloric water immediately before administration after overnight fasting |
| caloric water | Active comparator | Drug: Acetaminophen, Drug: Talinolol, Drug: Amoxicillin, Other: caloric water500 mg paracetamol, 50 mg talinolol and 500 mg amoxicillin dissolved in 240 ml caloric water immediately before oral administration after overnight fasting |
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: white
- body weight between 19 and 27 kg/m²
- good health as evidenced by the results of the clinical examination, ECG, 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)
- weight less than 45 kg
- claustrophobia
- cardiac pacemakers, metallic implants or metal-containing tatoos
- known allergic reactions to the active ingredients used or to constituents of the study medication
- bronchial asthma (all stages)
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 |
|---|---|---|
| Acetaminophenadministration of 500 mg paracetamol | Drug | caloric water, non-caloric water |
| Talinololadministration of 50 mg talinolol | Drug | caloric water, non-caloric water |
| Amoxicillinadministration of 500 mg amoxicillin | Drug | caloric water, non-caloric water |
| non-caloric wateradministration of 240 ml water | Other | non-caloric water |
| caloric wateradministration of 240 ml caloric water (containing 25.5 g sucrose) | Other | caloric water |
Primary outcome
Correlation between volume of water in stomach and AUC of study medication
Time frame: 0 to 48 h
4 secondary outcomes
area under the concentrations-time curve (AUC)
Time frame: 0, 5, 10, 15, 20, 30, 40, 50, 60, 75, 90, 105 min and 2, 3, 4, 6, 8, 12, 24 and 48 h after drug administration
maximum concentration (Cmax)
Time frame: 0, 5, 10, 15, 20, 30, 40, 50, 60, 75, 90, 105 min and 2, 3, 4, 6, 8, 12, 24 and 48 h after drug administration
volumen of water in stomach
Time frame: before and 1.5, 6.5, 11.5, 16.5, 21.5, 26.5, 31.5, 36.5, 41.5, 46.5, 51.5, 56.5, 61.5, 66.5, 71.5, 76.5, 81.5, 86.5, 91.5, 96.5, 101.5, 106.5, 111.5, and 116.5 min after administration of the study medication
volumen of water in small intestine
Time frame: before and 1.5, 6.5, 11.5, 16.5, 21.5, 26.5, 31.5, 36.5, 41.5, 46.5, 51.5, 56.5, 61.5, 66.5, 71.5, 76.5, 81.5, 86.5, 91.5, 96.5, 101.5, 106.5, 111.5, and 116.5 min after administration of the 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 9 Jul 2012.
Related trials for Gastrointestinal Motility Disorder
RecruitingObservational study
A Study to Evaluate the Efficacy and Safety of Long-term Administration of K-CAB Tab./K-CAB ODT(Tegoprazan) 25 mg as Maintenance Therapy Following the Treatment of GERD
Maintenance Therapy Following Treatment for Gastroesophageal Reflux Disease(GERD)
RecruitingObservational study
Natural History of Bronchiectasis
Bronchiectasis, Cystic Fibrosis
Not yet recruiting
Effects of Epetôme on Gastrointestinal Function, Inflammation and Wellbeing in Adults With IBS-like Symptoms (EPEGUT)
IBS - Irritable Bowel Syndrome, Gastrointestinal Motility Disorder
Active, not recruitingObservational study
RETHINK REFLUX Registry
Gastroesophageal Reflux
Recruiting
Transcatheter Mitral Valve Replacement in Patients With Severe Symptomatic Mitral Regurgitation - APOLLO-EU Trial
Mitral Regurgitation
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 Acetaminophen, Talinolol and Amoxicillin in people with Gastrointestinal Motility Disorder, 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 9 Jul 2012. 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?
Correlation between volume of water in stomach and AUC of study medication (time frame: 0 to 48 h). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 9 Jul 2012.