Gastroretentive Drug Formulation of FurosemidePhase 1NCT01887379
Magnetic Marker Monitoring of Furosemide-containing Gastroretentive Formulation in Healthy Male Subjects (Fasting and Fed Conditions)
A Phase 1 study testing GRDF furosemide in people with Gastroretentive Drug Formulation of Furosemide and Oedema, run by LTS Lohmann Therapie-Systeme AG at 1 site in Germany.
Trial summary
Furosemide is a diuretic drug, used in the treatment of oedematous states associated with cardiac, renal, and hepatic disorder, and may be effective in patients unresponsive to thiazide diuretics. Furosemide is also used in the treatment of hypertension. Read more about this study
- Who is it for?
- Ages 18 to 55 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Gastroretentive Drug Formulation of Furosemide, Oedema
- What is being tested?
- GRDF furosemide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteGermany
- Study dates
- Jun 2013to Aug 2013
- 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 55 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- sex: male
- ethnic origin: Caucasian
- age: 18 years to 55 years
- body-mass index (BMI): > or = 19 kg/m² and < or = 27 kg/m²
- good state of health
- non-smoker or ex-smoker for at least 1 month
- written informed consent, after having been informed about benefits and potential risks of the clinical trial, as well as details of the insurance taken out to cover the subjects participating in the clinical trial
Who cannot join
- existing cardiac and/or haematological diseases or pathological findings, which might interfere with the safety or tolerability of the active ingredient
- existing hepatic and/or renal diseases or pathological findings, which might interfere with the safety or tolerability of the active ingredient
- existing gastrointestinal diseases or pathological findings, which might interfere with the safety and tolerability or with gastric emptying and the gastrointestinal transport (e.g. inflammatory bowel diseases, ileus)
- history of relevant central nervous system (CNS) and/or psychiatric disorders and/or currently treated CNS and/or psychiatric disorders
- any surgery at the gastrointestinal tract, which might interfere with the safety of the test product or any stomach reduction like Bioenterics Intragastric Balloon (BIB) or gastric banding
- known allergic reactions to the active ingredients used or to constituents of the pharmaceutical preparations
Show all 36Show fewer
- known allergic reactions to sulphonamide
- subjects with severe allergies or multiple drug allergies unless it is judged as not relevant for the clinical trial by the investigator
- heart rate < 50 bpm or > 90 bpm
- systolic blood pressure of < 100 mmHg and > 140 mmHg, diastolic blood pressure of < 60 mmHg and >90 mmHg
- laboratory values, especially for sodium, potassium, calcium, creatinine, urea, uric acid, and blood glucose out of normal range unless the deviation from normal is judged as not relevant for the clinical trial by the investigator
- positive anti-human immunodeficiency virus-test (if positive to be verified by western blot), surface antigen of the hepatitis B virus (HBs-AG)test [if positive to be verified by test for hepatitis B Core (HBc-IgM)] or anti-hepatitis C virus-test
- renal failure with anuria
- coma and praecoma hepatica
- severe hypokalemia and/or hyponatremia
- hypovolemia or dehydration
- subjects with manifest or latent diabetes mellitus or gout
- subjects with cerebrovascular insufficiency or coronary heart disease
- subjects with bladder outlet obstruction (BOO) e.g. prostatic hypertrophy, hydronephrosis or ureteral stenosis
- hypoproteinemia
- liver cirrhosis and simultaneous limitation of kidney function
- acute or chronic diseases which could affect gastric emptying and the gastrointestinal transport
- history of or current drug or alcohol dependence
- positive alcohol or drug test at screening examination
- regular intake of alcoholic food or beverages of ≥ 40 g pure ethanol for male per day
- subjects who are on a diet which could affect gastric emptying and the gastro-intestinal transport
- regular intake of caffeine containing food or beverages of ≥ 500 mg caffeine per day
- subjects with claustrophobia
- ferromagnetic implants or any other magnetic disturbance, which can affect the Magnetic Marker Monitoring measurement
- blood donation or other blood loss of more than 400 ml within the last two months prior to individual enrolment of the subject
- participation in a clinical trial during the last two months prior to individual enrolment of the subject
- regular treatment with any systemically available medication including all ototoxic medication like aminoglycosides and medication which could affect gastric emptying and the gastrointestinal transport (e.g. laxatives, metoclopramide, loperamide, antacids, H2-receptor antagonists) or antibiotics
- subjects, who report a frequent occurrence of migraine attacks
- 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 during their participation in the clinical trial
- subjects who have forfeited their own freedom by administrative or legal award, or who are under guardianship or have been admitted in a sanitary or social institution
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Characterisation of Gastric Residence of a Furosemide-containing New Gastric Retention System by Means of MMM Measurement and Determination of Pharmacokinetics, Pharmacodynamics and Safety
Furosemide is a diuretic drug, used in the treatment of oedematous states associated with cardiac, renal, and hepatic disorder, and may be effective in patients unresponsive to thiazide diuretics. Furosemide is also used in the treatment of hypertension.
Absorption of furosemide from the gastrointestinal tract is fairly rapid; bioavailability is 60-70%, but variable and not predictable, with large intra- and inter-individual variability, and are influenced by dosage form, underlying diseases, and by the presence of food after oral administration. Data from animal model show that furosemide administered into the stomach is more rapidly absorbed than if is administered into the small intestine.
Read more
To increase the residency of furosemide in the stomach after oral administration, a gastroretentive dosage form (GRDF) of furosemide has been developed. In the current study, the new formulation (30mg furosemide coated tablet) will be tested in healthy male subjects. Absorption will be characterised by an effective and safe imaging technique - Magnetic Marker Monitoring (MMM), based on Fe3O4 added to the drug product to generate magnetic signal that can be used for up to 12 h after furosemide administration to localize the medication in the gastrointestinal tract. Fe3O4 is frequently used as colouring pigment in medicinal products. It does not exhibit own pharmacodynamic activity and is considered as an inactive ingredient.
In the current study, GRDF formulation of furosemide will be evaluated for: gastric residence as well as pharmacokinetic and pharmacodynamic characteristics under fasting and fed conditions. As part of the study, the subjects will be hospitalized for 1 day during each drug administration. The duration of the stay will depend on the intestinal behaviour of the investigational product.
Read the detailed description
Furosemide is a diuretic drug, widely used in the treatment of oedematous states associated with cardiac, renal, and hepatic disorder, and may be effective in patients unresponsive to thiazide diuretics. Furosemide is also used in the treatment of hypertension.
Absorption of furosemide from the gastrointestinal tract is fairly rapid. Bioavailability is reported as 60-70%, but is variable and not predictable. The rate and extent of absorption show a large intra- and inter-individual variability and are influenced by dosage form, underlying diseases, and by the presence of food after oral administration. Results obtained with an animal model indicate that furosemide administered into the stomach is more rapidly absorbed than if is is administered into the small intestine.
To increase the residency of furosemide in the stomach after oral administration, a gastroretentive dosage form (GRDF) of furosemide has been developed. In this study, the new formulation(30mg furosemide coated tablet) will be tested in healthy male subjects. Absorption will be characterised by imaging technique - Magnetic Marker Monitoring (MMM), which is the most effective and safe imaging technique currently available. MMM is based on a iron-III-oxide (Fe3O4) added to the drug product to generate magnetic signal that can be used to localize the administered medication in the gastrointestinal tract.
Fe3O4 is frequently used as colouring pigment in medicinal products. It does not exhibit own pharmacodynamic activity and thus, it is considered as clinically inactive ingredient. Fe3O4 exhibits a dipole moment and thus, after magnetisation of solid oral dosage forms containing homogenously distributed Fe3O4, the product generates a magnetic signal, which can be used for localisation of the dosage form in the gastrointestinal tract by Magnetic Marker Monitoring technique.
The aim of the current study is to evaluate the GRDF formulation of furosemide for: gastric residence, pharmacokinetic and pharmacodynamic characteristics under fasting and fed conditions. As part of the study, the subjects will be hospitalized for 1 day during each drug administration (i.e. a total of two days). The duration of the stay will depend on the intestinal behaviour of the investigational product. The MMM monitoring be performed for up to 12 h after furosemide administration. For pharmacokinetic determinations, liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) will be used to analyze furosemide in plasma.
- Being tested
- GRDF furosemide
- Keywords
- Gastroretentive drug formulation, Furosemide, Magnetic Marker Monitoring, Magnetic marker, Oedema
- Medical subject headings
- Edema
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GRDF furosemideDrug
Also called GRDF furosemide is a gastro retentive dosage form of furesomide
The GRDF furosemide tablet contains Fe3O4, which serves as an inactive magnetic marker to allow monitoring of the tablet transit through the gastrointestinal tract, using the MMM imaging technique.
| Study group | Role | What they receive |
|---|---|---|
| GRDF furosemide fasting conditions | Experimental | Subjects will be tested under fasting conditions after administration of GRDF Furosemide. Receives: Drug: GRDF furosemide |
| GRDF furosemide fed conditions | Experimental | Subjects will be tested under fed conditions after administration of GRDF Furosemide. Receives: Drug: GRDF furosemide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Residency time of GRDF furosemide in the gastrointestinal tract, evaluated with MMM technique, under fasted and fed conditions.
Residency time of GRDF furosemide in the gastrointestinal track will be monitored using the non-invasive MMM technique under fasted and fed conditions. Measurements will start after each administration and last until 2 hours after gastric emptying indicated by the MMM measurement, but not longer than 12 h post administration. Each observation interval for each subject will last for a minimum of 10 min followed by a break of maximum 20 min. For meal intake, a break of the MMM measuring of 30 minutes will be performed.
Anatomical localisation within the measuring sequences will be listed for each subject and treatment
Statistical evaluation of gastric emptying time will include: arithmetic means, medians, minimum , maximum, standard deviation.
GRDF=Gastro retentive dosage formulation
Measured: every 30 min for up to 12 h after drug administration; maximal observation time 12 h
Secondary outcomes (20)
Cmax of GRDF furosemide under fasted conditions
Characterization of the pharmacokinetic (PK) properties of GRDF furosemide, with special focus on the absorption phase of furosemide. Compare results during fasted and fed state.
Blood samples for the determination of furosemide concentration will be taken at pre-dose (within 1 h prior to administration) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, and 24 h after administration.
LC-MS/MS will be used to analyze furosemide in plasma.
Cmax = maximum concentration in plasma; GRDF=Gastro retentive dosage formulation
Measured: pre-dose (within 1 h prior to drug administration) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, and 24 h after drug administration.
Cmax of GRDF furosemide under fed conditions
Characterization of the pharmacokinetic (PK) properties of GRDF furosemide, with special focus on the absorption phase of furosemide. Compare results during fasted and fed state.
Blood samples for the determination of furosemide concentration will be taken at pre-dose (within 1 h prior to administration) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, and 24 h after administration.
LC-MS/MS will be used to analyze furosemide in plasma.
Cmax = maximum concentration in plasma; GRDF=Gastro retentive dosage formulation
Measured: pre-dose (within 1 h prior to drug administration) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, and 24 h after drug administration.
tmax of GRDF furosemide under fasted conditions
Characterization of the pharmacokinetic (PK) properties of GRDF furosemide, with special focus on the absorption phase of furosemide. Compare results during fasted and fed state.
Blood samples for the determination of furosemide concentration will be taken at pre-dose (within 1 h prior to administration) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, and 24 h after administration.
LC-MS/MS will be used to analyze furosemide in plasma.
tmax = time to reach maximum concentration in plasma; GRDF=Gastro retentive dosage formulation
Measured: pre-dose (within 1 h prior to drug administration) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, and 24 h after drug administration.
tmax of GRDF furosemide under fed conditions
Characterization of the pharmacokinetic (PK) properties of GRDF furosemide, with special focus on the absorption phase of furosemide. Compare results during fasted and fed state.
Blood samples for the determination of furosemide concentration will be taken at pre-dose (within 1 h prior to administration) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, and 24 h after administration.
LC-MS/MS will be used to analyze furosemide in plasma.
tmax = time to reach maximum concentration in plasma; GRDF=Gastro retentive dosage formulation
Measured: pre-dose (within 1 h prior to drug administration) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, and 24 h after drug administration.
t1/2 of GRDF furosemide under fasted conditions
Characterization of the pharmacokinetic (PK) properties of GRDF furosemide, with special focus on the absorption phase of furosemide. Compare results during fasted and fed state.
Blood samples for the determination of furosemide concentration will be taken at pre-dose (within 1 h prior to administration) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, and 24 h after administration.
LC-MS/MS will be used to analyze furosemide in plasma.
t1/2 = apparent terminal elimination half-life; GRDF=Gastro retentive dosage formulation
Measured: pre-dose (within 1 h prior to drug administration) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, and 24 h after drug administration.
t1/2 of GRDF furosemide under fed conditions
Characterization of the pharmacokinetic (PK) properties of GRDF furosemide, with special focus on the absorption phase of furosemide. Compare results during fasted and fed state.
Blood samples for the determination of furosemide concentration will be taken at pre-dose (within 1 h prior to administration) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, and 24 h after administration.
LC-MS/MS will be used to analyze furosemide in plasma.
t1/2 = apparent terminal elimination half-life; GRDF=Gastro retentive dosage formulation
Measured: pre-dose (within 1 h prior to drug administration) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, and 24 h after drug administration.
AUC0-tlast of GRDF furosemide under fasted conditions
Characterization of the pharmacokinetic (PK) properties of GRDF furosemide, with special focus on the absorption phase of furosemide. Compare results during fasted and fed state.
Blood samples for the determination of furosemide concentration will be taken at pre-dose (within 1 h prior to administration) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, and 24 h after administration.
LC-MS/MS will be used to analyze furosemide in plasma.
AUC0 = area under the plasma concentration vs. time curve from dosing time to the last measurement time point with a concentration value above the lower limit of quantitation, calculated by means of the linear up/log down method (linear trapezoidal rule for increases in concentration/logarithmic trapezoidal rule for decreases in concentrations; GRDF=Gastro retentive dosage formulation
Measured: pre-dose (within 1 h prior to drug administration) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, and 24 h after drug administration.
AUC0-tlast of GRDF furosemide under fed conditions
Characterization of the pharmacokinetic (PK) properties of GRDF furosemide, with special focus on the absorption phase of furosemide. Compare results during fasted and fed state.
Blood samples for the determination of furosemide concentration will be taken at pre-dose (within 1 h prior to administration) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, and 24 h after administration.
LC-MS/MS will be used to analyze furosemide in plasma.
AUC0-tlast = area under the plasma concentration vs. time curve from dosing time to the last measurement time point with a concentration value above the lower limit of quantitation, calculated by means of the linear up/log down method (linear trapezoidal rule for increases in concentration/logarithmic trapezoidal rule for decreases in concentrations; GRDF=Gastro retentive dosage formulation
Measured: pre-dose (within 1 h prior to drug administration) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, and 24 h after drug administration.
AUC 0-infinity of GRDF furosemide under fasted conditions
Characterization of the pharmacokinetic (PK) properties of GRDF furosemide, with special focus on the absorption phase of furosemide. Compare results during fasted and fed state.
Blood samples for the determination of furosemide concentration will be taken at pre-dose (within 1 h prior to administration) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, and 24 h after administration.
LC-MS/MS will be used to analyze furosemide in plasma.
AUC0-infinity = AUC0-tlast + AUCexpol; GRDF=Gastro retentive dosage formulation
Measured: pre-dose (within 1 h prior to drug administration) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, and 24 h after drug administration.
AUC 0-infinity of GRDF furosemide under fed conditions
Characterization of the pharmacokinetic (PK) properties of GRDF furosemide, with special focus on the absorption phase of furosemide. Compare results during fasted and fed state.
Blood samples for the determination of furosemide concentration will be taken at pre-dose (within 1 h prior to administration) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, and 24 h after administration.
LC-MS/MS will be used to analyze furosemide in plasma.
AUC0-infinity = AUC0-tlast + AUCexpol; GRDF=Gastro retentive dosage formulation
Measured: pre-dose (within 1 h prior to drug administration) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, and 24 h after drug administration.
AUCextrapol of GRDF furosemide under fasted conditions
Characterization of the pharmacokinetic (PK) properties of GRDF furosemide, with special focus on the absorption phase of furosemide. Compare results during fasted and fed state.
Blood samples for the determination of furosemide concentration will be taken at pre-dose (within 1 h prior to administration) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, and 24 h after administration.
LC-MS/MS will be used to analyze furosemide in plasma.
AUCextrapol = AUCextrapolated = Clast/lamda; lamda = apparent terminal elimination rate constant determined by log-linear regression; GRDF=Gastro retentive dosage formulation
Measured: pre-dose (within 1 h prior to drug administration) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, and 24 h after drug administration.
AUCextrapol of GRDF furosemide under fed conditions
Characterization of the pharmacokinetic (PK) properties of GRDF furosemide, with special focus on the absorption phase of furosemide. Compare results during fasted and fed state.
Blood samples for the determination of furosemide concentration will be taken at pre-dose (within 1 h prior to administration) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, and 24 h after administration.
LC-MS/MS will be used to analyze furosemide in plasma.
AUCextrapol = AUCextrapolated = Clast/lamda; lamda = apparent terminal elimination rate constant determined by log-linear regression; GRDF=Gastro retentive dosage formulation
Measured: pre-dose (within 1 h prior to drug administration) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, and 24 h after drug administration.
CL_f of GRDF furosemide under fasted conditions
Characterization of the pharmacodynamic properties of GRDF furosemide, with special focus on the absorption phase of furosemide. Compare results during fasted and fed state.
Blood samples for the determination of furosemide concentration will be taken at pre-dose (within 1 h prior to administration) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, and 24 h after administration.
LC-MS/MS will be used to analyze furosemide in plasma.
CL_f = apparent total body clearance of furosemide: dose / AUC0-∞; GRDF=Gastro retentive dosage formulation
Measured: pre-dose (within 1 h prior to drug administration) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, and 24 h after drug administration.
CL_f of GRDF furosemide under fed conditions
Characterization of the pharmacodynamic properties of GRDF furosemide, with special focus on the absorption phase of furosemide. Compare results during fasted and fed state.
Blood samples for the determination of furosemide concentration will be taken at pre-dose (within 1 h prior to administration) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, and 24 h after administration.
LC-MS/MS will be used to analyze furosemide in plasma.
CL_f = apparent total body clearance of furosemide: dose / AUC0-∞; GRDF=Gastro retentive dosage formulation
Measured: pre-dose (within 1 h prior to drug administration) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, and 24 h after drug administration.
Vdz of GRDF furosemide under fasted conditions
Characterization of the pharmacodynamic properties of GRDF furosemide, with special focus on the absorption phase of furosemide. Compare results during fasted and fed state.
Blood samples for the determination of furosemide concentration will be taken at pre-dose (within 1 h prior to administration) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, and 24 h after administration.
LC-MS/MS will be used to analyze furosemide in plasma.
Vdz = apparent volume of distribution of furosemide: dose / (AUC0-∞ x λ); GRDF=Gastro retentive dosage formulation; λ=apparent terminal elimination rate constant determined by log-linear regression
Measured: pre-dose (within 1 h prior to drug administration) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, and 24 h after drug administration.
Vdz of GRDF furosemide under fed conditions
Characterization of the pharmacodynamic properties of GRDF furosemide, with special focus on the absorption phase of furosemide. Compare results during fasted and fed state.
Blood samples for the determination of furosemide concentration will be taken at pre-dose (within 1 h prior to administration) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, and 24 h after administration.
LC-MS/MS will be used to analyze furosemide in plasma.
Vdz = apparent volume of distribution of furosemide: dose / (AUC0-∞ x λ); GRDF=Gastro retentive dosage formulation; λ=apparent terminal elimination rate constant determined by log-linear regression
Measured: pre-dose (within 1 h prior to drug administration) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, and 24 h after drug administration.
Sodium excretion over time under fasted conditions
Sodium in urine will be measured for each time interval and total sampling time. Urine will be collected and sampled during the following sample intervals: pre-dose (within 1 hour prior to administration), 0-2h, 2-4h, 4-8h, and 8-12h after administration.
Measured: pre-dose (within 1 hour prior to administration), 0-2h, 2-4h, 4-8h, and 8-12h after administration.
Sodium excretion over time under fed conditions
Sodium in urine will be measured for each time interval and total sampling time. Urine will be collected and sampled during the following sample intervals: pre-dose (within 1 hour prior to administration), 0-2h, 2-4h, 4-8h, and 8-12h after administration.
Measured: pre-dose (within 1 hour prior to administration), 0-2h, 2-4h, 4-8h, and 8-12h after administration.
Urine excretion over time under fasted conditions
Urine volume will be measured for each time interval and total sampling time. Urine will be collected and sampled during the following sample intervals: pre-dose (within 1 hour prior to administration), 0-2h, 2-4h, 4-8h, and 8-12h after administration.
Measured: pre-dose (within 1 hour prior to administration), 0-2h, 2-4h, 4-8h, and 8-12h after administration.
Urine excretion over time under fed conditions
Urine volume will be measured for each time interval and total sampling time. Urine will be collected and sampled during the following sample intervals: pre-dose (within 1 hour prior to administration), 0-2h, 2-4h, 4-8h, and 8-12h after administration.
Measured: pre-dose (within 1 hour prior to administration), 0-2h, 2-4h, 4-8h, and 8-12h after administration.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jun 2013 (estimated)
- Study startJun 2013
- Primary completionAug 2013
- Study completionAug 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Gastroretentive Drug Formulation of FurosemideStudies 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- LTS Lohmann Therapie-Systeme AG
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Frank Donath, MD, Principal investigator, SocraTec R&D GmbH, Clinical Pharmacology Unit
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01887379
- Sponsor's protocol ID
- LTS 03/10
- Other IDs
- 2013-001063-23
- Status last verified
- Dec 2013
- First submitted
- 24 Jun 2013
- Last updated
- 12 Dec 2013
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Dec 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Characterisation of Gastric Residence of a Furosemide-containing New Gastric Retention System by Means of MMM Measurement and Determination of Pharmacokinetics, Pharmacodynamics and Safety
- ClinicalTrials.gov ID
- NCT01887379
- Acronym / sponsor ID
- LTS 03/10
- Keywords
- Gastroretentive drug formulation, Furosemide, Magnetic Marker Monitoring, Magnetic marker, Oedema
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- LTS Lohmann Therapie-Systeme AGIndustry (pharma, biotech, devices)
- Study start
- Jun 2013
- Primary completion
- Aug 2013 (actual)
- Study completion
- Aug 2013 (actual)
- First posted
- 26 Jun 2013 (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.
Furosemide is a diuretic drug, used in the treatment of oedematous states associated with cardiac, renal, and hepatic disorder, and may be effective in patients unresponsive to thiazide diuretics. Furosemide is also used in the treatment of hypertension.
Absorption of furosemide from the gastrointestinal tract is fairly rapid; bioavailability is 60-70%, but variable and not predictable, with large intra- and inter-individual variability, and are influenced by dosage form, underlying diseases, and by the presence of food after oral administration. Data from animal model show that furosemide administered into the stomach is more rapidly absorbed than if is administered into the small intestine.
To increase the residency of furosemide in the stomach after oral administration, a gastroretentive dosage form (GRDF) of furosemide has been developed. In the current study, the new formulation (30mg furosemide coated tablet) will be tested in healthy male subjects. Absorption will be characterised by an effective and safe imaging technique - Magnetic Marker Monitoring (MMM), based on Fe3O4 added to the drug product to generate magnetic signal that can be used for up to 12 h after furosemide administration to localize the medication in the gastrointestinal tract. Fe3O4 is frequently used as colouring pigment in medicinal products. It does not exhibit own pharmacodynamic activity and is considered as an inactive ingredient.
In the current study, GRDF formulation of furosemide will be evaluated for: gastric residence as well as pharmacokinetic and pharmacodynamic characteristics under fasting and fed conditions. As part of the study, the subjects will be hospitalized for 1 day during each drug administration. The duration of the stay will depend on the intestinal behaviour of the investigational product.
Detailed description
Furosemide is a diuretic drug, widely used in the treatment of oedematous states associated with cardiac, renal, and hepatic disorder, and may be effective in patients unresponsive to thiazide diuretics. Furosemide is also used in the treatment of hypertension.
Absorption of furosemide from the gastrointestinal tract is fairly rapid. Bioavailability is reported as 60-70%, but is variable and not predictable. The rate and extent of absorption show a large intra- and inter-individual variability and are influenced by dosage form, underlying diseases, and by the presence of food after oral administration. Results obtained with an animal model indicate that furosemide administered into the stomach is more rapidly absorbed than if is is administered into the small intestine.
To increase the residency of furosemide in the stomach after oral administration, a gastroretentive dosage form (GRDF) of furosemide has been developed. In this study, the new formulation(30mg furosemide coated tablet) will be tested in healthy male subjects. Absorption will be characterised by imaging technique - Magnetic Marker Monitoring (MMM), which is the most effective and safe imaging technique currently available. MMM is based on a iron-III-oxide (Fe3O4) added to the drug product to generate magnetic signal that can be used to localize the administered medication in the gastrointestinal tract.
Fe3O4 is frequently used as colouring pigment in medicinal products. It does not exhibit own pharmacodynamic activity and thus, it is considered as clinically inactive ingredient. Fe3O4 exhibits a dipole moment and thus, after magnetisation of solid oral dosage forms containing homogenously distributed Fe3O4, the product generates a magnetic signal, which can be used for localisation of the dosage form in the gastrointestinal tract by Magnetic Marker Monitoring technique.
The aim of the current study is to evaluate the GRDF formulation of furosemide for: gastric residence, pharmacokinetic and pharmacodynamic characteristics under fasting and fed conditions. As part of the study, the subjects will be hospitalized for 1 day during each drug administration (i.e. a total of two days). The duration of the stay will depend on the intestinal behaviour of the investigational product. The MMM monitoring be performed for up to 12 h after furosemide administration. For pharmacokinetic determinations, liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) will be used to analyze furosemide in plasma.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| GRDF furosemide fasting conditions | Experimental | Drug: GRDF furosemideSubjects will be tested under fasting conditions after administration of GRDF Furosemide. |
| GRDF furosemide fed conditions | Experimental | Drug: GRDF furosemideSubjects will be tested under fed conditions after administration of GRDF Furosemide. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- sex: male
- ethnic origin: Caucasian
- age: 18 years to 55 years
- body-mass index (BMI): > or = 19 kg/m² and < or = 27 kg/m²
- good state of health
Key exclusion criteria (36 listed)
- existing cardiac and/or haematological diseases or pathological findings, which might interfere with the safety or tolerability of the active ingredient
- existing hepatic and/or renal diseases or pathological findings, which might interfere with the safety or tolerability of the active ingredient
- existing gastrointestinal diseases or pathological findings, which might interfere with the safety and tolerability or with gastric emptying and the gastrointestinal transport (e.g. inflammatory bowel diseases, ileus)
- history of relevant central nervous system (CNS) and/or psychiatric disorders and/or currently treated CNS and/or psychiatric disorders
- any surgery at the gastrointestinal tract, which might interfere with the safety of the test product or any stomach reduction like Bioenterics Intragastric Balloon (BIB) or gastric banding
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 |
|---|---|---|
| GRDF furosemideAlso: GRDF furosemide is a gastro retentive dosage form of furesomideThe GRDF furosemide tablet contains Fe3O4, which serves as an inactive magnetic marker to allow monitoring of the tablet transit through the gastrointestinal tract, using the MMM imaging technique. | Drug | GRDF furosemide fasting conditions, GRDF furosemide fed conditions |
Primary outcome
Residency time of GRDF furosemide in the gastrointestinal tract, evaluated with MMM technique, under fasted and fed conditions.
Time frame: every 30 min for up to 12 h after drug administration; maximal observation time 12 h
Residency time of GRDF furosemide in the gastrointestinal track will be monitored using the non-invasive MMM technique under fasted and fed conditions. Measurements will start after each administration and last until 2 hours after gastric emptying indicated by the MMM measurement, but not longer than 12 h post administration. Each observation interval for each subject will last for a minimum of 10 min followed by a break of maximum 20 min. For meal intake, a break of the MMM measuring of 30 minutes will be performed. Anatomical localisation within the measuring sequences will be listed for each subject and treatment Statistical evaluation of gastric emptying time will include: arithmetic means, medians, minimum , maximum, standard deviation. GRDF=Gastro retentive dosage formulation
20 secondary outcomes
Cmax of GRDF furosemide under fasted conditions
Time frame: pre-dose (within 1 h prior to drug administration) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, and 24 h after drug administration.
Cmax of GRDF furosemide under fed conditions
Time frame: pre-dose (within 1 h prior to drug administration) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, and 24 h after drug administration.
tmax of GRDF furosemide under fasted conditions
Time frame: pre-dose (within 1 h prior to drug administration) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, and 24 h after drug administration.
tmax of GRDF furosemide under fed conditions
Time frame: pre-dose (within 1 h prior to drug administration) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, and 24 h after drug administration.
t1/2 of GRDF furosemide under fasted conditions
Time frame: pre-dose (within 1 h prior to drug administration) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, and 24 h after drug administration.
t1/2 of GRDF furosemide under fed conditions
Time frame: pre-dose (within 1 h prior to drug administration) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, and 24 h after drug administration.
AUC0-tlast of GRDF furosemide under fasted conditions
Time frame: pre-dose (within 1 h prior to drug administration) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, and 24 h after drug administration.
AUC0-tlast of GRDF furosemide under fed conditions
Time frame: pre-dose (within 1 h prior to drug administration) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, and 24 h after drug administration.
AUC 0-infinity of GRDF furosemide under fasted conditions
Time frame: pre-dose (within 1 h prior to drug administration) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, and 24 h after drug administration.
AUC 0-infinity of GRDF furosemide under fed conditions
Time frame: pre-dose (within 1 h prior to drug administration) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, and 24 h after drug administration.
AUCextrapol of GRDF furosemide under fasted conditions
Time frame: pre-dose (within 1 h prior to drug administration) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, and 24 h after drug administration.
AUCextrapol of GRDF furosemide under fed conditions
Time frame: pre-dose (within 1 h prior to drug administration) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, and 24 h after drug administration.
CL_f of GRDF furosemide under fasted conditions
Time frame: pre-dose (within 1 h prior to drug administration) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, and 24 h after drug administration.
CL_f of GRDF furosemide under fed conditions
Time frame: pre-dose (within 1 h prior to drug administration) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, and 24 h after drug administration.
Vdz of GRDF furosemide under fasted conditions
Time frame: pre-dose (within 1 h prior to drug administration) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, and 24 h after drug administration.
Vdz of GRDF furosemide under fed conditions
Time frame: pre-dose (within 1 h prior to drug administration) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, and 24 h after drug administration.
Sodium excretion over time under fasted conditions
Time frame: pre-dose (within 1 hour prior to administration), 0-2h, 2-4h, 4-8h, and 8-12h after administration.
Sodium excretion over time under fed conditions
Time frame: pre-dose (within 1 hour prior to administration), 0-2h, 2-4h, 4-8h, and 8-12h after administration.
Urine excretion over time under fasted conditions
Time frame: pre-dose (within 1 hour prior to administration), 0-2h, 2-4h, 4-8h, and 8-12h after administration.
Urine excretion over time under fed conditions
Time frame: pre-dose (within 1 hour prior to administration), 0-2h, 2-4h, 4-8h, and 8-12h after administration.
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 12 Dec 2013.
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.
Frank Donath, MD principal investigator
SocraTec R&D GmbH, Clinical Pharmacology Unit
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 GRDF furosemide in people with Gastroretentive Drug Formulation of Furosemide and Oedema, run by LTS Lohmann Therapie-Systeme AG 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 7 inclusion and 36 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 12 Dec 2013. 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?
Residency time of GRDF furosemide in the gastrointestinal tract, evaluated with MMM technique, under fasted and fed conditions. (time frame: every 30 min for up to 12 h after drug administration; maximal observation time 12 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 12 Dec 2013.