Magnetic Marker Monitoring of Furosemide-containing Gastroretentive Formulation in Healthy Male Subjects (Fasting and Fed Conditions)

NCT01887379 | Completed Phase 1

• 2 other identifiers: LTS 03/102013-001063-23
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Gastroretentive Drug Formulation of Furosemide; Oedema

Keywords

Gastroretentive drug formulation; Furosemide; Magnetic Marker Monitoring; Magnetic marker; Oedema

Outcome Measures

Primary Outcomes (1)

• 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

  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

  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

  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

  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

  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

  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.

Study Arms (2)

GRDF furosemide fasting conditions

EXPERIMENTAL

Subjects will be tested under fasting conditions after administration of GRDF Furosemide.

Drug: GRDF furosemide

GRDF furosemide fed conditions

EXPERIMENTAL

Subjects will be tested under fed conditions after administration of GRDF Furosemide.

Drug: GRDF furosemide

Interventions

GRDF furosemide DRUG

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.

Also known as: GRDF furosemide is a gastro retentive dosage form of furesomide

GRDF furosemide fasting conditions; GRDF furosemide fed conditions

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• LTS Lohmann Therapie-Systeme AG: lead

Study Sites (1)

SocraTec R&D GmbH Clinical Pharmacology Unit

Berlin, 10578, Germany

Location

MeSH Terms

Conditions

Edema

Condition Hierarchy (Ancestors)

Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Frank Donath, MD

  SocraTec R&D GmbH, Clinical Pharmacology Unit

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 24, 2013
• First Posted: June 26, 2013
• Study Start: June 1, 2013
• Primary Completion: August 1, 2013
• Study Completion: August 1, 2013
• Last Updated: December 12, 2013

Record last verified: 2013-12

Locations

DE (1)