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

• Status: Completed
• Trial end date: 2013-08-01
• Target enrollment: 0
• Participant gender: Male

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: LTS Lohmann Therapie-Systeme AG
• Treatments: Furosemide

Criteria

Inclusion Criteria:

1. sex: male

2. ethnic origin: Caucasian

3. age: 18 years to 55 years

4. body-mass index (BMI): > or = 19 kg/m² and < or = 27 kg/m²

5. good state of health

6. non-smoker or ex-smoker for at least 1 month

7. 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

Exclusion Criteria:

1. existing cardiac and/or haematological diseases or pathological findings, which might interfere with the safety or tolerability of the active ingredient

2. existing hepatic and/or renal diseases or pathological findings, which might interfere with the safety or tolerability of the active ingredient

3. 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)

4. history of relevant central nervous system (CNS) and/or psychiatric disorders and/or currently treated CNS and/or psychiatric disorders

5. 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

6. known allergic reactions to the active ingredients used or to constituents of the pharmaceutical preparations

7. known allergic reactions to sulphonamide

8. subjects with severe allergies or multiple drug allergies unless it is judged as not relevant for the clinical trial by the investigator

9. heart rate < 50 bpm or > 90 bpm

10. systolic blood pressure of < 100 mmHg and > 140 mmHg, diastolic blood pressure of < 60 mmHg and >90 mmHg

11. 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

12. 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

13. renal failure with anuria

14. coma and praecoma hepatica

15. severe hypokalemia and/or hyponatremia

16. hypovolemia or dehydration

17. subjects with manifest or latent diabetes mellitus or gout

18. subjects with cerebrovascular insufficiency or coronary heart disease

19. subjects with bladder outlet obstruction (BOO) e.g. prostatic hypertrophy, hydronephrosis or ureteral stenosis

20. hypoproteinemia

21. liver cirrhosis and simultaneous limitation of kidney function

22. acute or chronic diseases which could affect gastric emptying and the gastrointestinal transport

23. history of or current drug or alcohol dependence

24. positive alcohol or drug test at screening examination

25. regular intake of alcoholic food or beverages of ≥ 40 g pure ethanol for male per day

26. subjects who are on a diet which could affect gastric emptying and the gastro-intestinal transport

27. regular intake of caffeine containing food or beverages of ≥ 500 mg caffeine per day

28. subjects with claustrophobia

29. ferromagnetic implants or any other magnetic disturbance, which can affect the Magnetic Marker Monitoring measurement

30. blood donation or other blood loss of more than 400 ml within the last two months prior to individual enrolment of the subject

31. participation in a clinical trial during the last two months prior to individual enrolment of the subject

32. 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

33. subjects, who report a frequent occurrence of migraine attacks

34. subjects suspected or known not to follow instructions

35. 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

36. 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