Clinical trial NCT04982874: Bioequivalence Study of Furosemide 40 mg Tablet in 24 Indonesian Healthy Volunteers
Official title: Bioequivalence Study of Furosemide in Indonesian Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Drug Use
Keywords: bioequivalence
furosemide
Indonesian healthy volunteers
Lead sponsor: PT. Kimia Farma (Persero) Tbk
Sponsor class: INDUSTRY
Collaborators: name: PT Pharma Metric Labs
First posted: 2021-07-29
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: randomized, single blind, single dose, 2-period, cross-over design with one week washout period between each treatment in 24 healthy volunteers beneath fasting condition
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of this research was to investigate whether Furosemide 40 mg tablet manufactured by PT. Kimia Farma Tbk was bioequivalent to its reference drug and Lasix® 40 mg Tablet manufactured by PT. Aventis Pharma, Indonesia.

Detailed description: Twenty four healty volunteers were given a single dose of Furosemide 40 mg Tablet or Lasix® 40 mg Tablet with 240 mL of water beneath fasting condition. Then the blood samples for Furosemide were drawn and analyzed using UPLC. All subjects sample plasma were analyzed for pharmacokinetic evaluation

Eligibility criteria: Inclusion Criteria:

* have read the subject information and signed informed consent documents
* age 18 - 55 years
* body mass index between 18-25 kg/m2
* have a normal electrocardiogram
* blood pressure within normal range (systolic 90-120 mmHg and diastolic 60-80 mmHg)
* heart rate within normal range (60-100 bpm)
* with absence of significant disease or clinically significant abnormal laboratory values on laboratory evaluation, medical history or physical examination during screening
* acceptance to use protection (condom) during intercourse with their spouse throughout the study

Exclusion Criteria:

* those who are pregnant and/or nursing women
* those with a history of hypersensitivity to furosemide, or other diuretics or other ingredients in the drugs or a history of serious allergic reaction to any drug, a significant allergic disease, or allergic reaction
* those with a history or presence of medical condition which might significantly influence the pharmacokinetic of the study drug, e.g. chronic gastrointestinal disease, diarrhea, gastric surgery, renal insufficiency, hepatic dysfunction or cardiovascular disease.
* those with a history or presence of any coagulation disorder or clinically significant hematology abnormalities
* those who are using any medication (prescription or non-prescription drug, food supplement, herbal medicine), particularly the medication known to affect the pharmacokinetic of the study drug, within one week prior to the drug administration day
* those who have participated in any clinical study within 3 months prior to the study (\< 90 days)
* those who have donated or lost 300 ml (or more) of blood within 3 months prior to the study
* those who smoke more than 10 cigarettes a day
* those who are positive to HIV, HBsAg, and HCV tests (to be kept confidential)
* those with a history of drug or alcohol abuse within 12 months prior to screening for this study
* those who are unlikely to comply with the protocol, e.g uncooperative attitude, inability to return for follow up visits, poor venous access

Primary outcomes:
measure: Geometric Mean Ratio of Maximum Concentration
timeFrame: before dosing (0 h) and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 16 and 24 hours after drug administration
measure: Geometric Mean Ratio of Area Under Curve
timeFrame: before dosing (0 h) and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 16 and 24 hours after drug administration
Secondary outcomes:
measure: Pharmacokinetics Parameter
timeFrame: before dosing (0 h) and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 16 and 24 hours after drug administration
measure: Pharmacokinetics Parameter
timeFrame: before dosing (0 h) and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 16 and 24 hours after drug administration
Other outcomes:
Locations:
city: Jakarta Pusat
country: Indonesia
facility: PT Pharma Metric Labs
state: DKI Jakarta
Study officials:
affiliation: PT Pharma Metric Labs
name: Frans D Suyatna
role: PRINCIPAL_INVESTIGATOR
affiliation: PT Pharma Metric Labs
name: I Gusti Putu Bagus Diana Virgo
role: STUDY_DIRECTOR
References:
citation: Chow SC. Bioavailability and Bioequivalence in Drug Development. Wiley Interdiscip Rev Comput Stat. 2014;6(4):304-312. doi: 10.1002/wics.1310.
citation: Oh SW, Han SY. Loop Diuretics in Clinical Practice. Electrolyte Blood Press. 2015 Jun;13(1):17-21. doi: 10.5049/EBP.2015.13.1.17. Epub 2015 Jun 30.
citation: Najib N, Idkaidek N, Beshtawi M, Bader M, Admour I, Alam SM, Zaman Q, Dham R. Bioequivalence evaluation of two brands of furosemide 40 mg tablets (Salurin and Lasix) in healthy human volunteers. Biopharm Drug Dispos. 2003 Sep;24(6):245-9. doi: 10.1002/bdd.361.
citation: Shankar SS, Brater DC. Loop diuretics: from the Na-K-2Cl transporter to clinical use. Am J Physiol Renal Physiol. 2003 Jan;284(1):F11-21. doi: 10.1152/ajprenal.00119.2002.
citation: Brater DC. Diuretic therapy. N Engl J Med. 1998 Aug 6;339(6):387-95. doi: 10.1056/NEJM199808063390607. No abstract available.
citation: Sica DA. Diuretic use in renal disease. Nat Rev Nephrol. 2011 Dec 20;8(2):100-9. doi: 10.1038/nrneph.2011.175.
citation: Ponto LL, Schoenwald RD. Furosemide (frusemide). A pharmacokinetic/pharmacodynamic review (Part I). Clin Pharmacokinet. 1990 May;18(5):381-408. doi: 10.2165/00003088-199018050-00004.
citation: Midha KK, McKay G. Bioequivalence; its history, practice, and future. AAPS J. 2009 Dec;11(4):664-70. doi: 10.1208/s12248-009-9142-z. Epub 2009 Oct 6. No abstract available.