Bioequivalence Study of Cefixime Trihydrate Dry Syrup in Indonesia Healthy Volunteers

Bioequivalence Study of Cefixime Trihydrate 100 mg/5 mL DS in Indonesia Healthy Volunteers

This study was conducted to investigate whether 100 mg/5 mL cefixime trihydrate dry syrup manufactured by PT. Bernofarm, Indonesia was bioequivalent to its reference product, 100 mg/5 mL Suprax® dry syrup manufactured by Odan Laboratories Ltd., Canada registered trademark of Astellas Pharma Inc., Japan.

Study Overview

• Status: Completed
• Conditions: Drug Use
• Intervention / Treatment: Drug: Cefixime Trihydrate 100 mg/5 mL Dry Syrup; Drug: Suprax 100 MG in 5 mL Oral Suspension

Detailed Description

Twenty two healty subjects were given a single dose of 100 mg/5 mL cefixime trihydrate dry syrup or or 100 mg/5 mL Suprax® dry syrup with 240 mL of water. Then the blood samples for cefixime trihydrate was drawn and analyzed using HPLC. All subjects sample plasma were analyzed for pharmacokinetic evaluation.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Indonesia
  • DKI Jakarta
    • Jakarta, DKI Jakarta, Indonesia, 10520
      • PT Pharma Metric Labs

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Healthy male or female subjects
2. Had read the subject information and signed informed consent documents
3. Age 18 - 55 years
4. Body mass index between 18-25 kg/m2
5. Had a normal electrocardiogram
6. Blood pressure within normal range (systolic 90-120 mmHg and diastolic 60-80 mmHg)
7. Heart rate within normal range (60-100 bpm)
8. The absence of significant disease or clinically significant abnormal laboratory values on laboratory evaluation, medical history or physical examination during screening

Exclusion Criteria:

1. those who were pregnant and/or nursing women.
2. those who had a history of contraindication or hypersensitivity to cefixime, other antibiotics or other ingredients in the drugs or a history of serious allergic reaction to any drug, significant allergic disease or allergic reaction
3. those who had a history or present medical condition which might significantly influence the pharmacokinetics of the study drug, e.g. chronic gastrointestinal disease, diarrhea, gastric surgery, renal insufficiency, hepatic dysfunction, and cardiovascular disease.
4. those who had a history or presence of any coagulation disorder or clinically significant hematology abnormalities.
5. those who were using any medication (prescription or non-prescription drug, food supplement, herbal medicine), particularly the medication known to affect the pharmacokinetics of the study drug, within one week prior to the drug administration day.
6. those who had participated in any clinical study within 3 months prior to the study (< 90 days).
7. those who had donated or lost 300 ml (or more) of blood within 3 months prior to the study.
8. those who smoked more than 10 cigarettes a day.
9. those who had a history of traveling to another city within the last 14 days
10. those with a history of direct contact with a COVID-19 positive person in the subject neighborhood
11. those with a history or presence of sore throat, fever (with temperature more than 37°C) or short of breath within the last 14 days
12. those who were positive to COVID-19
13. those who were positive to HIV, HBsAg, and HCV tests (to be kept confidential).
14. those with a history of drug or alcohol abuse within 12 months prior to screening for this study.
15. those who were unlikely to comply with the protocol, e.g uncooperative attitude, inability to return for follow-up visits, poor venous access.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cefixime trihydrate 100 mg/5 mL dry syrup; Cefixime trihydrate 100 mg/5 mL dry syrup was dissolved by 20 mL of water split in 2 portions. Then the drug was shaken well for at least 30 seconds at each addition of water.	Drug: Cefixime Trihydrate 100 mg/5 mL Dry Syrup; Participants received a single dose of 5 mL of cefixime dry syrup with 240 mL of water
Active Comparator: Suprax® 100 mg/5 mL dry syrup; Suprax® 100 mg/5 mL dry syrup was dissolved by 33 mL of water split in 2 portions. Then the drug was shaken well for at least 30 seconds at each addition of water.	Drug: Suprax 100 MG in 5 mL Oral Suspension; Participants received a single dose of 5 mL of Suprax with 240 mL of water; Other Names: Cefixime Trihydrate 100 mg/5 mL Dry Syrup

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric Mean Ratio	The ratio between test drug and reference drug	32 hours
90% confidence intervals	The two products are considered bioequivalent when the 90% confidence intervals of the cefixime trihydrate geometric mean ratio between test and reference product fall within the range of 80.00-125.00% for AUCt and Cmax.	32 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics parameter	Maximum plasma concentration (Cmax)	32 hours
Pharmacokinetics parameter	Area Under Curve from 0 to 32 hours (AUCt)	pre-dose at (0 h) and post dose at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, 24 and 32 hours

Collaborators and Investigators

• Sponsor: PT Bernofarm
• Collaborators: PT Pharma Metric Labs
• Investigators: Study Director: I Gusti Putu Bagus Diana Virgo, PT Pharma Metric Labs, Indonesia; Principal Investigator: Arini Setiawati, PT Pharma Metric Labs, Indonesia

Publications and helpful links

General Publications

• Asiri YA, Al-Said MS, Al-Khamis KI, Niazy EM, El-Sayed YM, Al-Rashood KA, Al-Yamani MJ, Alsarra IA, Al-Balla SA. Comparative bioavailability study of cefixime (equivalent to 100 mg/5 ml) suspension (Winex vs Suprax) in healthy male volunteers. Int J Clin Pharmacol Ther. 2005 Oct;43(10):499-504. doi: 10.5414/cpp43499.
• Kees F, Naber KG, Sigl G, Ungethum W, Grobecker H. Relative bioavailability of three cefixime formulations. Arzneimittelforschung. 1990 Mar;40(3):293-7.
• Morais JA, Lobato Mdo R. The new European Medicines Agency guideline on the investigation of bioequivalence. Basic Clin Pharmacol Toxicol. 2010 Mar;106(3):221-5. doi: 10.1111/j.1742-7843.2009.00518.x. Epub 2010 Jan 7.

Helpful Links

• Clinical Pharmacology and Biopharmaceutic Review
• Guideline For Good Clinical Practice

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2020
• Primary Completion (Actual): August 15, 2020
• Study Completion (Actual): August 25, 2020

Study Registration Dates

• First Submitted: July 23, 2021
• First Submitted That Met QC Criteria: July 23, 2021
• First Posted (Actual): July 29, 2021

Study Record Updates

• Last Update Posted (Actual): August 11, 2021
• Last Update Submitted That Met QC Criteria: August 4, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: Indonesia; bioequivalence study; cefixime trihydrate; dry syrup
• Additional Relevant MeSH Terms: Anti-Infective Agents; Anti-Bacterial Agents; Cefixime
• Other Study ID Numbers: 432/STD/PML/2018

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No