Bioequivalence Study of Apixaban 5 mg Film-Coated Tablet

Bioequivalence Study of Apixaban 5 mg Film-Coated Tablet Produced by PT Dexa Medica in Comparison With the Comparator Drug (Eliquis® 5 mg Film Coated Tablet, Bristol-Myers Squibb Company, Puerto Rico, Packed and Released By Bristol-Myers Squibb S.R.L., Italy, Imported by PT Pfizer Indonesia)

This was an open-label, randomized, single-dose, two-period, two-sequence, cross-over study under fasting condition which included 24 healthy adult male and female subjects. The objective of this study was to find out whether the bioavailability of apixaban 5 mg film-coated tablet produced by PT Dexa Medica in comparison with the comparator drug (Eliquis® 5 mg filmcoated tablet, Bristol-Myers Squibb Company, Puerto Rico, packed and released by Bristol Myers Squibb S.r.l., Italy, imported by PT Pfizer Indonesia).

Study Overview

• Status: Completed
• Conditions: Health
• Intervention / Treatment: Drug: Apixaban 5 mg Film-Coated Tablet (produced by PT Dexa Medica); Drug: Eliquis® 5 mg film-coated tablet (Bristol-Myers Squibb Company, Puerto Rico, packed and released by Bristol-Myers Squibb S.r.l., Italy, imported by PT Pfizer Indonesia)

Detailed Description

The objective of this study was to find out whether the bioavailability of apixaban 5 mg film-coated tablet produced by PT Dexa Medica in comparison with the comparator drug (Eliquis® 5 mg filmcoated tablet, Bristol-Myers Squibb Company, Puerto Rico, packed and released by Bristol-Myers Squibb S.r.l., Italy, imported by PT Pfizer Indonesia). This was an open-label, randomized, single dose, two-period, two-sequence, cross-over study under fasting condition which included 24 healthy adult male and female subjects. The participating subjects were required to have an 8 hours overnight fast and in the next morning (first day of period) were given orally the test drug (apixaban 5 mg film-coated tablet produced by PT Dexa Medica) or the comparator drug (Eliquis® 5 mg Film Coated Tablet, Bristol-Myers Squibb Company, Puerto Rico, packed and released by Bristol-Myers Squibb S.r.l., Italy, imported by PT Pfizer Indonesia) with 200 mL of water. The subject's oral cavity was checked thoroughly to confirm complete medication and fluid consumption after dosing. Blood samples were drawn before taking the drug (control), and at 0.50, 1.00, 1.50, 2.00, 2.50, 3.00, 3.33, 3.67, 4.00, 4.50, 5.00, 6.00, 9.00, 12.00, 24.00, 36.00, and 48.00 hours after drug administration. These blood samples were used to investigate the pharmacokinetic parameters of apixaban following single dose administration. The plasma concentrations of apixaban were determined by using a validated ultra-performance liquid chromatography with tandem mass spectrometry detection (UPLC-MS/MS).

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• Indonesia
  • Jakarta, Indonesia
    • PT Equilab International

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Able to participate, communicate well with the investigators and willing to provide written informed consent to participate in the study.
2. Healthy male and female subjects with absence of significant disease or clinically significant abnormal laboratory values on laboratory evaluation, medical history or physical examination during screening and could be considered healthy based on the evaluation.
3. Aged 18 - 55 years inclusive.
4. Preferably non-smokers or smoke less than 10 cigarettes per day.
5. Body mass index within 18 to 25 kg/m2.
6. Normal prothrombin time (PT) and normal partial thromboplastin time (aPTT)
7. Creatinine clearance > 50 mL/min

8. Vital signs (after 10 minutes rest) must be within the following ranges:

   • Systolic blood pressure: 100 - 129 mmHg
   • Diastolic blood pressure: 60 - 84 mmHg
   • Pulse rate: 60 - 90 bpm.

Exclusion Criteria:

1. History of allergy or hypersensitivity or contraindication to apixaban or factor Xa inhibitors or allied drug.
2. Pregnant or lactating female (urinary pregnancy test was applied to female subjects at screening and before taking the study drug).
3. Any major illness in the past 90 days or clinically significant ongoing chronic medical illness.
4. Presence of any clinically significant abnormal values during screening e.g. significant abnormality of liver function test (AST, ALT, alkaline phosphatase, total bilirubin, direct bilirubin ≥ 1.5 ULN), renal function test (serum creatinine concentration > 1.4 mg/dL and ureum ≥ 1.5 ULN), etc.
5. Positive Hepatitis B surface antigen (HBsAg), anti-HCV, or anti-HIV.
6. Clinically significant hematology abnormalities.
7. Positive result for COVID-19 antigen rapid test.
8. Clinically significant electrocardiogram (ECG) abnormalities.
9. Any surgical or medical condition (present or history) which might significantly alter the absorption, distribution, metabolism or excretion of the study drug, e.g. gastrointestinal disease including gastric or duodenal ulcers or history of gastric surgery.
10. Past history of anaphylaxis or angioedema.
11. History of drug or alcohol abuse within 12 months prior to screening for this study.
12. Participation in any clinical trial within the past 90 days calculated from the last visit until this study's first dosing day.
13. History of any bleeding or coagulative disorders.
14. History of significant head injury within the last two years.
15. Presence of difficulty in accessibility of veins in left or right arm.
16. A donation or significant blood loss within 90 days before this study's first dosing day.
17. Intake of any prescription, (especially apixaban, other anticoagulants, azole antimycotics), non-prescription drug, (including hormonal contraception), food supplements or herbal medicines within 21 days of this study's first dosing day

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Test Apixaban 5 mg Film-Coated Tablet PT Dexa Medica; Apixaban 5 mg Film-Coated Tablet (produced by PT Dexa Medica)	Drug: Apixaban 5 mg Film-Coated Tablet (produced by PT Dexa Medica); One tablet of the test drug was given orally under fasting condition
Active Comparator: Reference Eliquis® 5 mg film-coated tablet, Bristol-Myers Squibb; Eliquis® 5 mg film-coated tablet, Bristol-Myers Squibb Company, Puerto Rico, packed and released by Bristol-Myers Squibb S.r.l., Italy, imported by PT Pfizer Indonesia	Drug: Eliquis® 5 mg film-coated tablet (Bristol-Myers Squibb Company, Puerto Rico, packed and released by Bristol-Myers Squibb S.r.l., Italy, imported by PT Pfizer Indonesia); One tablet of the reference drug was given orally under fasting condition

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	Maximum plasma concentration	48 hours
AUC(0-t)	Area under the plasma concentration-time curve to the last observer quantifiable concentration at time t	48 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC(0-inf)	Area under the plasma concentration-time curve extrapolated to infinitive time	48 hours
T1/2	Plasma half-life	48 hours
Tmax	Time taken to reach maximum observed plasma concentration	48 hours

Collaborators and Investigators

• Sponsor: Dexa Medica Group
• Collaborators: PT Equilab International
• Investigators: Principal Investigator: Danang A Yunaidi, PT Equilab International

Study record dates

Study Major Dates

• Study Start (Actual): April 15, 2021
• Primary Completion (Actual): April 24, 2021
• Study Completion (Actual): June 3, 2021

Study Registration Dates

• First Submitted: February 5, 2025
• First Submitted That Met QC Criteria: February 5, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 5, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Protease Inhibitors; Enzyme Inhibitors; Anticoagulants; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Apixaban
• Other Study ID Numbers: BE. 644/EQL/2020

Drug and device information, study documents

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