Bioequivalence Study of a Generic Enoxaparin Sodium to Clexane® After Single Subcutaneous Dose in Healthy Human Subjects
Condition: Healthy
Study type: Interventional
Phase: Phase 1

Summary: 
      This is a single-dose, randomized, double-blind, two-period, two-treatment, two-sequence,
      crossover, balanced, pharmacodynamic (PD) study with 7 days wash-out period. The objective of
      this study is to assess the bioequivalence between the Enoxaparin (Venus Remedies Limited,
      India) and its innovator product (Clexane®, Sanofi, Germany).
    

Detailed description: 
      Enoxaparin is a widely used low-molecular-weight heparin (LMWH) obtained by alkaline
      β-eliminative cleavage of heparin benzyl ester derived from the porcine intestinal mucosa.
      Currently, several biosimilars/generics of LMWHs with differing potencies are being developed
      and marketed in various parts of the world. They differ in their PK and PD properties, which
      could be possibly due to the depolymerization processes or the manufacturing methods that
      result in its structural variability. Therefore, it is important that the potency of each
      biosimilar LMWH be compared with its innovator's molecule.

      The PK properties and bioavailability of LMWHs are routinely determined by pharmacodynamic
      (PD) surrogates such as Anti-Xa activity, Anti-IIa activity, tissue factor pathway inhibitor
      (TFPI) and activated partial thromboplastin time (aPTT).

      This study was designed as a double-blind, randomized, two-period, two-treatment,
      two-sequence, crossover, balanced, single-dose pharmacodynamic study in healthy, adult, human
      subjects under fasting conditions to compare and evaluate the pharmacodynamic profile of test
      product [Enoxaparin Sodium prefilled syringe BP; 40 mg/0.4 mL (Venus Remedies Limited,
      India)] with that of reference product ['Clexane®' Enoxaparin Sodium prefilled syringe; 40
      mg/0.4 mL (Sanofi, Germany)]. The study was conducted with 24 subjects in accordance with
      protocol.

      After overnight fasting of at least 08 hours, a single dose of either test product or
      reference product was administered to the subjects slowly by subcutaneous route (shaved
      abdominal wall) alternated in both period between left or right anterolaterally in a supine
      posture under the supervision of trained study personnel.

      The subjects received the test product (A) and reference product (B) in the study as per the
      randomization schedule. Participants were randomly selected for one of the two sequences:
      either AB or BA. The washout period between administration of study drugs in each period was
      7 days. Blood samples to assess PD parameters were collected in both study periods at the
      following time points: pre-dose (0.0 hour) and at 0.5, 1.0, 1.5, 2.0, 2.333, 2.667, 3.0,
      3.333, 3.667, 4.0, 4.5, 5.0, 6.0, 8.0, 10.0, 12.0, 16.0, and 24.0 hours after dosing.

      The Anti-Xa and Anti-IIa activity was measured by the chromogenic method using commercial
      reagent kits - STA®-liquid Anti-Xa, Diagnostica Stago and Actichrome® Heparin (Anti-IIa) kit,
      Biomedica Diagnostics, respectively. TFPI was assessed using Enzyme-Linked Immunosorbent
      Assay (ELISA) kit (Quantikine® Human TFPI ELISA kit) and aPTT was determined using clotting
      assay reagent kit - STA-C.K. Prest® 5-Diagnostica Stago.

      Statistical analysis was performed on the pharmacodynamic data to assess bioequivalence
      between the test product to the reference product. The average bioequivalence of the products
      was concluded if two-sided 90% CI for the test to the reference ratio of the population means
      was within 80% and 125% interval for each of the Ln-transformed data, Amax and AUECt for
      Anti-Xa and Anti-IIa (primary objective).
    

Intervention name(s): Enoxaparin Sodium (Venus Remedies Limited); Enoxaparin Sodium (Sanofi)
Intervention type(s): Drug; Drug
Intervention description(s): The test drug is enoxaparin sodium pre-filled syringe 40 mg/0.4mL of Venus Remedies Limited, India; The reference drug is enoxaparin sodium pre-filled syringe 40 mg/0.4mL of Sanofi, Germany
Other intervention name(s): Cloti-Xa; Clexane
Intervention MeSH terms: Enoxaparin; Enoxaparin sodium
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: enoxaparin; low molecular weight heparin; bioequivalence; anticoagulant; antithrombotic; heparin; pharmacodynamic equivalence