Bioequivalence Study of a Generic Enoxaparin Sodium to Clexane® After Single Subcutaneous Dose in Healthy Human Subjects

NCT05265676 | Completed Phase 1

• 1 other identifier: C1B00548
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Healthy

Keywords

enoxaparin; low molecular weight heparin; bioequivalence; anticoagulant; antithrombotic; heparin; pharmacodynamic equivalence

Outcome Measures

Primary Outcomes (2)

• Amax for Anti-Xa and Anti-IIa

  Maximum measured Anti-Xa and Anti-IIa plasma activity over the time span specified

  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 drug administration

• AUECt for Anti-Xa and Anti-IIa

  The area under the plasma activity/concentration-time curve from the time 0 to the last measurable concentration, as calculated by the linear trapezoidal method, for Anti-Xa and Anti-IIa

  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 drug administration

Secondary Outcomes (7)

• AUECi for Anti-Xa and Anti-IIa

  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 drug administration

• Tmax for Anti-Xa and Anti-IIa

  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 drug administration

• t1/2 for Anti-Xa and Anti-IIa

  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 drug administration

• Kel for Anti-Xa and Anti-IIa

  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 drug administration

• Amax for ratio of Anti-Xa/Anti-IIa activity, TFPI (Baseline corrected and baseline uncorrected) and aPTT (Baseline corrected and baseline uncorrected).

  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 drug administration

Study Arms (2)

Cohort 1 - AB treatment sequence

EXPERIMENTAL

Period 1 - Test Product (A): Enoxaparin Sodium pre-filled syringe BP 40 mg/0.4 ml of Venus Remedies Limited, India. Period 2 - Reference Product (B): 'Clexane®' (Enoxaparin Sodium pre-filled syringe; 40 mg/0.4 ml) of Sanofi, Germany.

Drug: Enoxaparin Sodium (Venus Remedies Limited); Drug: Enoxaparin Sodium (Sanofi)

Cohort 2 - BA treatment sequence

EXPERIMENTAL

Period 1 - Reference Product (B): 'Clexane®' (Enoxaparin Sodium pre-filled syringe; 40 mg/0.4 ml) of Sanofi, Germany. Period 2 - Test Product (A): Enoxaparin Sodium pre-filled syringe BP 40 mg/0.4 ml of Venus Remedies Limited, India.

Drug: Enoxaparin Sodium (Venus Remedies Limited); Drug: Enoxaparin Sodium (Sanofi)

Interventions

Enoxaparin Sodium (Venus Remedies Limited) DRUG

The test drug is enoxaparin sodium pre-filled syringe 40 mg/0.4mL of Venus Remedies Limited, India

Also known as: Cloti-Xa

Cohort 1 - AB treatment sequence; Cohort 2 - BA treatment sequence

Enoxaparin Sodium (Sanofi) DRUG

The reference drug is enoxaparin sodium pre-filled syringe 40 mg/0.4mL of Sanofi, Germany

Also known as: Clexane

Cohort 1 - AB treatment sequence; Cohort 2 - BA treatment sequence

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age: 18 to 45 years old, both inclusive.
• Gender: Male and/or non-pregnant, non-lactating female.
• A. Female of childbearing potential must have a negative serum beta human chorionic gonadotropin (β-HCG) pregnancy test performed within 28 days prior to first dosing day. They must be using an acceptable form of contraception.
• B. For female of childbearing potential, acceptable forms of contraception include the following:
• i. Non hormonal intrauterine device in place for at least 3 months prior to the start of the study and remaining in place during the study period, or
• ii. Barrier methods containing or used in conjunction with a spermicidal agent, or
• iii. Surgical sterilization or
• iv. Practicing sexual abstinence throughout the course of the study.
• C. Female will not be considered of childbearing potential if one of the following is reported and documented on the medical history:
• i. Postmenopausal with spontaneous amenorrhea for at least one year, or
• ii. Bilateral oophorectomy with or without a hysterectomy and an absence of bleeding for at least 6 months, or
• iii. Total hysterectomy and an absence of bleeding for at least 3 months.
• BMI: 18.5 to 30.0 kg/m2, both inclusive; BMI value should be rounded off to one significant digit after decimal point (e.g. 30.04 rounds down to 30.0, while 18.45 rounds up to 18.5).
• Volunteer with at least 50 kg weight
• Able to read \& understand informed consent document and give written informed consent to participate in the study

You may not qualify if:

• Volunteers must not be enrolled in the study if they meet any one of the following criteria:
• History of hypersensitivity or idiosyncratic reaction to Enoxaparin Sodium, pork, heparin or its derivatives, other low molecular weight heparins or other related drugs, or any of its formulation ingredients.
• Have significant diseases or clinically significant abnormal findings during screening \[medical history, physical examination (clinical examination), laboratory evaluations, ECG, chest X-ray recording, obstetrics and gynecological history and examination (for female volunteers)\].
• Any disease or condition like diabetes, psychosis or others, which might compromise the haemopoeitic, gastrointestinal, renal, hepatic, cardiovascular, respiratory, central nervous system or any other body system.
• History or presence of bronchial asthma.
• Use of any hormone replacement therapy within 3 months prior to the first dose of study medication.
• A depot injection or implant of any drug within 3 months prior to the first dose of study medication.
• Use of CYP enzyme inhibitors or inducers within 30 days prior to the first dose of study medication (see http://medicine.iupui.edu/clinpharm/ddis/main-table).
• History or evidence of drug dependence.
• History of difficulty with donating blood or difficulty in accessibility of veins.
• A positive hepatitis screen (includes subtypes B \& C).
• A positive test result for HIV antibody and / or syphilis (RPR).
• Volunteers who have received a known investigational or equivalent to this drug within seven elimination half-life of the administered drug prior to the first dose of study medication.
• Volunteers who have donated blood or loss of blood 50 ml to 100 ml within 30 days or 101 ml to 200 ml within 60 days or \>200 ml within 90 days (excluding volume drawn at screening for this study) prior to first dose of study medication, whichever is greater.
• Intolerance to venipuncture

Sponsors & Collaborators

• Venus Remedies Limited: lead

Study Sites (1)

Cliantha Research Limited

Ahmedabad, Gujarat, 380054, India

Location

Related Publications (1)

• Saxena S, Chaudhary M, Chaudhary S, Aggarwal A. Bioequivalence of a biosimilar enoxaparin (Cloti-Xa) and its innovator (Clexane(R) ): A single-dose, randomized, double-blind, two-period, two-treatment, two-sequence, crossover, balanced study in healthy human subjects. Pharmacol Res Perspect. 2022 Aug;10(4):e00979. doi: 10.1002/prp2.979.

  PMID: 35762448 DERIVED

MeSH Terms

Interventions

enoxaparin sodium; Enoxaparin

Intervention Hierarchy (Ancestors)

Heparin, Low-Molecular-Weight; Heparin; Glycosaminoglycans; Polysaccharides; Carbohydrates

Study Officials

• Dr. Mayur Soni

  Cliantha Research Limited, India

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 22, 2022
• First Posted: March 3, 2022
• Study Start: February 26, 2021
• Primary Completion: March 7, 2021
• Study Completion: March 11, 2021
• Last Updated: March 3, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

IN (1)