Study of Pharmacodynamic Equivalence of Enoxaparin Rovi to Clexane®, in Healthy Volunteers

NCT03363477 | Completed Phase 1

• 2 other identifiers: ROV-RO20-2015-012015-003489-10
• Study Type: interventional
• Target: 46
• Locations: 0 countries
• Sites: N/A

Brief Summary

To demonstrate the pharmacodynamic (PD) equivalence of enoxaparin Rovi (100 mg/mL) 100-mg SC injection to Clexane® (100 mg/mL) 100-mg SC injection in healthy volunteers. As secondary objective, to evaluate the safety and tolerability of enoxaparin Rovi (100 mg/mL) in healthy volunteers.

Conditions

Healthy

Keywords

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

Outcome Measures

Primary Outcomes (3)

• AUEC0-inf for anti-FXa

  area under the effect curve (AUEC) from time 0 to infinity, for anti-FXa

  Day -1 (Periods 1 and 2), before dosing (Pre-dose), and between 0.5 and 36 hours after dosing on Day 1 (Periods 1 and 2)

• AUEC0-T for anti-FXa and anti-FIIa

  area under the effect curve (AUEC) from time 0 to the last measured activity (T), for anti-FXa and anti-FIIa

  Day -1 (Periods 1 and 2), before dosing (Pre-dose), and between 0.5 and 36 hours after dosing on Day 1 (Periods 1 and 2)

• Amax for anti-FXa and anti-FIIa

  peak effect for anti-FXa activity (anti-FXamax), and anti-FIIa activity (anti-FIIamax)

  Day -1 (Periods 1 and 2), before dosing (Pre-dose), and between 0.5 and 36 hours after dosing on Day 1 (Periods 1 and 2)

Secondary Outcomes (17)

• RAUEC

  Day -1 (Periods 1 and 2), before dosing (Pre-dose), and between 0.5 and 36 hours after dosing on Day 1 (Periods 1 and 2)

• Amax for TFPI levels

  Day -1 (Periods 1 and 2), before dosing (Pre-dose), and between 0.5 and 36 hours after dosing on Day 1 (Periods 1 and 2)

• AUEC0-T for TFPI levels

  Day -1 (Periods 1 and 2), before dosing (Pre-dose), and between 0.5 and 36 hours after dosing on Day 1 (Periods 1 and 2)

• AUEC0-inf for TFPI levels

  Day -1 (Periods 1 and 2), before dosing (Pre-dose), and between 0.5 and 36 hours after dosing on Day 1 (Periods 1 and 2)

• Tmax for anti-FXa and anti-FIIa

  Day -1 (Periods 1 and 2), before dosing (Pre-dose), and between 0.5 and 36 hours after dosing on Day 1 (Periods 1 and 2)

Study Arms (2)

AB treatment sequence

EXPERIMENTAL

Period 1-Test Treatment A: enoxaparin (100 mg/mL) 100-mg SC injection, manufactured by Rovi (Spain) Period 2-Reference Treatment B: Clexane (100 mg/mL) 100-mg SC injection, manufactured by Sanofi (EU)

Drug: Enoxaparin; Drug: Clexane

BA treatment sequence

ACTIVE COMPARATOR

Period 1-Reference Treatment B: Clexane (100 mg/mL) 100-mg SC injection, manufactured by Sanofi (EU) Period 2-Test Treatment A: enoxaparin (100 mg/mL) 100-mg SC injection, manufactured by Rovi (Spain)

Drug: Enoxaparin; Drug: Clexane

Interventions

Enoxaparin DRUG

Also known as: Enoxaparin (Rovi, Spain), enoxaparin sodium

AB treatment sequence; BA treatment sequence

Clexane DRUG

Also known as: Clexane (Sanofi, EU), enoxaparin sodium

AB treatment sequence; BA treatment sequence

Eligibility Criteria

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

You may qualify if:

• Subject provides informed consent (approved by an Independent Ethical Committee (IEC)) before any study specific evaluation is performed.
• Subject is between the ages of 18 and 45 years, inclusive.
• All female subjects must have a negative pregnancy test at Screening and upon check-in to the clinic.
• Women of childbearing potential must use or have used one of the following acceptable birth control methods: Surgical sterilization (bilateral tubal ligation, hysterectomy, bilateral oophorectomy) for at least 6 months before the first dose of study drug;Intrauterine device in place for at least 3 months before the first dose of study drug; or barrier method (condom, diaphragm) for at least 21 days before the first dose of study drug and throughout the study.
• Subject has a body mass index between 18 and 30 kg/m2, inclusive.
• Subject is able and willing to abstain from alcohol from 48 hours before the first dose of study drug through the end of the study.
• Subject has no clinically significant abnormalities in medical history, vital sign measurements, or physical examination findings.
• Subject has computerized 12-lead electrocardiogram (ECG) results showing no signs of clinically relevant pathology or deviations, as judged by the investigator.
• Subject has hematology, serum chemistry, coagulation, and urinalysis test results within the reference ranges (Hb ≥7.5 mmol/L and ≥8.5 mmol/L for female and male, respectively) or showing no clinically relevant deviations, as judged by the investigator. Thrombocytes at screening have to be within the normal range.
• Subject is a nonsmoker or has quit smoking at least 6 months before the first dose of study drug.

You may not qualify if:

• Subjects are excluded from the study if any of the following criteria are met:
• Subject has active or recurring clinically significant skin, head, ears, eyes, nose, throat, respiratory, cardiovascular, gastrointestinal, endocrine/metabolic, genitourinary, neurologic, hematologic, musculoskeletal, immunologic, allergic, psychological/psychiatric, or other disease requiring medical treatment.
• Female subject with weight \< 45 kg or male subject with weight \< 57 kg.
• Subject is a woman who is pregnant or breastfeeding.
• Subject has systolic blood pressure greater than 150 mm Hg or diastolic blood pressure greater than 90 mm Hg at Screening (confirmed upon repeat measurement).
• Subject has a calculated (Cockroft \& Gault formula) creatinine clearance less than 80 mL/minute and the value does not return to within reference range upon retest.
• Subject has Hb \<7.5 mmol/L and \<8.5 mmol/L for female and male, respectively.
• Subject has an active malignancy of any type other than nonmelanomatous skin malignancies.
• Subject has any history of alcohol abuse or drug addiction.
• Subject has any history of relevant drug and/or food allergies.
• Subject has used an investigational drug within 60 days before the first dose of study drug.
• Subject has used any prescription drugs (with special attention to antiplatelet or anticoagulant medication, eg, acetyl salicylic acid, NSADs, clopidogrel, warfarin, acenocumarol, heparin, low molecular weight heparin, dabigatran, rivaroxaban, apixaban) or over-the-counter medication that may affect coagulation (including aspirin or NSAIDs) within 4 weeks before dosing, or any other over-the-counter medication (including vitamins, herbal supplements, or dietary supplements) within 2 weeks before dosing.
• Subject has donated or lost 550 mL or more of blood (including plasmapheresis) within 60 days before the first dose of study drug.
• Subject has a positive test result for drugs of abuse (opiates, methadone, cocaine, amphetamines, cannabinoids, barbiturates, benzodiazepines, tricyclic antidepressants, oxycodone), cotinine, or alcohol.
• Subject has a positive test result for human immunodeficiency virus (1 or 2) antibody, hepatitis B surface antigen, or hepatitis C virus antibody.

Sponsors & Collaborators

• Rovi Pharmaceuticals Laboratories: lead
• PRA Health Sciences: collaborator

MeSH Terms

Interventions

Enoxaparin; enoxaparin sodium

Intervention Hierarchy (Ancestors)

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

Study Officials

• Maria Velinova, MD, PhD

  PRA Health Sciences (PRA) - Early Development Services (EDS)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: This study will be double blinded in that the subjects and laboratories will be blinded. While the enoxaparin (manufactured by Rovi, Spain) and Clexane (manufactured by Sanofi, EU) solutions for SC injection may be identical in appearance, the prefilled syringes for both study drugs may not be identical. Therefore, the unblinded pharmacist will be responsible for dispensing the study drug in a manner consistent with maintaining the blind and a dedicated unblinded team member will perform study drug administration.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: single-dose, randomized, double-blind, 2-period, 2-sequence crossover study

Study Record Dates

• First Submitted: November 29, 2017
• First Posted: December 6, 2017
• Study Start: September 25, 2015
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: December 6, 2017

Record last verified: 2017-12

Data Sharing

• IPD Sharing: Will not share