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HealthyPhase 1NCT03363477

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

A Phase 1 study testing Enoxaparin and Clexane in people with Healthy, run by Rovi Pharmaceuticals Laboratories.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 45 yearsHealthy volunteers can take part
Conditions the study is for
Healthy
What is being tested?
Enoxaparin and Clexane
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
46 participants
Where
No sites listed yet
Study dates
25 Sep 2015to 1 Dec 2015
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 45 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.
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  • 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.
  • Subject has any illness within 5 days before the first dose of study drug.
  • Subject has a positive test for fecal occult blood at Screening.
  • Subject has any history and/or current conditions of bleeding tendency such as: active bleeding, known bleeding diathesis or hemostatic defects due to severe hepatic or renal disease; recent gastrointestinal or genitourinary bleeding (10 days before study entry) women of child-bearing potential with normal cyclic bleeding which is not considered as heavy menstruation by the investigator, are allowed for inclusion; diabetic hemorrhagic retinopathy, or other hemorrhagic ophthalmic conditions.
  • Subject has a known history or family history of any relevant congenital or acquired coagulation disorder (eg, hemophilia, von Willebrand-Jürgens syndrome, or activated protein C resistance based upon Factor V Leiden mutation).
  • Subject has a history of thrombocytopenia, including heparin induced thrombocytopenia.
  • Subject has a known history of hypersensitivity to drugs with a similar chemical structure to enoxaparin sodium (eg, unfractionated heparin, low molecular weight heparin) or to pork products.
  • Subject is a member of the professional or ancillary personnel involved in the study.
  • Subject is deemed not suitable for entry into the study in the opinion of the investigator.

About this study

Official title: Demonstration of Pharmacodynamic Equivalence of Enoxaparin Rovi (100-mg Subcutaneous Injection) to Clexane® (100-mg Subcutaneous Injection) in Healthy Volunteers

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.

Read the detailed description

This is a single-dose, randomized, double-blind, 2-period, 2 sequence crossover study. Subjects will be screened up to 30 days before the study begins and admitted to the clinic on Day -1 of Period 1 for baseline assessments. Before dosing on Day 1 of Period 1, subjects will be randomly assigned to a treatment sequence. Subjects will receive a single dose of study drug on Day 1 of each treatment period.

On Day 1 of Period 1, subjects will receive a single dose by subcutaneous route of the assigned study drug: enoxaparin (100 mg/mL) 100-mg SC injection manufactured by Rovi Spain, or Clexane (100 mg/mL) 100-mg SC injection manufactured by Sanofi EU; after an overnight fasting period of at least 10 hours. Subjects will continue fasting for at least 4 hours after study drug administration.

The washout period between administrations of study drug in each period will be at least 7 days.

On Day 1 of Period 2, subjects will cross over to receive the dose of the other drug, after an overnight fasting period of at least 10 hours. The total duration of the study will be approximately 6 weeks.

Conditions
Healthy
Being tested
Enoxaparin, Clexane
Keywords
antithrombotic, heparin, anticoagulant, low molecular weight heparin, pharmacodynamic equivalence

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EnoxaparinDrug

    Also called Enoxaparin (Rovi, Spain), enoxaparin sodium

  • ClexaneDrug

    Also called Clexane (Sanofi, EU), enoxaparin sodium

Study groups in NCT03363477
Study groupRoleWhat they receive
AB treatment sequenceExperimentalPeriod 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)
Receives: Drug: Enoxaparin; Drug: Clexane
BA treatment sequenceActive comparatorPeriod 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)
Receives: Drug: Enoxaparin; Drug: Clexane

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. AUEC0-inf for anti-FXa

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

    Measured: 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)

  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

    Measured: 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)

  3. Amax for anti-FXa and anti-FIIa

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

    Measured: 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)
  1. RAUEC

    ratio of AUEC0-T of anti-FXa to anti-FIIa

    Measured: 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)

  2. Amax for TFPI levels

    peak effect activity (Amax) forTissue factor pathway inhibitor (TFPI)

    Measured: 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)

  3. AUEC0-T for TFPI levels

    Area under the effect curve (AUEC) from time 0 to the last measured activity (T) forTissue factor pathway inhibitor (TFPI)

    Measured: 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)

  4. AUEC0-inf for TFPI levels

    Area under the effect curve (AUEC) from time 0 to infinity forTissue factor pathway inhibitor (TFPI)

    Measured: 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)

  5. Tmax for anti-FXa and anti-FIIa

    time of observed maximum measured plasma activity for anti-FXa and anti-FIIa

    Measured: 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)

  6. t1/2 for anti-FXa and anti-FIIa

    apparent first order terminal elimination half-life for anti-FXa and anti-FIIa

    Measured: 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)

  7. CL/F for anti-FXa and anti-FIIa

    apparent plasma clearance after extravascular administration for anti-FXa and anti-FIIa

    Measured: 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)

  8. MRT for anti-FXa and anti-FIIa

    mean residence time for anti-FXa and anti-FIIa

    Measured: 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)

  9. Adverse Events (AEs)

    All treatment emergent AEs (TEAEs), relationship of TEAEs to study drug, severity of TEAEs, treatment emergent serious AEs, relationship of treatment emergent serious AEs to study drug, and TEAEs leading to study drug discontinuation. The frequency of TEAEs will be summarized by system organ class and preferred term

    Measured: from Informed Consent signature until 14 days after the last study drug administration (independently of the period)

  10. hematology

    clinical laboratory results

    Measured: at Screening, Day -1 (Period 1 only), and Day 3 (Period 2 only) and at the follow up visit (Day 7 of Period 2 only)

  11. Serum chemistry

    measurements of a variety of compounds in the serum layer of blood

    Measured: at Screening, Day -1 (Period 1 only), and Day 3 (Period 2 only) and at the follow up visit (Day 7 of Period 2 only)

  12. Coagulation

    Prothrombin time (reported in seconds) and activated partial thromboplastin time (aPTT)

    Measured: at Screening, Day -1 (Period 1 only), and Day 3 (Period 2 only) and at the follow up visit (Day 7 of Period 2 only)

  13. Urianalysis

    measurements of a variety of compounds in urine

    Measured: at Screening, Day -1 (Period 1 only), and Day 3 (Period 2 only) and at the follow up visit (Day 7 of Period 2 only)

  14. Blood presure

    systolic and diastolic blood presure recorded after the subject had been resting for at least 5 minutes

    Measured: at Screening, Day -1 (Period 1 only), and before dosing (Pre-dose) and 0.5 hours after dosing on Day 1 (Periods 1 and 2)

  15. Pulse rate

    recorded after the subject had been resting

    Measured: at Screening, Day -1 (Period 1 only), and before dosing (Pre-dose) and 0.5 hours after dosing on Day 1 (Periods 1 and 2)

  16. Respiratory rate

    measured subsequently to pulse rate

    Measured: at Screening, Day -1 (Period 1 only), and before dosing (Pre-dose) and 0.5 hours after dosing on Day 1 (Periods 1 and 2)

  17. Tympanic temperature

    measured subsequently to pulse rate

    Measured: at Screening, Day -1 (Period 1 only), and before dosing (Pre-dose) and 0.5 hours after dosing on Day 1 (Periods 1 and 2)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Dec 2017
  2. Study start25 Sep 2015
  3. Primary completion1 Dec 2015
  4. Study completion1 Dec 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Model description
single-dose, randomized, double-blind, 2-period, 2-sequence crossover study
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
46 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03363477
Sponsor's protocol ID
ROV-RO20-2015-01
Other IDs
2015-003489-10, 2015
Status last verified
Dec 2017
First submitted
29 Nov 2017
Last updated
6 Dec 2017
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Enoxaparin and Clexane in people with Healthy, run by Rovi Pharmaceuticals Laboratories.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Dec 2017. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

AUEC0-inf for anti-FXa (time frame: 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)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Dec 2017.

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