<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03841396</url>
  </required_header>
  <id_info>
    <org_study_id>CSA-15-ASP-002</org_study_id>
    <nct_id>NCT03841396</nct_id>
  </id_info>
  <brief_title>A Study Comparing the Local Tolerability of Two Subcutaneous Heparins in Healthy Volunteers.</brief_title>
  <official_title>A Phase IV, Randomised, Double-blind Study Comparing the Local Tolerability of Two Subcutaneous Heparins, Fraxiparine and Clexane, in Healthy Volunteers.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Aspen Global Incorporated</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Aspen Global Incorporated</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      A Phase IV, Randomised, Double-blind, Single-centre clinical trial in healthy male and female&#xD;
      participants aged 18 to 55, that was designed to assess and compare the pain intensity at an&#xD;
      injection site as well as the duration of pain following a single dose subcutaneous&#xD;
      administration of two low molecular weight heparins (LMWH) respectively.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This was a Phase IV, Randomised, Double-blind, Single-centre clinical trial in healthy male&#xD;
      and female participants aged 18 to 55, that was designed to assess and compare the pain&#xD;
      intensity at an injection site as well as the duration of pain following a single dose&#xD;
      subcutaneous administration of two LMWHs respectively. This study included an approximate&#xD;
      seven-day screening period (screening visit to day 0), followed by three visits (Visit 2, 3&#xD;
      and 4) in one-week intervals, in which each participant should have received a single&#xD;
      sequence of subcutaneous injections of Placebo, Fraxiparine and Clexane, in a randomised&#xD;
      order, on the three separate occasions. This was then followed by a safety follow-up visit,&#xD;
      one week after the administration of the last dose of the study product.&#xD;
&#xD;
      Fifteen (N = 15) healthy, consenting participants, fulfilling the inclusion criteria, were&#xD;
      randomised to take part in this study. All participants received a single sequence of&#xD;
      subcutaneous injections, on separate occasions at one week intervals, over the duration of&#xD;
      the treatment phase of the study. Fifteen (N=15) participants received Fraxiparine, fifteen&#xD;
      (N=15) participants received Clexane and fifteen (N=15) participants received Placebo. Two&#xD;
      participants were screened however did not meet the eligibility criteria and therefore were&#xD;
      not included into the study. Informed consent was obtained at Screening Visit 1 (day -7 to 0)&#xD;
      before any trial-related procedures were be performed. Visual analogue and 11-point numeric&#xD;
      rating scales were utilised to measure pain intensity after a single injection of&#xD;
      investigational product. These scales were also used to assess burning and pruritus. All&#xD;
      scales were be completed at set time intervals over a 30 minute period, i.e. 1, 3, 5, 10, 15&#xD;
      and 30 minutes after the injections were completed. Hematoma, erythema and oedema were&#xD;
      measured minutes and 1, 2 and 3 days after the injection, using transparent millimetric&#xD;
      measuring paper. Safety bloods were drawn at each visit.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 2, 2016</start_date>
  <completion_date type="Actual">July 15, 2016</completion_date>
  <primary_completion_date type="Actual">July 15, 2016</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>This study was planned to be a replicated 3x3 Latin square design (5 replicates), each enrolled and randomised participant should have received a single sequence of subcutaneous injections of Placebo, Fraxiparine and Clexane, in randomised order, on three separate occasions.</intervention_model_description>
    <primary_purpose>Other</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
    <masking_description>This was a double blind study and it was conducted under double blind conditions. The study medications, as well as the placebo, were contained in pre-packaged syringes which are different in physical appearance. Therefore to ensure double blinding conditions, the study medications (Fraxiparine, Clexane and Placebo) were packaged in an identical boxes and labelled identically (apart from the treatment number). To further ensure that the participants remained blinded during the study, a blindfold was put over the eyes of each participant at each visit that required IP administration.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Comparison of Visual Analog Scale (VAS) scores of pain intensity at injection site following a single subcutaneous injection of placebo, Fraxiparine or Clexane</measure>
    <time_frame>Over a period of 30 minutes</time_frame>
    <description>Visual Analogue Scales for pain intensity was performed at different time points namely 1, 3, 5, 10, 15 and 30 minutes after administration of the investigational product (IP) at Visit 2, 3 and 4. Pain intensity: 0 mm - No pain; 100 mm - Worst pain</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Comparison of Numeric Rating Scale (NRS) scores of pain intensity at injection site following a single subcutaneous injection of placebo, Fraxiparine or Clexane.</measure>
    <time_frame>Over a period of 30 minutes</time_frame>
    <description>11-point NRS for pain intensity was performed at different time points namely 1, 3, 5, 10, 15 and 30 minutes after administration of the investigational product (IP) at Visit 2, 3 and 4. Pain intensity: 0 - No pain; 10 - Worst pain</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Quantification of local injection site reaction</measure>
    <time_frame>10 and 30 minutes and 1, 2 and 3 days after the injection.</time_frame>
    <description>Hematoma, erythema and oedema were measured 10 and 30 minutes and 1, 2 and 3 days after the injection, using transparent millimetric measuring paper.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pain duration</measure>
    <time_frame>1, 3, 5, 10, 15 and 30 minutes after administration of IP.</time_frame>
    <description>Duration of pain at injection site.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">15</enrollment>
  <condition>Injection Site Reaction</condition>
  <arm_group>
    <arm_group_label>Fraxiparine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Nadroparine, Pre-filled syringe, 3800IU, single dose</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Clexane</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Enoxaparin, Pre-filled syringe, 40 mg, single dose</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sodium chloride</intervention_name>
    <description>All participants received a single dose of sodium chloride as placebo</description>
    <arm_group_label>Clexane</arm_group_label>
    <arm_group_label>Fraxiparine</arm_group_label>
    <other_name>Saline 0.4mL saline</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or Female participant.&#xD;
&#xD;
          2. Aged 18 years to 55 years.&#xD;
&#xD;
          3. Medically healthy participants.&#xD;
&#xD;
          4. Weight Females: ≥ 45 kg; Males ≥ 57 kg.&#xD;
&#xD;
          5. Body Mass Index (BMI) of 18,5 to 29,9 kg/m2.&#xD;
&#xD;
          6. Female participants of child-bearing potential must have a negative urine pregnancy&#xD;
             test at screening and be willing to use effective contraceptives throughout the trial&#xD;
             duration.&#xD;
&#xD;
          7. Participants must be able to understand and follow the instructions of the&#xD;
             Investigator, understand and give informed consent, and be willing, committed, and&#xD;
             able to return for all site visits and complete all study-related procedures.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. A known hypersensitivity to Clexane or Fraxiparine or any components thereof -&#xD;
             especially allergies to latex, pork products, sulfites and benzyl alcohols.&#xD;
&#xD;
          2. Female participants who are pregnant or lactating.&#xD;
&#xD;
          3. Any coagulopathy - Anaemia, thrombocytopenia, hemophilia, haemorrhagic diathesis&#xD;
             (Bleeding, Bruising, Clotting disorders).&#xD;
&#xD;
          4. Active gastric or duodenal ulcer or history of previous gastric duodenal bleeding or&#xD;
             gastrointestinal bleeding.&#xD;
&#xD;
          5. Participants on the following medications: Anti-coagulants, Non-Steroidal&#xD;
             Anti-inflammatory Drugs (NSAID)s, glycoprotein IIb/IIIa anticoagulants, thrombolytic&#xD;
             agents, platelet-inhibitors, acetylsalicylic acid, sulfinpyrazone, quinine -&#xD;
             containing remedies and/drinks, treprostinil, apixaban, drotecogin alfa, danshen, dong&#xD;
             quai, evening primrose oil, gingko, policosanol and willow bark as well as&#xD;
             hyperkalemia aggravators in the last 7 days.&#xD;
&#xD;
          6. A Cerebrovascular incident (hemorrhagic or ischemic).&#xD;
&#xD;
          7. Deep Vein Thrombosis and/ Pulmonary embolism.&#xD;
&#xD;
          8. Acute infective endocarditis or history of acute endocarditis.&#xD;
&#xD;
          9. Participants with Hypertension.&#xD;
&#xD;
         10. Diabetics.&#xD;
&#xD;
         11. Any injuries or surgery of the ears, eyes, brain or spinal cord within the last 18&#xD;
             months.&#xD;
&#xD;
         12. Renal insufficiency (Creatinine and Urea not within normal ranges).&#xD;
&#xD;
         13. Hepatic Insufficiency ( aspartate aminotransferase (AST) and alanine transaminase&#xD;
             (ALT) within normal ranges).&#xD;
&#xD;
         14. Participants with Heamorrhagic Retinopathy.&#xD;
&#xD;
         15. Participants with prosthetic heart valve/s.&#xD;
&#xD;
         16. Participants currently receiving any other treatments administered via subcutaneous or&#xD;
             intramuscular routes.&#xD;
&#xD;
         17. Participants with a history or current endocrine, pulmonary, cardiovascular,&#xD;
             gastrointestinal, neurological, immunological, renal, hepatic, dermatologic,&#xD;
             haematologic, psychiatric disease other than specified that might have/cause unwanted&#xD;
             effects/outcomes in this clinical trial.&#xD;
&#xD;
         18. Alcohol and/ or drug abuse in the past year.&#xD;
&#xD;
         19. In the opinion of the investigator, the participant is not reliable to participate in&#xD;
             the trial.&#xD;
&#xD;
         20. Participants that have taken part in a clinical trial involving Clexane and/&#xD;
             Fraxiparine.&#xD;
&#xD;
             -&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>January 29, 2019</study_first_submitted>
  <study_first_submitted_qc>February 13, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 15, 2019</study_first_posted>
  <last_update_submitted>February 13, 2019</last_update_submitted>
  <last_update_submitted_qc>February 13, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">February 15, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Injection Site Reaction</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03841396
org study id: CSA-15-ASP-002
nct id: NCT03841396
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
A Phase IV, Randomised, Double-blind, Single-centre clinical trial in healthy male and female
      participants aged 18 to 55, that was designed to assess and compare the pain intensity at an
      injection site as well as the duration of pain following a single dose subcutaneous
      administration of two low molecular weight heparins (LMWH) respectively.
This was a Phase IV, Randomised, Double-blind, Single-centre clinical trial in healthy male
      and female participants aged 18 to 55, that was designed to assess and compare the pain
      intensity at an injection site as well as the duration of pain following a single dose
      subcutaneous administration of two LMWHs respectively. This study included an approximate
      seven-day screening period (screening visit to day 0), followed by three visits (Visit 2, 3
      and 4) in one-week intervals, in which each participant should have received a single
      sequence of subcutaneous injections of Placebo, Fraxiparine and Clexane, in a randomised
      order, on the three separate occasions. This was then followed by a safety follow-up visit,
      one week after the administration of the last dose of the study product.

      Fifteen (N = 15) healthy, consenting participants, fulfilling the inclusion criteria, were
      randomised to take part in this study. All participants received a single sequence of
      subcutaneous injections, on separate occasions at one week intervals, over the duration of
      the treatment phase of the study. Fifteen (N=15) participants received Fraxiparine, fifteen
      (N=15) participants received Clexane and fifteen (N=15) participants received Placebo. Two
      participants were screened however did not meet the eligibility criteria and therefore were
      not included into the study. Informed consent was obtained at Screening Visit 1 (day -7 to 0)
      before any trial-related procedures were be performed. Visual analogue and 11-point numeric
      rating scales were utilised to measure pain intensity after a single injection of
      investigational product. These scales were also used to assess burning and pruritus. All
      scales were be completed at set time intervals over a 30 minute period, i.e. 1, 3, 5, 10, 15
      and 30 minutes after the injections were completed. Hematoma, erythema and oedema were
      measured minutes and 1, 2 and 3 days after the injection, using transparent millimetric
      measuring paper. Safety bloods were drawn at each visit.
allocation: Randomized
intervention model: Single Group Assignment
intervention model description: This study was planned to be a replicated 3x3 Latin square design (5 replicates), each enrolled and randomised participant should have received a single sequence of subcutaneous injections of Placebo, Fraxiparine and Clexane, in randomised order, on three separate occasions.
primary purpose: Other
masking: Double (Participant, Investigator)
masking description: This was a double blind study and it was conducted under double blind conditions. The study medications, as well as the placebo, were contained in pre-packaged syringes which are different in physical appearance. Therefore to ensure double blinding conditions, the study medications (Fraxiparine, Clexane and Placebo) were packaged in an identical boxes and labelled identically (apart from the treatment number). To further ensure that the participants remained blinded during the study, a blindfold was put over the eyes of each participant at each visit that required IP administration.
measure: Comparison of Visual Analog Scale (VAS) scores of pain intensity at injection site following a single subcutaneous injection of placebo, Fraxiparine or Clexane
time frame: Over a period of 30 minutes
description: Visual Analogue Scales for pain intensity was performed at different time points namely 1, 3, 5, 10, 15 and 30 minutes after administration of the investigational product (IP) at Visit 2, 3 and 4. Pain intensity: 0 mm - No pain; 100 mm - Worst pain
measure: Comparison of Numeric Rating Scale (NRS) scores of pain intensity at injection site following a single subcutaneous injection of placebo, Fraxiparine or Clexane.
time frame: Over a period of 30 minutes
description: 11-point NRS for pain intensity was performed at different time points namely 1, 3, 5, 10, 15 and 30 minutes after administration of the investigational product (IP) at Visit 2, 3 and 4. Pain intensity: 0 - No pain; 10 - Worst pain
measure: Quantification of local injection site reaction
time frame: 10 and 30 minutes and 1, 2 and 3 days after the injection.
description: Hematoma, erythema and oedema were measured 10 and 30 minutes and 1, 2 and 3 days after the injection, using transparent millimetric measuring paper.
measure: Pain duration
time frame: 1, 3, 5, 10, 15 and 30 minutes after administration of IP.
description: Duration of pain at injection site.
arm group label: Fraxiparine
arm group type: Active Comparator
description: Nadroparine, Pre-filled syringe, 3800IU, single dose
arm group label: Clexane
arm group type: Active Comparator
description: Enoxaparin, Pre-filled syringe, 40 mg, single dose
intervention type: Drug
intervention name: Sodium chloride
description: All participants received a single dose of sodium chloride as placebo
arm group label: Clexane
arm group label: Fraxiparine
other name: Saline 0.4mL saline
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
responsible party type: Sponsor
mesh term: Injection Site Reaction
sharing ipd: No