<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/NCT01689363</url>
  </required_header>
  <id_info>
    <org_study_id>API-H001-CLN-A2</org_study_id>
    <nct_id>NCT01689363</nct_id>
  </id_info>
  <brief_title>Evaluation of the Allergenicity of AMPHADASE INJECTION (Hyaluronidase Injection USP)</brief_title>
  <acronym>H001-A2</acronym>
  <official_title>A Randomized, Double-Blinded, Negative- and Positive-Controlled Study for Evaluation of the Allergenicity of Amphadase® in Healthy Volunteers Using Intradermal Skin Test</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Amphastar Pharmaceuticals, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Amphastar Pharmaceuticals, Inc.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is designed to evaluate the allergenicity of Amphadase® in healthy volunteers&#xD;
      using an intradermal skin test.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>September 2012</start_date>
  <completion_date type="Actual">December 2012</completion_date>
  <primary_completion_date type="Actual">November 2012</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Screening</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Positive Allergic Reaction to Amphadase® in the Per-Protocol Population (PPP)</measure>
    <time_frame>Up to 30 minutes after the final study drug injection</time_frame>
    <description>Subjects received intradermal injections at 4 injection sites following a randomized configuration of study medications. Injection sites were monitored for any characteristic immediate reactions after the study drug injections. A positive reaction consisted of: a) reaction appearing within 30 minutes of drug placement; b) wheal (&gt;8 mm) with or without pseudopods; c) reaction accompanying erythema; and d) reaction accompanying localized itching.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Positive Allergic Reaction to Amphadase® in the Intent-to-Treat Population (ITT)</measure>
    <time_frame>Up to 30 minutes after the final study drug injection</time_frame>
    <description>Subjects received intradermal injections at 4 injection sites following a randomized configuration of study medications. Injection sites were monitored for any characteristic immediate reactions after the study drug injections. A positive reaction consisted of: a) reaction appearing within 30 minutes of drug placement; b) wheal (&gt;8 mm) with or without pseudopods; c) reaction accompanying erythema; and d) reaction accompanying localized itching.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Observed Wheal Size in the Per-Protocol Population (PPP)</measure>
    <time_frame>Up to 30 minutes after the final study drug injection</time_frame>
    <description>Subjects received intradermal injections at 4 injection sites following a randomized configuration of study medications. Injection sites were monitored for any characteristic immediate reactions after the study drug injections. The observed wheal size is the greatest wheal diameter measured at the injection site(s) for a specific study drug injection.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Observed Erythema Size in the Per-Protocol Population (PPP)</measure>
    <time_frame>Up to 30 minutes after the final study drug injection</time_frame>
    <description>Subjects received intradermal injections at 4 injection sites following a randomized configuration of study medications. Injection sites were monitored for any characteristic immediate reactions after the study drug injections. The observed erythema size is the greatest erythema diameter measured at the injection site(s) for a specific study drug injection.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Allergic Wheal Size in the Per-Protocol Population (PPP)</measure>
    <time_frame>Up to 30 minutes after the final study drug injection</time_frame>
    <description>Subjects received intradermal injections at 4 injection sites following a randomized configuration of study medications. Injection sites were monitored for any characteristic immediate reactions after the study drug injections. The allergic wheal size is the greatest wheal diameter with accompanying erythema and localized itching measured at the injection site(s) for a specific study drug injection.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Allergic Erythema Size in the Per-Protocol Population (PPP)</measure>
    <time_frame>Up to 30 minutes after the final study drug injection</time_frame>
    <description>Subjects received intradermal injections at 4 injection sites following a randomized configuration of study medications. Injection sites were monitored for any characteristic immediate reactions after the study drug injections. The allergic erythema size is the greatest erythema diameter with accompanying localized itching measured at the injection site(s) for a specific study drug injection.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Local Itchiness Rate in the Per-Protocol Population (PPP)</measure>
    <time_frame>Up to 30 minutes after the final study drug injection</time_frame>
    <description>Subjects received intradermal injections at 4 injection sites following a randomized configuration of study medications. Injection sites were monitored for any characteristic immediate reactions after the study drug injections. The local itchiness rate is the percentage of subjects that reported localized itching at the injection site(s) for a specific study drug injection.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Erythema Responder Rate in the Per-Protocol Population (PPP)</measure>
    <time_frame>Up to 30 minutes after the final study drug injection</time_frame>
    <description>Subjects received intradermal injections at 4 injection sites following a randomized configuration of study medications. Injection sites were monitored for any characteristic immediate reactions after the study drug injections. The erythema responder rate is the percentage of subjects that showed an erythema reaction at the injection site(s) for a specific study drug injection.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Observed Wheal Size in the Intent-to-Treat Population (ITT)</measure>
    <time_frame>Up to 30 minutes after the final study drug injection</time_frame>
    <description>Subjects received intradermal injections at 4 injection sites following a randomized configuration of study medications. Injection sites were monitored for any characteristic immediate reactions after the study drug injections. The observed wheal size is the greatest wheal diameter measured at the injection site(s) for a specific study drug injection.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Observed Erythema Size in the Intent-to-Treat Population (ITT)</measure>
    <time_frame>Up to 30 minutes after the final study drug injection</time_frame>
    <description>Subjects received intradermal injections at 4 injection sites following a randomized configuration of study medications. Injection sites were monitored for any characteristic immediate reactions after the study drug injections. The observed erythema size is the greatest erythema diameter measured at the injection site(s) for a specific study drug injection.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Allergic Erythema Size in the Intent-to-Treat Population (ITT)</measure>
    <time_frame>Up to 30 minutes after the final study drug injection</time_frame>
    <description>Subjects received intradermal injections at 4 injection sites following a randomized configuration of study medications. Injection sites were monitored for any characteristic immediate reactions after the study drug injections. The allergic erythema size is the greatest erythema diameter with accompanying localized itching measured at the injection site(s) for a specific study drug injection.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Local Itchiness Rate in the Intent-to-Treat Population (ITT)</measure>
    <time_frame>Up to 30 minutes after the final study drug injection</time_frame>
    <description>Subjects received intradermal injections at 4 injection sites following a randomized configuration of study medications. Injection sites were monitored for any characteristic immediate reactions after the study drug injections. The local itchiness rate is the percentage of subjects that reported localized itching at the injection site(s) for a specific study drug injection.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Erythema Responder Rate in the Intent-to-Treat Population (ITT)</measure>
    <time_frame>Up to 30 minutes after the final study drug injection</time_frame>
    <description>Subjects received intradermal injections at 4 injection sites following a randomized configuration of study medications. Injection sites were monitored for any characteristic immediate reactions after the study drug injections. The erythema responder rate is the percentage of subjects that showed an erythema reaction at the injection site(s) for a specific study drug injection.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Allergic Wheal Size in the Intent-to-Treat Population (ITT)</measure>
    <time_frame>Up to 30 minutes after the final study drug injection</time_frame>
    <description>Subjects received intradermal injections at 4 injection sites following a randomized configuration of study medications. Injection sites were monitored for any characteristic immediate reactions after the study drug injections. The allergic wheal size is the greatest wheal diameter with accompanying erythema and localized itching measured at the injection site(s) for a specific study drug injection.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">253</enrollment>
  <condition>Allergic Skin Reaction</condition>
  <arm_group>
    <arm_group_label>Arm H</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Intradermal injection of Amphadase (hyaluronidase 150 USP units/mL)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm P</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Intradermal injection of Histatrol (histamine base 0.1 mg/mL)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm N</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Intradermal injection of saline (0.02 mL)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Hyaluronidase</intervention_name>
    <description>Subjects received intradermal injections of 0.02 mL Amphadase® (hyaluronidase 150 USP units/mL) at two random sites on their forearms.</description>
    <arm_group_label>Arm H</arm_group_label>
    <other_name>Amphadase®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Histamine</intervention_name>
    <description>Subjects received one intradermal injection of 0.02 mL Histatrol® (histamine base 0.1 mg/mL) at one random sites on their forearms.</description>
    <arm_group_label>Arm P</arm_group_label>
    <other_name>Histatrol®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Saline</intervention_name>
    <description>Subjects received one intradermal injection of 0.02 mL saline at one random site on their forearm.</description>
    <arm_group_label>Arm N</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Healthy volunteers of either gender; Those without clinically significant cardiovascular&#xD;
        gastrointestinal, hepatic, neurological, psychiatric, endocrine, or other major systemic&#xD;
        disease that would unduly risk the subject's safety or interfere with the interpretation of&#xD;
        results, assessed according to the judgment of the Principal Investigator. A non-inclusive&#xD;
        list which would not be exclusionary and define healthy individual for the purposes of this&#xD;
        study are:&#xD;
&#xD;
          -  hypothyroidism,&#xD;
&#xD;
          -  stable hypertension except those subjects on beta blockers including ocular&#xD;
             preparations,&#xD;
&#xD;
          -  seasonal/perennial allergic rhinitis if able to wash out of antihistamines,&#xD;
&#xD;
          -  stable, mild intermittent asthma (subjects using beta agonists as a monotherapy on an&#xD;
             as-needed basis, excluding daily usage),&#xD;
&#xD;
          -  migraine if not taking excluded medications,&#xD;
&#xD;
          -  mild anxiety/depression if not taking excluded medications, and&#xD;
&#xD;
          -  mild arthritic conditions if not taking excluded medications.&#xD;
&#xD;
               -  Willingness and ability to sign an informed consent document;&#xD;
&#xD;
               -  18 - 80 years of age;&#xD;
&#xD;
               -  Intact skin at the forearm ;&#xD;
&#xD;
               -  Female participants are currently practicing effective birth control methods or&#xD;
                  abstinence.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Known allergy, hypersensitivity or contraindications to hyaluronidase, thimerosal,&#xD;
             edetate disodium (EDTA);&#xD;
&#xD;
          -  Use of medications within a duration considered to interfere with skin testing.&#xD;
&#xD;
          -  Known dermographism which may interfere with skin testing.&#xD;
&#xD;
          -  Pregnant or lactating women.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Selina Su, MPH</last_name>
    <role>Study Chair</role>
    <affiliation>A:mphastar Pharmaceuticals, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Amphastar Site 0022</name>
      <address>
        <city>Eugene</city>
        <state>Oregon</state>
        <zip>97401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Amphastar Site 0023</name>
      <address>
        <city>Lake Oswego</city>
        <state>Oregon</state>
        <zip>97035</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Amphastar Site 0026</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Amphastar Site 0038</name>
      <address>
        <city>Renton</city>
        <state>Washington</state>
        <zip>98057</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Amphastar Site 0034</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Barr J, Kirkpatrick N, Dick A, Leonard L, Hawksworth G, Noble DW. Effects of adrenaline and hyaluronidase on plasma concentrations of lignocaine and bupivacaine after peribulbar anaesthesia. Br J Anaesth. 1995 Dec;75(6):692-7. doi: 10.1093/bja/75.6.692.</citation>
    <PMID>8672315</PMID>
  </reference>
  <reference>
    <citation>Brydon CW, Basler M, Kerr WJ. An evaluation of two concentrations of hyaluronidase for supplementation of peribulbar anaesthesia. Anaesthesia. 1995 Nov;50(11):998-1000. doi: 10.1111/j.1365-2044.1995.tb05940.x.</citation>
    <PMID>8678264</PMID>
  </reference>
  <reference>
    <citation>Ahluwalia HS, Lukaris A, Lane CM. Delayed allergic reaction to hyaluronidase: a rare sequel to cataract surgery. Eye (Lond). 2003 Mar;17(2):263-6. doi: 10.1038/sj.eye.6700243. No abstract available.</citation>
    <PMID>12640426</PMID>
  </reference>
  <reference>
    <citation>Agrawal A, McLure HA, Dabbs TR. Allergic reaction to hyaluronidase after a peribulbar injection. Anaesthesia. 2003 May;58(5):493-4. doi: 10.1046/j.1365-2044.2003.03154_17.x. No abstract available.</citation>
    <PMID>12694021</PMID>
  </reference>
  <reference>
    <citation>Kempeneers A, Dralands L, Ceuppens J. Hyaluronidase induced orbital pseudotumor as complication of retrobulbar anesthesia. Bull Soc Belge Ophtalmol. 1992;243:159-66.</citation>
    <PMID>1302146</PMID>
  </reference>
  <reference>
    <citation>Minning CA Jr. Hyaluronidase allergy simulating expulsive choroidal hemorrhage. Arch Ophthalmol. 1994 May;112(5):585-6. doi: 10.1001/archopht.1994.01090170029012. No abstract available.</citation>
    <PMID>8185511</PMID>
  </reference>
  <reference>
    <citation>Szepfalusi Z, Nentwich I, Dobner M, Pillwein K, Urbanek R. IgE-mediated allergic reaction to hyaluronidase in paediatric oncological patients. Eur J Pediatr. 1997 Mar;156(3):199-203. doi: 10.1007/s004310050582.</citation>
    <PMID>9083759</PMID>
  </reference>
  <reference>
    <citation>Allergy testing. American College of Physicians. Ann Intern Med. 1989 Feb 15;110(4):317-20. No abstract available.</citation>
    <PMID>2578014</PMID>
  </reference>
  <reference>
    <citation>Poulsen LK. In vivo and in vitro techniques to determine the biological activity of food allergens. J Chromatogr B Biomed Sci Appl. 2001 May 25;756(1-2):41-55. doi: 10.1016/s0378-4347(01)00070-6.</citation>
    <PMID>11419727</PMID>
  </reference>
  <reference>
    <citation>Howard A, Mercer P, Nataraj HC, Kang BC. Bevel-down superior to bevel-up in intradermal skin testing. Ann Allergy Asthma Immunol. 1997 Jun;78(6):594-6. doi: 10.1016/s1081-1206(10)63222-x.</citation>
    <PMID>9207725</PMID>
  </reference>
  <reference>
    <citation>Barbaud A, Reichert-Penetrat S, Trechot P, Jacquin-Petit MA, Ehlinger A, Noirez V, Faure GC, Schmutz JL, Bene MC. The use of skin testing in the investigation of cutaneous adverse drug reactions. Br J Dermatol. 1998 Jul;139(1):49-58. doi: 10.1046/j.1365-2133.1998.02313.x.</citation>
    <PMID>9764148</PMID>
  </reference>
  <reference>
    <citation>Fisher MM, Bowey CJ. Intradermal compared with prick testing in the diagnosis of anaesthetic allergy. Br J Anaesth. 1997 Jul;79(1):59-63. doi: 10.1093/bja/79.1.59.</citation>
    <PMID>9301390</PMID>
  </reference>
  <reference>
    <citation>Ruzicka T, Gerstmeier M, Przybilla B, Ring J. Allergy to local anesthetics: comparison of patch test with prick and intradermal test results. J Am Acad Dermatol. 1987 Jun;16(6):1202-8. doi: 10.1016/s0190-9622(87)70158-3.</citation>
    <PMID>3597862</PMID>
  </reference>
  <verification_date>January 2017</verification_date>
  <study_first_submitted>September 13, 2012</study_first_submitted>
  <study_first_submitted_qc>September 17, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 21, 2012</study_first_posted>
  <results_first_submitted>July 25, 2016</results_first_submitted>
  <results_first_submitted_qc>January 18, 2017</results_first_submitted_qc>
  <results_first_posted type="Estimate">January 20, 2017</results_first_posted>
  <last_update_submitted>January 18, 2017</last_update_submitted>
  <last_update_submitted_qc>January 18, 2017</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 20, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>hyaluronidase</keyword>
  <keyword>enzymes with tissue spreading activity</keyword>
  <keyword>allergic reaction</keyword>
  <keyword>intradermal skin testing</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Histamine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>H, N, H, P</title>
          <description>Subjects received four intradermal injections where study drug was injected to sites on the subject's forearms in the following order: 1) 0.02 mL Amphadase® (hyaluronidase 150 USP units/mL) at the upper-left forearm; 2) 0.02 mL saline at the lower-left forearm; 3) 0.02 mL Amphadase® (hyaluronidase 150 USP units/mL) at the upper-right forearm; 4) 0.02 mL Histatrol® (histamine base 0.1 mg/mL) at the lower-right forearm</description>
        </group>
        <group group_id="P2">
          <title>H, N, P, H</title>
          <description>Subjects received four intradermal injections where study drug was injected to sites on the subject's forearms in the following order: 1) 0.02 mL Amphadase® (hyaluronidase 150 USP units/mL) at the upper-left forearm; 2) 0.02 mL saline at the lower-left forearm; 3) 0.02 mL Histatrol® (histamine base 0.1 mg/mL) at the upper-right forearm; 4) 0.02 mL Amphadase® (hyaluronidase 150 USP units/mL) at the lower-right forearm</description>
        </group>
        <group group_id="P3">
          <title>H, P, H, N</title>
          <description>Subjects received four intradermal injections where study drug was injected to sites on the subject's forearms in the following order: 1) 0.02 mL Amphadase® (hyaluronidase 150 USP units/mL) at the upper-left forearm; 2) 0.02 mL Histatrol® (histamine base 0.1 mg/mL) at the lower-left forearm; 3) 0.02 mL Amphadase® (hyaluronidase 150 USP units/mL) at the upper-right forearm; 4) 0.02 mL saline at the lower-right forearm</description>
        </group>
        <group group_id="P4">
          <title>H, P, N, H</title>
          <description>Subjects received four intradermal injections where study drug was injected to sites on the subject's forearms in the following order: 1) 0.02 mL Amphadase® (hyaluronidase 150 USP units/mL) at the upper-left forearm; 2) 0.02 mL Histatrol® (histamine base 0.1 mg/mL) at the lower-left forearm; 3) 0.02 mL saline at the upper-right forearm; 4) 0.02 mL Amphadase® (hyaluronidase 150 USP units/mL) at the lower-right forearm</description>
        </group>
        <group group_id="P5">
          <title>N, H, H, P</title>
          <description>Subjects received four intradermal injections where study drug was injected to sites on the subject's forearms in the following order: 1) 0.02 mL saline at the upper-left forearm; 2) 0.02 mL Amphadase® (hyaluronidase 150 USP units/mL) at the lower-left forearm; 3) 0.02 mL Amphadase® (hyaluronidase 150 USP units/mL) at the upper-right forearm; 4) 0.02 mL Histatrol® (histamine base 0.1 mg/mL) at the lower-right forearm</description>
        </group>
        <group group_id="P6">
          <title>N, H, P, H</title>
          <description>Subjects received four intradermal injections where study drug was injected to sites on the subject's forearms in the following order: 1) 0.02 mL saline at the upper-left forearm; 2) 0.02 mL Amphadase® (hyaluronidase 150 USP units/mL) at the lower-left forearm; 3) 0.02 mL Histatrol® (histamine base 0.1 mg/mL) at the upper-right forearm; 4) 0.02 mL Amphadase® (hyaluronidase 150 USP units/mL) at the lower-right forearm</description>
        </group>
        <group group_id="P7">
          <title>P, H, H, N</title>
          <description>Subjects received four intradermal injections where study drug was injected to sites on the subject's forearms in the following order: 1) 0.02 mL Histatrol® (histamine base 0.1 mg/mL) at the upper-left forearm; 2) 0.02 mL Amphadase® (hyaluronidase 150 USP units/mL) at the lower-left forearm; 3) 0.02 mL Amphadase® (hyaluronidase 150 USP units/mL) at the upper-right forearm; 4) 0.02 mL saline at the lower-right forearm</description>
        </group>
        <group group_id="P8">
          <title>P, H, N, H</title>
          <description>Subjects received four intradermal injections where study drug was injected to sites on the subject's forearms in the following order: 1) 0.02 mL Histatrol® (histamine base 0.1 mg/mL) at the upper-left forearm; 2) 0.02 mL Amphadase® (hyaluronidase 150 USP units/mL) at the lower-left forearm; 3) 0.02 mL saline at the upper-right forearm; 4) 0.02 mL Amphadase® (hyaluronidase 150 USP units/mL) at the lower-right forearm</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="32"/>
                <participants group_id="P2" count="32"/>
                <participants group_id="P3" count="32"/>
                <participants group_id="P4" count="31"/>
                <participants group_id="P5" count="31"/>
                <participants group_id="P6" count="31"/>
                <participants group_id="P7" count="32"/>
                <participants group_id="P8" count="32"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="32"/>
                <participants group_id="P2" count="31"/>
                <participants group_id="P3" count="32"/>
                <participants group_id="P4" count="31"/>
                <participants group_id="P5" count="31"/>
                <participants group_id="P6" count="31"/>
                <participants group_id="P7" count="32"/>
                <participants group_id="P8" count="32"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Total Study Population</title>
          <description>Subjects received four intradermal injections of study drug (two injections of 0.02 mL Amphadase® (hyaluronidase 150 USP units/mL), one injection of 0.02 mL Histatrol® (histamine base 0.1 mg/mL), one injection of 0.02 mL saline) in a random order at four locations on the subjects' forearms.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="253"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="239"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="34.9" spread="14.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="127"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="126"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="253"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Positive Allergic Reaction to Amphadase® in the Per-Protocol Population (PPP)</title>
        <description>Subjects received intradermal injections at 4 injection sites following a randomized configuration of study medications. Injection sites were monitored for any characteristic immediate reactions after the study drug injections. A positive reaction consisted of: a) reaction appearing within 30 minutes of drug placement; b) wheal (&gt;8 mm) with or without pseudopods; c) reaction accompanying erythema; and d) reaction accompanying localized itching.</description>
        <time_frame>Up to 30 minutes after the final study drug injection</time_frame>
        <population>Subjects who: a) have received the right treatment; b) have a negative reaction for the negative control; c) have a positive reaction for the positive control; and d) have the same reaction for both Amphadase® treatments</population>
        <group_list>
          <group group_id="O1">
            <title>Per-Protocol Population (PPP)</title>
            <description>Subjects who: a) have received the right treatment; b) have a negative reaction for the negative control; c) have a positive reaction for the positive control; and d) have the same reaction for both Amphadase® treatments</description>
          </group>
        </group_list>
        <measure>
          <title>Positive Allergic Reaction to Amphadase® in the Per-Protocol Population (PPP)</title>
          <description>Subjects received intradermal injections at 4 injection sites following a randomized configuration of study medications. Injection sites were monitored for any characteristic immediate reactions after the study drug injections. A positive reaction consisted of: a) reaction appearing within 30 minutes of drug placement; b) wheal (&gt;8 mm) with or without pseudopods; c) reaction accompanying erythema; and d) reaction accompanying localized itching.</description>
          <population>Subjects who: a) have received the right treatment; b) have a negative reaction for the negative control; c) have a positive reaction for the positive control; and d) have the same reaction for both Amphadase® treatments</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="183"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Positive Allergic Reaction to Amphadase® in the Intent-to-Treat Population (ITT)</title>
        <description>Subjects received intradermal injections at 4 injection sites following a randomized configuration of study medications. Injection sites were monitored for any characteristic immediate reactions after the study drug injections. A positive reaction consisted of: a) reaction appearing within 30 minutes of drug placement; b) wheal (&gt;8 mm) with or without pseudopods; c) reaction accompanying erythema; and d) reaction accompanying localized itching.</description>
        <time_frame>Up to 30 minutes after the final study drug injection</time_frame>
        <population>Subjects who have been randomized</population>
        <group_list>
          <group group_id="O1">
            <title>Intent-to-Treat Population (ITT)</title>
            <description>Subjects who have been randomized</description>
          </group>
        </group_list>
        <measure>
          <title>Positive Allergic Reaction to Amphadase® in the Intent-to-Treat Population (ITT)</title>
          <description>Subjects received intradermal injections at 4 injection sites following a randomized configuration of study medications. Injection sites were monitored for any characteristic immediate reactions after the study drug injections. A positive reaction consisted of: a) reaction appearing within 30 minutes of drug placement; b) wheal (&gt;8 mm) with or without pseudopods; c) reaction accompanying erythema; and d) reaction accompanying localized itching.</description>
          <population>Subjects who have been randomized</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="253"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Observed Wheal Size in the Per-Protocol Population (PPP)</title>
        <description>Subjects received intradermal injections at 4 injection sites following a randomized configuration of study medications. Injection sites were monitored for any characteristic immediate reactions after the study drug injections. The observed wheal size is the greatest wheal diameter measured at the injection site(s) for a specific study drug injection.</description>
        <time_frame>Up to 30 minutes after the final study drug injection</time_frame>
        <population>Subjects who: a) have received the right treatment; b) have a negative reaction for the negative control; c) have a positive reaction for the positive control; and d) have the same reaction for both Amphadase® treatments</population>
        <group_list>
          <group group_id="O1">
            <title>Arm H</title>
            <description>Subjects received intradermal injections of 0.02 mL Amphadase® (hyaluronidase 150 USP units/mL) at two sites on their forearms</description>
          </group>
          <group group_id="O2">
            <title>Arm N</title>
            <description>Subjects received an intradermal injection of 0.02 mL saline at one site on their forearms</description>
          </group>
          <group group_id="O3">
            <title>Arm P</title>
            <description>Subjects received an intradermal injection of 0.02 mL Histatrol® (histamine base 0.1 mg/mL) at one site on their forearms</description>
          </group>
        </group_list>
        <measure>
          <title>Observed Wheal Size in the Per-Protocol Population (PPP)</title>
          <description>Subjects received intradermal injections at 4 injection sites following a randomized configuration of study medications. Injection sites were monitored for any characteristic immediate reactions after the study drug injections. The observed wheal size is the greatest wheal diameter measured at the injection site(s) for a specific study drug injection.</description>
          <population>Subjects who: a) have received the right treatment; b) have a negative reaction for the negative control; c) have a positive reaction for the positive control; and d) have the same reaction for both Amphadase® treatments</population>
          <units>mm</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="183"/>
                <count group_id="O2" value="183"/>
                <count group_id="O3" value="183"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.1" spread="2.6"/>
                    <measurement group_id="O2" value="1.7" spread="2.7"/>
                    <measurement group_id="O3" value="15.3" spread="4.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Observed Erythema Size in the Per-Protocol Population (PPP)</title>
        <description>Subjects received intradermal injections at 4 injection sites following a randomized configuration of study medications. Injection sites were monitored for any characteristic immediate reactions after the study drug injections. The observed erythema size is the greatest erythema diameter measured at the injection site(s) for a specific study drug injection.</description>
        <time_frame>Up to 30 minutes after the final study drug injection</time_frame>
        <population>Subjects who: a) have received the right treatment; b) have a negative reaction for the negative control; c) have a positive reaction for the positive control; and d) have the same reaction for both Amphadase® treatments</population>
        <group_list>
          <group group_id="O1">
            <title>Arm H</title>
            <description>Subjects received intradermal injections of 0.02 mL Amphadase® (hyaluronidase 150 USP units/mL) at two sites on their forearms</description>
          </group>
          <group group_id="O2">
            <title>Arm N</title>
            <description>Subjects received an intradermal injection of 0.02 mL saline at one site on their forearms</description>
          </group>
          <group group_id="O3">
            <title>Arm P</title>
            <description>Subjects received an intradermal injection of 0.02 mL Histatrol® (histamine base 0.1 mg/mL) at one site on their forearms</description>
          </group>
        </group_list>
        <measure>
          <title>Observed Erythema Size in the Per-Protocol Population (PPP)</title>
          <description>Subjects received intradermal injections at 4 injection sites following a randomized configuration of study medications. Injection sites were monitored for any characteristic immediate reactions after the study drug injections. The observed erythema size is the greatest erythema diameter measured at the injection site(s) for a specific study drug injection.</description>
          <population>Subjects who: a) have received the right treatment; b) have a negative reaction for the negative control; c) have a positive reaction for the positive control; and d) have the same reaction for both Amphadase® treatments</population>
          <units>mm</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="183"/>
                <count group_id="O2" value="183"/>
                <count group_id="O3" value="183"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.3" spread="7.0"/>
                    <measurement group_id="O2" value="0.6" spread="3.7"/>
                    <measurement group_id="O3" value="44.4" spread="11.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Allergic Wheal Size in the Per-Protocol Population (PPP)</title>
        <description>Subjects received intradermal injections at 4 injection sites following a randomized configuration of study medications. Injection sites were monitored for any characteristic immediate reactions after the study drug injections. The allergic wheal size is the greatest wheal diameter with accompanying erythema and localized itching measured at the injection site(s) for a specific study drug injection.</description>
        <time_frame>Up to 30 minutes after the final study drug injection</time_frame>
        <population>Subjects who: a) have received the right treatment; b) have a negative reaction for the negative control; c) have a positive reaction for the positive control; and d) have the same reaction for both Amphadase® treatments</population>
        <group_list>
          <group group_id="O1">
            <title>Arm H</title>
            <description>Subjects received intradermal injections of 0.02 mL Amphadase® (hyaluronidase 150 USP units/mL) at two sites on their forearms</description>
          </group>
          <group group_id="O2">
            <title>Arm N</title>
            <description>Subjects received an intradermal injection of 0.02 mL saline at one site on their forearms</description>
          </group>
          <group group_id="O3">
            <title>Arm P</title>
            <description>Subjects received an intradermal injection of 0.02 mL Histatrol® (histamine base 0.1 mg/mL) at one site on their forearms</description>
          </group>
        </group_list>
        <measure>
          <title>Allergic Wheal Size in the Per-Protocol Population (PPP)</title>
          <description>Subjects received intradermal injections at 4 injection sites following a randomized configuration of study medications. Injection sites were monitored for any characteristic immediate reactions after the study drug injections. The allergic wheal size is the greatest wheal diameter with accompanying erythema and localized itching measured at the injection site(s) for a specific study drug injection.</description>
          <population>Subjects who: a) have received the right treatment; b) have a negative reaction for the negative control; c) have a positive reaction for the positive control; and d) have the same reaction for both Amphadase® treatments</population>
          <units>mm</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="183"/>
                <count group_id="O2" value="183"/>
                <count group_id="O3" value="183"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.1" spread="0.9"/>
                    <measurement group_id="O2" value="0.0" spread="0.0"/>
                    <measurement group_id="O3" value="15.2" spread="4.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Allergic Erythema Size in the Per-Protocol Population (PPP)</title>
        <description>Subjects received intradermal injections at 4 injection sites following a randomized configuration of study medications. Injection sites were monitored for any characteristic immediate reactions after the study drug injections. The allergic erythema size is the greatest erythema diameter with accompanying localized itching measured at the injection site(s) for a specific study drug injection.</description>
        <time_frame>Up to 30 minutes after the final study drug injection</time_frame>
        <population>Subjects who: a) have received the right treatment; b) have a negative reaction for the negative control; c) have a positive reaction for the positive control; and d) have the same reaction for both Amphadase® treatments</population>
        <group_list>
          <group group_id="O1">
            <title>Arm H</title>
            <description>Subjects received intradermal injections of 0.02 mL Amphadase® (hyaluronidase 150 USP units/mL) at two sites on their forearms</description>
          </group>
          <group group_id="O2">
            <title>Arm N</title>
            <description>Subjects received an intradermal injection of 0.02 mL saline at one site on their forearms</description>
          </group>
          <group group_id="O3">
            <title>Arm P</title>
            <description>Subjects received an intradermal injection of 0.02 mL Histatrol® (histamine base 0.1 mg/mL) at one site on their forearms</description>
          </group>
        </group_list>
        <measure>
          <title>Allergic Erythema Size in the Per-Protocol Population (PPP)</title>
          <description>Subjects received intradermal injections at 4 injection sites following a randomized configuration of study medications. Injection sites were monitored for any characteristic immediate reactions after the study drug injections. The allergic erythema size is the greatest erythema diameter with accompanying localized itching measured at the injection site(s) for a specific study drug injection.</description>
          <population>Subjects who: a) have received the right treatment; b) have a negative reaction for the negative control; c) have a positive reaction for the positive control; and d) have the same reaction for both Amphadase® treatments</population>
          <units>mm</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="183"/>
                <count group_id="O2" value="183"/>
                <count group_id="O3" value="183"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.1" spread="5.0"/>
                    <measurement group_id="O2" value="0.0" spread="0.1"/>
                    <measurement group_id="O3" value="44.1" spread="11.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Local Itchiness Rate in the Per-Protocol Population (PPP)</title>
        <description>Subjects received intradermal injections at 4 injection sites following a randomized configuration of study medications. Injection sites were monitored for any characteristic immediate reactions after the study drug injections. The local itchiness rate is the percentage of subjects that reported localized itching at the injection site(s) for a specific study drug injection.</description>
        <time_frame>Up to 30 minutes after the final study drug injection</time_frame>
        <population>Subjects who: a) have received the right treatment; b) have a negative reaction for the negative control; c) have a positive reaction for the positive control; and d) have the same reaction for both Amphadase® treatments</population>
        <group_list>
          <group group_id="O1">
            <title>Arm H</title>
            <description>Subjects received intradermal injections of 0.02 mL Amphadase® (hyaluronidase 150 USP units/mL) at two sites on their forearms</description>
          </group>
          <group group_id="O2">
            <title>Arm N</title>
            <description>Subjects received an intradermal injection of 0.02 mL saline at one site on their forearms</description>
          </group>
          <group group_id="O3">
            <title>Arm P</title>
            <description>Subjects received an intradermal injection of 0.02 mL Histatrol® (histamine base 0.1 mg/mL) at one site on their forearms</description>
          </group>
        </group_list>
        <measure>
          <title>Local Itchiness Rate in the Per-Protocol Population (PPP)</title>
          <description>Subjects received intradermal injections at 4 injection sites following a randomized configuration of study medications. Injection sites were monitored for any characteristic immediate reactions after the study drug injections. The local itchiness rate is the percentage of subjects that reported localized itching at the injection site(s) for a specific study drug injection.</description>
          <population>Subjects who: a) have received the right treatment; b) have a negative reaction for the negative control; c) have a positive reaction for the positive control; and d) have the same reaction for both Amphadase® treatments</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="183"/>
                <count group_id="O2" value="183"/>
                <count group_id="O3" value="183"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.7"/>
                    <measurement group_id="O2" value="1.1"/>
                    <measurement group_id="O3" value="100.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Erythema Responder Rate in the Per-Protocol Population (PPP)</title>
        <description>Subjects received intradermal injections at 4 injection sites following a randomized configuration of study medications. Injection sites were monitored for any characteristic immediate reactions after the study drug injections. The erythema responder rate is the percentage of subjects that showed an erythema reaction at the injection site(s) for a specific study drug injection.</description>
        <time_frame>Up to 30 minutes after the final study drug injection</time_frame>
        <population>Subjects who: a) have received the right treatment; b) have a negative reaction for the negative control; c) have a positive reaction for the positive control; and d) have the same reaction for both Amphadase® treatments</population>
        <group_list>
          <group group_id="O1">
            <title>Arm H</title>
            <description>Subjects received intradermal injections of 0.02 mL Amphadase® (hyaluronidase 150 USP units/mL) at two sites on their forearms</description>
          </group>
          <group group_id="O2">
            <title>Arm N</title>
            <description>Subjects received an intradermal injection of 0.02 mL saline at one site on their forearms</description>
          </group>
          <group group_id="O3">
            <title>Arm P</title>
            <description>Subjects received an intradermal injection of 0.02 mL Histatrol® (histamine base 0.1 mg/mL) at one site on their forearms</description>
          </group>
        </group_list>
        <measure>
          <title>Erythema Responder Rate in the Per-Protocol Population (PPP)</title>
          <description>Subjects received intradermal injections at 4 injection sites following a randomized configuration of study medications. Injection sites were monitored for any characteristic immediate reactions after the study drug injections. The erythema responder rate is the percentage of subjects that showed an erythema reaction at the injection site(s) for a specific study drug injection.</description>
          <population>Subjects who: a) have received the right treatment; b) have a negative reaction for the negative control; c) have a positive reaction for the positive control; and d) have the same reaction for both Amphadase® treatments</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="183"/>
                <count group_id="O2" value="183"/>
                <count group_id="O3" value="183"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="51.4"/>
                    <measurement group_id="O2" value="8.7"/>
                    <measurement group_id="O3" value="100.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Observed Wheal Size in the Intent-to-Treat Population (ITT)</title>
        <description>Subjects received intradermal injections at 4 injection sites following a randomized configuration of study medications. Injection sites were monitored for any characteristic immediate reactions after the study drug injections. The observed wheal size is the greatest wheal diameter measured at the injection site(s) for a specific study drug injection.</description>
        <time_frame>Up to 30 minutes after the final study drug injection</time_frame>
        <population>Subjects who have been randomized</population>
        <group_list>
          <group group_id="O1">
            <title>Arm H</title>
            <description>Subjects received intradermal injections of 0.02 mL Amphadase® (hyaluronidase 150 USP units/mL) at two sites on their forearms</description>
          </group>
          <group group_id="O2">
            <title>Arm N</title>
            <description>Subjects received an intradermal injection of 0.02 mL saline at one site on their forearms</description>
          </group>
          <group group_id="O3">
            <title>Arm P</title>
            <description>Subjects received an intradermal injection of 0.02 mL Histatrol® (histamine base 0.1 mg/mL) at one site on their forearms</description>
          </group>
        </group_list>
        <measure>
          <title>Observed Wheal Size in the Intent-to-Treat Population (ITT)</title>
          <description>Subjects received intradermal injections at 4 injection sites following a randomized configuration of study medications. Injection sites were monitored for any characteristic immediate reactions after the study drug injections. The observed wheal size is the greatest wheal diameter measured at the injection site(s) for a specific study drug injection.</description>
          <population>Subjects who have been randomized</population>
          <units>mm</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="253"/>
                <count group_id="O2" value="253"/>
                <count group_id="O3" value="253"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.5" spread="3.3"/>
                    <measurement group_id="O2" value="1.7" spread="2.8"/>
                    <measurement group_id="O3" value="14.1" spread="5.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Observed Erythema Size in the Intent-to-Treat Population (ITT)</title>
        <description>Subjects received intradermal injections at 4 injection sites following a randomized configuration of study medications. Injection sites were monitored for any characteristic immediate reactions after the study drug injections. The observed erythema size is the greatest erythema diameter measured at the injection site(s) for a specific study drug injection.</description>
        <time_frame>Up to 30 minutes after the final study drug injection</time_frame>
        <population>Subjects who have been randomized</population>
        <group_list>
          <group group_id="O1">
            <title>Arm H</title>
            <description>Subjects received intradermal injections of 0.02 mL Amphadase® (hyaluronidase 150 USP units/mL) at two sites on their forearms</description>
          </group>
          <group group_id="O2">
            <title>Arm N</title>
            <description>Subjects received an intradermal injection of 0.02 mL saline at one site on their forearms</description>
          </group>
          <group group_id="O3">
            <title>Arm P</title>
            <description>Subjects received an intradermal injection of 0.02 mL Histatrol® (histamine base 0.1 mg/mL) at one site on their forearms</description>
          </group>
        </group_list>
        <measure>
          <title>Observed Erythema Size in the Intent-to-Treat Population (ITT)</title>
          <description>Subjects received intradermal injections at 4 injection sites following a randomized configuration of study medications. Injection sites were monitored for any characteristic immediate reactions after the study drug injections. The observed erythema size is the greatest erythema diameter measured at the injection site(s) for a specific study drug injection.</description>
          <population>Subjects who have been randomized</population>
          <units>mm</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="253"/>
                <count group_id="O2" value="253"/>
                <count group_id="O3" value="253"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.4" spread="9.6"/>
                    <measurement group_id="O2" value="0.9" spread="4.5"/>
                    <measurement group_id="O3" value="41.5" spread="14.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Allergic Erythema Size in the Intent-to-Treat Population (ITT)</title>
        <description>Subjects received intradermal injections at 4 injection sites following a randomized configuration of study medications. Injection sites were monitored for any characteristic immediate reactions after the study drug injections. The allergic erythema size is the greatest erythema diameter with accompanying localized itching measured at the injection site(s) for a specific study drug injection.</description>
        <time_frame>Up to 30 minutes after the final study drug injection</time_frame>
        <population>Subjects who have been randomized</population>
        <group_list>
          <group group_id="O1">
            <title>Arm H</title>
            <description>Subjects received intradermal injections of 0.02 mL Amphadase® (hyaluronidase 150 USP units/mL) at two sites on their forearms</description>
          </group>
          <group group_id="O2">
            <title>Arm N</title>
            <description>Subjects received an intradermal injection of 0.02 mL saline at one site on their forearms</description>
          </group>
          <group group_id="O3">
            <title>Arm P</title>
            <description>Subjects received an intradermal injection of 0.02 mL Histatrol® (histamine base 0.1 mg/mL) at one site on their forearms</description>
          </group>
        </group_list>
        <measure>
          <title>Allergic Erythema Size in the Intent-to-Treat Population (ITT)</title>
          <description>Subjects received intradermal injections at 4 injection sites following a randomized configuration of study medications. Injection sites were monitored for any characteristic immediate reactions after the study drug injections. The allergic erythema size is the greatest erythema diameter with accompanying localized itching measured at the injection site(s) for a specific study drug injection.</description>
          <population>Subjects who have been randomized</population>
          <units>mm</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="253"/>
                <count group_id="O2" value="253"/>
                <count group_id="O3" value="253"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.1" spread="8.0"/>
                    <measurement group_id="O2" value="0.1" spread="1.9"/>
                    <measurement group_id="O3" value="34.0" spread="21.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Local Itchiness Rate in the Intent-to-Treat Population (ITT)</title>
        <description>Subjects received intradermal injections at 4 injection sites following a randomized configuration of study medications. Injection sites were monitored for any characteristic immediate reactions after the study drug injections. The local itchiness rate is the percentage of subjects that reported localized itching at the injection site(s) for a specific study drug injection.</description>
        <time_frame>Up to 30 minutes after the final study drug injection</time_frame>
        <population>Subjects who have been randomized</population>
        <group_list>
          <group group_id="O1">
            <title>Arm H</title>
            <description>Subjects received intradermal injections of 0.02 mL Amphadase® (hyaluronidase 150 USP units/mL) at two sites on their forearms</description>
          </group>
          <group group_id="O2">
            <title>Arm N</title>
            <description>Subjects received an intradermal injection of 0.02 mL saline at one site on their forearms</description>
          </group>
          <group group_id="O3">
            <title>Arm P</title>
            <description>Subjects received an intradermal injection of 0.02 mL Histatrol® (histamine base 0.1 mg/mL) at one site on their forearms</description>
          </group>
        </group_list>
        <measure>
          <title>Local Itchiness Rate in the Intent-to-Treat Population (ITT)</title>
          <description>Subjects received intradermal injections at 4 injection sites following a randomized configuration of study medications. Injection sites were monitored for any characteristic immediate reactions after the study drug injections. The local itchiness rate is the percentage of subjects that reported localized itching at the injection site(s) for a specific study drug injection.</description>
          <population>Subjects who have been randomized</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="253"/>
                <count group_id="O2" value="253"/>
                <count group_id="O3" value="253"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.3"/>
                    <measurement group_id="O2" value="1.6"/>
                    <measurement group_id="O3" value="79.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Erythema Responder Rate in the Intent-to-Treat Population (ITT)</title>
        <description>Subjects received intradermal injections at 4 injection sites following a randomized configuration of study medications. Injection sites were monitored for any characteristic immediate reactions after the study drug injections. The erythema responder rate is the percentage of subjects that showed an erythema reaction at the injection site(s) for a specific study drug injection.</description>
        <time_frame>Up to 30 minutes after the final study drug injection</time_frame>
        <population>Subjects who have been randomized</population>
        <group_list>
          <group group_id="O1">
            <title>Arm H</title>
            <description>Subjects received intradermal injections of 0.02 mL Amphadase® (hyaluronidase 150 USP units/mL) at two sites on their forearms</description>
          </group>
          <group group_id="O2">
            <title>Arm N</title>
            <description>Subjects received an intradermal injection of 0.02 mL saline at one site on their forearms</description>
          </group>
          <group group_id="O3">
            <title>Arm P</title>
            <description>Subjects received an intradermal injection of 0.02 mL Histatrol® (histamine base 0.1 mg/mL) at one site on their forearms</description>
          </group>
        </group_list>
        <measure>
          <title>Erythema Responder Rate in the Intent-to-Treat Population (ITT)</title>
          <description>Subjects received intradermal injections at 4 injection sites following a randomized configuration of study medications. Injection sites were monitored for any characteristic immediate reactions after the study drug injections. The erythema responder rate is the percentage of subjects that showed an erythema reaction at the injection site(s) for a specific study drug injection.</description>
          <population>Subjects who have been randomized</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="253"/>
                <count group_id="O2" value="253"/>
                <count group_id="O3" value="253"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="53.8"/>
                    <measurement group_id="O2" value="11.1"/>
                    <measurement group_id="O3" value="97.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Allergic Wheal Size in the Intent-to-Treat Population (ITT)</title>
        <description>Subjects received intradermal injections at 4 injection sites following a randomized configuration of study medications. Injection sites were monitored for any characteristic immediate reactions after the study drug injections. The allergic wheal size is the greatest wheal diameter with accompanying erythema and localized itching measured at the injection site(s) for a specific study drug injection.</description>
        <time_frame>Up to 30 minutes after the final study drug injection</time_frame>
        <population>Subjects who have been randomized</population>
        <group_list>
          <group group_id="O1">
            <title>Arm H</title>
            <description>Subjects received intradermal injections of 0.02 mL Amphadase® (hyaluronidase 150 USP units/mL) at two sites on their forearms</description>
          </group>
          <group group_id="O2">
            <title>Arm N</title>
            <description>Subjects received an intradermal injection of 0.02 mL saline at one site on their forearms</description>
          </group>
          <group group_id="O3">
            <title>Arm P</title>
            <description>Subjects received an intradermal injection of 0.02 mL Histatrol® (histamine base 0.1 mg/mL) at one site on their forearms</description>
          </group>
        </group_list>
        <measure>
          <title>Allergic Wheal Size in the Intent-to-Treat Population (ITT)</title>
          <description>Subjects received intradermal injections at 4 injection sites following a randomized configuration of study medications. Injection sites were monitored for any characteristic immediate reactions after the study drug injections. The allergic wheal size is the greatest wheal diameter with accompanying erythema and localized itching measured at the injection site(s) for a specific study drug injection.</description>
          <population>Subjects who have been randomized</population>
          <units>mm</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="253"/>
                <count group_id="O2" value="253"/>
                <count group_id="O3" value="253"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.5" spread="2.4"/>
                    <measurement group_id="O2" value="0.0" spread="0.7"/>
                    <measurement group_id="O3" value="11.5" spread="7.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Signing of Informed Consent until Adverse Event Resolution/Stabilization (approximately 30 days)</time_frame>
      <desc>Adverse drug events (ADEs), whether observed by investigators or reported by the subjects, will be documented, evaluated, followed up, and treated if deemed necessary. ADEs will be followed until stabilized/resolved or 30 days from the date the subject has finished the study, whichever is sooner.</desc>
      <group_list>
        <group group_id="E1">
          <title>Arm H</title>
          <description>Subjects received intradermal injections of 0.02 mL Amphadase® (hyaluronidase 150 USP units/mL) at two sites on their forearms</description>
        </group>
        <group group_id="E2">
          <title>Arm N</title>
          <description>Subjects received an intradermal injection of 0.02 mL saline at one site on their forearms</description>
        </group>
        <group group_id="E3">
          <title>Arm P</title>
          <description>Subjects received an intradermal injection of 0.02 mL Histatrol® (histamine base 0.1 mg/mL) at one site on their forearms</description>
        </group>
        <group group_id="E4">
          <title>All Arms</title>
          <description>Cannot identify which study drug may be associated with the ADE because the subject received all four injections almost at the same time</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="253"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="253"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="253"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="253"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>3</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="253"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="253"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="253"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="253"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Gisela Sharp</name_or_title>
      <organization>Amphastar Pharmaceuticals, Inc.</organization>
      <phone>(909) 980-9484 ext 2016</phone>
      <email>GiselaS@amphastar.com</email>
    </point_of_contact>
  </clinical_results>
</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/NCT01689363
org study id: API-H001-CLN-A2
nct id: NCT01689363
lead sponsor: 
has dmc: Yes
This study is designed to evaluate the allergenicity of Amphadase® in healthy volunteers
      using an intradermal skin test.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Screening
masking: Triple (Participant, Care Provider, Investigator)
measure: Positive Allergic Reaction to Amphadase® in the Per-Protocol Population (PPP)
time frame: Up to 30 minutes after the final study drug injection
description: Subjects received intradermal injections at 4 injection sites following a randomized configuration of study medications. Injection sites were monitored for any characteristic immediate reactions after the study drug injections. A positive reaction consisted of: a) reaction appearing within 30 minutes of drug placement; b) wheal (>8 mm) with or without pseudopods; c) reaction accompanying erythema; and d) reaction accompanying localized itching.
measure: Positive Allergic Reaction to Amphadase® in the Intent-to-Treat Population (ITT)
time frame: Up to 30 minutes after the final study drug injection
description: Subjects received intradermal injections at 4 injection sites following a randomized configuration of study medications. Injection sites were monitored for any characteristic immediate reactions after the study drug injections. A positive reaction consisted of: a) reaction appearing within 30 minutes of drug placement; b) wheal (>8 mm) with or without pseudopods; c) reaction accompanying erythema; and d) reaction accompanying localized itching.
measure: Observed Wheal Size in the Per-Protocol Population (PPP)
time frame: Up to 30 minutes after the final study drug injection
description: Subjects received intradermal injections at 4 injection sites following a randomized configuration of study medications. Injection sites were monitored for any characteristic immediate reactions after the study drug injections. The observed wheal size is the greatest wheal diameter measured at the injection site(s) for a specific study drug injection.
measure: Observed Erythema Size in the Per-Protocol Population (PPP)
time frame: Up to 30 minutes after the final study drug injection
description: Subjects received intradermal injections at 4 injection sites following a randomized configuration of study medications. Injection sites were monitored for any characteristic immediate reactions after the study drug injections. The observed erythema size is the greatest erythema diameter measured at the injection site(s) for a specific study drug injection.
measure: Allergic Wheal Size in the Per-Protocol Population (PPP)
time frame: Up to 30 minutes after the final study drug injection
description: Subjects received intradermal injections at 4 injection sites following a randomized configuration of study medications. Injection sites were monitored for any characteristic immediate reactions after the study drug injections. The allergic wheal size is the greatest wheal diameter with accompanying erythema and localized itching measured at the injection site(s) for a specific study drug injection.
measure: Allergic Erythema Size in the Per-Protocol Population (PPP)
time frame: Up to 30 minutes after the final study drug injection
description: Subjects received intradermal injections at 4 injection sites following a randomized configuration of study medications. Injection sites were monitored for any characteristic immediate reactions after the study drug injections. The allergic erythema size is the greatest erythema diameter with accompanying localized itching measured at the injection site(s) for a specific study drug injection.
measure: Local Itchiness Rate in the Per-Protocol Population (PPP)
time frame: Up to 30 minutes after the final study drug injection
description: Subjects received intradermal injections at 4 injection sites following a randomized configuration of study medications. Injection sites were monitored for any characteristic immediate reactions after the study drug injections. The local itchiness rate is the percentage of subjects that reported localized itching at the injection site(s) for a specific study drug injection.
measure: Erythema Responder Rate in the Per-Protocol Population (PPP)
time frame: Up to 30 minutes after the final study drug injection
description: Subjects received intradermal injections at 4 injection sites following a randomized configuration of study medications. Injection sites were monitored for any characteristic immediate reactions after the study drug injections. The erythema responder rate is the percentage of subjects that showed an erythema reaction at the injection site(s) for a specific study drug injection.
measure: Observed Wheal Size in the Intent-to-Treat Population (ITT)
time frame: Up to 30 minutes after the final study drug injection
description: Subjects received intradermal injections at 4 injection sites following a randomized configuration of study medications. Injection sites were monitored for any characteristic immediate reactions after the study drug injections. The observed wheal size is the greatest wheal diameter measured at the injection site(s) for a specific study drug injection.
measure: Observed Erythema Size in the Intent-to-Treat Population (ITT)
time frame: Up to 30 minutes after the final study drug injection
description: Subjects received intradermal injections at 4 injection sites following a randomized configuration of study medications. Injection sites were monitored for any characteristic immediate reactions after the study drug injections. The observed erythema size is the greatest erythema diameter measured at the injection site(s) for a specific study drug injection.
measure: Allergic Erythema Size in the Intent-to-Treat Population (ITT)
time frame: Up to 30 minutes after the final study drug injection
description: Subjects received intradermal injections at 4 injection sites following a randomized configuration of study medications. Injection sites were monitored for any characteristic immediate reactions after the study drug injections. The allergic erythema size is the greatest erythema diameter with accompanying localized itching measured at the injection site(s) for a specific study drug injection.
measure: Local Itchiness Rate in the Intent-to-Treat Population (ITT)
time frame: Up to 30 minutes after the final study drug injection
description: Subjects received intradermal injections at 4 injection sites following a randomized configuration of study medications. Injection sites were monitored for any characteristic immediate reactions after the study drug injections. The local itchiness rate is the percentage of subjects that reported localized itching at the injection site(s) for a specific study drug injection.
measure: Erythema Responder Rate in the Intent-to-Treat Population (ITT)
time frame: Up to 30 minutes after the final study drug injection
description: Subjects received intradermal injections at 4 injection sites following a randomized configuration of study medications. Injection sites were monitored for any characteristic immediate reactions after the study drug injections. The erythema responder rate is the percentage of subjects that showed an erythema reaction at the injection site(s) for a specific study drug injection.
measure: Allergic Wheal Size in the Intent-to-Treat Population (ITT)
time frame: Up to 30 minutes after the final study drug injection
description: Subjects received intradermal injections at 4 injection sites following a randomized configuration of study medications. Injection sites were monitored for any characteristic immediate reactions after the study drug injections. The allergic wheal size is the greatest wheal diameter with accompanying erythema and localized itching measured at the injection site(s) for a specific study drug injection.
arm group label: Arm H
arm group type: Experimental
description: Intradermal injection of Amphadase (hyaluronidase 150 USP units/mL)
arm group label: Arm P
arm group type: Active Comparator
description: Intradermal injection of Histatrol (histamine base 0.1 mg/mL)
arm group label: Arm N
arm group type: Placebo Comparator
description: Intradermal injection of saline (0.02 mL)
intervention type: Drug
intervention name: Hyaluronidase
description: Subjects received intradermal injections of 0.02 mL Amphadase® (hyaluronidase 150 USP units/mL) at two random sites on their forearms.
arm group label: Arm H
other name: Amphadase®
intervention type: Drug
intervention name: Histamine
description: Subjects received one intradermal injection of 0.02 mL Histatrol® (histamine base 0.1 mg/mL) at one random sites on their forearms.
arm group label: Arm P
other name: Histatrol®
intervention type: Drug
intervention name: Saline
description: Subjects received one intradermal injection of 0.02 mL saline at one random site on their forearm.
arm group label: Arm N
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Selina Su, MPH
role: Study Chair
affiliation: A:mphastar Pharmaceuticals, Inc.
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
citation: Barr J, Kirkpatrick N, Dick A, Leonard L, Hawksworth G, Noble DW. Effects of adrenaline and hyaluronidase on plasma concentrations of lignocaine and bupivacaine after peribulbar anaesthesia. Br J Anaesth. 1995 Dec;75(6):692-7. doi: 10.1093/bja/75.6.692.
PMID: 8672315
citation: Brydon CW, Basler M, Kerr WJ. An evaluation of two concentrations of hyaluronidase for supplementation of peribulbar anaesthesia. Anaesthesia. 1995 Nov;50(11):998-1000. doi: 10.1111/j.1365-2044.1995.tb05940.x.
PMID: 8678264
citation: Ahluwalia HS, Lukaris A, Lane CM. Delayed allergic reaction to hyaluronidase: a rare sequel to cataract surgery. Eye (Lond). 2003 Mar;17(2):263-6. doi: 10.1038/sj.eye.6700243. No abstract available.
PMID: 12640426
citation: Agrawal A, McLure HA, Dabbs TR. Allergic reaction to hyaluronidase after a peribulbar injection. Anaesthesia. 2003 May;58(5):493-4. doi: 10.1046/j.1365-2044.2003.03154_17.x. No abstract available.
PMID: 12694021
citation: Kempeneers A, Dralands L, Ceuppens J. Hyaluronidase induced orbital pseudotumor as complication of retrobulbar anesthesia. Bull Soc Belge Ophtalmol. 1992;243:159-66.
PMID: 1302146
citation: Minning CA Jr. Hyaluronidase allergy simulating expulsive choroidal hemorrhage. Arch Ophthalmol. 1994 May;112(5):585-6. doi: 10.1001/archopht.1994.01090170029012. No abstract available.
PMID: 8185511
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responsible party type: Sponsor
mesh term: Histamine
sharing ipd: No
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 