Evaluation of the Allergenicity of AMPHADASE INJECTION (Hyaluronidase Injection USP)

• Hyaluronidase (Drug), also known as Amphadase®: Subjects received intradermal injections of 0.02 mL Amphadase® (hyaluronidase 150 USP units/mL) at two random sites on their forearms.
• Histamine (Drug), also known as Histatrol®: Subjects received one intradermal injection of 0.02 mL Histatrol® (histamine base 0.1 mg/mL) at one random sites on their forearms.
• Saline (Drug): Subjects received one intradermal injection of 0.02 mL saline at one random site on their forearm.

Primary outcomes

• Positive Allergic Reaction to Amphadase® in the Per-Protocol Population (PPP) [Up to 30 minutes after the final study drug injection]: 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.
• Positive Allergic Reaction to Amphadase® in the Intent-to-Treat Population (ITT) [Up to 30 minutes after the final study drug injection]: 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.

Secondary outcomes

• Observed Wheal Size in the Per-Protocol Population (PPP) [Up to 30 minutes after the final study drug injection]: 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.
• Observed Erythema Size in the Per-Protocol Population (PPP) [Up to 30 minutes after the final study drug injection]: 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.
• Allergic Wheal Size in the Per-Protocol Population (PPP) [Up to 30 minutes after the final study drug injection]: 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.
• Allergic Erythema Size in the Per-Protocol Population (PPP) [Up to 30 minutes after the final study drug injection]: 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.
• Local Itchiness Rate in the Per-Protocol Population (PPP) [Up to 30 minutes after the final study drug injection]: 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.
• Erythema Responder Rate in the Per-Protocol Population (PPP) [Up to 30 minutes after the final study drug injection]: 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.
• Observed Wheal Size in the Intent-to-Treat Population (ITT) [Up to 30 minutes after the final study drug injection]: 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.
• Observed Erythema Size in the Intent-to-Treat Population (ITT) [Up to 30 minutes after the final study drug injection]: 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.
• Allergic Erythema Size in the Intent-to-Treat Population (ITT) [Up to 30 minutes after the final study drug injection]: 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.
• Local Itchiness Rate in the Intent-to-Treat Population (ITT) [Up to 30 minutes after the final study drug injection]: 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.
• Erythema Responder Rate in the Intent-to-Treat Population (ITT) [Up to 30 minutes after the final study drug injection]: 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.
• Allergic Wheal Size in the Intent-to-Treat Population (ITT) [Up to 30 minutes after the final study drug injection]: 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.

Sex: All, ages: 18 Years to 80 Years, accepts healthy volunteers

Inclusion Criteria:

Healthy volunteers of either gender; Those without clinically significant cardiovascular gastrointestinal, hepatic, neurological, psychiatric, endocrine, or other major systemic disease that would unduly risk the subject's safety or interfere with the interpretation of results, assessed according to the judgment of the Principal Investigator. A non-inclusive list which would not be exclusionary and define healthy individual for the purposes of this study are:

* hypothyroidism,
* stable hypertension except those subjects on beta blockers including ocular preparations,
* seasonal/perennial allergic rhinitis if able to wash out of antihistamines,
* stable, mild intermittent asthma (subjects using beta agonists as a monotherapy on an as-needed basis, excluding daily usage),
* migraine if not taking excluded medications,
* mild anxiety/depression if not taking excluded medications, and
* mild arthritic conditions if not taking excluded medications.

  * Willingness and ability to sign an informed consent document;
  * 18 - 80 years of age;
  * Intact skin at the forearm ;
  * Female participants are currently practicing effective birth control methods or abstinence.

Exclusion Criteria:

* Known allergy, hypersensitivity or contraindications to hyaluronidase, thimerosal, edetate disodium (EDTA);
* Use of medications within a duration considered to interfere with skin testing.
* Known dermographism which may interfere with skin testing.
* Pregnant or lactating women.

Participant flow

Outcome results

• Positive Allergic Reaction to Amphadase® in the Per-Protocol Population (PPP) (Primary), Number, participants: Per-Protocol Population (PPP) 0
• Positive Allergic Reaction to Amphadase® in the Intent-to-Treat Population (ITT) (Primary), Number, participants: Intent-to-Treat Population (ITT) 7
• Observed Wheal Size in the Per-Protocol Population (PPP) (Secondary), Mean, mm: Arm H 1.1 +/- 2.6; Arm N 1.7 +/- 2.7; Arm P 15.3 +/- 4.9
• Observed Erythema Size in the Per-Protocol Population (PPP) (Secondary), Mean, mm: Arm H 4.3 +/- 7.0; Arm N 0.6 +/- 3.7; Arm P 44.4 +/- 11.7
• Allergic Wheal Size in the Per-Protocol Population (PPP) (Secondary), Mean, mm: Arm H 0.1 +/- 0.9; Arm N 0.0 +/- 0.0; Arm P 15.2 +/- 4.9
• Allergic Erythema Size in the Per-Protocol Population (PPP) (Secondary), Mean, mm: Arm H 1.1 +/- 5.0; Arm N 0.0 +/- 0.1; Arm P 44.1 +/- 11.8
• Local Itchiness Rate in the Per-Protocol Population (PPP) (Secondary), Number, percentage of participants: Arm H 7.7; Arm N 1.1; Arm P 100.0
• Erythema Responder Rate in the Per-Protocol Population (PPP) (Secondary), Number, percentage of participants: Arm H 51.4; Arm N 8.7; Arm P 100.0
• Observed Wheal Size in the Intent-to-Treat Population (ITT) (Secondary), Mean, mm: Arm H 1.5 +/- 3.3; Arm N 1.7 +/- 2.8; Arm P 14.1 +/- 5.6
• Observed Erythema Size in the Intent-to-Treat Population (ITT) (Secondary), Mean, mm: Arm H 5.4 +/- 9.6; Arm N 0.9 +/- 4.5; Arm P 41.5 +/- 14.7
• Allergic Erythema Size in the Intent-to-Treat Population (ITT) (Secondary), Mean, mm: Arm H 2.1 +/- 8.0; Arm N 0.1 +/- 1.9; Arm P 34.0 +/- 21.1
• Local Itchiness Rate in the Intent-to-Treat Population (ITT) (Secondary), Number, percentage of participants: Arm H 10.3; Arm N 1.6; Arm P 79.1
• Erythema Responder Rate in the Intent-to-Treat Population (ITT) (Secondary), Number, percentage of participants: Arm H 53.8; Arm N 11.1; Arm P 97.6
• Allergic Wheal Size in the Intent-to-Treat Population (ITT) (Secondary), Mean, mm: Arm H 0.5 +/- 2.4; Arm N 0.0 +/- 0.7; Arm P 11.5 +/- 7.6

Adverse events

Time frame: Signing of Informed Consent until Adverse Event Resolution/Stabilization (approximately 30 days)

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• Selina Su, MPH, Study chair, A:mphastar Pharmaceuticals, Inc.