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

Allergic Skin Reaction Clinical Trial

— H001-A2  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01689363
• Other study ID #: API-H001-CLN-A2
• Status: Completed
• Phase: Phase 2
• First received: September 13, 2012
• Last updated: January 18, 2017
• Start date: September 2012
• Est. completion date: December 2012

Study information

• Verified date: January 2017
• Source: Amphastar Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is designed to evaluate the allergenicity of Amphadase® in healthy volunteers using an intradermal skin test.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 253
• Est. completion date: December 2012
• Est. primary completion date: November 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Allergic Skin Reaction

Intervention

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

Locations

Country	Name	City	State
United States	Amphastar Site 0022	Eugene	Oregon
United States	Amphastar Site 0023	Lake Oswego	Oregon
United States	Amphastar Site 0026	Portland	Oregon
United States	Amphastar Site 0038	Renton	Washington
United States	Amphastar Site 0034	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Amphastar Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (13)

Agrawal A, McLure HA, Dabbs TR. Allergic reaction to hyaluronidase after a peribulbar injection. Anaesthesia. 2003 May;58(5):493-4. — View 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. Review. — View Citation

Allergy testing. American College of Physicians. Ann Intern Med. 1989 Feb 15;110(4):317-20. — View Citation

Barbaud A, Reichert-Penetrat S, Tréchot P, Jacquin-Petit MA, Ehlinger A, Noirez V, Faure GC, Schmutz JL, Béné MC. The use of skin testing in the investigation of cutaneous adverse drug reactions. Br J Dermatol. 1998 Jul;139(1):49-58. — View 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. — View 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. — View 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. — View 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. — View Citation

Kempeneers A, Dralands L, Ceuppens J. Hyaluronidase induced orbital pseudotumor as complication of retrobulbar anesthesia. Bull Soc Belge Ophtalmol. 1992;243:159-66. — View Citation

Minning CA Jr. Hyaluronidase allergy simulating expulsive choroidal hemorrhage. Arch Ophthalmol. 1994 May;112(5):585-6. — View 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. Review. — View 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. — View Citation

Szépfalusi 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. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Positive Allergic Reaction to Amphadase® in the Per-Protocol Population (PPP)	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.	Up to 30 minutes after the final study drug injection
Primary	Positive Allergic Reaction to Amphadase® in the Intent-to-Treat Population (ITT)	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.	Up to 30 minutes after the final study drug injection
Secondary	Observed Wheal Size in the Per-Protocol Population (PPP)	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.	Up to 30 minutes after the final study drug injection
Secondary	Observed Erythema Size in the Per-Protocol Population (PPP)	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.	Up to 30 minutes after the final study drug injection
Secondary	Allergic Wheal Size in the Per-Protocol Population (PPP)	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.	Up to 30 minutes after the final study drug injection
Secondary	Allergic Erythema Size in the Per-Protocol Population (PPP)	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.	Up to 30 minutes after the final study drug injection
Secondary	Local Itchiness Rate in the Per-Protocol Population (PPP)	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.	Up to 30 minutes after the final study drug injection
Secondary	Erythema Responder Rate in the Per-Protocol Population (PPP)	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.	Up to 30 minutes after the final study drug injection
Secondary	Observed Wheal Size in the Intent-to-Treat Population (ITT)	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.	Up to 30 minutes after the final study drug injection
Secondary	Observed Erythema Size in the Intent-to-Treat Population (ITT)	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.	Up to 30 minutes after the final study drug injection
Secondary	Allergic Erythema Size in the Intent-to-Treat Population (ITT)	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.	Up to 30 minutes after the final study drug injection
Secondary	Local Itchiness Rate in the Intent-to-Treat Population (ITT)	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.	Up to 30 minutes after the final study drug injection
Secondary	Erythema Responder Rate in the Intent-to-Treat Population (ITT)	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.	Up to 30 minutes after the final study drug injection
Secondary	Allergic Wheal Size in the Intent-to-Treat Population (ITT)	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.	Up to 30 minutes after the final study drug injection