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

NCT01689363 | Completed Phase 2 Results DMC

• 1 other identifier: API-H001-CLN-A2
• Study Type: interventional
• Target: 253
• Locations: 1 country
• Sites: 5

Brief Summary

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

Conditions

Allergic Skin Reaction

Keywords

hyaluronidase; enzymes with tissue spreading activity; allergic reaction; intradermal skin testing

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (12)

• Observed Wheal Size in the Per-Protocol Population (PPP)

  Up to 30 minutes after the final study drug injection

• Observed Erythema Size in the Per-Protocol Population (PPP)

  Up to 30 minutes after the final study drug injection

• Allergic Wheal Size in the Per-Protocol Population (PPP)

  Up to 30 minutes after the final study drug injection

• Allergic Erythema Size in the Per-Protocol Population (PPP)

  Up to 30 minutes after the final study drug injection

• Local Itchiness Rate in the Per-Protocol Population (PPP)

  Up to 30 minutes after the final study drug injection

Study Arms (3)

Arm H

EXPERIMENTAL

Intradermal injection of Amphadase (hyaluronidase 150 USP units/mL)

Drug: Hyaluronidase

Arm P

ACTIVE COMPARATOR

Intradermal injection of Histatrol (histamine base 0.1 mg/mL)

Drug: Histamine

Arm N

PLACEBO COMPARATOR

Intradermal injection of saline (0.02 mL)

Drug: Saline

Interventions

Hyaluronidase DRUG

Subjects received intradermal injections of 0.02 mL Amphadase® (hyaluronidase 150 USP units/mL) at two random sites on their forearms.

Also known as: Amphadase®

Arm H

Histamine DRUG

Subjects received one intradermal injection of 0.02 mL Histatrol® (histamine base 0.1 mg/mL) at one random sites on their forearms.

Also known as: Histatrol®

Arm P

Saline DRUG

Subjects received one intradermal injection of 0.02 mL saline at one random site on their forearm.

Arm N

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• years of age;
• Intact skin at the forearm ;
• Female participants are currently practicing effective birth control methods or abstinence.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Amphastar Pharmaceuticals, Inc.: lead

Study Sites (5)

Amphastar Site 0022

Eugene, Oregon, 97401, United States

Location

Amphastar Site 0023

Lake Oswego, Oregon, 97035, United States

Location

Amphastar Site 0026

Portland, Oregon, 97202, United States

Location

Amphastar Site 0038

Renton, Washington, 98057, United States

Location

Amphastar Site 0034

Seattle, Washington, 98115, United States

Location

Related Publications (13)

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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.

  PMID: 9083759 BACKGROUND

• Allergy testing. American College of Physicians. Ann Intern Med. 1989 Feb 15;110(4):317-20. No abstract available.

  PMID: 2578014 BACKGROUND

• 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.

  PMID: 11419727 BACKGROUND

• 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.

  PMID: 9207725 BACKGROUND

• 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.

  PMID: 9764148 BACKGROUND

• 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.

  PMID: 9301390 BACKGROUND

• 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.

  PMID: 3597862 BACKGROUND

MeSH Terms

Conditions

Hypersensitivity

Interventions

Hyaluronoglucosaminidase; Chondroitinases and Chondroitin Lyases; Histamine; Sodium Chloride

Condition Hierarchy (Ancestors)

Immune System Diseases

Intervention Hierarchy (Ancestors)

Glycoside Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Polysaccharide-Lyases; Carbon-Oxygen Lyases; Lyases; Sulfatases; Esterases; Biogenic Monoamines; Biogenic Amines; Amines; Organic Chemicals; Ethylamines; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Autacoids; Inflammation Mediators; Biological Factors; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Results Point of Contact

• Title: Gisela Sharp
• Organization: Amphastar Pharmaceuticals, Inc.

GiselaS@amphastar.com

(909) 980-9484

Study Officials

• Selina Su, MPH

  A:mphastar Pharmaceuticals, Inc.

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: SCREENING
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 13, 2012
• First Posted: September 21, 2012
• Study Start: September 1, 2012
• Primary Completion: November 1, 2012
• Study Completion: December 1, 2012
• Last Updated: January 20, 2017
• Results First Posted: January 20, 2017

Record last verified: 2017-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)