This is a multicenter, parallel group, randomized, double-blind pilot Phase III clinical study of JDP-205 (cetirizine) injection, versus diphenhydramine injection, 50 mg/mL (Benadryl or generic equivalent), in approximately 36 patients with acute urticaria requiring treatment in Hospital Emergency Departments, Urgent Care Centers and Allergy Clinics.

Multicenter, parallel group, randomized, double-blind pilot Phase III clinical study of JDP-205 (cetirizine) injection, versus diphenhydramine injection, 50 mg/mL (Benadryl or generic equivalent), in approximately 36 patients with acute urticaria requiring treatment in Hospital Emergency Departments, Urgent Care Centers and Allergy Clinics. This study will be conducted in 33 patient who either present themselves to the hospital emergency department, allergy clinic or urgent care centers with acute urticaria or developed acute urticaria following a allergen challenge at an allergy clinic.

Following informed consent, eligibility will be established, capturing baseline data including vitals, age, medical history, and medications taken prior to coming to the clinical study site. Following data collection, study subjects will be randomized in a 1:1 ratio to receive study drug of either cetirizine 10 mg IV or diphenhydramine, 50 mg IV. Baseline data including vital signs, the extent of urticaria and erythema, the severity of pruritus, and the level of sedation will be recorded prior to and at 1 hour and 2 hours post study drug administration, and at the time of "Readiness for Discharge". The actual time at which the investigator determines that the subject is ready for discharge (physically and mentally fit) from the study site will also be recorded. At these same time intervals, subjects will be asked to self-rate (recorded by study staff) severity of their pruritus and level of sedation (recorded by study staff).

Twenty-four hours following discharge from the study site, study staff will call the subject to ask them a few short questions to follow-up on the treatment of their acute urticaria. All adverse and serious adverse events experienced by the subjects following informed consent, and all data captured will be recorded in the source documents and/or case report forms.

Patients are eligible to be included in the study only if they meet all of the following criteria:

Inclusion Criteria:

• Male or female patients with a diagnosis of acute urticaria associated with an acute allergic reaction to a known (e.g. food, medication, insect bites) or unknown allergen who need treatment with an injectable antihistamine to alleviate their symptoms;
• 18 years of age or older;
• Be willing and able to give informed consent;
• Patients with a Physician Pruritus Severity Score ≥ 1 (determined by the investigator);
• Patients with an Extent of Urticaria/Erythema Score ≥ 1 (determined by the investigator).

Exclusion Criteria:

• Receipt of an investigational drug or device, within the past 30 days;
• Patients in whom an antihistamine may be contraindicated (e.g. narrow angle glaucoma, symptomatic prostatic hypertrophy);
• Patients who, in the opinion of the investigator, may not tolerate an IV injection of diphenhydramine 50 mg, or cetirizine 10 mg;
• Receipt of any antihistamine (H1 antagonist) within the past 4 hours regardless of the route of administration, e.g. diphenhydramine, cetirizine, loratadine, fexofenadine, levocetirizine, desloratadine;
• Receipt of an H2 antagonist within the past 12 hours;
• Receipt of doxepin within the past 48 hours; doxepin is an antidepressant, but it also has antihistamine properties;
• Receipt of steroids by the oral, IV, IM, or inhalational routes route within the past 48 hours to manage an acute allergic reaction;
• Receipt of epinephrine (EpiPen or any other brand) within the past 1 hour;
• Has known allergy to hydroxyzine, cetirizine or levocetirizine, or diphenhydramine;
• Pregnancy or breastfeeding;
• Patients who require epinephrine immediately to manage their acute allergic symptoms;
• Patients who have an acute reaction to medication they are taking (e.g. antibiotics, ACE inhibitors, NSAIDs) and who cannot stop the medication;
• Patients who, based on their medical history or in the opinion of the investigator, have chronic idiopathic urticaria, hereditary angioedema, urticaria refractory to antihistamines, or dermatological disease that interferes with evaluation of a therapeutic response;
• Urticaria not associated with an acute allergic reaction;
• Any condition that in the view of the investigator makes the subject unsuitable for enrollment in this study;
• History of HIV or other known immunodeficiency;
• Major medical or psychiatric illness, other than acute urticaria, at the time of presentation;
• Inability to provide informed consent.

Adverse events were collected from time of informed consent through the 24-hour follow-up after discharge (an average of 36 hours)

This was a pilot Phase 3 study, therefore a description of the statistical analyses was not documented in a separate Statistical Analysis Plan, and instead, are described within the content of the protocol and within the CSR.

The adverse event data were collected in a non-systematic fashion, consisting of adverse events documented as observed by the study site staff and captured based on verbal communication (phone call) to the patient during the follow-up period.