Clinical Trial Comparing JDP-205 to Diphenhydramine Injection for the Treatment of Acute Urticaria

Study Overview
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Brief Summary
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This is a multicenter, parallel group, randomized, double-blind, active controlled, Phase III clinical study of cetirizine injection, 10 mg/mL, compared to diphenhydramine injection, 50 mg/mL (Benadryl or generic equivalent) with acute urticaria requiring treatment.

Detailed Description
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This was a multi-center, parallel group, randomized, double-blind, active controlled, Phase III clinical trial of cetirizine injection 10 mg/mL versus diphenhydramine injection 50 mg/mL (Benadryl or generic equivalent) in approximately 256 subjects who either presented to Emergency Departments, hospitals, allergy clinics or Urgent Care Centers with acute urticaria, or developed acute urticaria following allergen challenge at an Allergy Clinic. Patients signed an informed consent and were evaluated for eligibility for inclusion to treat. Eligible subjects were assessed for baseline characteristics, medical and surgical histories, concomitant medications and given a brief physical exam. Subjects were then randomized, in a 1:1 ratio, to blindly receive either cetirizine 10 mg/mL injection or diphenhydramine 50 mg/mL injection. Efficacy assessments included patient-rated severity of pruritus, physician assessments of extent of urticaria/erythema, and sedation score. Subjects remained in the treatment center for at least after the 1 hr assessment, after which they may have been discharged at the physician's discretion. Safety was monitored through the reporting of adverse events for up to 28 days following treatments and by monitoring vital signs at planned intervals from admission into the treating facility until readiness for discharge. After 24 and 48 hrs after discharge, subjects were contacted by phone for follow-up questions regarding recurrence of symptoms, new symptoms, additional medication taken, side effects from medication taken after discharge, relapse requiring a return to treatment center, and return to normal activities.

Official Title
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A Phase III, Multi-center, Double Blind, Randomized, Active Controlled Clinical Trial to Evaluate the Non-Inferiority Comparing Cetirizine Injection 10 mg to Diphenhydramine Injection, 50 mg, for the Treatment of Acute Urticaria

Conditions
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Acute Urticaria

Intervention / Treatment
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* Drug: Test Drug (JDP-205)
* Drug: Active Control (Diphenhydramine)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients with a diagnosis of acute urticaria who need treatment with antihistamine to alleviate their symptoms; 18 years of age or older; Be willing and able to give informed consent; Patients with a Patient rated Pruritus Severity Score ≥ 1 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 2 hours regardless of the route of administration, e.g. diphenhydramine, cetirizine, loratadine, fexofenadine, levocetirizine, desloratadine; Receipt of an H2 antagonist within the past 2 hours; Receipt of doxepin within the past 2 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 4 hours to manage an acute allergic reaction; Receipt of epinephrine (EpiPen or any other brand) within the past 20 minutes; Anaphylaxis prior to the acute anaphylactic symptoms having been treated. Has known allergy to hydroxyzine, cetirizine or levocetirizine, or diphenhydramine; Pregnancy or breastfeeding; Patients who have an acute allergic reaction to medication they are taking (e.g. antibiotics, NSAIDs, etc.) and who cannot stop the medication; Patients who, based on their medical history or in the opinion of the investigator, have chronic urticaria, hereditary angioedema, urticaria refractory to antihistamines, or dermatological disease that interferes with evaluation of a therapeutic response; 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. Patients on concomitant p-glycoprotein inhibitors

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Test Drug<br>JDP-205 Injection, 10 mg/mL, 1 mL | Drug: Test Drug (JDP-205)<br>* Cetirizine, 10mg/mL; a single 1.0 mL injection via intravenous (IV) push over a period of  2 minutes<br>* Other names: QUZYTTIR;|
| Active Comparator: Control<br>Diphenhydramine Injection, 50 mg/mL, 1 mL | Drug: Active Control (Diphenhydramine)<br>* Diphenhydramine Injection, 50 mg/mL;a single 1.0 mL injection via intravenous (IV) push over a period of  2 minutes<br>* Other names: Benadryl;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of Patient Rated Pruritus Score | Change from baseline to 2 hours in patient-rated pruritus Severity score (values at 2 hours minus Baseline) Patient Pruritus Severity Score Ask the patient How severely are your hives itching at the moment? 0 = none = mild (minimal awareness, easily tolerated) = moderate (definite awareness, quite bothersome) = severe (difficult to tolerate) | 2 hr | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients Who Needed to Return to Treatment Center | Number of patients who needed to return to treatment center approximately 24 hours after discharge | up to 24 hrs | 
| Time to Discharge | Time spent (hours) at the treatment center | up to 24 hours | 
| Patient Sedation Scores | Patient Sedation Score at 2 hours Ask the patient How drowsy do you feel at the moment? 0 = None (Not drowsy at all) = Mild (Slightly drowsy) = Moderate (Quite drowsy) = Severe (Extremely drowsy) | 2 hours |