Acute Urticaria
Conditions
Keywords
urticaria, allergic reaction, cetirizine, JDP-205
Brief summary
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.
Detailed description
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.
Interventions
DRUGJDP-205 Injection
Cetirizine, 10mg/mL; a single 1.0 mL injection via intravenous (IV) push over a period of \ 2 minutes
DRUGDiphenhydramine
Diphenhydramine Injection, 50 mg/mL; a single 1.0 mL injection via intravenous (IV) push over a period of \ 2 minutes
Sponsors
JDP Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Extent of Urticaria/Erythema Score (Physician Assessment) | Baseline, 1 hour, 2 hour, Discharge (up to 4 hours) | Extent of Urticaria/Erythema Score (Physician Assessment), capturing extent of urticaria/erythema, using the Body Chart (adopted from Burn Chart). Extent of Urticaria/Erythema Score is the average of the 2 scores: 1. Percentage of body area using the body chart (adopted from burn Chart) 0 = none, 1= mild (,25% body coverage), 2 = moderate (25-50% body coverage, 3 = Severe/intense .50% body coverage 2. Intensity of redness (adopted from PASI) 0 = none, 1 = mile (light pink) 2= moderate (pink), 3 =severe/intense (red) |
| Physician Pruritus Severity Score | Baseline, 1 hour, 2 hour, discharge or up to 4 hours post intervention, whichever came first | Physician Pruritus Severity Score based on patient expression of severity of itchiness. 0= none 1 = Mild (patient expresses itchiness but tolerable, and does not scratch 2= moderate definite awareness, bothersome, intermittently scratch affected area 3= severe difficult to tolerate scratch vigorously |
| Patient Pruritis Severity Score | Baseline, 1 hour, 2 hour, discharge or up to 4 hours post intervention, whichever came first | Patient Pruritis Severity Score based on severity of itching at time of assessment. How severly are your hives itching at the moment? 0 = none 1= mild minimal awareness easily tolerated 2 = moderate definite awareness quite bothersome 3= severe difficult to tolerate |
| Composite Acute Urticaria Score Change From Baseline | Baseline, 1 hour, 2 hour, Discharge (an average of 1 day) | A composite acute urticaria score, the sum of Extent of urticaria/erythema score (Physician), Physician pruritis score and Patient pruritis severity score. A composite acute urticaria score which the sum of the above three parameters (i.e. 0-9) was calculated post hoc for each patient at each time point and then their score change from the baseline were compared between the two treatment groups. Higher values indicate a worse outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients Requiring Additional Medication | Baseline, 1 hour, 2 hour, Discharge (an average of 1 day) | Percentage of Patients Requiring Additional Medication (Rescue Medication) |
| Sedation Scores and Time to Readiness for Discharge HH:MM | Assessed at discharge or up to 4 hours post intervention, whichever came first data at discharge reported. | Time from study drug injection to time to readiness for discharge based on Physician and Patient Sedation Scores Physician Sedation Score: 0 = None 1 = Mild 2 = Moderate 3= Severe 4 = Extremely Severe Patient Sedation Score 0= None 1- Mild 2 = Moderate 3= Severe 4 = Extremely Severe Higher scores = worse outcome |
| Sedation Scores and Time to Readiness for Discharge | Assessed at discharge or up to 4 hours post intervention, whichever came first data at discharge reported. | Time from study drug injection to time to readiness for discharge based on composite sedation score at readiness for discharge consist of Physician Sedation Score and Patient Sedation Score Physician Sedation Score Score ranged from 0 to 4 (0=min, 4=max) 0 = None (Patient is completely alert. Does not look tired at all), 1 = Mild (Patient sitting/lying comfortably, and looks tired), 2 = Moderate (Drowsy, with occasional eyes closing), 3 = Severe (Asleep, with eyes closed but responds to minor motor stimulation), 4 = Extremely Severe (Asleep; does not respond to minor motor stimulation) Patient Sedation Score Score ranged from 0 to 4 (0=min, 4=max) 0 = None (Not drowsy at all), 1 = Mild (Slightly drowsy), 2 = Moderate (Quite drowsy), 3 = Severe (Extremely drowsy), 4 = Extremely Severe (Asleep, cannot self-rate) Higher the sedation score = worse outcome A composite sedation score which is the sum of the two parameters. |
Countries
Canada, United States
Participant flow
Recruitment details
Recruitment of patients who either present to Hospital Emergency Departments, allergy clinics or Urgent Care Centers with acute urticaria, or develop acute urticaria following allergen challenge at an Allergy Clinic.
Participants by arm
| Arm | Count |
|---|---|
| Test Drug 10 mg/mL, 1 mL
JDP-205 Injection | 16 |
| Control 50 mg/mL, 1 mL
Diphenhydramine | 17 |
| Total | 33 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| 24-Hour Follow-Up | Lost to Follow-up | 0 | 2 |
Baseline characteristics
| Characteristic | Test Drug | Control | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 0 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants | 17 Participants | 32 Participants |
| Age, Continuous | 36 Years STANDARD_DEVIATION 17 | 39 Years STANDARD_DEVIATION 14 | 37 Years STANDARD_DEVIATION 15 |
| Region of Enrollment Canada | 9 participants | 10 participants | 19 participants |
| Region of Enrollment United States | 7 participants | 7 participants | 14 participants |
| Sex: Female, Male Female | 6 Participants | 9 Participants | 15 Participants |
| Sex: Female, Male Male | 10 Participants | 8 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 17 |
| other Total, other adverse events | 14 / 16 | 12 / 17 |
| serious Total, serious adverse events | 0 / 16 | 0 / 17 |
Outcome results
Primary
Composite Acute Urticaria Score Change From Baseline
A composite acute urticaria score, the sum of Extent of urticaria/erythema score (Physician), Physician pruritis score and Patient pruritis severity score. A composite acute urticaria score which the sum of the above three parameters (i.e. 0-9) was calculated post hoc for each patient at each time point and then their score change from the baseline were compared between the two treatment groups. Higher values indicate a worse outcome.
Time frame: Baseline, 1 hour, 2 hour, Discharge (an average of 1 day)
Population: 33 subjects (100%) completed the following treatment assessments for 1 hour and Discharge 2 hour assessment: 9 participants in the Test Drug Arm/Group and 10 participants in the Control Arm/Group). Some subjects were discharged prior to the 2-hour assessment, resulting in the reduced N at 2 hours.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Test Drug | Composite Acute Urticaria Score Change From Baseline | 1-Hour Assessment | -3.13 score on a scale | Standard Deviation 1.41 |
| Test Drug | Composite Acute Urticaria Score Change From Baseline | 2-Hour Assessment | -4.28 score on a scale | Standard Deviation 1.12 |
| Test Drug | Composite Acute Urticaria Score Change From Baseline | Discharge Assessment | -3.81 score on a scale | Standard Deviation 1.12 |
| Control | Composite Acute Urticaria Score Change From Baseline | 1-Hour Assessment | -3.26 score on a scale | Standard Deviation 2.1 |
| Control | Composite Acute Urticaria Score Change From Baseline | 2-Hour Assessment | -3.65 score on a scale | Standard Deviation 2.21 |
| Control | Composite Acute Urticaria Score Change From Baseline | Discharge Assessment | -3.82 score on a scale | Standard Deviation 2.28 |
Primary
Extent of Urticaria/Erythema Score (Physician Assessment)
Extent of Urticaria/Erythema Score (Physician Assessment), capturing extent of urticaria/erythema, using the Body Chart (adopted from Burn Chart). Extent of Urticaria/Erythema Score is the average of the 2 scores: 1. Percentage of body area using the body chart (adopted from burn Chart) 0 = none, 1= mild (,25% body coverage), 2 = moderate (25-50% body coverage, 3 = Severe/intense .50% body coverage 2. Intensity of redness (adopted from PASI) 0 = none, 1 = mile (light pink) 2= moderate (pink), 3 =severe/intense (red)
Time frame: Baseline, 1 hour, 2 hour, Discharge (up to 4 hours)
Population: Extent of Urticaria/Erythema (Physician Score) 0 = none, 1= mild (patient expresses itchiness, but tolerable and does not scratch, 2 = moderate definite awareness, bothersome, intermittently scratch affected area, 3 = severe difficult to tolerate, scratch vigorously
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Test Drug | Extent of Urticaria/Erythema Score (Physician Assessment) | 1 Hour | 1.53 units on a scale | Standard Deviation 0.74 |
| Test Drug | Extent of Urticaria/Erythema Score (Physician Assessment) | Baseline | 1.91 units on a scale | Standard Deviation 0.61 |
| Test Drug | Extent of Urticaria/Erythema Score (Physician Assessment) | 2 Hour | 0.89 units on a scale | Standard Deviation 0.6 |
| Test Drug | Extent of Urticaria/Erythema Score (Physician Assessment) | Discharge | 1.09 units on a scale | Standard Deviation 0.55 |
| Control | Extent of Urticaria/Erythema Score (Physician Assessment) | Discharge | 0.97 units on a scale | Standard Deviation 0.94 |
| Control | Extent of Urticaria/Erythema Score (Physician Assessment) | 2 Hour | 1.35 units on a scale | Standard Deviation 1.03 |
| Control | Extent of Urticaria/Erythema Score (Physician Assessment) | Baseline | 1.74 units on a scale | Standard Deviation 0.89 |
| Control | Extent of Urticaria/Erythema Score (Physician Assessment) | 1 Hour | 1.12 units on a scale | Standard Deviation 1.05 |
Primary
Patient Pruritis Severity Score
Patient Pruritis Severity Score based on severity of itching at time of assessment. How severly are your hives itching at the moment? 0 = none 1= mild minimal awareness easily tolerated 2 = moderate definite awareness quite bothersome 3= severe difficult to tolerate
Time frame: Baseline, 1 hour, 2 hour, discharge or up to 4 hours post intervention, whichever came first
Population: Patient Pruritis Severity Score Some subjects were discharged prior to the 2-hour assessment, resulting in the reduced N at 2 hours.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Test Drug | Patient Pruritis Severity Score | Baseline | 2.19 score on a scale | Standard Deviation 0.66 |
| Test Drug | Patient Pruritis Severity Score | 2 Hour | 0.56 score on a scale | Standard Deviation 0.53 |
| Test Drug | Patient Pruritis Severity Score | Discharge | 0.50 score on a scale | Standard Deviation 0.52 |
| Test Drug | Patient Pruritis Severity Score | 1 Hour | 0.56 score on a scale | Standard Deviation 0.63 |
| Control | Patient Pruritis Severity Score | Discharge | 0.59 score on a scale | Standard Deviation 1.06 |
| Control | Patient Pruritis Severity Score | Baseline | 2.24 score on a scale | Standard Deviation 1.03 |
| Control | Patient Pruritis Severity Score | 1 Hour | 0.82 score on a scale | Standard Deviation 1.01 |
| Control | Patient Pruritis Severity Score | 2 Hour | 0.90 score on a scale | Standard Deviation 1.29 |
Primary
Physician Pruritus Severity Score
Physician Pruritus Severity Score based on patient expression of severity of itchiness. 0= none 1 = Mild (patient expresses itchiness but tolerable, and does not scratch 2= moderate definite awareness, bothersome, intermittently scratch affected area 3= severe difficult to tolerate scratch vigorously
Time frame: Baseline, 1 hour, 2 hour, discharge or up to 4 hours post intervention, whichever came first
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Test Drug | Physician Pruritus Severity Score | 2 hour Assessment | 1.0 score on a scale |
| Test Drug | Physician Pruritus Severity Score | Baseline Assessment | 2. score on a scale |
| Test Drug | Physician Pruritus Severity Score | 1 hour Assessment | 1.0 score on a scale |
| Test Drug | Physician Pruritus Severity Score | Discharge Assessment | 1.0 score on a scale |
| Control | Physician Pruritus Severity Score | Discharge Assessment | 0.0 score on a scale |
| Control | Physician Pruritus Severity Score | 2 hour Assessment | 1.0 score on a scale |
| Control | Physician Pruritus Severity Score | 1 hour Assessment | 1. score on a scale |
| Control | Physician Pruritus Severity Score | Baseline Assessment | 2.00 score on a scale |
Secondary
Percentage of Patients Requiring Additional Medication
Percentage of Patients Requiring Additional Medication (Rescue Medication)
Time frame: Baseline, 1 hour, 2 hour, Discharge (an average of 1 day)
Population: Subjects who required additional medication. Rescue medication defined as epinephrine, bronchodilators, and steroids usage.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Test Drug | Percentage of Patients Requiring Additional Medication | Rescue Required at Discharge ]Reported by HCP | 1 Participants |
| Test Drug | Percentage of Patients Requiring Additional Medication | Additional Rescue Required 24 Hours After Discharged as Reported by Patient | 10 Participants |
| Control | Percentage of Patients Requiring Additional Medication | Rescue Required at Discharge ]Reported by HCP | 2 Participants |
| Control | Percentage of Patients Requiring Additional Medication | Additional Rescue Required 24 Hours After Discharged as Reported by Patient | 13 Participants |
Secondary
Sedation Scores and Time to Readiness for Discharge
Time from study drug injection to time to readiness for discharge based on composite sedation score at readiness for discharge consist of Physician Sedation Score and Patient Sedation Score Physician Sedation Score Score ranged from 0 to 4 (0=min, 4=max) 0 = None (Patient is completely alert. Does not look tired at all), 1 = Mild (Patient sitting/lying comfortably, and looks tired), 2 = Moderate (Drowsy, with occasional eyes closing), 3 = Severe (Asleep, with eyes closed but responds to minor motor stimulation), 4 = Extremely Severe (Asleep; does not respond to minor motor stimulation) Patient Sedation Score Score ranged from 0 to 4 (0=min, 4=max) 0 = None (Not drowsy at all), 1 = Mild (Slightly drowsy), 2 = Moderate (Quite drowsy), 3 = Severe (Extremely drowsy), 4 = Extremely Severe (Asleep, cannot self-rate) Higher the sedation score = worse outcome A composite sedation score which is the sum of the two parameters.
Time frame: Assessed at discharge or up to 4 hours post intervention, whichever came first data at discharge reported.
Population: A summary of treatment effectiveness as evaluated by the investigators at time of discharge.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Test Drug | Sedation Scores and Time to Readiness for Discharge | Physician sedation score at Readiness for Discharge | 0.19 score on a scale | Standard Deviation 0.4 |
| Test Drug | Sedation Scores and Time to Readiness for Discharge | Patient sedation score at Readiness for Discharge | 0.25 score on a scale | Standard Deviation 0.45 |
| Test Drug | Sedation Scores and Time to Readiness for Discharge | Composite sedation score at Readiness for Discharge | 0.44 score on a scale | Standard Deviation 0.81 |
| Control | Sedation Scores and Time to Readiness for Discharge | Physician sedation score at Readiness for Discharge | 0.35 score on a scale | Standard Deviation 0.49 |
| Control | Sedation Scores and Time to Readiness for Discharge | Patient sedation score at Readiness for Discharge | 0.71 score on a scale | Standard Deviation 0.69 |
| Control | Sedation Scores and Time to Readiness for Discharge | Composite sedation score at Readiness for Discharge | 1.06 score on a scale | Standard Deviation 0.97 |
Secondary
Sedation Scores and Time to Readiness for Discharge HH:MM
Time from study drug injection to time to readiness for discharge based on Physician and Patient Sedation Scores Physician Sedation Score: 0 = None 1 = Mild 2 = Moderate 3= Severe 4 = Extremely Severe Patient Sedation Score 0= None 1- Mild 2 = Moderate 3= Severe 4 = Extremely Severe Higher scores = worse outcome
Time frame: Assessed at discharge or up to 4 hours post intervention, whichever came first data at discharge reported.
Population: A summary of treatment effectiveness as evaluated by the investigators at time of discharge.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test Drug | Sedation Scores and Time to Readiness for Discharge HH:MM | 1.65 Hours | Standard Deviation 0.53 |
| Control | Sedation Scores and Time to Readiness for Discharge HH:MM | 2.23 Hours | Standard Deviation 1.2 |