Acute Urticaria
Conditions
Brief summary
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
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.
Interventions
DRUGTest Drug (JDP-205)
Cetirizine, 10mg/mL; a single 1.0 mL injection via intravenous (IV) push over a period of \ 2 minutes
DRUGActive Control (Diphenhydramine)
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
1. Male or female patients with a diagnosis of acute urticaria who need treatment with antihistamine to alleviate their symptoms; 2. 18 years of age or older; 3. Be willing and able to give informed consent; 4. Patients with a Patient rated Pruritus Severity Score ≥ 1
Exclusion criteria
1. Receipt of an investigational drug or device, within the past 30 days; 2. Patients in whom an antihistamine may be contraindicated (e.g. narrow angle glaucoma, symptomatic prostatic hypertrophy); 3. Patients who, in the opinion of the investigator, may not tolerate an IV injection of diphenhydramine 50 mg, or cetirizine 10 mg; 4. 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; 5. Receipt of an H2 antagonist within the past 2 hours; 6. Receipt of doxepin within the past 2 hours; doxepin is an antidepressant, but it also has antihistamine properties; 7. Receipt of steroids by the oral, IV, IM, or inhalational routes route within the past 4 hours to manage an acute allergic reaction; 8. Receipt of epinephrine (EpiPen or any other brand) within the past 20 minutes; 9. Anaphylaxis prior to the acute anaphylactic symptoms having been treated. 10. Has known allergy to hydroxyzine, cetirizine or levocetirizine, or diphenhydramine; 11. Pregnancy or breastfeeding; 12. Patients who have an acute allergic reaction to medication they are taking (e.g. antibiotics, NSAIDs, etc.) and who cannot stop the medication; 13. 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; 14. Any condition that in the view of the investigator makes the subject unsuitable for enrollment in this study; 15. History of HIV or other known immunodeficiency; 16. Major medical or psychiatric illness, other than acute urticaria, at the time of presentation; 17. Inability to provide informed consent. 18. Patients on concomitant p-glycoprotein inhibitors
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change of Patient Rated Pruritus Score | 2 hr | 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 1. = mild (minimal awareness, easily tolerated) 2. = moderate (definite awareness, quite bothersome) 3. = severe (difficult to tolerate) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Who Needed to Return to Treatment Center | up to 24 hrs | Number of patients who needed to return to treatment center approximately 24 hours after discharge |
| Time to Discharge | up to 24 hours | Time spent (hours) at the treatment center |
| Patient Sedation Scores | 2 hours | Patient Sedation Score at 2 hours Ask the patient How drowsy do you feel at the moment? 0 = None (Not drowsy at all) 1. = Mild (Slightly drowsy) 2. = Moderate (Quite drowsy) 3. = Severe (Extremely drowsy) |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Test Drug JDP-205 Injection, 10 mg/mL, 1 mL
Test Drug (JDP-205): JDP-205 Injection, 10 mg/mL, 1 mL | 127 |
| Control Diphenhydramine Injection, 50 mg/mL, 1 mL
Active Control (Diphenhydramine): Diphenhydramine Injection, 50 mg/mL | 135 |
| Total | 262 |
Baseline characteristics
| Characteristic | Test Drug | Total | Control |
|---|---|---|---|
| Age, Continuous | 39.0 years STANDARD_DEVIATION 16.28 | 39.1 years STANDARD_DEVIATION 16.08 | 39.2 years STANDARD_DEVIATION 15.96 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 9 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 41 Participants | 85 Participants | 44 Participants |
| Race (NIH/OMB) More than one race | 17 Participants | 41 Participants | 24 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 64 Participants | 126 Participants | 62 Participants |
| Region of Enrollment United States | 127 participants | 262 participants | 135 participants |
| Sex: Female, Male Female | 77 Participants | 165 Participants | 88 Participants |
| Sex: Female, Male Male | 50 Participants | 97 Participants | 47 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 127 | 0 / 135 |
| other Total, other adverse events | 5 / 127 | 18 / 135 |
| serious Total, serious adverse events | 0 / 127 | 1 / 135 |
Outcome results
Primary
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 1. = mild (minimal awareness, easily tolerated) 2. = moderate (definite awareness, quite bothersome) 3. = severe (difficult to tolerate)
Time frame: 2 hr
Population: Intent To Treat population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test Drug | Change of Patient Rated Pruritus Score | -1.61 score on a scale | Standard Deviation 0.944 |
| Control | Change of Patient Rated Pruritus Score | -1.50 score on a scale | Standard Deviation 0.984 |
Secondary
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
Time frame: up to 24 hrs
Population: Intent To Treat Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Test Drug | Number of Patients Who Needed to Return to Treatment Center | 7 Participants |
| Control | Number of Patients Who Needed to Return to Treatment Center | 19 Participants |
Secondary
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) 1. = Mild (Slightly drowsy) 2. = Moderate (Quite drowsy) 3. = Severe (Extremely drowsy)
Time frame: 2 hours
Population: Intent To Treat Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test Drug | Patient Sedation Scores | 0.46 score on a scale | Standard Deviation 0.721 |
| Control | Patient Sedation Scores | 0.88 score on a scale | Standard Deviation 0.955 |
Secondary
Time to Discharge
Time spent (hours) at the treatment center
Time frame: up to 24 hours
Population: Intent To Treat Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test Drug | Time to Discharge | 1.71 hours | Standard Deviation 0.868 |
| Control | Time to Discharge | 2.07 hours | Standard Deviation 1.112 |