Allergic Rhinitis
Conditions
Brief summary
Allergen challenge facilities have been utilized for many years in clinical drug trials studying onset of action, proof of concept, duration of action, and efficacy. Each facility has somewhat different design characteristics and pollen dispersal technologies. Facilities are located in disparate geographic areas and have populations of participants who are sensitized to allergens unique to that area. Therefore, facilities have operated as single sites with little effort to evaluate facility comparability or to attempt standardization across facilities. The purpose of this study is to compare the two sites and assess whether the sites are able to achieve similar symptom scores.
Detailed description
When CACF have been designed with a high degree of rigor, quality assurance and validation testing, the exposure to controlled levels of pollen in such facilities as the Environmental Exposure Unit (EEU) and the Biogenics Research Chamber (BRC) will demonstrate comparable/standardized symptomatic responses. This will be demonstrable not only following pollen exposure but will also have similar reductions in symptoms following treatment with a Food and Drug Administration (FDA) approved medication known to be effective for the treatment of seasonal allergic rhinoconjunctivitis ( SAR); cetirizine 10mg. Because of quality assurance and validation testing completed at these facilities a priori, this comparability will be demonstrated despite their disparate geographical physical locations and the utilization of these facilities of somewhat different mechanical and technical materials and methods to achieve similar outcomes. This multi-center study of SAR will enroll 50 participants at each site. These participants will be age 18-65, male and female, with a mixture of ethnic groups. The study will involve 3 Phases: Screening, Treatment Exposure Visit, and a cross-over Treatment Exposure Visit. In all stages, a CACF visit will be pivotal to determine participant eligibility for enrollment and response to therapy. The qualifying participants will receive a double-blinded, placebo-controlled, crossover intervention with cetirizine HCl 10mg. All participants will give written informed consent prior to any study related procedures being performed. Participants who meet all inclusion/exclusion criteria during the screening process will be asked to return to the EEU for their first pollen exposure visit (Treatment Visit #1). At the Screening Visit participants will provide a full medical history and undergo a physical examination. They will have their height/weight and vitals measured and skin testing will be performed to confirm allergic response to a panel of common aeroallergens. Women of child bearing potential will undergo a urine pregnancy test to rule out pregnancy. Eligible participants will be invited back to the research centre for 4 pollen exposure visits at 2 of these visits participants will receive either cetirizine or placebo. All participants will receive placebo at some point throughout the study.
Interventions
DRUGCetirizine
Participants will receive either cetirizine (10mg tablet, orally) or a placebo (sugar pill) at one of the two treatment visits.
OTHERPlacebo
Participants will receive either a placebo or cetirizine (10mg tablet, orally) at one of the two treatment visits
Sponsors
Biogenics Research Chamber, LLC
Queen's University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* history of rhinoconjunctivitis during ragweed season for a minimum of 2 years, including the previous 2 ragweed seasons. * positive skin test to ragweed allergen.
Exclusion criteria
* participant is pregnant, lactating or actively trying to conceive. * has a history of receiving immunotherapy containing short ragweed within the last 3 years. * participant has current allergy symptoms.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Comparison of TRSS From Baseline Between the EEU and BRC in the Cetirizine 10 mg and Placebo Groups. | First treatment visit and second treatment visit. | Participants recorded their nasal and ocular symptoms at baseline and during the intervention visits. The TRSS is a composite score comprised of 4 nasal (runny nose, sneezing, nasal itch, nasal congestion) and 3 ocular (itchy eyes, watery eyes, red/burning eyes) symptoms. The severity of each individual symptom is rated on a 4-point scale (0 to 3) and are summed for a maximum TRSS of 21 (0 to 21).The 4-point scale includes a severity score of 0 (None: no sign/symptom is evident), 1 (Mild: Sign/symptom clearly present, but minimal awareness; easily tolerated), 2 (Moderate: Definite awareness of sign/symptom that is bothersome, but tolerable), 3 (Severe: Sign/symptom that is hard to tolerate; causes interference with activities during the challenge session. A higher score indicates higher symptom severity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Comparison of TNSS From Baseline Between the EEU and BRC in the Cetirizine 10 mg and Placebo Groups. | First treatment visit and second treatment visit. | Participants recorded their nasal and ocular symptoms at baseline and during the intervention visits. The Total Nasal Symptom Score (TNSS) is a composite score comprised of 4 nasal (runny nose, sneezing, nasal itch, nasal congestion) symptoms. The severity of each individual symptom is rated on a 4-point scale (0 to 3) and are summed for a maximum TNSS of 12 (0 to 12) .The 4-point scale includes a severity score of 0 (None: no sign/symptom is evident), 1 (Mild: Sign/symptom clearly present, but minimal awareness; easily tolerated), 2 (Moderate: Definite awareness of sign/symptom that is bothersome, but tolerable), 3 (Severe: Sign/symptom that is hard to tolerate; causes interference with activities during the challenge session. A higher score indicates higher symptom severity. |
| Comparison of TOSS From Baseline Between the EEU and BRC in the Cetirizine 10 mg and Placebo Groups. | First treatment visit and second treatment visit. | Participants recorded their nasal and ocular symptoms at baseline and during the intervention visits. The Total Ocular Symptom Score (TOSS) is a composite score comprised of 3 ocular (itchy eyes, watery eyes, red/burning eyes) symptoms. The severity of each individual symptom is rated on a 4-point scale (0 to 3) and are summed for a maximum TOSS of 9 (0 to 9) .The 4-point scale includes a severity score of 0 (None: no sign/symptom is evident), 1 (Mild: Sign/symptom clearly present, but minimal awareness; easily tolerated), 2 (Moderate: Definite awareness of sign/symptom that is bothersome, but tolerable), 3 (Severe: Sign/symptom that is hard to tolerate; causes interference with activities during the challenge session. A higher score indicates higher symptom severity. |
| Comparison of GRCS From Baseline Between the EEU and BRC in the Cetirizine 10 mg and Placebo Groups. | First treatment visit and second treatment visit. | Participants recorded how they were feeling at baseline and at the end of both treatment visits. The Global Rating of Change Scale documents the changes in the participant's emotions. The scale ranges from +7 (A very great deal better) to -7 (A very great deal worse) with 0 being no change. A higher score indicates a better outcome. |
| Comparison of VAS From Baseline Between the EEU and BRC in the Cetirizine 10 mg and Placebo Groups. | First treatment visit and second treatment visit. | Participants recorded the severity of all nasal and ocular symptoms at baseline and at the end of both treatment visits. The Visual Analogue Scale (VAS) is a single overall rating of the severity of all nasal and ocular symptoms experienced by the participant. The scale ranges from 0 to 100 mm with 0 mm being no symptoms and 100 mm being the worst symptoms the participant has ever felt. |
Countries
Canada, United States
Participant flow
Recruitment details
A total of 149 individuals were screened across both study sites; 78 individuals were screened at the Environmental Exposure Unit in Kingston, Ontario, Canada. 71 individuals were screened at the Biogenics Research Chamber in San Antonio, Texas, USA.
Pre-assignment details
A total of 98 of 149 individuals were randomized (51 individuals for the Environmental Exposure Unit, 47 individuals for the Biogenics Research Chamber). Of those not randomized, 5 did not meet inclusion criteria, and 46 were discontinued prior to randomization due to not meeting eligibility criteria.
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants Includes all participants at the EEU and BRC sites. All participants were randomized to receive both interventions (Cetirizine 10 mg and Placebo). | 98 |
| Total | 98 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Second Priming Visit | Adverse Event | 1 | 0 | 0 | 0 |
| Second Priming Visit | Withdrawal by Subject | 0 | 2 | 2 | 2 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Continuous | 44.2 years STANDARD_DEVIATION 11.8 |
| Race/Ethnicity, Customized Hispanic or Latino | 27 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 71 Participants |
| Sex: Female, Male Female | 57 Participants |
| Sex: Female, Male Male | 41 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 51 | 0 / 47 | 0 / 51 | 0 / 47 |
| other Total, other adverse events | 0 / 51 | 0 / 47 | 0 / 51 | 0 / 47 |
| serious Total, serious adverse events | 0 / 51 | 0 / 47 | 0 / 51 | 0 / 47 |
Outcome results
Primary
Comparison of TRSS From Baseline Between the EEU and BRC in the Cetirizine 10 mg and Placebo Groups.
Participants recorded their nasal and ocular symptoms at baseline and during the intervention visits. The TRSS is a composite score comprised of 4 nasal (runny nose, sneezing, nasal itch, nasal congestion) and 3 ocular (itchy eyes, watery eyes, red/burning eyes) symptoms. The severity of each individual symptom is rated on a 4-point scale (0 to 3) and are summed for a maximum TRSS of 21 (0 to 21).The 4-point scale includes a severity score of 0 (None: no sign/symptom is evident), 1 (Mild: Sign/symptom clearly present, but minimal awareness; easily tolerated), 2 (Moderate: Definite awareness of sign/symptom that is bothersome, but tolerable), 3 (Severe: Sign/symptom that is hard to tolerate; causes interference with activities during the challenge session. A higher score indicates higher symptom severity.
Time frame: First treatment visit and second treatment visit.
Population: Efficacy analyses included all randomized participants who received at least 1 dose of study medication (Cetirizine 10 mg or Placebo).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| EEU Placebo | Comparison of TRSS From Baseline Between the EEU and BRC in the Cetirizine 10 mg and Placebo Groups. | 11.9 score on a scale | Standard Error 0.49 |
| BRC Placebo | Comparison of TRSS From Baseline Between the EEU and BRC in the Cetirizine 10 mg and Placebo Groups. | 11.7 score on a scale | Standard Error 0.51 |
| EEU Cetirizine | Comparison of TRSS From Baseline Between the EEU and BRC in the Cetirizine 10 mg and Placebo Groups. | 11.5 score on a scale | Standard Error 0.49 |
| BRC Cetirizine | Comparison of TRSS From Baseline Between the EEU and BRC in the Cetirizine 10 mg and Placebo Groups. | 10.8 score on a scale | Standard Error 0.52 |
Secondary
Comparison of GRCS From Baseline Between the EEU and BRC in the Cetirizine 10 mg and Placebo Groups.
Participants recorded how they were feeling at baseline and at the end of both treatment visits. The Global Rating of Change Scale documents the changes in the participant's emotions. The scale ranges from +7 (A very great deal better) to -7 (A very great deal worse) with 0 being no change. A higher score indicates a better outcome.
Time frame: First treatment visit and second treatment visit.
Population: Efficacy analyses included all randomized participants who received at least 1 dose of study medication (Cetirizine 10 mg or Placebo).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| EEU Placebo | Comparison of GRCS From Baseline Between the EEU and BRC in the Cetirizine 10 mg and Placebo Groups. | 1.2 score on a scale | Standard Error 0.55 |
| BRC Placebo | Comparison of GRCS From Baseline Between the EEU and BRC in the Cetirizine 10 mg and Placebo Groups. | -0.1 score on a scale | Standard Error 0.57 |
| EEU Cetirizine | Comparison of GRCS From Baseline Between the EEU and BRC in the Cetirizine 10 mg and Placebo Groups. | 1.8 score on a scale | Standard Error 0.55 |
| BRC Cetirizine | Comparison of GRCS From Baseline Between the EEU and BRC in the Cetirizine 10 mg and Placebo Groups. | 0.9 score on a scale | Standard Error 0.58 |
Secondary
Comparison of TNSS From Baseline Between the EEU and BRC in the Cetirizine 10 mg and Placebo Groups.
Participants recorded their nasal and ocular symptoms at baseline and during the intervention visits. The Total Nasal Symptom Score (TNSS) is a composite score comprised of 4 nasal (runny nose, sneezing, nasal itch, nasal congestion) symptoms. The severity of each individual symptom is rated on a 4-point scale (0 to 3) and are summed for a maximum TNSS of 12 (0 to 12) .The 4-point scale includes a severity score of 0 (None: no sign/symptom is evident), 1 (Mild: Sign/symptom clearly present, but minimal awareness; easily tolerated), 2 (Moderate: Definite awareness of sign/symptom that is bothersome, but tolerable), 3 (Severe: Sign/symptom that is hard to tolerate; causes interference with activities during the challenge session. A higher score indicates higher symptom severity.
Time frame: First treatment visit and second treatment visit.
Population: Efficacy analyses included all randomized participants who received at least 1 dose of study medication (Cetirizine 10 mg or Placebo).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| EEU Placebo | Comparison of TNSS From Baseline Between the EEU and BRC in the Cetirizine 10 mg and Placebo Groups. | 7.3 score on a scale | Standard Error 0.3 |
| BRC Placebo | Comparison of TNSS From Baseline Between the EEU and BRC in the Cetirizine 10 mg and Placebo Groups. | 7.5 score on a scale | Standard Error 0.32 |
| EEU Cetirizine | Comparison of TNSS From Baseline Between the EEU and BRC in the Cetirizine 10 mg and Placebo Groups. | 7.1 score on a scale | Standard Error 0.3 |
| BRC Cetirizine | Comparison of TNSS From Baseline Between the EEU and BRC in the Cetirizine 10 mg and Placebo Groups. | 6.9 score on a scale | Standard Error 0.32 |
Secondary
Comparison of TOSS From Baseline Between the EEU and BRC in the Cetirizine 10 mg and Placebo Groups.
Participants recorded their nasal and ocular symptoms at baseline and during the intervention visits. The Total Ocular Symptom Score (TOSS) is a composite score comprised of 3 ocular (itchy eyes, watery eyes, red/burning eyes) symptoms. The severity of each individual symptom is rated on a 4-point scale (0 to 3) and are summed for a maximum TOSS of 9 (0 to 9) .The 4-point scale includes a severity score of 0 (None: no sign/symptom is evident), 1 (Mild: Sign/symptom clearly present, but minimal awareness; easily tolerated), 2 (Moderate: Definite awareness of sign/symptom that is bothersome, but tolerable), 3 (Severe: Sign/symptom that is hard to tolerate; causes interference with activities during the challenge session. A higher score indicates higher symptom severity.
Time frame: First treatment visit and second treatment visit.
Population: Efficacy analyses included all randomized participants who received at least 1 dose of study medication (Cetirizine 10 mg or Placebo).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| EEU Placebo | Comparison of TOSS From Baseline Between the EEU and BRC in the Cetirizine 10 mg and Placebo Groups. | 4.6 score on a scale | Standard Error 0.23 |
| BRC Placebo | Comparison of TOSS From Baseline Between the EEU and BRC in the Cetirizine 10 mg and Placebo Groups. | 4.2 score on a scale | Standard Error 0.24 |
| EEU Cetirizine | Comparison of TOSS From Baseline Between the EEU and BRC in the Cetirizine 10 mg and Placebo Groups. | 4.4 score on a scale | Standard Error 0.23 |
| BRC Cetirizine | Comparison of TOSS From Baseline Between the EEU and BRC in the Cetirizine 10 mg and Placebo Groups. | 3.9 score on a scale | Standard Error 0.24 |
Secondary
Comparison of VAS From Baseline Between the EEU and BRC in the Cetirizine 10 mg and Placebo Groups.
Participants recorded the severity of all nasal and ocular symptoms at baseline and at the end of both treatment visits. The Visual Analogue Scale (VAS) is a single overall rating of the severity of all nasal and ocular symptoms experienced by the participant. The scale ranges from 0 to 100 mm with 0 mm being no symptoms and 100 mm being the worst symptoms the participant has ever felt.
Time frame: First treatment visit and second treatment visit.
Population: Efficacy analyses included all randomized participants who received at least 1 dose of study medication (Cetirizine 10 mg or Placebo).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| EEU Placebo | Comparison of VAS From Baseline Between the EEU and BRC in the Cetirizine 10 mg and Placebo Groups. | 52.7 units on a scale | Standard Error 3.98 |
| BRC Placebo | Comparison of VAS From Baseline Between the EEU and BRC in the Cetirizine 10 mg and Placebo Groups. | 47.7 units on a scale | Standard Error 4.18 |
| EEU Cetirizine | Comparison of VAS From Baseline Between the EEU and BRC in the Cetirizine 10 mg and Placebo Groups. | 45.3 units on a scale | Standard Error 4 |
| BRC Cetirizine | Comparison of VAS From Baseline Between the EEU and BRC in the Cetirizine 10 mg and Placebo Groups. | 44.1 units on a scale | Standard Error 4.19 |