Allergies, Nasal Allergies
Conditions
Keywords
Healthy subjects, Nasal allergies, Allergies, Environmental Exposure Chamber, EEC, Ragweed
Brief summary
The purpose of this study was to determine the maximum tolerated dose of AL-53817 (Stage A) and evaluate the safety and efficacy of AL-53817 for the treatment of allergic rhinitis (Stage B).
Detailed description
Stage A was a 1-day, single ascending dose study utilizing 7 separate cohorts of unique subjects (healthy normal volunteers). Each cohort was administered a different dose of AL-53817 Nasal Spray Solution in order to determine the maximum tolerated dose (MTD). In Stage B, 2 different cohorts of unique, ragweed-sensitive subjects were administered the MTD for up to 5 days twice a day to determine the safety and efficacy of AL-53817 Nasal Spray Solution for the treatment of allergic rhinitis. Subjects were required to meet minimum allergic rhinitis scores at two qualifying EEC visits to participate in the study. Subjects were continually housed in clinic during the 5-day treatment period.
Interventions
DRUGAL-53817 nasal spray solution
Active ingredients administered in 1 of 3 concentrations during Stage A to determine maximum tolerated dose (MTD), and administered at maximum tolerated dose during Stage B.
OTHERVehicle nasal spray
Inactive ingredients used as placebo comparator during Stage A and Stage B.
Sponsors
Alcon Research
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
Stage A Inclusion Criteria: * Willing and able to give written informed consent. * In good health in the opinion of an appropriately qualified physician. * Females of childbearing potential (who are not at least 1 year post-menopausal or surgically sterilized) must have a negative urine pregnancy test at Visit 1, and must not be nursing or plan to become pregnant during the course of the study. * Other protocol-defined inclusion criteria may apply. Stage B Inclusion Criteria: * History of non-recalcitrant seasonal allergic rhinitis during the fall allergy season. * Allergy to short ragweed allergen, defined by positive skin prick test for short ragweed allergen within the 12 months prior to Visit 1. * Be in good health in the opinion of an appropriately qualified physician. * Females of childbearing potential (who are not at least 1 year post-menopausal or surgically sterilized) must have negative urine pregnancy test at Visit 1, and must not be nursing or plan to become pregnant during the course of the study. * Other protocol-defined inclusion criteria may apply. Stage A
Exclusion criteria
* Hypersensitivity to the study drug or any component of the test articles, including benzalkonium chloride. * Using any prescription or non-prescription systemic or topical medications, vitamins or dietary supplements within 14 days prior to the check-in day (except for acetaminophen at doses of \< 2 grams/day or topical, hormonal-oral, implantable or injectable contraceptives). * Current or recent history of severe, unstable, or uncontrolled conditions based upon a review of medical history and/or physical examination. * Any nasal disorder that could preclude safe administration of study medication and/or interfere with the evaluation of the study medication. * History of HIV, hepatitis B or active hepatitis A as determined by medical history and/or by serology at the Screening Visit. * Any screening clinical laboratory result (hematology, serum chemistry or urinalysis) outside the normal range that is clinically relevant in the opinion of an appropriately qualified physician and/or Alcon physician. * Participation in any investigational study within 30 days of entry into this study or concomitantly with this study. * Other protocol-defined
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Adverse Events in Stage A | Day 1 | Adverse events, including serious adverse events and deaths, were reported regardless of test article relationship. |
| Mean Change From Baseline in Nasal Congestion Over a 6-hour Period in the EEC at Day 5 | Baseline (pretreatment), Day 5 | Stage B: Nasal congestion was assessed by the subject before entering the EEC and at 14 timepoints over a 6-hour period after entering the EEC. Nasal congestion was scored on a scale from 0-3, where 0=none and 3=severe. Baseline EEC was conducted up to 21 days prior to the 5-day treatment period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Total Nasal Symptom Scores (TNSS) Over a 6-hour Period in the EEC at Day 5 | Baseline (pretreatment), Day 5 | Stage B: Nasal symptoms were assessed by the subject before entering the EEC and at 14 timepoints over a 6-hour period after entering the EEC. TNSS score (0-12) was a sum of scores for nasal congestion, sneezing, itchy nose, and runny nose scores, each individually assessed on a 0 to 3 scale, where 0=none and 3=severe. Baseline EEC was conducted up to 21 days prior to the 5-day treatment period. |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited from one study center in Canada.
Pre-assignment details
50 healthy volunteers were enrolled in Stage A and subsequently exited from the study. 60 unique patients were enrolled in Stage B.
Participants by arm
| Arm | Count |
|---|---|
| Stage A/Healthy Volunteers AL-53817 nasal spray solution in 1 of 3 concentration doses, 1 or 2 sprays per nostril, OR Vehicle, 1 spray per nostril | 50 |
| Stage B/AL-53817 AL-53817 nasal spray solution, 1 spray per nostril twice a day for 4 days. On Day 5, 1 spray per nostril 60 minutes before entering the EEC. | 40 |
| Stage B/Vehicle Vehicle nasal spray, 1 spray per nostril twice a day for 4 days. On Day 5, 1 spray per nostril 60 minutes before entering the EEC. | 20 |
| Total | 110 |
Baseline characteristics
| Characteristic | Stage A/Healthy Volunteers | Stage B/AL-53817 | Stage B/Vehicle | Total |
|---|---|---|---|---|
| Age, Customized <65 | 49 participants | 39 participants | 20 participants | 108 participants |
| Age, Customized ≥65 | 1 participants | 1 participants | 0 participants | 2 participants |
| Region of Enrollment Canada | 50 participants | 40 participants | 20 participants | 110 participants |
| Sex: Female, Male Female | 25 Participants | 23 Participants | 15 Participants | 63 Participants |
| Sex: Female, Male Male | 25 Participants | 17 Participants | 5 Participants | 47 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 | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 35 | 2 / 15 | 31 / 40 | 5 / 20 |
| serious Total, serious adverse events | 0 / 35 | 0 / 15 | 0 / 40 | 0 / 20 |
Outcome results
Primary
Mean Change From Baseline in Nasal Congestion Over a 6-hour Period in the EEC at Day 5
Stage B: Nasal congestion was assessed by the subject before entering the EEC and at 14 timepoints over a 6-hour period after entering the EEC. Nasal congestion was scored on a scale from 0-3, where 0=none and 3=severe. Baseline EEC was conducted up to 21 days prior to the 5-day treatment period.
Time frame: Baseline (pretreatment), Day 5
Population: Stage B: This reporting group includes all randomized subjects who satisfied inclusion/exclusion criteria and had EEC data at baseline and Day 5, per protocol.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage A/AL-53817 | Mean Change From Baseline in Nasal Congestion Over a 6-hour Period in the EEC at Day 5 | 1 hour | -0.6 Units on a scale | Standard Deviation 0.9 |
| Stage A/AL-53817 | Mean Change From Baseline in Nasal Congestion Over a 6-hour Period in the EEC at Day 5 | 5 hours | -0.7 Units on a scale | Standard Deviation 0.9 |
| Stage A/AL-53817 | Mean Change From Baseline in Nasal Congestion Over a 6-hour Period in the EEC at Day 5 | 0 hour | 0.1 Units on a scale | Standard Deviation 0.7 |
| Stage A/AL-53817 | Mean Change From Baseline in Nasal Congestion Over a 6-hour Period in the EEC at Day 5 | 0.25 hour | -0.1 Units on a scale | Standard Deviation 0.9 |
| Stage A/AL-53817 | Mean Change From Baseline in Nasal Congestion Over a 6-hour Period in the EEC at Day 5 | 0.5 hour | -0.5 Units on a scale | Standard Deviation 0.7 |
| Stage A/AL-53817 | Mean Change From Baseline in Nasal Congestion Over a 6-hour Period in the EEC at Day 5 | 0.75 hour | -0.6 Units on a scale | Standard Deviation 0.7 |
| Stage A/AL-53817 | Mean Change From Baseline in Nasal Congestion Over a 6-hour Period in the EEC at Day 5 | 1.5 hours | -0.8 Units on a scale | Standard Deviation 0.8 |
| Stage A/AL-53817 | Mean Change From Baseline in Nasal Congestion Over a 6-hour Period in the EEC at Day 5 | 2 hours | -0.6 Units on a scale | Standard Deviation 0.9 |
| Stage A/AL-53817 | Mean Change From Baseline in Nasal Congestion Over a 6-hour Period in the EEC at Day 5 | 2.5 hours | -0.7 Units on a scale | Standard Deviation 0.8 |
| Stage A/AL-53817 | Mean Change From Baseline in Nasal Congestion Over a 6-hour Period in the EEC at Day 5 | 3 hours | -0.5 Units on a scale | Standard Deviation 0.8 |
| Stage A/AL-53817 | Mean Change From Baseline in Nasal Congestion Over a 6-hour Period in the EEC at Day 5 | 3.5 hours | -0.7 Units on a scale | Standard Deviation 0.9 |
| Stage A/AL-53817 | Mean Change From Baseline in Nasal Congestion Over a 6-hour Period in the EEC at Day 5 | 4 hours | -0.6 Units on a scale | Standard Deviation 1 |
| Stage A/AL-53817 | Mean Change From Baseline in Nasal Congestion Over a 6-hour Period in the EEC at Day 5 | 4.5 hours | -0.7 Units on a scale | Standard Deviation 0.8 |
| Stage A/AL-53817 | Mean Change From Baseline in Nasal Congestion Over a 6-hour Period in the EEC at Day 5 | 5.5 hours | -0.6 Units on a scale | Standard Deviation 0.9 |
| Stage A/AL-53817 | Mean Change From Baseline in Nasal Congestion Over a 6-hour Period in the EEC at Day 5 | 6 hours | -0.6 Units on a scale | Standard Deviation 0.8 |
| Stage A/Vehicle | Mean Change From Baseline in Nasal Congestion Over a 6-hour Period in the EEC at Day 5 | 3.5 hours | -0.2 Units on a scale | Standard Deviation 0.7 |
| Stage A/Vehicle | Mean Change From Baseline in Nasal Congestion Over a 6-hour Period in the EEC at Day 5 | 4.5 hours | -0.3 Units on a scale | Standard Deviation 0.9 |
| Stage A/Vehicle | Mean Change From Baseline in Nasal Congestion Over a 6-hour Period in the EEC at Day 5 | 2 hours | -0.2 Units on a scale | Standard Deviation 1 |
| Stage A/Vehicle | Mean Change From Baseline in Nasal Congestion Over a 6-hour Period in the EEC at Day 5 | 5 hours | -0.2 Units on a scale | Standard Deviation 1 |
| Stage A/Vehicle | Mean Change From Baseline in Nasal Congestion Over a 6-hour Period in the EEC at Day 5 | 6 hours | -0.2 Units on a scale | Standard Deviation 0.9 |
| Stage A/Vehicle | Mean Change From Baseline in Nasal Congestion Over a 6-hour Period in the EEC at Day 5 | 0 hour | 0.1 Units on a scale | Standard Deviation 0.8 |
| Stage A/Vehicle | Mean Change From Baseline in Nasal Congestion Over a 6-hour Period in the EEC at Day 5 | 2.5 hours | -0.1 Units on a scale | Standard Deviation 0.8 |
| Stage A/Vehicle | Mean Change From Baseline in Nasal Congestion Over a 6-hour Period in the EEC at Day 5 | 0.25 hour | 0.2 Units on a scale | Standard Deviation 0.8 |
| Stage A/Vehicle | Mean Change From Baseline in Nasal Congestion Over a 6-hour Period in the EEC at Day 5 | 4 hours | -0.3 Units on a scale | Standard Deviation 1 |
| Stage A/Vehicle | Mean Change From Baseline in Nasal Congestion Over a 6-hour Period in the EEC at Day 5 | 0.5 hour | -0.1 Units on a scale | Standard Deviation 0.6 |
| Stage A/Vehicle | Mean Change From Baseline in Nasal Congestion Over a 6-hour Period in the EEC at Day 5 | 3 hours | -0.1 Units on a scale | Standard Deviation 1 |
| Stage A/Vehicle | Mean Change From Baseline in Nasal Congestion Over a 6-hour Period in the EEC at Day 5 | 0.75 hour | -0.3 Units on a scale | Standard Deviation 0.7 |
| Stage A/Vehicle | Mean Change From Baseline in Nasal Congestion Over a 6-hour Period in the EEC at Day 5 | 1 hour | -0.3 Units on a scale | Standard Deviation 0.6 |
| Stage A/Vehicle | Mean Change From Baseline in Nasal Congestion Over a 6-hour Period in the EEC at Day 5 | 5.5 hours | -0.2 Units on a scale | Standard Deviation 1 |
| Stage A/Vehicle | Mean Change From Baseline in Nasal Congestion Over a 6-hour Period in the EEC at Day 5 | 1.5 hours | 0.0 Units on a scale | Standard Deviation 1 |
Primary
Number of Adverse Events in Stage A
Adverse events, including serious adverse events and deaths, were reported regardless of test article relationship.
Time frame: Day 1
Population: This reporting group includes all subjects exposed to test article during Stage A.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Stage A/AL-53817 | Number of Adverse Events in Stage A | Adverse events, not including serious | 9 Adverse Events |
| Stage A/AL-53817 | Number of Adverse Events in Stage A | Serious adverse events, not including deaths | 0 Adverse Events |
| Stage A/AL-53817 | Number of Adverse Events in Stage A | Deaths | 0 Adverse Events |
| Stage A/Vehicle | Number of Adverse Events in Stage A | Adverse events, not including serious | 3 Adverse Events |
| Stage A/Vehicle | Number of Adverse Events in Stage A | Serious adverse events, not including deaths | 0 Adverse Events |
| Stage A/Vehicle | Number of Adverse Events in Stage A | Deaths | 0 Adverse Events |
Secondary
Mean Change From Baseline in Total Nasal Symptom Scores (TNSS) Over a 6-hour Period in the EEC at Day 5
Stage B: Nasal symptoms were assessed by the subject before entering the EEC and at 14 timepoints over a 6-hour period after entering the EEC. TNSS score (0-12) was a sum of scores for nasal congestion, sneezing, itchy nose, and runny nose scores, each individually assessed on a 0 to 3 scale, where 0=none and 3=severe. Baseline EEC was conducted up to 21 days prior to the 5-day treatment period.
Time frame: Baseline (pretreatment), Day 5
Population: Stage B: This reporting group includes all randomized subjects who satisfied inclusion/exclusion criteria and had EEC data at baseline and Day 5, per protocol.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage A/AL-53817 | Mean Change From Baseline in Total Nasal Symptom Scores (TNSS) Over a 6-hour Period in the EEC at Day 5 | 0.75 hour | -2.3 Units on a scale | Standard Deviation 2.8 |
| Stage A/AL-53817 | Mean Change From Baseline in Total Nasal Symptom Scores (TNSS) Over a 6-hour Period in the EEC at Day 5 | 3 hours | -2.2 Units on a scale | Standard Deviation 2.9 |
| Stage A/AL-53817 | Mean Change From Baseline in Total Nasal Symptom Scores (TNSS) Over a 6-hour Period in the EEC at Day 5 | 0 hour | -0.3 Units on a scale | Standard Deviation 2.3 |
| Stage A/AL-53817 | Mean Change From Baseline in Total Nasal Symptom Scores (TNSS) Over a 6-hour Period in the EEC at Day 5 | 3.5 hours | -2.9 Units on a scale | Standard Deviation 2.8 |
| Stage A/AL-53817 | Mean Change From Baseline in Total Nasal Symptom Scores (TNSS) Over a 6-hour Period in the EEC at Day 5 | 1 hour | -2.3 Units on a scale | Standard Deviation 3.2 |
| Stage A/AL-53817 | Mean Change From Baseline in Total Nasal Symptom Scores (TNSS) Over a 6-hour Period in the EEC at Day 5 | 4 hours | -2.7 Units on a scale | Standard Deviation 3.1 |
| Stage A/AL-53817 | Mean Change From Baseline in Total Nasal Symptom Scores (TNSS) Over a 6-hour Period in the EEC at Day 5 | 0.5 hour | -1.5 Units on a scale | Standard Deviation 2.5 |
| Stage A/AL-53817 | Mean Change From Baseline in Total Nasal Symptom Scores (TNSS) Over a 6-hour Period in the EEC at Day 5 | 4.5 hours | -2.7 Units on a scale | Standard Deviation 2.6 |
| Stage A/AL-53817 | Mean Change From Baseline in Total Nasal Symptom Scores (TNSS) Over a 6-hour Period in the EEC at Day 5 | 1.5 hour | -3.1 Units on a scale | Standard Deviation 2.9 |
| Stage A/AL-53817 | Mean Change From Baseline in Total Nasal Symptom Scores (TNSS) Over a 6-hour Period in the EEC at Day 5 | 5 hours | -2.7 Units on a scale | Standard Deviation 2.8 |
| Stage A/AL-53817 | Mean Change From Baseline in Total Nasal Symptom Scores (TNSS) Over a 6-hour Period in the EEC at Day 5 | 0.25 hour | -0.7 Units on a scale | Standard Deviation 2.8 |
| Stage A/AL-53817 | Mean Change From Baseline in Total Nasal Symptom Scores (TNSS) Over a 6-hour Period in the EEC at Day 5 | 5.5 hours | -2.7 Units on a scale | Standard Deviation 3.2 |
| Stage A/AL-53817 | Mean Change From Baseline in Total Nasal Symptom Scores (TNSS) Over a 6-hour Period in the EEC at Day 5 | 2 hours | -2.8 Units on a scale | Standard Deviation 3.1 |
| Stage A/AL-53817 | Mean Change From Baseline in Total Nasal Symptom Scores (TNSS) Over a 6-hour Period in the EEC at Day 5 | 6 hours | -2.3 Units on a scale | Standard Deviation 2.7 |
| Stage A/AL-53817 | Mean Change From Baseline in Total Nasal Symptom Scores (TNSS) Over a 6-hour Period in the EEC at Day 5 | 2.5 hours | -2.8 Units on a scale | Standard Deviation 3.2 |
| Stage A/Vehicle | Mean Change From Baseline in Total Nasal Symptom Scores (TNSS) Over a 6-hour Period in the EEC at Day 5 | 6 hours | -1.0 Units on a scale | Standard Deviation 2.8 |
| Stage A/Vehicle | Mean Change From Baseline in Total Nasal Symptom Scores (TNSS) Over a 6-hour Period in the EEC at Day 5 | 0 hour | 0.3 Units on a scale | Standard Deviation 1.7 |
| Stage A/Vehicle | Mean Change From Baseline in Total Nasal Symptom Scores (TNSS) Over a 6-hour Period in the EEC at Day 5 | 0.25 hour | 0.8 Units on a scale | Standard Deviation 2.4 |
| Stage A/Vehicle | Mean Change From Baseline in Total Nasal Symptom Scores (TNSS) Over a 6-hour Period in the EEC at Day 5 | 0.5 hour | 0.1 Units on a scale | Standard Deviation 1.8 |
| Stage A/Vehicle | Mean Change From Baseline in Total Nasal Symptom Scores (TNSS) Over a 6-hour Period in the EEC at Day 5 | 0.75 hour | -0.9 Units on a scale | Standard Deviation 2.5 |
| Stage A/Vehicle | Mean Change From Baseline in Total Nasal Symptom Scores (TNSS) Over a 6-hour Period in the EEC at Day 5 | 1 hour | -1.1 Units on a scale | Standard Deviation 2.5 |
| Stage A/Vehicle | Mean Change From Baseline in Total Nasal Symptom Scores (TNSS) Over a 6-hour Period in the EEC at Day 5 | 1.5 hour | -0.3 Units on a scale | Standard Deviation 3.5 |
| Stage A/Vehicle | Mean Change From Baseline in Total Nasal Symptom Scores (TNSS) Over a 6-hour Period in the EEC at Day 5 | 2.5 hours | -0.8 Units on a scale | Standard Deviation 3.2 |
| Stage A/Vehicle | Mean Change From Baseline in Total Nasal Symptom Scores (TNSS) Over a 6-hour Period in the EEC at Day 5 | 3 hours | -0.5 Units on a scale | Standard Deviation 2.6 |
| Stage A/Vehicle | Mean Change From Baseline in Total Nasal Symptom Scores (TNSS) Over a 6-hour Period in the EEC at Day 5 | 3.5 hours | -0.8 Units on a scale | Standard Deviation 2.9 |
| Stage A/Vehicle | Mean Change From Baseline in Total Nasal Symptom Scores (TNSS) Over a 6-hour Period in the EEC at Day 5 | 4 hours | -1.3 Units on a scale | Standard Deviation 2.6 |
| Stage A/Vehicle | Mean Change From Baseline in Total Nasal Symptom Scores (TNSS) Over a 6-hour Period in the EEC at Day 5 | 4.5 hours | -1.4 Units on a scale | Standard Deviation 3.1 |
| Stage A/Vehicle | Mean Change From Baseline in Total Nasal Symptom Scores (TNSS) Over a 6-hour Period in the EEC at Day 5 | 5 hours | -1.3 Units on a scale | Standard Deviation 2.8 |
| Stage A/Vehicle | Mean Change From Baseline in Total Nasal Symptom Scores (TNSS) Over a 6-hour Period in the EEC at Day 5 | 5.5 hours | -1.4 Units on a scale | Standard Deviation 3.4 |
| Stage A/Vehicle | Mean Change From Baseline in Total Nasal Symptom Scores (TNSS) Over a 6-hour Period in the EEC at Day 5 | 2 hours | -1.3 Units on a scale | Standard Deviation 3.2 |