Allergic Rhinitis, Rhinitis, Allergic, Perennial
Conditions
Keywords
fluticasone propionate, Vienna Challenge Chamber, glucocorticosteroids, allergic rhinitis
Brief summary
This is a single-centre, randomised, double-blind, four-period, incomplete block, crossover study, with 8 days repeat dosing of intranasal Fluticasone Propionate (25, 50, 100, 200ug) and/or placebo in the Vienna Challenge Chamber in subjects with allergic rhinitis.
Interventions
DRUGFluticasone propionate
Corticosteriod, with anti-inflammatory effects
DRUGPlacebo
Placebo comparator
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* The subject is healthy with the exception of seasonal allergic rhinitis. Healthy as determined by a responsible physician, based on a medical evaluation including history, physical examination, laboratory tests, cardiac monitoring. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator considers that the finding will not introduce additional risk factors and will not interfere with the study procedures. * Males and females who are aged between 18 and 65 years of age. A female is eligible to enter and participate in the study if she is of: 1. Non-childbearing potential (i.e., physiologically incapable of becoming pregnant), including any female who is post menopausal. For the purposes of this study, post menopausal is defined as 1 year without menses (FSH/LH will be also tested to confirm menopausal status); or 2. Child bearing potential, has a negative pregnancy test (urine) at entry, and agrees to one of the following acceptable contraceptive methods when used consistently and correctly (i.e., in accordance with the approved product label and the instructions of a physician for the duration of the study - screening visit to follow-up contact): * Complete abstinence from intercourse from the first visit, throughout the trial and for a minimum of 7 days after the completion of the trial; or * Male partner was sterile prior to the female subject's entry into the study, or * Implants of levonorgestrel inserted for at least 1 month prior to the study * Injectable progestogen administered for at least 1 month prior to the study * Oral contraceptive (combined or progestogen only) administered for a least one monthly cycle prior to study medication administration; or * The contraceptive transdermal patch, such as norelgestromin / ethinyl estradiol transdermal system (if the subject is less than 89kg); or * Double-barrier method - spermicide plus a mechanical barrier (e.g., spermicide plus a male condom or a spermicide and female diaphragm . * Condom and occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository; or * An intrauterine device (IUD) or intrauterine system (IUS), inserted by a qualified physician, * Subjects who are current non-smokers, who have not used any inhaled tobacco products (snuff is permitted) in the 12 month period preceding the screening visit and who have a pack history of less than 10 pack years. Pack years = Number of cigarettes per day x Number of years smoked 20 * They exhibit a moderate response to up to 1500 grass pollen grains/m3 after 2 hours in the Vienna Challenge Chamber, which is defined as a nasal symptom score of at least 6. (Nasal symptom score is the sum of nasal obstruction, rhinorrhoea, nasal itch and sneeze, each of which are scored on a scale from 0 to 3) * They have a positive skin prick test (wheal ³ 4mm) for grass pollen at or within the 12 months preceding the screening visit. * They have a positive RAST (Radioallergosorbent Test) (³ class 2) for grass pollen at or within the 12 months preceding the screening visit. * They have a TNSS score (Total Nasal Symptom Score)of less than 3 and a score of no more than 1 for any single symptom of the TNSS prior to the screening allergen challenge. * There are no conditions or factors that would make the subject unlikely to be able to stay in the trial * Able to provide written informed consent. * The subject is able to understand and comply with the protocol requirements, instructions and protocol-stated restrictions. * Demonstrated ability to use the intranasal device in a satisfactory and repeatable manner.
Exclusion criteria
* As a result of medical interview, physical examination or screening investigations, the principle investigator or delegate physician deems the subject unsuitable for the study. Subjects must not have a systolic blood pressure above 150 mmHg or a diastolic pressure above 90 mmHg unless the Investigator confirms that it is satisfactory for their age. * The subject has been treated for or diagnosed with depression within six months of screening or has a history of significant psychiatric illness. * Pregnant or nursing females. * Women of childbearing potential who are unwilling or unable to use an appropriate method of contraception as outlined (Inclusion Criteria 2) * On examination the subject is found to have any structural nasal abnormalities or nasal polyposis, a history of frequent nosebleeds, recent nasal surgery or recent (within 2 weeks) or ongoing upper respiratory tract infection which in the Responsible Physician's opinion renders the subject unsuitable for participation in the study. * Any respiratory disease other than mild stable asthma that is controlled with occasional use of as-needed short-acting beta-agonists and associated with normal lung function. * The subject is likely to be unable to abstain from salbutamol use for 8 hours before a challenge. * The subject has a screening QTcB value \>450msec (based on single or average QTc value of triplicate ECGs obtained over a brief recording period), PQ interval outside the range 120 to 200msec or an ECG that is not suitable for QT measurements (e.g. poorly defined termination of the T-wave). In addition subjects will be excluded if they have a history of atrial or ventricular arrhythmia. * The subject has a history of drug or other allergy that, in the opinion of the physician responsible, contraindicates their participation. * History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the physician responsible, contraindicates their participation. * The subject has taken prescription or non-prescription drugs, within 7 days prior to the first dose of study medication, unless in the opinion of the Investigator and Sponsor the medication will not interfere with the study procedures or compromise subject safety. * History of alcohol/drug abuse or dependence within 12 months of the study. Abuse of alcohol defined as an average weekly intake of greater than 21 units or an average daily intake of greater than 3 units (males) or defined as an average weekly intake of greater than 14 units or an average daily intake of greater than 2 units (females). 1 unit is equivalent to a half-pint (220mL) of beer or 1 (25ml) measure of spirits or 1 glass (125ml) of wine). * The subject has participated in a clinical trial and has received a drug or a new chemical entity within 30 days or 5 half-lives, or twice the duration of the biological effect of any drug (whichever is longer) prior to the first dose of current study medication. * Exposure to more than four new chemical entities within 12 months prior to the first dosing day. * The subject has donated a unit of blood (450 mL) within the previous 16 weeks or intends to donate within 16 weeks after completing the study. * A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening. * The subject has tested positive for HIV antibodies (if tested according to site Standard Operating Procedures). * The subject has a positive pre-study urine drug/ urine alcohol screen. A minimum list of drugs that will be screened for include Amphetamines, Barbiturates, Cocaine, Opiates, Cannabinoids (THC) and Benzodiazepines.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Weighted Mean Total Nasal Symptom Score (TNSS) at 2-5 Hours Post-dose (1-4 Hours Post-start of Challenge [PSC]) in the Vienna Challenge Chamber (VCC) | Day 8 of each study period (Periods 1-4); up to Day 158 | The TNSS (score of 0-12), defined as the sum of the symptom scores for nasal obstruction, rhinorrhea, nasal itch, and sneeze (each scored on 0-3 scale \[0=none, 1=mild, 2=moderate, 3=severe\]) was measured at pre-challenge, and then every 15 minutes from 0.25 to 4 hours PSC. In the VCC, aerosolized allergen is administered in a sealed chamber to evaluate the efficacy of antihistamines/other treatments. Weighted mean TNSS was calculated by dividing the value of the area under the response time curve between 1 and 4 hours (calculated by trapezoidal rule) by the time interval of available data. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Weighted Mean Nasal Secretion at 2-5 Hours Post-dose (1-4 Hours Post-start of Challenge) | Day 8 of each study period (Periods 1-4); up to Day 158 | Nasal secretion was measured by weighing tissues used by participants. Wet tissue weight assessments were made pre-challenge, and then every 30 minutes from 0.5 to 4 hours post start of challenge chamber throughout the study. Weighted mean nasal secretion was calculated by dividing the value of the area under the response time curve between 1 and 4 hours (calculated by trapezoidal rule) by the time interval of available data. |
| Weighted Mean Eye Symptom Score at 2-5 Hours Post-dose (1-4 Hours Post-start of Challenge) | Day 8 of each study period (Periods 1-4); up to Day 158 | The eye symptom score (total score of 0 \[none\] to 9 \[severe\]) was calculated as the sum of the symptom scores for watery eyes, itchy eyes, and red eyes, each of which was scored on a categorical scale from 0 to 3 (0=none, 1=mild, 2=moderate, 3=severe), and was measured at pre-challenge, and then every 15 minutes from 0.25 to 4 hours post-start of challenge chamber. Weighted mean eye symptom score was calculated by dividing the value of the area under the response time curve between 1 and 4 hours (calculated by trapezoidal rule) by the time interval of available data. |
| Weighted Mean Nasal Airflow at 2-5 Hours Post-dose (1-4 Hours Post-start of Challenge) | Day 8 of each study period (Periods 1-4); up to Day 158 | Allergic rhinitis decreases the passage of air through the nose (nasal airflow) by increasing the nasal airway resistance. Rhinomanometry is used as an objective measurement of airway resistance. Nasal airflow was measured using active anterior rhinomanometry at pre-challenge, and then every 30 minutes from 0.5 to 4 hours post start of VCC. Weighted mean nasal airflow was calculated by dividing the value of the area under the response time curve between 1 and 4 hours (calculated by trapezoidal rule) by the time interval of available data. |
| Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: CCL2 | Day 1 (pre-dose) and Day 8 of each study period (Periods 1-4); up to Day 158 | AROS Applied Biotechnology (AB) analyzed the nasal epithelial scrapings of participants and generated TaqMan (type of chemistry developed by AB to detect polymerase chain reaction \[PCR\] products) messenger ribonucleic acid (mRNA) biomarker expression data for CCL2, a steroid-responsive gene. Preliminary analysis of the mRNA abundance data was performed by Discovery Statistics. mRNA abundance data were normalized to the scores of GAPDH and 18S housekeeping genes. B-actin was not used. CCL2 data are presented by period to show the treatment-by-period interaction. ng, nanograms. |
| Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: 18S, B-actin, DUSP_1_T1, FKBP5, GAPDH, GILZ, PLAU, PTGS2, and RGS2 | Day 1 (pre-dose) and Day 8 of each study period (Periods 1-4); up to Day 158 | AROS Applied Biotechnology (AB) analyzed the nasal epithelial scrapings of participants and generated TaqMan (type of chemistry developed by AB to detect polymerase chain reaction \[PCR\] products) messenger ribonucleic acid (mRNA) biomarker expression data for 7 steroid-responsive genes (DUSP\_1\_TI, FKBP5, GILZ, PLAU, CCL2, PTGS2, and RGS2) and 3 housekeeping reference genes (GAPDH, 18S, and b-actin). Preliminary analysis of the mRNA abundance data was performed by Discovery Statistics. mRNA abundance data were normalized to the scores of GAPDH and 18S housekeeping genes. B-actin was not used. |
| Weighted Mean Global Symptom Score (GSS) at 5 Hours Post-dose (1-4 Hours Post-start of Challenge) | Day 8 of each study period (Periods 1-4); up to Day 158 | GSS (total score=0-30) is calculated as the sum of sneeze, nasal itch, rhinorrhea, nasal obstruction, cough, itchy throat, itchy ears, watery eyes, itchy eyes, and red eyes SSs, each of which was scored on a categorical scale from 0 to 3 (0=none, 1=mild, 2=moderate, 3=severe), as was measured at pre-challenge, and then every 15 mins from 0.25 to 4 hours post-start of challenge chamber. Weighted mean global symptom score was evaluated by dividing the value of the area under the response time curve between 1 and 4 hours (calculated by trapezoidal rule) by the time interval of available data. |
Countries
Austria
Participant flow
Pre-assignment details
Participants (par.) were randomized to receive treatment in one of five sequences in four study periods: ABCD, EABC, DEAB, CDEA, BCDE (A, Placebo; B, fluticasone propionate \[FP\] 25 micrograms \[µg\]: C, FP 50 µg; D, FP 100 µg; E, FP 200 µg). One par. randomized to ABCD withdrew due to an adverse event; one par. randomized to EABC withdrew consent.
Participants by arm
| Arm | Count |
|---|---|
| Placebo/FP 25, 50, 100, 200 µg Participants received placebo/fluticasone propionate (FP) in a dose of 25, 50, 100, and 200 micrograms (µg) once daily as 1 nasal spray into each nostril from 2 separate devices for 8 days each, in a crossover design. Treatment was given in one of five sequences in Periods 1, 2, 3, and 4 (with a minimum of a 14-day washout period between treatments): ABCD, EABC, DEAB, CDEA, and BCDE (A, Placebo; B, FP 25 µg: C, FP 50 µg; D, FP 100 µg; E, FP 200 µg). On Day 8 of each treatment period (1 hour post-dose), participants entered the Vienna Challenge Chamber (VCC) for a 4-hour period, and the assessments were conducted 2-5 hours post-dose. All participants attended a follow-up visit within 2 to 4 weeks after their final dose, and the overall duration for participation in the study (screening to follow-up) did not exceed 158 days. | 59 |
| Total | 59 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Placebo/FP 25, 50, 100, 200 µg |
|---|---|
| Age Continuous | 27.2 Years STANDARD_DEVIATION 5.3 |
| Race/Ethnicity, Customized Japanese/East Asian Heritage (EAH)/South EAH | 1 participants |
| Race/Ethnicity, Customized White | 58 participants |
| Sex: Female, Male Female | 30 Participants |
| Sex: Female, Male Male | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 4 / 46 | 6 / 46 | 3 / 46 | 2 / 46 | 1 / 47 |
| serious Total, serious adverse events | 0 / 46 | 0 / 46 | 0 / 46 | 0 / 46 | 0 / 47 |
Outcome results
Primary
Weighted Mean Total Nasal Symptom Score (TNSS) at 2-5 Hours Post-dose (1-4 Hours Post-start of Challenge [PSC]) in the Vienna Challenge Chamber (VCC)
The TNSS (score of 0-12), defined as the sum of the symptom scores for nasal obstruction, rhinorrhea, nasal itch, and sneeze (each scored on 0-3 scale \[0=none, 1=mild, 2=moderate, 3=severe\]) was measured at pre-challenge, and then every 15 minutes from 0.25 to 4 hours PSC. In the VCC, aerosolized allergen is administered in a sealed chamber to evaluate the efficacy of antihistamines/other treatments. Weighted mean TNSS was calculated by dividing the value of the area under the response time curve between 1 and 4 hours (calculated by trapezoidal rule) by the time interval of available data.
Time frame: Day 8 of each study period (Periods 1-4); up to Day 158
Population: All Subjects Population: all participants randomized to receive at least one dose of study treatment. Only those participants contributing data at the indicated time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Weighted Mean Total Nasal Symptom Score (TNSS) at 2-5 Hours Post-dose (1-4 Hours Post-start of Challenge [PSC]) in the Vienna Challenge Chamber (VCC) | 7.17 scores on a scale | Standard Deviation 2.912 |
| 25 µg FP | Weighted Mean Total Nasal Symptom Score (TNSS) at 2-5 Hours Post-dose (1-4 Hours Post-start of Challenge [PSC]) in the Vienna Challenge Chamber (VCC) | 5.54 scores on a scale | Standard Deviation 2.437 |
| 50 µg FP | Weighted Mean Total Nasal Symptom Score (TNSS) at 2-5 Hours Post-dose (1-4 Hours Post-start of Challenge [PSC]) in the Vienna Challenge Chamber (VCC) | 5.66 scores on a scale | Standard Deviation 2.28 |
| 100 µg FP | Weighted Mean Total Nasal Symptom Score (TNSS) at 2-5 Hours Post-dose (1-4 Hours Post-start of Challenge [PSC]) in the Vienna Challenge Chamber (VCC) | 5.29 scores on a scale | Standard Deviation 2.218 |
| 200 µg FP | Weighted Mean Total Nasal Symptom Score (TNSS) at 2-5 Hours Post-dose (1-4 Hours Post-start of Challenge [PSC]) in the Vienna Challenge Chamber (VCC) | 4.77 scores on a scale | Standard Deviation 2.433 |
95% CI: [-2.08, -0.68]
95% CI: [-2.16, -0.93]
95% CI: [-2.33, -1.11]
95% CI: [-2.6, -1.19]
Secondary
Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: 18S, B-actin, DUSP_1_T1, FKBP5, GAPDH, GILZ, PLAU, PTGS2, and RGS2
AROS Applied Biotechnology (AB) analyzed the nasal epithelial scrapings of participants and generated TaqMan (type of chemistry developed by AB to detect polymerase chain reaction \[PCR\] products) messenger ribonucleic acid (mRNA) biomarker expression data for 7 steroid-responsive genes (DUSP\_1\_TI, FKBP5, GILZ, PLAU, CCL2, PTGS2, and RGS2) and 3 housekeeping reference genes (GAPDH, 18S, and b-actin). Preliminary analysis of the mRNA abundance data was performed by Discovery Statistics. mRNA abundance data were normalized to the scores of GAPDH and 18S housekeeping genes. B-actin was not used.
Time frame: Day 1 (pre-dose) and Day 8 of each study period (Periods 1-4); up to Day 158
Population: All Subjects Population. The data presented are an average of the data collected on Day 1 and Day 8 of each treatment period. Only those participants contributing data at the indicated time points were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Placebo | Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: 18S, B-actin, DUSP_1_T1, FKBP5, GAPDH, GILZ, PLAU, PTGS2, and RGS2 | 18S | 6439292568 RNA copies detected per 50 ng total RNA |
| Placebo | Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: 18S, B-actin, DUSP_1_T1, FKBP5, GAPDH, GILZ, PLAU, PTGS2, and RGS2 | GAPDH | 5776051.293 RNA copies detected per 50 ng total RNA |
| Placebo | Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: 18S, B-actin, DUSP_1_T1, FKBP5, GAPDH, GILZ, PLAU, PTGS2, and RGS2 | GILZ | 13601.9459 RNA copies detected per 50 ng total RNA |
| Placebo | Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: 18S, B-actin, DUSP_1_T1, FKBP5, GAPDH, GILZ, PLAU, PTGS2, and RGS2 | B-actin | 1978137.142 RNA copies detected per 50 ng total RNA |
| Placebo | Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: 18S, B-actin, DUSP_1_T1, FKBP5, GAPDH, GILZ, PLAU, PTGS2, and RGS2 | PTGS2 | 42479.35246 RNA copies detected per 50 ng total RNA |
| Placebo | Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: 18S, B-actin, DUSP_1_T1, FKBP5, GAPDH, GILZ, PLAU, PTGS2, and RGS2 | RGS2 | 55084.11432 RNA copies detected per 50 ng total RNA |
| Placebo | Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: 18S, B-actin, DUSP_1_T1, FKBP5, GAPDH, GILZ, PLAU, PTGS2, and RGS2 | PLAU | 26364.53138 RNA copies detected per 50 ng total RNA |
| Placebo | Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: 18S, B-actin, DUSP_1_T1, FKBP5, GAPDH, GILZ, PLAU, PTGS2, and RGS2 | DUSP_1_T1 | 107004.8077 RNA copies detected per 50 ng total RNA |
| Placebo | Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: 18S, B-actin, DUSP_1_T1, FKBP5, GAPDH, GILZ, PLAU, PTGS2, and RGS2 | FKBP5 | 28739.3975 RNA copies detected per 50 ng total RNA |
| 25 µg FP | Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: 18S, B-actin, DUSP_1_T1, FKBP5, GAPDH, GILZ, PLAU, PTGS2, and RGS2 | FKBP5 | 155791.0745 RNA copies detected per 50 ng total RNA |
| 25 µg FP | Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: 18S, B-actin, DUSP_1_T1, FKBP5, GAPDH, GILZ, PLAU, PTGS2, and RGS2 | GILZ | 26629.75763 RNA copies detected per 50 ng total RNA |
| 25 µg FP | Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: 18S, B-actin, DUSP_1_T1, FKBP5, GAPDH, GILZ, PLAU, PTGS2, and RGS2 | DUSP_1_T1 | 104633.517 RNA copies detected per 50 ng total RNA |
| 25 µg FP | Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: 18S, B-actin, DUSP_1_T1, FKBP5, GAPDH, GILZ, PLAU, PTGS2, and RGS2 | GAPDH | 6143058.472 RNA copies detected per 50 ng total RNA |
| 25 µg FP | Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: 18S, B-actin, DUSP_1_T1, FKBP5, GAPDH, GILZ, PLAU, PTGS2, and RGS2 | B-actin | 1481307.983 RNA copies detected per 50 ng total RNA |
| 25 µg FP | Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: 18S, B-actin, DUSP_1_T1, FKBP5, GAPDH, GILZ, PLAU, PTGS2, and RGS2 | RGS2 | 45255.7763 RNA copies detected per 50 ng total RNA |
| 25 µg FP | Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: 18S, B-actin, DUSP_1_T1, FKBP5, GAPDH, GILZ, PLAU, PTGS2, and RGS2 | 18S | 6109603485 RNA copies detected per 50 ng total RNA |
| 25 µg FP | Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: 18S, B-actin, DUSP_1_T1, FKBP5, GAPDH, GILZ, PLAU, PTGS2, and RGS2 | PTGS2 | 31120.01509 RNA copies detected per 50 ng total RNA |
| 25 µg FP | Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: 18S, B-actin, DUSP_1_T1, FKBP5, GAPDH, GILZ, PLAU, PTGS2, and RGS2 | PLAU | 18550.2079 RNA copies detected per 50 ng total RNA |
| 50 µg FP | Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: 18S, B-actin, DUSP_1_T1, FKBP5, GAPDH, GILZ, PLAU, PTGS2, and RGS2 | 18S | 5822423622 RNA copies detected per 50 ng total RNA |
| 50 µg FP | Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: 18S, B-actin, DUSP_1_T1, FKBP5, GAPDH, GILZ, PLAU, PTGS2, and RGS2 | GAPDH | 6451580.253 RNA copies detected per 50 ng total RNA |
| 50 µg FP | Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: 18S, B-actin, DUSP_1_T1, FKBP5, GAPDH, GILZ, PLAU, PTGS2, and RGS2 | B-actin | 1629006.342 RNA copies detected per 50 ng total RNA |
| 50 µg FP | Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: 18S, B-actin, DUSP_1_T1, FKBP5, GAPDH, GILZ, PLAU, PTGS2, and RGS2 | DUSP_1_T1 | 107031.4158 RNA copies detected per 50 ng total RNA |
| 50 µg FP | Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: 18S, B-actin, DUSP_1_T1, FKBP5, GAPDH, GILZ, PLAU, PTGS2, and RGS2 | FKBP5 | 174963.5715 RNA copies detected per 50 ng total RNA |
| 50 µg FP | Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: 18S, B-actin, DUSP_1_T1, FKBP5, GAPDH, GILZ, PLAU, PTGS2, and RGS2 | GILZ | 29304.22353 RNA copies detected per 50 ng total RNA |
| 50 µg FP | Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: 18S, B-actin, DUSP_1_T1, FKBP5, GAPDH, GILZ, PLAU, PTGS2, and RGS2 | PLAU | 18810.56868 RNA copies detected per 50 ng total RNA |
| 50 µg FP | Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: 18S, B-actin, DUSP_1_T1, FKBP5, GAPDH, GILZ, PLAU, PTGS2, and RGS2 | PTGS2 | 35049.7556 RNA copies detected per 50 ng total RNA |
| 50 µg FP | Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: 18S, B-actin, DUSP_1_T1, FKBP5, GAPDH, GILZ, PLAU, PTGS2, and RGS2 | RGS2 | 54186.44212 RNA copies detected per 50 ng total RNA |
| 100 µg FP | Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: 18S, B-actin, DUSP_1_T1, FKBP5, GAPDH, GILZ, PLAU, PTGS2, and RGS2 | GILZ | 28832.53255 RNA copies detected per 50 ng total RNA |
| 100 µg FP | Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: 18S, B-actin, DUSP_1_T1, FKBP5, GAPDH, GILZ, PLAU, PTGS2, and RGS2 | 18S | 6218835383 RNA copies detected per 50 ng total RNA |
| 100 µg FP | Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: 18S, B-actin, DUSP_1_T1, FKBP5, GAPDH, GILZ, PLAU, PTGS2, and RGS2 | PLAU | 20918.214 RNA copies detected per 50 ng total RNA |
| 100 µg FP | Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: 18S, B-actin, DUSP_1_T1, FKBP5, GAPDH, GILZ, PLAU, PTGS2, and RGS2 | PTGS2 | 38443.85612 RNA copies detected per 50 ng total RNA |
| 100 µg FP | Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: 18S, B-actin, DUSP_1_T1, FKBP5, GAPDH, GILZ, PLAU, PTGS2, and RGS2 | FKBP5 | 177935.1307 RNA copies detected per 50 ng total RNA |
| 100 µg FP | Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: 18S, B-actin, DUSP_1_T1, FKBP5, GAPDH, GILZ, PLAU, PTGS2, and RGS2 | RGS2 | 50507.30739 RNA copies detected per 50 ng total RNA |
| 100 µg FP | Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: 18S, B-actin, DUSP_1_T1, FKBP5, GAPDH, GILZ, PLAU, PTGS2, and RGS2 | GAPDH | 6008446.351 RNA copies detected per 50 ng total RNA |
| 100 µg FP | Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: 18S, B-actin, DUSP_1_T1, FKBP5, GAPDH, GILZ, PLAU, PTGS2, and RGS2 | DUSP_1_T1 | 118158.2593 RNA copies detected per 50 ng total RNA |
| 100 µg FP | Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: 18S, B-actin, DUSP_1_T1, FKBP5, GAPDH, GILZ, PLAU, PTGS2, and RGS2 | B-actin | 1630387.679 RNA copies detected per 50 ng total RNA |
| 200 µg FP | Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: 18S, B-actin, DUSP_1_T1, FKBP5, GAPDH, GILZ, PLAU, PTGS2, and RGS2 | DUSP_1_T1 | 113323.9632 RNA copies detected per 50 ng total RNA |
| 200 µg FP | Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: 18S, B-actin, DUSP_1_T1, FKBP5, GAPDH, GILZ, PLAU, PTGS2, and RGS2 | GILZ | 27304.24721 RNA copies detected per 50 ng total RNA |
| 200 µg FP | Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: 18S, B-actin, DUSP_1_T1, FKBP5, GAPDH, GILZ, PLAU, PTGS2, and RGS2 | B-actin | 1543748.32 RNA copies detected per 50 ng total RNA |
| 200 µg FP | Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: 18S, B-actin, DUSP_1_T1, FKBP5, GAPDH, GILZ, PLAU, PTGS2, and RGS2 | FKBP5 | 151362.3934 RNA copies detected per 50 ng total RNA |
| 200 µg FP | Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: 18S, B-actin, DUSP_1_T1, FKBP5, GAPDH, GILZ, PLAU, PTGS2, and RGS2 | PLAU | 21692.66346 RNA copies detected per 50 ng total RNA |
| 200 µg FP | Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: 18S, B-actin, DUSP_1_T1, FKBP5, GAPDH, GILZ, PLAU, PTGS2, and RGS2 | GAPDH | 5972472.493 RNA copies detected per 50 ng total RNA |
| 200 µg FP | Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: 18S, B-actin, DUSP_1_T1, FKBP5, GAPDH, GILZ, PLAU, PTGS2, and RGS2 | 18S | 6222906532 RNA copies detected per 50 ng total RNA |
| 200 µg FP | Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: 18S, B-actin, DUSP_1_T1, FKBP5, GAPDH, GILZ, PLAU, PTGS2, and RGS2 | RGS2 | 50373.91657 RNA copies detected per 50 ng total RNA |
| 200 µg FP | Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: 18S, B-actin, DUSP_1_T1, FKBP5, GAPDH, GILZ, PLAU, PTGS2, and RGS2 | PTGS2 | 33657.71928 RNA copies detected per 50 ng total RNA |
Secondary
Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: CCL2
AROS Applied Biotechnology (AB) analyzed the nasal epithelial scrapings of participants and generated TaqMan (type of chemistry developed by AB to detect polymerase chain reaction \[PCR\] products) messenger ribonucleic acid (mRNA) biomarker expression data for CCL2, a steroid-responsive gene. Preliminary analysis of the mRNA abundance data was performed by Discovery Statistics. mRNA abundance data were normalized to the scores of GAPDH and 18S housekeeping genes. B-actin was not used. CCL2 data are presented by period to show the treatment-by-period interaction. ng, nanograms.
Time frame: Day 1 (pre-dose) and Day 8 of each study period (Periods 1-4); up to Day 158
Population: All Subjects Population. The data presented for each period are an average of the data collected on Day 1 and Day 8 of each period. Only those participants contributing data at the indicated time points were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Placebo | Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: CCL2 | Period 4, n=12, 11, 11, 11, 12 | 10111.38124 Copies of RNA detected per 50ng of total |
| Placebo | Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: CCL2 | Period 3, n=11, 11, 11, 12, 12 | 4135.167835 Copies of RNA detected per 50ng of total |
| Placebo | Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: CCL2 | Period 2, n=11, 11, 11, 12, 11 | 4206.320679 Copies of RNA detected per 50ng of total |
| Placebo | Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: CCL2 | Period 1, n=12, 12, 12, 11, 11 | 12396.08096 Copies of RNA detected per 50ng of total |
| 25 µg FP | Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: CCL2 | Period 2, n=11, 11, 11, 12, 11 | 2192.232108 Copies of RNA detected per 50ng of total |
| 25 µg FP | Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: CCL2 | Period 3, n=11, 11, 11, 12, 12 | 3612.444351 Copies of RNA detected per 50ng of total |
| 25 µg FP | Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: CCL2 | Period 4, n=12, 11, 11, 11, 12 | 3523.276415 Copies of RNA detected per 50ng of total |
| 25 µg FP | Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: CCL2 | Period 1, n=12, 12, 12, 11, 11 | 1377.248941 Copies of RNA detected per 50ng of total |
| 50 µg FP | Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: CCL2 | Period 2, n=11, 11, 11, 12, 11 | 1765.627412 Copies of RNA detected per 50ng of total |
| 50 µg FP | Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: CCL2 | Period 4, n=12, 11, 11, 11, 12 | 2615.352938 Copies of RNA detected per 50ng of total |
| 50 µg FP | Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: CCL2 | Period 1, n=12, 12, 12, 11, 11 | 1231.251053 Copies of RNA detected per 50ng of total |
| 50 µg FP | Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: CCL2 | Period 3, n=11, 11, 11, 12, 12 | 2184.76185 Copies of RNA detected per 50ng of total |
| 100 µg FP | Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: CCL2 | Period 2, n=11, 11, 11, 12, 11 | 2342.488506 Copies of RNA detected per 50ng of total |
| 100 µg FP | Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: CCL2 | Period 4, n=12, 11, 11, 11, 12 | 1917.918706 Copies of RNA detected per 50ng of total |
| 100 µg FP | Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: CCL2 | Period 1, n=12, 12, 12, 11, 11 | 3340.460181 Copies of RNA detected per 50ng of total |
| 100 µg FP | Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: CCL2 | Period 3, n=11, 11, 11, 12, 12 | 1229.316666 Copies of RNA detected per 50ng of total |
| 200 µg FP | Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: CCL2 | Period 4, n=12, 11, 11, 11, 12 | 1071.598621 Copies of RNA detected per 50ng of total |
| 200 µg FP | Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: CCL2 | Period 3, n=11, 11, 11, 12, 12 | 2505.03196 Copies of RNA detected per 50ng of total |
| 200 µg FP | Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: CCL2 | Period 2, n=11, 11, 11, 12, 11 | 2821.11204 Copies of RNA detected per 50ng of total |
| 200 µg FP | Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: CCL2 | Period 1, n=12, 12, 12, 11, 11 | 3377.403394 Copies of RNA detected per 50ng of total |
Secondary
Weighted Mean Eye Symptom Score at 2-5 Hours Post-dose (1-4 Hours Post-start of Challenge)
The eye symptom score (total score of 0 \[none\] to 9 \[severe\]) was calculated as the sum of the symptom scores for watery eyes, itchy eyes, and red eyes, each of which was scored on a categorical scale from 0 to 3 (0=none, 1=mild, 2=moderate, 3=severe), and was measured at pre-challenge, and then every 15 minutes from 0.25 to 4 hours post-start of challenge chamber. Weighted mean eye symptom score was calculated by dividing the value of the area under the response time curve between 1 and 4 hours (calculated by trapezoidal rule) by the time interval of available data.
Time frame: Day 8 of each study period (Periods 1-4); up to Day 158
Population: All Subjects Population. Only those participants contributing data at the indicated time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Weighted Mean Eye Symptom Score at 2-5 Hours Post-dose (1-4 Hours Post-start of Challenge) | 2.35 scores on a scale | Standard Deviation 2.24 |
| 25 µg FP | Weighted Mean Eye Symptom Score at 2-5 Hours Post-dose (1-4 Hours Post-start of Challenge) | 1.52 scores on a scale | Standard Deviation 1.678 |
| 50 µg FP | Weighted Mean Eye Symptom Score at 2-5 Hours Post-dose (1-4 Hours Post-start of Challenge) | 1.44 scores on a scale | Standard Deviation 1.711 |
| 100 µg FP | Weighted Mean Eye Symptom Score at 2-5 Hours Post-dose (1-4 Hours Post-start of Challenge) | 1.93 scores on a scale | Standard Deviation 1.726 |
| 200 µg FP | Weighted Mean Eye Symptom Score at 2-5 Hours Post-dose (1-4 Hours Post-start of Challenge) | 1.41 scores on a scale | Standard Deviation 1.491 |
Secondary
Weighted Mean Global Symptom Score (GSS) at 5 Hours Post-dose (1-4 Hours Post-start of Challenge)
GSS (total score=0-30) is calculated as the sum of sneeze, nasal itch, rhinorrhea, nasal obstruction, cough, itchy throat, itchy ears, watery eyes, itchy eyes, and red eyes SSs, each of which was scored on a categorical scale from 0 to 3 (0=none, 1=mild, 2=moderate, 3=severe), as was measured at pre-challenge, and then every 15 mins from 0.25 to 4 hours post-start of challenge chamber. Weighted mean global symptom score was evaluated by dividing the value of the area under the response time curve between 1 and 4 hours (calculated by trapezoidal rule) by the time interval of available data.
Time frame: Day 8 of each study period (Periods 1-4); up to Day 158
Population: All Subjects Population. Only those participants contributing data at the indicated time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Weighted Mean Global Symptom Score (GSS) at 5 Hours Post-dose (1-4 Hours Post-start of Challenge) | 11.14 scores on a scale | Standard Deviation 5.407 |
| 25 µg FP | Weighted Mean Global Symptom Score (GSS) at 5 Hours Post-dose (1-4 Hours Post-start of Challenge) | 8.17 scores on a scale | Standard Deviation 4.302 |
| 50 µg FP | Weighted Mean Global Symptom Score (GSS) at 5 Hours Post-dose (1-4 Hours Post-start of Challenge) | 8.24 scores on a scale | Standard Deviation 4.231 |
| 100 µg FP | Weighted Mean Global Symptom Score (GSS) at 5 Hours Post-dose (1-4 Hours Post-start of Challenge) | 8.69 scores on a scale | Standard Deviation 4.346 |
| 200 µg FP | Weighted Mean Global Symptom Score (GSS) at 5 Hours Post-dose (1-4 Hours Post-start of Challenge) | 7.13 scores on a scale | Standard Deviation 3.487 |
Secondary
Weighted Mean Nasal Airflow at 2-5 Hours Post-dose (1-4 Hours Post-start of Challenge)
Allergic rhinitis decreases the passage of air through the nose (nasal airflow) by increasing the nasal airway resistance. Rhinomanometry is used as an objective measurement of airway resistance. Nasal airflow was measured using active anterior rhinomanometry at pre-challenge, and then every 30 minutes from 0.5 to 4 hours post start of VCC. Weighted mean nasal airflow was calculated by dividing the value of the area under the response time curve between 1 and 4 hours (calculated by trapezoidal rule) by the time interval of available data.
Time frame: Day 8 of each study period (Periods 1-4); up to Day 158
Population: All Subjects Population. Only those participants contributing data at the indicated time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Weighted Mean Nasal Airflow at 2-5 Hours Post-dose (1-4 Hours Post-start of Challenge) | 335.20 Milliliters per second (mL/s) | Standard Deviation 145.373 |
| 25 µg FP | Weighted Mean Nasal Airflow at 2-5 Hours Post-dose (1-4 Hours Post-start of Challenge) | 368.66 Milliliters per second (mL/s) | Standard Deviation 144.23 |
| 50 µg FP | Weighted Mean Nasal Airflow at 2-5 Hours Post-dose (1-4 Hours Post-start of Challenge) | 375.94 Milliliters per second (mL/s) | Standard Deviation 142.105 |
| 100 µg FP | Weighted Mean Nasal Airflow at 2-5 Hours Post-dose (1-4 Hours Post-start of Challenge) | 362.59 Milliliters per second (mL/s) | Standard Deviation 142.216 |
| 200 µg FP | Weighted Mean Nasal Airflow at 2-5 Hours Post-dose (1-4 Hours Post-start of Challenge) | 411.65 Milliliters per second (mL/s) | Standard Deviation 160.148 |
Secondary
Weighted Mean Nasal Secretion at 2-5 Hours Post-dose (1-4 Hours Post-start of Challenge)
Nasal secretion was measured by weighing tissues used by participants. Wet tissue weight assessments were made pre-challenge, and then every 30 minutes from 0.5 to 4 hours post start of challenge chamber throughout the study. Weighted mean nasal secretion was calculated by dividing the value of the area under the response time curve between 1 and 4 hours (calculated by trapezoidal rule) by the time interval of available data.
Time frame: Day 8 of each study period (Periods 1-4); up to Day 158
Population: All Subjects Population. Only those participants contributing data at the indicated time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Weighted Mean Nasal Secretion at 2-5 Hours Post-dose (1-4 Hours Post-start of Challenge) | 2.43 grams (g) | Standard Deviation 2.203 |
| 25 µg FP | Weighted Mean Nasal Secretion at 2-5 Hours Post-dose (1-4 Hours Post-start of Challenge) | 1.63 grams (g) | Standard Deviation 1.893 |
| 50 µg FP | Weighted Mean Nasal Secretion at 2-5 Hours Post-dose (1-4 Hours Post-start of Challenge) | 1.43 grams (g) | Standard Deviation 1.458 |
| 100 µg FP | Weighted Mean Nasal Secretion at 2-5 Hours Post-dose (1-4 Hours Post-start of Challenge) | 1.26 grams (g) | Standard Deviation 1.55 |
| 200 µg FP | Weighted Mean Nasal Secretion at 2-5 Hours Post-dose (1-4 Hours Post-start of Challenge) | 1.02 grams (g) | Standard Deviation 1.271 |