Allergic Rhinitis
Conditions
Brief summary
An H3 receptor antagonist should reduce the congestion associated with allergic rhinitis. A nasal allergen challenge will be given to patients to induce rhinitis symptoms and acoustic rhinometry will be used to measure the congestion.
Interventions
DRUGPlacebo
A single oral dose of Placebo is dosed during the study in order to ascertain the effect of placebo on measures and in order to maintain the blind of the other drugs.
DRUGAllegra
A single oral dose of Allegra is dosed to subjects in combination with PF-03654746.
DRUGAllegra-D
A single oral dose of Allegra-D is dosed to subjects as an active comparator.
DRUGPF-03654746
A single oral dose of PF-03654746 is the investigational drug being studied.
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
19 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* Male or female subjects 19-55 years with allergic rhinitis requiring treatment within the previous 2 years. * Subjects that respond to a ragweed nasal allergen challenge at screening.
Exclusion criteria
* History of asthma or FEV1 \< 80% predicted. * Significant concomitant disease or medications. * Symptoms of allergic rhinitis within 2 weeks prior to screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Nasal Volume Proportion Measured Using Acoustic Rhinometry | 2 hrs 10 min, 2 hrs 25 min, 2 hrs 40 min post dose (Baseline); 2 hrs 55 min, 3 hrs 10 min, 3 hrs 25 min post dose on Day 1 of each intervention period | Acoustic rhinometry: a technique intended for assessment of the geometry of nasal cavity and nasopharynx and for evaluating nasal obstruction. At each time point, there were 2 acoustic rhinometry measurements taken, one for each nostril. Mean of the left and right nostril measurements was taken as measurement at each time point. Nasal volume at Baseline was defined as mean of 3, 'post-diluent, pre-allergen challenge' measures for each intervention period at 2 hrs 10 min, 2 hrs 25 min and 2 hrs 40 min post PF-03654746/placebo dose. Nasal volume 'post-allergen challenge' measures recorded at 2 hrs 55 min, 3 hrs 10 min and 3 hrs 25 min post PF-03654746/placebo dose for each intervention period was averaged to derive single 'post-allergen challenge' value. Nasal volume proportion was defined as ratio of 'post-allergen challenge' value and 'Baseline/pre-allergen challenge value'. Diluent used was saline and allergen was short ragweed extract. |
| Minimum Cross-Sectional Area (Amin) Proportion Measured Using Acoustic Rhinometry | 2 hrs 10 min, 2 hrs 25 min, 2 hrs 40 min post dose (Baseline); 2 hrs 55 min, 3 hrs 10 min, 3 hrs 25 min post dose on Day 1 of each intervention period | Acoustic rhinometry: a technique intended for assessment of the geometry of nasal cavity and nasopharynx and for evaluating nasal obstruction. At each time point, there were 2 acoustic rhinometry measurements taken, one for each nostril. Mean of the left and right nostril measurements was taken as measurement at each time point. Minimum Cross-Sectional Area (Amin) at Baseline was defined as mean of 3, 'post-diluent, pre-allergen challenge' measures for each intervention period at 2 hours (hrs) 10 minutes (min), 2 hrs 25 min and 2 hrs 40 min post PF-03654746/placebo dose. Amin 'post-allergen challenge' measures recorded at 2 hrs 55 min, 3 hrs 10 min and 3 hrs 25 min post PF-03654746/placebo dose for each intervention period was averaged to derive single 'post-allergen challenge' value. Amin proportion was defined as ratio of 'post-allergen challenge' value and 'Baseline/pre-allergen challenge value'. Diluent used was saline and allergen was short ragweed extract. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Nasal Volume Maximum Fall Measured Using Acoustic Rhinometry | 2 hrs 10 min, 2 hrs 25 min, 2 hrs 40 min post dose (Baseline); 2 hrs 55 min, 3 hrs 10 min, 3 hrs 25 min post dose on Day 1 of each intervention period | Acoustic rhinometry: a technique intended for assessment of the geometry of the nasal cavity and nasopharynx and for evaluating nasal obstruction. At each time point, there were 2 acoustic rhinometry measurements taken, one for each nostril. The mean of the left and right nostril measurements was taken as the measurement at each time point. Nasal volume at Baseline was defined as mean of the 3, 'post-diluent, pre-allergen challenge' measures for each intervention period at 2 hrs 10 min, 2 hrs 25 min and 2 hrs 40 min post PF-03654746/placebo dose. Nasal volume 'post-allergen challenge' measures were recorded at 2 hrs 55 min, 3 hrs 10 min and 3 hrs 25 min post PF-03654746/placebo dose for each intervention period. The maximum fall for nasal volume was calculated as baseline measure minus smallest 'post-allergen challenge' nasal volume measurement among the 3 measures. |
| Nasal Symptom Scores: Sneezing | 2 hrs 10 min, 2 hrs 25 min, 2 hrs 40 min post dose (Baseline); 2 hrs 55 min, 3 hrs 10 min, 3 hrs 25 min post dose on Day 1 of each intervention period | The absolute number of sneezes was recorded by the participants under supervision of study personnel. Nasal symptom score for sneezing was assessed as the total number of sneezes of each intervention period at specified time-points for the post-diluent and post-challenge and post where 'post-diluent, pre-allergen challenge' included 2 hrs 10 min, 2 hrs 25 min and 2 hrs 40 min post PF-03654746/placebo dose at each intervention period and 'post-allergen challenge' included 2 hrs 55 min, 3 hrs 10 min and 3 hrs 25 min post PF-03654746/placebo dose at each intervention period. |
| Nasal Symptom Scores: Nasal Congestion, Nasal Itching, Rhinorrhea | 2 hrs 10 min, 2 hrs 25 min, 2 hrs 40 min post dose (Pre-allergen challenge); 2 hrs 55 min, 3 hrs 10 min, 3 hrs 25 min post dose (Post-allergen challenge); 3 hrs 40 min post dose (Post-oxymetazoline) on Day 1 of each intervention period | Nasal symptoms included; nasal congestion: participants rated sensation of nasal blockage on 0 (no blockage) to 5 (total blockage) scale, nasal itching: participants rated sensation of nasal itch on 0 (no itch) to 5 (very itchy) scale, rhinorrhea: participants rated sensation of runny nose on 0 (no running) to 5 (very runny) scale. Symptom scores were assessed as mean of each intervention period at specified time-points for 'post-diluent, pre-allergen challenge' measure and 'post-challenge' measure. Post-diluent, pre-allergen challenge (for congestion, itching, rhinorrhea) included 2 hrs 10 min, 2 hrs 25 min and 2 hrs 40 min post PF-03654746/placebo dose at each intervention period and post-allergen challenge (for congestion, itching, rhinorrhea) included 2 hrs 55 min, 3 hrs 10 min and 3 hrs 25 min post PF-03654746/placebo dose at each intervention period and (for congestion only) 3 hrs 40 min post PF-03654746/placebo dose (Post-oxymetazoline) at each intervention period. |
| Minimum Cross-Sectional Area (Amin) Maximum Fall Measured Using Acoustic Rhinometry | 2 hrs 10 min, 2 hrs 25 min, 2 hrs 40 min post dose (Baseline); 2 hrs 55 min, 3 hrs 10 min, 3 hrs 25 min post dose on Day 1 of each intervention period | Acoustic rhinometry: a technique intended for assessment of the geometry of the nasal cavity and nasopharynx and for evaluating nasal obstruction. At each time point, there were 2 acoustic rhinometry measurements taken, one for each nostril. The mean of the left and right nostril measurements was taken as the measurement at each time point. Minimum Cross-Sectional Area (Amin) at Baseline was defined as mean of the 3, 'post-diluent, pre-allergen challenge' measures for each intervention period at 2 hrs 10 min, 2 hrs 25 min and 2 hrs 40 min post PF-03654746/placebo dose. Amin 'post-allergen challenge' measures were recorded at 2 hrs 55 min, 3 hrs 10 min and 3 hrs 25 min post PF-03654746/placebo dose for each intervention period. The maximum fall in Amin was calculated as baseline measure minus smallest 'post-allergen challenge' Amin measurement of the 3 measures. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Serum PF-03654746 Concentration | 1 hr 30 min post dose on Day 1 of each intervention period | Only participants receiving PF-03654746 were analyzed for this outcome measure. Mean serum concentration of PF-03654746 was calculated of each intervention period. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Entire Study Population All participants randomized to any treatment (PF-03654746 10 mg capsule first, PF-03654746 1 mg capsule first, Allegra-D tablet-in-capsule first and placebo first). | 20 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| First Intervention Period | Adverse Event | 1 | 0 | 0 | 0 |
| First Intervention Period | Randomized but not Treated | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Entire Study Population |
|---|---|
| Age, Customized 18 to 44 years | 15 participants |
| Age, Customized 45 to 64 years | 5 participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 8 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 / 20 | 2 / 19 | 0 / 19 | 2 / 19 |
| serious Total, serious adverse events | 0 / 20 | 0 / 19 | 0 / 19 | 0 / 19 |
Outcome results
Primary
Minimum Cross-Sectional Area (Amin) Proportion Measured Using Acoustic Rhinometry
Acoustic rhinometry: a technique intended for assessment of the geometry of nasal cavity and nasopharynx and for evaluating nasal obstruction. At each time point, there were 2 acoustic rhinometry measurements taken, one for each nostril. Mean of the left and right nostril measurements was taken as measurement at each time point. Minimum Cross-Sectional Area (Amin) at Baseline was defined as mean of 3, 'post-diluent, pre-allergen challenge' measures for each intervention period at 2 hours (hrs) 10 minutes (min), 2 hrs 25 min and 2 hrs 40 min post PF-03654746/placebo dose. Amin 'post-allergen challenge' measures recorded at 2 hrs 55 min, 3 hrs 10 min and 3 hrs 25 min post PF-03654746/placebo dose for each intervention period was averaged to derive single 'post-allergen challenge' value. Amin proportion was defined as ratio of 'post-allergen challenge' value and 'Baseline/pre-allergen challenge value'. Diluent used was saline and allergen was short ragweed extract.
Time frame: 2 hrs 10 min, 2 hrs 25 min, 2 hrs 40 min post dose (Baseline); 2 hrs 55 min, 3 hrs 10 min, 3 hrs 25 min post dose on Day 1 of each intervention period
Population: Full analysis set included all participants randomized at baseline and who received at least 1 dose of double-blind treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PF-03654746 10 mg | Minimum Cross-Sectional Area (Amin) Proportion Measured Using Acoustic Rhinometry | 0.760 ratio | Standard Deviation 0.1504 |
| PF-03654746 1 mg | Minimum Cross-Sectional Area (Amin) Proportion Measured Using Acoustic Rhinometry | 0.742 ratio | Standard Deviation 0.2552 |
| Allegra-D | Minimum Cross-Sectional Area (Amin) Proportion Measured Using Acoustic Rhinometry | 0.717 ratio | Standard Deviation 0.1935 |
| Placebo | Minimum Cross-Sectional Area (Amin) Proportion Measured Using Acoustic Rhinometry | 0.795 ratio | Standard Deviation 0.3044 |
Comparison: An analysis of variance (ANOVA) mixed model was assessed with sequence, period and treatment as fixed effects and participant within sequence as a random effect.p-value: 0.302ANOVA
Comparison: An ANOVA mixed model was assessed with sequence, period and treatment as fixed effects and participant within sequence as a random effect.p-value: 0.134ANOVA
Comparison: An ANOVA mixed model was assessed with sequence, period and treatment as fixed effects and participant within sequence as a random effect.p-value: 0.229ANOVA
Comparison: An ANOVA mixed model was assessed with sequence, period and treatment as fixed effects and participant within sequence as a random effect.p-value: 0.544ANOVA
Comparison: An ANOVA mixed model was assessed with sequence, period and treatment as fixed effects and participant within sequence as a random effect.p-value: 0.71ANOVA
Comparison: An ANOVA mixed model was assessed with sequence, period and treatment as fixed effects and participant within sequence as a random effect.p-value: 0.816ANOVA
Primary
Nasal Volume Proportion Measured Using Acoustic Rhinometry
Acoustic rhinometry: a technique intended for assessment of the geometry of nasal cavity and nasopharynx and for evaluating nasal obstruction. At each time point, there were 2 acoustic rhinometry measurements taken, one for each nostril. Mean of the left and right nostril measurements was taken as measurement at each time point. Nasal volume at Baseline was defined as mean of 3, 'post-diluent, pre-allergen challenge' measures for each intervention period at 2 hrs 10 min, 2 hrs 25 min and 2 hrs 40 min post PF-03654746/placebo dose. Nasal volume 'post-allergen challenge' measures recorded at 2 hrs 55 min, 3 hrs 10 min and 3 hrs 25 min post PF-03654746/placebo dose for each intervention period was averaged to derive single 'post-allergen challenge' value. Nasal volume proportion was defined as ratio of 'post-allergen challenge' value and 'Baseline/pre-allergen challenge value'. Diluent used was saline and allergen was short ragweed extract.
Time frame: 2 hrs 10 min, 2 hrs 25 min, 2 hrs 40 min post dose (Baseline); 2 hrs 55 min, 3 hrs 10 min, 3 hrs 25 min post dose on Day 1 of each intervention period
Population: Full analysis set included all participants randomized at baseline and who received at least 1 dose of double-blind treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PF-03654746 10 mg | Nasal Volume Proportion Measured Using Acoustic Rhinometry | 0.800 ratio | Standard Deviation 0.1825 |
| PF-03654746 1 mg | Nasal Volume Proportion Measured Using Acoustic Rhinometry | 0.796 ratio | Standard Deviation 0.2641 |
| Allegra-D | Nasal Volume Proportion Measured Using Acoustic Rhinometry | 0.744 ratio | Standard Deviation 0.1594 |
| Placebo | Nasal Volume Proportion Measured Using Acoustic Rhinometry | 0.856 ratio | Standard Deviation 0.3859 |
Comparison: An analysis of variance (ANOVA) mixed model was assessed with sequence, period and treatment as fixed effects and participant within sequence as a random effect.p-value: 0.269ANOVA
Comparison: An ANOVA mixed model was assessed with sequence, period and treatment as fixed effects and participant within sequence as a random effect.p-value: 0.097ANOVA
Comparison: An ANOVA mixed model was assessed with sequence, period and treatment as fixed effects and participant within sequence as a random effect.p-value: 0.252ANOVA
Comparison: An ANOVA mixed model was assessed with sequence, period and treatment as fixed effects and participant within sequence as a random effect.p-value: 0.479ANOVA
Comparison: An ANOVA mixed model was assessed with sequence, period and treatment as fixed effects and participant within sequence as a random effect.p-value: 0.521ANOVA
Comparison: An ANOVA mixed model was assessed with sequence, period and treatment as fixed effects and participant within sequence as a random effect.p-value: 0.952ANOVA
Secondary
Minimum Cross-Sectional Area (Amin) Maximum Fall Measured Using Acoustic Rhinometry
Acoustic rhinometry: a technique intended for assessment of the geometry of the nasal cavity and nasopharynx and for evaluating nasal obstruction. At each time point, there were 2 acoustic rhinometry measurements taken, one for each nostril. The mean of the left and right nostril measurements was taken as the measurement at each time point. Minimum Cross-Sectional Area (Amin) at Baseline was defined as mean of the 3, 'post-diluent, pre-allergen challenge' measures for each intervention period at 2 hrs 10 min, 2 hrs 25 min and 2 hrs 40 min post PF-03654746/placebo dose. Amin 'post-allergen challenge' measures were recorded at 2 hrs 55 min, 3 hrs 10 min and 3 hrs 25 min post PF-03654746/placebo dose for each intervention period. The maximum fall in Amin was calculated as baseline measure minus smallest 'post-allergen challenge' Amin measurement of the 3 measures.
Time frame: 2 hrs 10 min, 2 hrs 25 min, 2 hrs 40 min post dose (Baseline); 2 hrs 55 min, 3 hrs 10 min, 3 hrs 25 min post dose on Day 1 of each intervention period
Population: Full analysis set included all participants randomized at baseline and who received at least 1 dose of double-blind treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PF-03654746 10 mg | Minimum Cross-Sectional Area (Amin) Maximum Fall Measured Using Acoustic Rhinometry | 0.155 square centimeter (cm^2) | Standard Deviation 0.0876 |
| PF-03654746 1 mg | Minimum Cross-Sectional Area (Amin) Maximum Fall Measured Using Acoustic Rhinometry | 0.157 square centimeter (cm^2) | Standard Deviation 0.1159 |
| Allegra-D | Minimum Cross-Sectional Area (Amin) Maximum Fall Measured Using Acoustic Rhinometry | 0.204 square centimeter (cm^2) | Standard Deviation 0.0951 |
| Placebo | Minimum Cross-Sectional Area (Amin) Maximum Fall Measured Using Acoustic Rhinometry | 0.190 square centimeter (cm^2) | Standard Deviation 0.151 |
Comparison: An analysis of variance (ANOVA) mixed model was assessed with sequence, period and treatment as fixed effects and participant within sequence as a random effect.p-value: 0.13ANOVA
Comparison: An ANOVA mixed model was assessed with sequence, period and treatment as fixed effects and participant within sequence as a random effect.p-value: 0.663ANOVA
Comparison: An ANOVA mixed model was assessed with sequence, period and treatment as fixed effects and participant within sequence as a random effect.p-value: 0.138ANOVA
Comparison: An ANOVA mixed model was assessed with sequence, period and treatment as fixed effects and participant within sequence as a random effect.p-value: 0.124ANOVA
Comparison: An ANOVA mixed model was assessed with sequence, period and treatment as fixed effects and participant within sequence as a random effect.p-value: 0.134ANOVA
Comparison: An ANOVA mixed model was assessed with sequence, period and treatment as fixed effects and participant within sequence as a random effect.p-value: 0.978ANOVA
Secondary
Nasal Symptom Scores: Nasal Congestion, Nasal Itching, Rhinorrhea
Nasal symptoms included; nasal congestion: participants rated sensation of nasal blockage on 0 (no blockage) to 5 (total blockage) scale, nasal itching: participants rated sensation of nasal itch on 0 (no itch) to 5 (very itchy) scale, rhinorrhea: participants rated sensation of runny nose on 0 (no running) to 5 (very runny) scale. Symptom scores were assessed as mean of each intervention period at specified time-points for 'post-diluent, pre-allergen challenge' measure and 'post-challenge' measure. Post-diluent, pre-allergen challenge (for congestion, itching, rhinorrhea) included 2 hrs 10 min, 2 hrs 25 min and 2 hrs 40 min post PF-03654746/placebo dose at each intervention period and post-allergen challenge (for congestion, itching, rhinorrhea) included 2 hrs 55 min, 3 hrs 10 min and 3 hrs 25 min post PF-03654746/placebo dose at each intervention period and (for congestion only) 3 hrs 40 min post PF-03654746/placebo dose (Post-oxymetazoline) at each intervention period.
Time frame: 2 hrs 10 min, 2 hrs 25 min, 2 hrs 40 min post dose (Pre-allergen challenge); 2 hrs 55 min, 3 hrs 10 min, 3 hrs 25 min post dose (Post-allergen challenge); 3 hrs 40 min post dose (Post-oxymetazoline) on Day 1 of each intervention period
Population: Full analysis set included all participants randomized at baseline and who received at least 1 dose of double-blind treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PF-03654746 10 mg | Nasal Symptom Scores: Nasal Congestion, Nasal Itching, Rhinorrhea | Nasal Itching: Post-allergen challenge | 0.4 units on a scale | Standard Deviation 0.71 |
| PF-03654746 10 mg | Nasal Symptom Scores: Nasal Congestion, Nasal Itching, Rhinorrhea | Rhinorrhea: Post-allergen challenge | 0.6 units on a scale | Standard Deviation 1.01 |
| PF-03654746 10 mg | Nasal Symptom Scores: Nasal Congestion, Nasal Itching, Rhinorrhea | Nasal congestion: Post-allergen challenge | 1.5 units on a scale | Standard Deviation 1.2 |
| PF-03654746 10 mg | Nasal Symptom Scores: Nasal Congestion, Nasal Itching, Rhinorrhea | Nasal congestion: Pre-allergen challenge | 0.2 units on a scale | Standard Deviation 0.36 |
| PF-03654746 10 mg | Nasal Symptom Scores: Nasal Congestion, Nasal Itching, Rhinorrhea | Rhinorrhea: Pre-allergen challenge | 0.1 units on a scale | Standard Deviation 0.23 |
| PF-03654746 10 mg | Nasal Symptom Scores: Nasal Congestion, Nasal Itching, Rhinorrhea | Nasal Itching: Pre-allergen challenge | 0.0 units on a scale | Standard Deviation 0.07 |
| PF-03654746 10 mg | Nasal Symptom Scores: Nasal Congestion, Nasal Itching, Rhinorrhea | Nasal congestion: Post-oxymetazoline | 0.8 units on a scale | Standard Deviation 1.16 |
| PF-03654746 1 mg | Nasal Symptom Scores: Nasal Congestion, Nasal Itching, Rhinorrhea | Nasal Itching: Pre-allergen challenge | 0.1 units on a scale | Standard Deviation 0.23 |
| PF-03654746 1 mg | Nasal Symptom Scores: Nasal Congestion, Nasal Itching, Rhinorrhea | Nasal Itching: Post-allergen challenge | 0.8 units on a scale | Standard Deviation 1.1 |
| PF-03654746 1 mg | Nasal Symptom Scores: Nasal Congestion, Nasal Itching, Rhinorrhea | Rhinorrhea: Post-allergen challenge | 1.1 units on a scale | Standard Deviation 1.48 |
| PF-03654746 1 mg | Nasal Symptom Scores: Nasal Congestion, Nasal Itching, Rhinorrhea | Nasal congestion: Post-allergen challenge | 1.8 units on a scale | Standard Deviation 1.3 |
| PF-03654746 1 mg | Nasal Symptom Scores: Nasal Congestion, Nasal Itching, Rhinorrhea | Nasal congestion: Pre-allergen challenge | 0.4 units on a scale | Standard Deviation 0.42 |
| PF-03654746 1 mg | Nasal Symptom Scores: Nasal Congestion, Nasal Itching, Rhinorrhea | Nasal congestion: Post-oxymetazoline | 0.8 units on a scale | Standard Deviation 1.21 |
| PF-03654746 1 mg | Nasal Symptom Scores: Nasal Congestion, Nasal Itching, Rhinorrhea | Rhinorrhea: Pre-allergen challenge | 0.1 units on a scale | Standard Deviation 0.17 |
| Allegra-D | Nasal Symptom Scores: Nasal Congestion, Nasal Itching, Rhinorrhea | Nasal Itching: Pre-allergen challenge | 0.0 units on a scale | Standard Deviation 0.08 |
| Allegra-D | Nasal Symptom Scores: Nasal Congestion, Nasal Itching, Rhinorrhea | Nasal congestion: Pre-allergen challenge | 0.4 units on a scale | Standard Deviation 0.57 |
| Allegra-D | Nasal Symptom Scores: Nasal Congestion, Nasal Itching, Rhinorrhea | Nasal congestion: Post-allergen challenge | 1.9 units on a scale | Standard Deviation 1.42 |
| Allegra-D | Nasal Symptom Scores: Nasal Congestion, Nasal Itching, Rhinorrhea | Nasal congestion: Post-oxymetazoline | 0.9 units on a scale | Standard Deviation 0.85 |
| Allegra-D | Nasal Symptom Scores: Nasal Congestion, Nasal Itching, Rhinorrhea | Nasal Itching: Post-allergen challenge | 0.9 units on a scale | Standard Deviation 1.12 |
| Allegra-D | Nasal Symptom Scores: Nasal Congestion, Nasal Itching, Rhinorrhea | Rhinorrhea: Pre-allergen challenge | 0.2 units on a scale | Standard Deviation 0.39 |
| Allegra-D | Nasal Symptom Scores: Nasal Congestion, Nasal Itching, Rhinorrhea | Rhinorrhea: Post-allergen challenge | 1.3 units on a scale | Standard Deviation 1.3 |
| Placebo | Nasal Symptom Scores: Nasal Congestion, Nasal Itching, Rhinorrhea | Nasal congestion: Post-oxymetazoline | 0.9 units on a scale | Standard Deviation 1.2 |
| Placebo | Nasal Symptom Scores: Nasal Congestion, Nasal Itching, Rhinorrhea | Rhinorrhea: Post-allergen challenge | 1.9 units on a scale | Standard Deviation 1.42 |
| Placebo | Nasal Symptom Scores: Nasal Congestion, Nasal Itching, Rhinorrhea | Rhinorrhea: Pre-allergen challenge | 0.1 units on a scale | Standard Deviation 0.33 |
| Placebo | Nasal Symptom Scores: Nasal Congestion, Nasal Itching, Rhinorrhea | Nasal congestion: Post-allergen challenge | 2.2 units on a scale | Standard Deviation 1.48 |
| Placebo | Nasal Symptom Scores: Nasal Congestion, Nasal Itching, Rhinorrhea | Nasal congestion: Pre-allergen challenge | 0.4 units on a scale | Standard Deviation 0.59 |
| Placebo | Nasal Symptom Scores: Nasal Congestion, Nasal Itching, Rhinorrhea | Nasal Itching: Post-allergen challenge | 1.4 units on a scale | Standard Deviation 1.43 |
| Placebo | Nasal Symptom Scores: Nasal Congestion, Nasal Itching, Rhinorrhea | Nasal Itching: Pre-allergen challenge | 0.1 units on a scale | Standard Deviation 0.31 |
Comparison: Nasal congestion: An ANOVA mixed model was assessed with sequence, period and treatment as fixed effects and participant within sequence as a random effect.p-value: 0.218ANOVA
Comparison: Nasal congestion: An ANOVA mixed model was assessed with sequence, period and treatment as fixed effects and participant within sequence as a random effect.p-value: 0.905ANOVA
Comparison: Nasal congestion: An ANOVA mixed model was assessed with sequence, period and treatment as fixed effects and participant within sequence as a random effect.p-value: 0.273ANOVA
Comparison: Nasal congestion: An ANOVA mixed model was assessed with sequence, period and treatment as fixed effects and participant within sequence as a random effect.p-value: 0.011ANOVA
Comparison: Nasal congestion: An ANOVA mixed model was assessed with sequence, period and treatment as fixed effects and participant within sequence as a random effect.p-value: 0.127ANOVA
Comparison: Nasal congestion: An ANOVA mixed model was assessed with sequence, period and treatment as fixed effects and participant within sequence as a random effect.p-value: 0.103ANOVA
Comparison: Nasal Itching: An ANOVA mixed model was assessed with sequence, period and treatment as fixed effects and participant within sequence as a random effect.p-value: 0ANOVA
Comparison: Nasal Itching: An ANOVA mixed model was assessed with sequence, period and treatment as fixed effects and participant within sequence as a random effect.p-value: 0.055ANOVA
Comparison: Nasal Itching: An ANOVA mixed model was assessed with sequence, period and treatment as fixed effects and participant within sequence as a random effect.p-value: 0.012ANOVA
Comparison: Nasal Itching: An ANOVA mixed model was assessed with sequence, period and treatment as fixed effects and participant within sequence as a random effect.p-value: 0.048ANOVA
Comparison: Nasal Itching: An ANOVA mixed model was assessed with sequence, period and treatment as fixed effects and participant within sequence as a random effect.p-value: 0.496ANOVA
Comparison: Nasal Itching: An ANOVA mixed model was assessed with sequence, period and treatment as fixed effects and participant within sequence as a random effect.p-value: 0.19ANOVA
Comparison: Rhinorrhea: An ANOVA mixed model was assessed with sequence, period and treatment as fixed effects and participant within sequence as a random effect.p-value: 0ANOVA
Comparison: Rhinorrhea: An ANOVA mixed model was assessed with sequence, period and treatment as fixed effects and participant within sequence as a random effect.p-value: 0.019ANOVA
Comparison: Rhinorrhea: An ANOVA mixed model was assessed with sequence, period and treatment as fixed effects and participant within sequence as a random effect.p-value: 0.009ANOVA
Comparison: Rhinorrhea: An ANOVA mixed model was assessed with sequence, period and treatment as fixed effects and participant within sequence as a random effect.p-value: 0.061ANOVA
Comparison: Rhinorrhea: An ANOVA mixed model was assessed with sequence, period and treatment as fixed effects and participant within sequence as a random effect.p-value: 0.778ANOVA
Comparison: Rhinorrhea: An ANOVA mixed model was assessed with sequence, period and treatment as fixed effects and participant within sequence as a random effect.p-value: 0.102ANOVA
Secondary
Nasal Symptom Scores: Sneezing
The absolute number of sneezes was recorded by the participants under supervision of study personnel. Nasal symptom score for sneezing was assessed as the total number of sneezes of each intervention period at specified time-points for the post-diluent and post-challenge and post where 'post-diluent, pre-allergen challenge' included 2 hrs 10 min, 2 hrs 25 min and 2 hrs 40 min post PF-03654746/placebo dose at each intervention period and 'post-allergen challenge' included 2 hrs 55 min, 3 hrs 10 min and 3 hrs 25 min post PF-03654746/placebo dose at each intervention period.
Time frame: 2 hrs 10 min, 2 hrs 25 min, 2 hrs 40 min post dose (Baseline); 2 hrs 55 min, 3 hrs 10 min, 3 hrs 25 min post dose on Day 1 of each intervention period
Population: Full analysis set included all participants randomized at baseline and who received at least 1 dose of double-blind treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PF-03654746 10 mg | Nasal Symptom Scores: Sneezing | Sneezing: Pre-allergen challenge | 0.0 sneezes | Standard Deviation 0.07 |
| PF-03654746 10 mg | Nasal Symptom Scores: Sneezing | Sneezing: Post-allergen challenge | 0.7 sneezes | Standard Deviation 1.54 |
| PF-03654746 1 mg | Nasal Symptom Scores: Sneezing | Sneezing: Post-allergen challenge | 0.6 sneezes | Standard Deviation 0.92 |
| PF-03654746 1 mg | Nasal Symptom Scores: Sneezing | Sneezing: Pre-allergen challenge | 0.1 sneezes | Standard Deviation 0.23 |
| Allegra-D | Nasal Symptom Scores: Sneezing | Sneezing: Pre-allergen challenge | 0.1 sneezes | Standard Deviation 0.61 |
| Allegra-D | Nasal Symptom Scores: Sneezing | Sneezing: Post-allergen challenge | 1.2 sneezes | Standard Deviation 1.94 |
| Placebo | Nasal Symptom Scores: Sneezing | Sneezing: Pre-allergen challenge | 0.1 sneezes | Standard Deviation 0.17 |
| Placebo | Nasal Symptom Scores: Sneezing | Sneezing: Post-allergen challenge | 3.6 sneezes | Standard Deviation 3.24 |
Comparison: An analysis of variance (ANOVA) mixed model was assessed with sequence, period and treatment as fixed effects and participant within sequence as a random effect.p-value: 0ANOVA
Comparison: An ANOVA mixed model was assessed with sequence, period and treatment as fixed effects and participant within sequence as a random effect.p-value: 0ANOVA
Comparison: An ANOVA mixed model was assessed with sequence, period and treatment as fixed effects and participant within sequence as a random effect.p-value: 0ANOVA
Comparison: An ANOVA mixed model was assessed with sequence, period and treatment as fixed effects and participant within sequence as a random effect.p-value: 0.217ANOVA
Comparison: An ANOVA mixed model was assessed with sequence, period and treatment as fixed effects and participant within sequence as a random effect.p-value: 0.156ANOVA
Comparison: An ANOVA mixed model was assessed with sequence, period and treatment as fixed effects and participant within sequence as a random effect.p-value: 0.848ANOVA
Secondary
Nasal Volume Maximum Fall Measured Using Acoustic Rhinometry
Acoustic rhinometry: a technique intended for assessment of the geometry of the nasal cavity and nasopharynx and for evaluating nasal obstruction. At each time point, there were 2 acoustic rhinometry measurements taken, one for each nostril. The mean of the left and right nostril measurements was taken as the measurement at each time point. Nasal volume at Baseline was defined as mean of the 3, 'post-diluent, pre-allergen challenge' measures for each intervention period at 2 hrs 10 min, 2 hrs 25 min and 2 hrs 40 min post PF-03654746/placebo dose. Nasal volume 'post-allergen challenge' measures were recorded at 2 hrs 55 min, 3 hrs 10 min and 3 hrs 25 min post PF-03654746/placebo dose for each intervention period. The maximum fall for nasal volume was calculated as baseline measure minus smallest 'post-allergen challenge' nasal volume measurement among the 3 measures.
Time frame: 2 hrs 10 min, 2 hrs 25 min, 2 hrs 40 min post dose (Baseline); 2 hrs 55 min, 3 hrs 10 min, 3 hrs 25 min post dose on Day 1 of each intervention period
Population: Full analysis set included all participants randomized at baseline and who received at least 1 dose of double-blind treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PF-03654746 10 mg | Nasal Volume Maximum Fall Measured Using Acoustic Rhinometry | 3.132 cubic centimeter (cm^3) | Standard Deviation 2.412 |
| PF-03654746 1 mg | Nasal Volume Maximum Fall Measured Using Acoustic Rhinometry | 3.244 cubic centimeter (cm^3) | Standard Deviation 2.3676 |
| Allegra-D | Nasal Volume Maximum Fall Measured Using Acoustic Rhinometry | 4.443 cubic centimeter (cm^3) | Standard Deviation 2.9502 |
| Placebo | Nasal Volume Maximum Fall Measured Using Acoustic Rhinometry | 3.275 cubic centimeter (cm^3) | Standard Deviation 2.7001 |
Comparison: An analysis of variance (ANOVA) mixed model was assessed with sequence, period and treatment as fixed effects and participant within sequence as a random effect.p-value: 0.357ANOVA
Comparison: An ANOVA mixed model was assessed with sequence, period and treatment as fixed effects and participant within sequence as a random effect.p-value: 0.952ANOVA
Comparison: An ANOVA mixed model was assessed with sequence, period and treatment as fixed effects and participant within sequence as a random effect.p-value: 0.48ANOVA
Comparison: An ANOVA mixed model was assessed with sequence, period and treatment as fixed effects and participant within sequence as a random effect.p-value: 0.043ANOVA
Comparison: An ANOVA mixed model was assessed with sequence, period and treatment as fixed effects and participant within sequence as a random effect.p-value: 0.087ANOVA
Comparison: An ANOVA mixed model was assessed with sequence, period and treatment as fixed effects and participant within sequence as a random effect.p-value: 0.753ANOVA
Other Pre-specified
Serum PF-03654746 Concentration
Only participants receiving PF-03654746 were analyzed for this outcome measure. Mean serum concentration of PF-03654746 was calculated of each intervention period.
Time frame: 1 hr 30 min post dose on Day 1 of each intervention period
Population: Full analysis set included all participants randomized at baseline and who received at least 1 dose of double-blind treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PF-03654746 10 mg | Serum PF-03654746 Concentration | 34.16 nanogram per milliliter (ng/mL) | Standard Deviation 17.85 |
| PF-03654746 1 mg | Serum PF-03654746 Concentration | 2.78 nanogram per milliliter (ng/mL) | Standard Deviation 1.55 |