Efficacy study in allergic rhinitis patients after intranasal administration of AZD8848

Study identifier:D0540C00014

ClinicalTrials.gov identifier:N/A

EudraCT identifier:2010-020747-13

CTIS identifier:N/A

Study Complete

Official Title

A double-blind, placebo controlled, randomised, parallel group phase IIa study to investigate the efficacy, tolerability, and safety of different dosing regimens of AZD8848 administered intranasally to seasonal allergic rhinitis patients out of pollen season in a nasal allergen challenge model

Medical condition

Allergic Rhinitis

Phase

Phase 2

Healthy volunteers

Study drug

AZD8848, Placebo, AZD8848 and placebo

Sex

All

Actual Enrollment

Study type

Interventional

Age

18 Years - 55 Years

Date

Study Start Date: 01 Sept 2010

Primary Completion Date: 01 Dec 2010

Study Completion Date: 01 Jan 2012

Study design

Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind
Primary Purpose: Treatment

Verification:

Verified 01 Dec 2015 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

Location

Research Site

Lund, Malmohus Lan, Sweden

Location

Research Site

HELSINGBORG, Sweden

Arms	Assigned Interventions
Experimental: 1. AZD8848 20 μg AZD8848 three times weekly	Drug: AZD8848 Nasal spray solution, intranasal, three times weekly for one month
Placebo Comparator: 2. Placebo Placebo three times weekly	Drug: Placebo Nasal spray solution, intranasal, three times weekly for one month
Experimental: 3. AZD8848 and placebo 60 μg AZD8848 once weekly and placebo twice weekly	Drug: AZD8848 and placebo Nasal spray solution, intranasal, three times weekly for one month

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
There were 93 patients enrolled in the study, who 83 of them were randomized. Of the 10 patients who were not randomized, 3 patients due to "patient decision" and 7 patients due to "Eligibility criteria not fulfilled" were not randomized.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups

	Description
AZD8848 20 μg x3	20 μg AZD8848 three times weekly
Placebo	Placebo three times weekly
AZD8848 60 μg	60 μg AZD8848 once weekly and placebo twice weekly

Participant Flow: Overall Study

	AZD8848 20 μg x3	Placebo	AZD8848 60 μg
STARTED	50	16	17
COMPLETED	49	15	16
NOT COMPLETED	1	1	1
Adverse Event	1	1	0
Personal reasons	0	0	1

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

Reporting Groups

	Description
AZD8848 20 μg x3	20 μg AZD8848 three times weekly
Placebo	Placebo three times weekly
AZD8848 60 μg	60 μg AZD8848 once weekly and placebo twice weekly

Baseline Measures

	AZD8848 20 μg x3	Placebo	AZD8848 60 μg	Total
Number of Participants [units: Participants]	50	16	17	83
Age Continuous [units: years] Mean ( Full Range )	29.7 (18 to 53)	28.8 (20 to 46)	31.0 (19 to 47)	29.8 (18 to 53)
Gender, Male/Female [units: Participants]
Female	6	2	2	10
Male	44	14	15	73

Outcome Measures

1. Primary Outcome Measure: Mean of Reflective (10 min) Total Nasal Symptom Score (TNSS) [ Time Frame: During 1st day to 7th day of Allergen challenge period. ]

Measure Type	Primary
Measure Name	Mean of Reflective (10 min) Total Nasal Symptom Score (TNSS)
Measure Description	Mean of Reflective Total Nasal Symptom Score (absolute values) for symptoms over the last 10 minutes after allergen challenge, collected during clinic visits. The Mean is calculated over the Allergen challenge period, which is a seven day period. Each individual symptom is scored 0 to 3, which 0 = Absence of symptoms, 1 = Mild symptoms, 2 = Moderate symptoms and 3 = Severe symptoms. The scores of each individual symptom (runny nose, blocked nose and the maximum score of nasal itching or sneezing) will be added together to give a TNSS of 0 to 9. TNSS Score 0 indicates better outcome and TNSS score 9 indicates worse outcome. Allergen challenge period starts 24 hrs post last dose (visit 15). Number of Participants Analyzed is based on all patients with evaluable efficacy and/or biomarker data from the challenge period (Visit 15).
Time Frame	During 1st day to 7th day of Allergen challenge period.
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
AZD8848 20 μg x3	20 μg AZD8848 three times weekly
Placebo	Placebo three times weekly
AZD8848 60 μg	60 μg AZD8848 once weekly and placebo twice weekly

Measured Values

	AZD8848 20 μg x3	Placebo	AZD8848 60 μg
Number of Participants Analyzed [units:participants]	50	15	16
Mean of Reflective (10 min) Total Nasal Symptom Score (TNSS) [units: Scores on a scale] Least Squares Mean (Full Range)	4.52 (1.43 to 7.71)	4.97 (2.86 to 6.43)	4.69 (3.14 to 7.00)

No statistical analysis provided for Mean of Reflective (10 min) Total Nasal Symptom Score (TNSS)

2. Primary Outcome Measure: Mean of Reflective (10 min) Total Nasal Symptom Score (TNSS) [ Time Frame: During 4th day to 7th day of Allergen challenge period. ]

Measure Type	Primary
Measure Name	Mean of Reflective (10 min) Total Nasal Symptom Score (TNSS)
Measure Description	Mean of Reflective Total Nasal Symptom Score (absolute values) for symptoms over the last 10 minutes after allergen challenge, collected during clinic visits. The Mean is calculated over 4th day to 7th day of the Allergen challenge period. Each individual symptom is scored 0 to 3, which 0 = Absence of symptoms, 1 = Mild symptoms, 2 = Moderate symptoms and 3 = Severe symptoms. The scores of each individual symptom (runny nose, blocked nose and the maximum score of nasal itching or sneezing) will be added together to give a TNSS of 0 to 9. TNSS Score 0 indicates better outcome and TNSS score 9 indicates worse outcome. Allergen challenge period starts 24 hrs post last dose. Number of Participants Analyzed is based on all patients with evaluable efficacy and/or biomarker data from the challenge period (Visit 15).
Time Frame	During 4th day to 7th day of Allergen challenge period.
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
AZD8848 20 μg x3	20 μg AZD8848 three times weekly
Placebo	Placebo three times weekly
AZD8848 60 μg	60 μg AZD8848 once weekly and placebo twice weekly

Measured Values

	AZD8848 20 μg x3	Placebo	AZD8848 60 μg
Number of Participants Analyzed [units:participants]	49	15	16
Mean of Reflective (10 min) Total Nasal Symptom Score (TNSS) [units: Scores on a scale] Least Squares Mean (Full Range)	4.45 (1.25 to 8.25)	5.36 (3.25 to 8.00)	4.42 (2.75 to 7.50)

No statistical analysis provided for Mean of Reflective (10 min) Total Nasal Symptom Score (TNSS)

3. Primary Outcome Measure: Mean of morning measurements of Reflective (12 hrs) Total Nasal Symptom Score (TNSS) [ Time Frame: During evening of the 1st day to the morning of the 8th day of Allergen challenge period. ]

Measure Type	Primary
Measure Name	Mean of morning measurements of Reflective (12 hrs) Total Nasal Symptom Score (TNSS)
Measure Description	Mean of morning measurements of Reflective Total Nasal Symptom Score (absolute values) of symptoms over the last 12 hours during allergen challenge, collected in patient diary. The Mean is calculated over the evening of the 1st day to the morning of 8th day of the Allergen challenge period. Each individual symptom is scored 0 to 3, which 0 = Absence of symptoms, 1 = Mild symptoms, 2 = Moderate symptoms and 3 = Severe symptoms. The scores of each individual symptom (runny nose, blocked nose and the maximum score of nasal itching or sneezing) will be added together to give a TNSS of 0 to 9. TNSS Score 0 indicates better outcome and TNSS score 9 indicates worse outcome. Allergen challenge period starts 24 hrs post last dose. Number of Participants Analyzed is based on all patients with evaluable efficacy and/or biomarker data from the challenge period (Visit 15).
Time Frame	During evening of the 1st day to the morning of the 8th day of Allergen challenge period.
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
AZD8848 20 μg x3	20 μg AZD8848 three times weekly
Placebo	Placebo three times weekly
AZD8848 60 μg	60 μg AZD8848 once weekly and placebo twice weekly

Measured Values

	AZD8848 20 μg x3	Placebo	AZD8848 60 μg
Number of Participants Analyzed [units:participants]	50	14	16
Mean of morning measurements of Reflective (12 hrs) Total Nasal Symptom Score (TNSS) [units: Scores on a scale] Least Squares Mean (Full Range)	1.81 (0.286 to 4.14)	2.14 (0.286 to 3.57)	1.48 (0.143 to 3.29)

No statistical analysis provided for Mean of morning measurements of Reflective (12 hrs) Total Nasal Symptom Score (TNSS)

4. Primary Outcome Measure: Mean of evening measurements of Reflective (12 hrs) Total Nasal Symptom Score (TNSS) [ Time Frame: During the evening of the 1st day to the morning of the 8th day of Allergen challenge period. ]

Measure Type	Primary
Measure Name	Mean of evening measurements of Reflective (12 hrs) Total Nasal Symptom Score (TNSS)
Measure Description	Mean of evening measurements of Reflective Total Nasal Symptom Score (absolute values) of symptoms over the last 12 hours during allergen challenge, collected in patient diary. The Mean is calculated over the evening of the 1st day to the morning of 8th day of the Allergen challenge period. Each individual symptom is scored 0 to 3, which 0 = Absence of symptoms, 1 = Mild symptoms, 2 = Moderate symptoms and 3 = Severe symptoms. The scores of each individual symptom (runny nose, blocked nose and the maximum score of nasal itching or sneezing) will be added together to give a TNSS of 0 to 9. TNSS Score 0 indicates better outcome and TNSS score 9 indicates worse outcome. Allergen challenge period starts 24 hrs post last dose. Number of Participants Analyzed is based on all patients with evaluable efficacy and/or biomarker data from the challenge period (Visit 15).
Time Frame	During the evening of the 1st day to the morning of the 8th day of Allergen challenge period.
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
AZD8848 20 μg x3	20 μg AZD8848 three times weekly
Placebo	Placebo three times weekly
AZD8848 60 μg	60 μg AZD8848 once weekly and placebo twice weekly

Measured Values

	AZD8848 20 μg x3	Placebo	AZD8848 60 μg
Number of Participants Analyzed [units:participants]	50	14	16
Mean of evening measurements of Reflective (12 hrs) Total Nasal Symptom Score (TNSS) [units: Scores on a scale] Least Squares Mean (Full Range)	2.06 (0.143 to 4.71)	2.32 (0 to 4.57)	1.96 (0.143 to 4.43)

No statistical analysis provided for Mean of evening measurements of Reflective (12 hrs) Total Nasal Symptom Score (TNSS)

5. Primary Outcome Measure: Mean of Peak Nasal Inspiratory Flow (PNIF) (10 min) [ Time Frame: During 1st day to 7th day of Allergen challenge period. ]

Measure Type	Primary
Measure Name	Mean of Peak Nasal Inspiratory Flow (PNIF) (10 min)
Measure Description	Mean of Peak Nasal Inspiratory Flow (absolute values) recorded immediately after TNSS scoring (recall period 10 min), during Allergen challenge period. The Mean is calculated over the Allergen challenge period, which is a seven day period. The patient will breathe out as much as he can. Then a mask (Portable Inspiratory Flow Meter) will be placed over the nose and mouth and the patient will inspire forcefully through the nose while the lips remain tightly closed. The highest PNIF (L/minute) out of 3 measurements will be recorded. Allergen challenge period starts 24 hrs post last dose. Number of Participants Analyzed is based on all patients with evaluable efficacy and/or biomarker data from the challenge period (Visit 15).
Time Frame	During 1st day to 7th day of Allergen challenge period.
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
AZD8848 20 μg x3	20 μg AZD8848 three times weekly
Placebo	Placebo three times weekly
AZD8848 60 μg	60 μg AZD8848 once weekly and placebo twice weekly

Measured Values

	AZD8848 20 μg x3	Placebo	AZD8848 60 μg
Number of Participants Analyzed [units:participants]	50	15	16
Mean of Peak Nasal Inspiratory Flow (PNIF) (10 min) [units: L/min] Least Squares Mean (Full Range)	117 (37.9 to 197)	127 (67.0 to 214)	129 (50.0 to 243)

No statistical analysis provided for Mean of Peak Nasal Inspiratory Flow (PNIF) (10 min)

6. Primary Outcome Measure: Mean of Peak Nasal Inspiratory Flow (PNIF) (10 min) [ Time Frame: During 4th day to 7th day of Allergen challenge period. ]

Measure Type	Primary
Measure Name	Mean of Peak Nasal Inspiratory Flow (PNIF) (10 min)
Measure Description	Mean of Peak Nasal Inspiratory Flow (absolute values) recorded immediately after TNSS scoring (recall period 10 min), during Allergen challenge period. The Mean is calculated over 4th day to 7th day of the Allergen challenge period. The patient will breathe out as much as he can. Then a mask (Portable Inspiratory Flow Meter) will be placed over the nose and mouth and the patient will inspire forcefully through the nose while the lips remain tightly closed. The highest PNIF (L/minute) out of 3 measurements will be recorded. Allergen challenge period starts 24 hrs post last dose. Number of Participants Analyzed is based on all patients with evaluable efficacy and/or biomarker data from the challenge period (Visit 15).
Time Frame	During 4th day to 7th day of Allergen challenge period.
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
AZD8848 20 μg x3	20 μg AZD8848 three times weekly
Placebo	Placebo three times weekly
AZD8848 60 μg	60 μg AZD8848 once weekly and placebo twice weekly

Measured Values

	AZD8848 20 μg x3	Placebo	AZD8848 60 μg
Number of Participants Analyzed [units:participants]	49	15	16
Mean of Peak Nasal Inspiratory Flow (PNIF) (10 min) [units: L/min] Least Squares Mean (Full Range)	121 (37.5 to 200)	128 (77.5 to 220)	135 (52.5 to 245)

No statistical analysis provided for Mean of Peak Nasal Inspiratory Flow (PNIF) (10 min)

7. Primary Outcome Measure: Mean of morning measurements of Peak Nasal Inspiratory Flow (PNIF) (12 hrs) [ Time Frame: During evening of the 1st day to the morning of the 8th day of Allergen challenge period. ]

Measure Type	Primary
Measure Name	Mean of morning measurements of Peak Nasal Inspiratory Flow (PNIF) (12 hrs)
Measure Description	Mean of morning measurements of Peak Nasal Inspiratory Flow (absolute values) of symptoms over the last 12 hours during allergen challenge, collected in patient diary. The Mean is calculated over the evening of the 1st day to the morning of 8th day of the Allergen challenge period. The patient will breathe out as much as he can. Then a mask (Portable Inspiratory Flow Meter) will be placed over the nose and mouth and the patient will inspire forcefully through the nose while the lips remain tightly closed. The highest PNIF (L/minute) out of 3 measurements will be recorded. Allergen challenge period starts 24 hrs post last dose. Number of Participants Analyzed is based on all patients with evaluable efficacy and/or biomarker data from the challenge period (Visit 15).
Time Frame	During evening of the 1st day to the morning of the 8th day of Allergen challenge period.
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
AZD8848 20 μg x3	20 μg AZD8848 three times weekly
Placebo	Placebo three times weekly
AZD8848 60 μg	60 μg AZD8848 once weekly and placebo twice weekly

Measured Values

	AZD8848 20 μg x3	Placebo	AZD8848 60 μg
Number of Participants Analyzed [units:participants]	50	14	16
Mean of morning measurements of Peak Nasal Inspiratory Flow (PNIF) (12 hrs) [units: L/min] Least Squares Mean (Full Range)	136 (51.4 to 237)	148 (84.3 to 237)	148 (71.4 to 234)

No statistical analysis provided for Mean of morning measurements of Peak Nasal Inspiratory Flow (PNIF) (12 hrs)

8. Primary Outcome Measure: of evening measurements of Peak Nasal Inspiratory Flow (PNIF) (12 hrs) [ Time Frame: During evening of the 1st day to the morning of the 8th day of Allergen challenge period. ]

Measure Type	Primary
Measure Name	of evening measurements of Peak Nasal Inspiratory Flow (PNIF) (12 hrs)
Measure Description	Mean of evening measurements of Peak Nasal Inspiratory Flow (absolute values) of symptoms over the last 12 hours during allergen challenge, collected in patient diary. The Mean is calculated over the evening of the 1st day to the morning of 8th day of the Allergen challenge period. The patient will breathe out as much as he can. Then a mask (Portable Inspiratory Flow Meter) will be placed over the nose and mouth and the patient will inspire forcefully through the nose while the lips remain tightly closed. The highest PNIF (L/minute) out of 3 measurements will be recorded. Allergen challenge period starts 24 hrs post last dose. Number of Participants Analyzed is based on all patients with evaluable efficacy and/or biomarker data from the challenge period (Visit 15).
Time Frame	During evening of the 1st day to the morning of the 8th day of Allergen challenge period.
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
AZD8848 20 μg x3	20 μg AZD8848 three times weekly
Placebo	Placebo three times weekly
AZD8848 60 μg	60 μg AZD8848 once weekly and placebo twice weekly

Measured Values

	AZD8848 20 μg x3	Placebo	AZD8848 60 μg
Number of Participants Analyzed [units:participants]	50	14	16
of evening measurements of Peak Nasal Inspiratory Flow (PNIF) (12 hrs) [units: L/min] Least Squares Mean (Full Range)	145 (52.9 to 222)	149 (71.4 to 253)	147 (68.6 to 251)

No statistical analysis provided for of evening measurements of Peak Nasal Inspiratory Flow (PNIF) (12 hrs)

9. Secondary Outcome Measure: Absolute mean value of instantaneous Total Nasal Symptom Score (TNSS) [ Time Frame: Pre-dose on visit 2 (baseline) ]

Measure Type	Secondary
Measure Name	Absolute mean value of instantaneous Total Nasal Symptom Score (TNSS)
Measure Description	Absolute mean value of Instantaneous Total Nasal Symptom Score (TNSS) for pre-dose symptoms on visit 2, during treatment period. Treatment period is one month, which starts at visit 2 and ends at visit 14. Each individual symptom is scored 0 to 3, which 0 = Absence of symptoms, 1 = Mild symptoms, 2 = Moderate symptoms and 3 = Severe symptoms. The scores of each individual symptom (runny nose, blocked nose and the maximum score of nasal itching or sneezing) will be added together to give a TNSS of 0 to 9. TNSS Score 0 indicates better outcome and TNSS score 9 indicate worse outcome. Number of Participants Analyzed is based on all patients with evaluable efficacy and/or biomarker data at visit 2.
Time Frame	Pre-dose on visit 2 (baseline)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
AZD8848 20 μg x3	20 μg AZD8848 three times weekly
Placebo	Placebo three times weekly
AZD8848 60 μg	60 μg AZD8848 once weekly and placebo twice weekly

Measured Values

	AZD8848 20 μg x3	Placebo	AZD8848 60 μg
Number of Participants Analyzed [units:participants]	50	16	17
Absolute mean value of instantaneous Total Nasal Symptom Score (TNSS) [units: Scores on a scale] Mean (Standard Deviation)	0.38 (0.697)	0.75 (1.291)	0.35 (0.493)

No statistical analysis provided for Absolute mean value of instantaneous Total Nasal Symptom Score (TNSS)

10. Secondary Outcome Measure: Absolute mean value of instantaneous Total Nasal Symptom Score (TNSS) [ Time Frame: Pre-dose on visit 11 (end of 3rd week of treatment) ]

Measure Type	Secondary
Measure Name	Absolute mean value of instantaneous Total Nasal Symptom Score (TNSS)
Measure Description	Absolute mean value of Instantaneous Total Nasal Symptom Score (TNSS) for pre-dose symptoms on visit11, during treatment period. Treatment period is one month, which starts at visit 2 and ends at visit 14. Each individual symptom is scored 0 to 3, which 0 = Absence of symptoms, 1 = Mild symptoms, 2 = Moderate symptoms and 3 = Severe symptoms. The scores of each individual symptom (runny nose, blocked nose and the maximum score of nasal itching or sneezing) will be added together to give a TNSS of 0 to 9. TNSS Score 0 indicates better outcome and TNSS score 9 indicates worse outcome. Number of Participants Analyzed is based on all patients with evaluable efficacy and/or biomarker data at visit 11.
Time Frame	Pre-dose on visit 11 (end of 3rd week of treatment)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
AZD8848 20 μg x3	20 μg AZD8848 three times weekly
Placebo	Placebo three times weekly
AZD8848 60 μg	60 μg AZD8848 once weekly and placebo twice weekly

Measured Values

	AZD8848 20 μg x3	Placebo	AZD8848 60 μg
Number of Participants Analyzed [units:participants]	49	15	15
Absolute mean value of instantaneous Total Nasal Symptom Score (TNSS) [units: Scores on a scale] Mean (Standard Deviation)	1.20 (1.020)	0.67 (1.047)	0.80 (0.862)

No statistical analysis provided for Absolute mean value of instantaneous Total Nasal Symptom Score (TNSS)

11. Secondary Outcome Measure: Absolute mean value of Peak Nasal Inspiratory Flow (PNIF) [ Time Frame: Pre-dose on visit 2 (baseline) ]

Measure Type	Secondary
Measure Name	Absolute mean value of Peak Nasal Inspiratory Flow (PNIF)
Measure Description	Absolute mean value of Peak Nasal Inspiratory Flow (PNIF) for pre-dose symptoms on visit 2, during treatment period. Treatment period is one month, which starts at visit 2 and ends at visit 14. The patient will breathe out as much as he can. Then a mask (Portable Inspiratory Flow Meter) will be placed over the nose and mouth and the patient will inspire forcefully through the nose while the lips remain tightly closed. The highest PNIF (L/minute) out of 3 measurements will be recorded. Number of Participants Analyzed is based on all patients with evaluable efficacy and/or biomarker data at visit 2.
Time Frame	Pre-dose on visit 2 (baseline)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
AZD8848 20 μg x3	20 μg AZD8848 three times weekly
Placebo	Placebo three times weekly
AZD8848 60 μg	60 μg AZD8848 once weekly and placebo twice weekly

Measured Values

	AZD8848 20 μg x3	Placebo	AZD8848 60 μg
Number of Participants Analyzed [units:participants]	50	16	17
Absolute mean value of Peak Nasal Inspiratory Flow (PNIF) [units: L/min] Mean (Standard Deviation)	170.4 (54.593)	176.9 (63.005)	169.4 (62.497)

No statistical analysis provided for Absolute mean value of Peak Nasal Inspiratory Flow (PNIF)

12. Secondary Outcome Measure: Absolute mean value of Peak Nasal Inspiratory Flow (PNIF) [ Time Frame: Pre-dose on visit 11 (end of 3rd week of treatment) ]

Measure Type	Secondary
Measure Name	Absolute mean value of Peak Nasal Inspiratory Flow (PNIF)
Measure Description	Absolute mean value of Peak Nasal Inspiratory Flow (PNIF) for pre-dose symptoms on visit 11, during treatment period. Treatment period is one month, which starts at visit 2 and ends at visit 14. The patient will breathe out as much as he can. Then a mask (Portable Inspiratory Flow Meter) will be placed over the nose and mouth and the patient will inspire forcefully through the nose while the lips remain tightly closed. The highest PNIF (L/minute) out of 3 measurements will be recorded. Number of Participants Analyzed is based on all patients with evaluable efficacy and/or biomarker data at visit 11.
Time Frame	Pre-dose on visit 11 (end of 3rd week of treatment)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
AZD8848 20 μg x3	20 μg AZD8848 three times weekly
Placebo	Placebo three times weekly
AZD8848 60 μg	60 μg AZD8848 once weekly and placebo twice weekly

Measured Values

	AZD8848 20 μg x3	Placebo	AZD8848 60 μg
Number of Participants Analyzed [units:participants]	49	15	15
Absolute mean value of Peak Nasal Inspiratory Flow (PNIF) [units: L/min] Mean (Standard Deviation)	168.1 (52.070)	191.3 (48.824)	182.7 (61.350)

No statistical analysis provided for Absolute mean value of Peak Nasal Inspiratory Flow (PNIF)

13. Secondary Outcome Measure: Change from baseline of C-X-C motif chemokine 10 (CXCL10) in plasma [ Time Frame: Baseline to 1st day of visit 15 ]

Measure Type	Secondary
Measure Name	Change from baseline of C-X-C motif chemokine 10 (CXCL10) in plasma
Measure Description	Change from baseline to 24 hours after last dose (day1 visit 15) of C-X-C motif chemokine 10 (CXCL10) in plasma, expressed as a ratio. The ratio is calculated as day1 of visit 15 / baseline. Number of Participants Analyzed is based on all patients with evaluable biomarker data at visit 2 and visit15.
Time Frame	Baseline to 1st day of visit 15
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
AZD8848 20 μg x3	20 μg AZD8848 three times weekly
Placebo	Placebo three times weekly
AZD8848 60 μg	60 μg AZD8848 once weekly and placebo twice weekly

Measured Values

	AZD8848 20 μg x3	Placebo	AZD8848 60 μg
Number of Participants Analyzed [units:participants]	46	15	16
Change from baseline of C-X-C motif chemokine 10 (CXCL10) in plasma [units: ratio] Geometric Mean (95% Confidence Interval)	2.89 (2.45 to 3.40)	0.803 (0.6 to 1.07)	3.90 (2.96 to 5.15)

No statistical analysis provided for Change from baseline of C-X-C motif chemokine 10 (CXCL10) in plasma

14. Secondary Outcome Measure: Change from baseline of C-X-C motif chemokine 10 (CXCL10) in nasal lavage [ Time Frame: Baseline to 1st day of visit 15 ]

Measure Type	Secondary
Measure Name	Change from baseline of C-X-C motif chemokine 10 (CXCL10) in nasal lavage
Measure Description	Change from baseline to 24 hours after last dose (day1 visit 15) of C-X-C motif chemokine 10 (CXCL10) in nasal lavage, expressed as a ratio. The ratio is calculated as day1 of visit 15 / baseline. Number of Participants Analyzed is based on all patients with evaluable biomarker data at visit 2 and visit 15.
Time Frame	Baseline to 1st day of visit 15
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
AZD8848 20 μg x3	20 μg AZD8848 three times weekly
Placebo	Placebo three times weekly
AZD8848 60 μg	60 μg AZD8848 once weekly and placebo twice weekly

Measured Values

	AZD8848 20 μg x3	Placebo	AZD8848 60 μg
Number of Participants Analyzed [units:participants]	48	14	15
Change from baseline of C-X-C motif chemokine 10 (CXCL10) in nasal lavage [units: ratio] Least Squares Mean (95% Confidence Interval)	30.0 (21.99 to 40.81)	1.66 (0.93 to 2.97)	26.9 (15.52 to 46.56)

No statistical analysis provided for Change from baseline of C-X-C motif chemokine 10 (CXCL10) in nasal lavage

Serious Adverse Events

Time Frame	No text entered.
Additional Description	No text entered.

Reporting Groups

	Description
AZD8848 20 μg x3	20 μg AZD8848 three times weekly
Placebo	Placebo three times weekly
AZD8848 60 μg	60 μg AZD8848 once weekly and placebo twice weekly

Serious Adverse Events

	AZD8848 20 μg x3	Placebo	AZD8848 60 μg
Total, serious adverse events
# participants affected / at risk	0/50 (0.00%)	0/16 (0.00%)	0/17 (0.00%)

Other Adverse Events

Time Frame	No text entered.
Additional Description	No text entered.

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
AZD8848 20 μg x3	20 μg AZD8848 three times weekly
Placebo	Placebo three times weekly
AZD8848 60 μg	60 μg AZD8848 once weekly and placebo twice weekly

Other Adverse Events

AZD8848 20 μg x3

Placebo

AZD8848 60 μg

Total, other (not including serious) adverse events