Trial Outcomes & Findings for Study of Triamcinolone Acetonide on the Growth Velocity of Children, Ages 3 to 9, With Perennial Allergic Rhinitis (PAR) (NCT NCT00449072)

Last Updated: 2012-08-10

Results Overview

Individual participant's growth velocity over double-blind treatment period was calculated using a linear regression of height over time. Height was measured on the same wall-mounted Harpenden stadiometer with the participant barefoot and in light clothing.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

299 participants

Primary outcome timeframe

Day 1 to end of treatment (Day 360)

Results posted on

2012-08-10

Participant Flow

The study was conducted between 14 March 2007 (first subject enrolled) and 12 October 2011 (last subject last visit) at 69 active centers located in the US.

299 participants were randomized, 298 were treated.

Participant milestones

Participant milestones
Measure	Placebo 3 to 9 year old participants with PAR administered * Placebo (once to demonstrate IP administration in the baseline/screening period) * Placebo in the double-blind treatment period All participants were provided Children's Claritin® Syrup as a rescue medication	TAA-AQ 3 to 9 year old participants with PAR administered * Placebo (once to demonstrate IP administration in the baseline/screening period) * TAA-AQ in the double-blind treatment period All participants were provided Children's Claritin® Syrup as a rescue medication
Overall Study STARTED	148	151
Overall Study COMPLETED	107	109
Overall Study NOT COMPLETED	41	42

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo 3 to 9 year old participants with PAR administered * Placebo (once to demonstrate IP administration in the baseline/screening period) * Placebo in the double-blind treatment period All participants were provided Children's Claritin® Syrup as a rescue medication	TAA-AQ 3 to 9 year old participants with PAR administered * Placebo (once to demonstrate IP administration in the baseline/screening period) * TAA-AQ in the double-blind treatment period All participants were provided Children's Claritin® Syrup as a rescue medication
Overall Study Adverse Event	3	1
Overall Study Protocol Violation	14	12
Overall Study Lost to Follow-up	5	7
Overall Study Withdrawal by Subject	11	8
Overall Study Lack of Efficacy	1	1
Overall Study Physician Decision	1	0
Overall Study Not treated	0	1
Overall Study Excluded medication	0	2
Overall Study Non-compliance	2	5
Overall Study Sponsor decision	1	3
Overall Study Relocation	3	2

Baseline Characteristics

Study of Triamcinolone Acetonide on the Growth Velocity of Children, Ages 3 to 9, With Perennial Allergic Rhinitis (PAR)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=148 Participants 3 to 9 year old participants with PAR administered * Placebo (once to demonstrate IP administration in the baseline/screening period) * Placebo in the double-blind treatment period All participants were provided Children's Claritin® Syrup as a rescue medication	TAA-AQ n=151 Participants 3 to 9 year old participants with PAR administered * Placebo (once to demonstrate IP administration in the baseline/screening period) * TAA-AQ in the double-blind treatment period All participants were provided Children's Claritin® Syrup as a rescue medication	Total n=299 Participants Total of all reporting groups
Age Continuous	6.24 years STANDARD_DEVIATION 1.55 • n=5 Participants	6.12 years STANDARD_DEVIATION 1.62 • n=7 Participants	6.18 years STANDARD_DEVIATION 1.58 • n=5 Participants
Age, Customized <=3 to <6 years	64 participants n=5 Participants	65 participants n=7 Participants	129 participants n=5 Participants
Age, Customized <=6 to <10 years	84 participants n=5 Participants	86 participants n=7 Participants	170 participants n=5 Participants
Sex/Gender, Customized Male	86 participants n=5 Participants	87 participants n=7 Participants	173 participants n=5 Participants
Sex/Gender, Customized Female	62 participants n=5 Participants	64 participants n=7 Participants	126 participants n=5 Participants
Race/Ethnicity, Customized Caucasian/White	114 participants n=5 Participants	111 participants n=7 Participants	225 participants n=5 Participants
Race/Ethnicity, Customized Black	22 participants n=5 Participants	28 participants n=7 Participants	50 participants n=5 Participants
Race/Ethnicity, Customized Asian/Oriental	4 participants n=5 Participants	1 participants n=7 Participants	5 participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or other Pacific Island	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
Race/Ethnicity, Customized Other	8 participants n=5 Participants	10 participants n=7 Participants	18 participants n=5 Participants
Race/Ethnicity, Customized Hispanic or Latino	23 participants n=5 Participants	33 participants n=7 Participants	56 participants n=5 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	125 participants n=5 Participants	118 participants n=7 Participants	243 participants n=5 Participants
Tanner classification at randomization Stage 1	148 participants n=5 Participants	151 participants n=7 Participants	299 participants n=5 Participants
Tanner classification at randomization Stage 2	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
Tanner classification at randomization Stage 3	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
Tanner classification at randomization Stage 4	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
Tanner classification at randomization Stage 5	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants

PRIMARY outcome

Timeframe: Day 1 to end of treatment (Day 360)

Population: The modified intent-to-treat (mITT) population included all intent-to-treat participants who had at least 3 postrandomization visits with recorded height measurements during the double-blind treatment period, excluding those from Good Clinical Practice (GCP) noncompliant sites.

Outcome measures

Outcome measures
Measure	Placebo n=133 Participants 3 to 9 year old participants with PAR administered * Placebo (once to demonstrate IP administration in the baseline/screening period) * Placebo in the double-blind treatment period All participants were provided Children's Claritin® Syrup as a rescue medication.	TAA-AQ n=134 Participants 3 to 9 year old participants with PAR administered * Placebo (once to demonstrate IP administration in the baseline/screening period) * TAA-AQ in the double-blind treatment period All participants were provided Children's Claritin® Syrup as a rescue medication.
Growth Velocity	6.09 cm/year Standard Error 0.122	5.65 cm/year Standard Error 0.122

SECONDARY outcome

Timeframe: For 7 days prior to randomization (Baseline) and everyday for 7 days prior to Day 360 (end of treatment)

Population: mITT population with scores available for TNSS: All randomized and treated participants with at least 3 post-randomization height measurements during the double-blind treatment period with scores available for TNSS, excluding those from GCP noncompliant sites.

PAR symptoms - nasal stuffiness, nasal discharge, sneezing, and nasal itching were scored upon arising in the morning according to the following 4-point scale: * 0 = symptom absent * 1 = mild (present but not annoying to self) * 2 = moderate (annoying to self but not interfering with sleep or daily living) * 3 = severe (interfered with daily living and/or sleep) TNSS was the sum of the individual symptom scores (ranging 0-3), and TNSS ranged from 0 (best outcome) to 12 (worst outcome). A negative value for change represents an improvement in symptoms.

Outcome measures

Outcome measures
Measure	Placebo n=102 Participants 3 to 9 year old participants with PAR administered * Placebo (once to demonstrate IP administration in the baseline/screening period) * Placebo in the double-blind treatment period All participants were provided Children's Claritin® Syrup as a rescue medication.	TAA-AQ n=104 Participants 3 to 9 year old participants with PAR administered * Placebo (once to demonstrate IP administration in the baseline/screening period) * TAA-AQ in the double-blind treatment period All participants were provided Children's Claritin® Syrup as a rescue medication.
Change From Baseline in Instantaneous Total Nasal Symptom Score (TNSS)	-2.68 score on a scale Standard Error 0.26	-2.80 score on a scale Standard Error 0.25

SECONDARY outcome

Timeframe: For 7 days prior to randomization (Baseline) and everyday for 7 days prior to Day 360 (end of treatment)

Population: mITT population with available nasal symptom scores: All randomized and treated participants with at least 3 post-randomization height measurements during the double-blind treatment period with available nasal symptom scores, excluding those from GCP noncompliant sites.

PAR symptoms - nasal stuffiness, nasal discharge, sneezing, and nasal itching were scored upon arising in the morning according to the following 4-point scale: * 0 = symptom absent * 1 = mild (present but not annoying to self) * 2 = moderate (annoying to self but not interfering with sleep or daily living) * 3 = severe (interfered with daily living and/or sleep) Individual symptom scores ranged from 0 (best outcome) to 3 (worst outcome). A negative value for change represents an improvement in symptoms.

Outcome measures

Outcome measures
Measure	Placebo n=133 Participants 3 to 9 year old participants with PAR administered * Placebo (once to demonstrate IP administration in the baseline/screening period) * Placebo in the double-blind treatment period All participants were provided Children's Claritin® Syrup as a rescue medication.	TAA-AQ n=134 Participants 3 to 9 year old participants with PAR administered * Placebo (once to demonstrate IP administration in the baseline/screening period) * TAA-AQ in the double-blind treatment period All participants were provided Children's Claritin® Syrup as a rescue medication.
Change From Baseline in Four Individual Nasal Symptom Scores at the End of Treatment Change in Nasal stuffiness (N=101, N=104)	-0.68 score on a scale Standard Error 0.08	-0.83 score on a scale Standard Error 0.08
Change From Baseline in Four Individual Nasal Symptom Scores at the End of Treatment Change in Nasal discharge (N=102, N=103)	-0.67 score on a scale Standard Error 0.07	-0.71 score on a scale Standard Error 0.07
Change From Baseline in Four Individual Nasal Symptom Scores at the End of Treatment Change in Sneezing (N=102, N=103)	-0.64 score on a scale Standard Error 0.07	-0.55 score on a scale Standard Error 0.07
Change From Baseline in Four Individual Nasal Symptom Scores at the End of Treatment Change in Nasal Itching (N=101, N=104)	-0.69 score on a scale Standard Error 0.08	-0.71 score on a scale Standard Error 0.08

SECONDARY outcome

Timeframe: Day 120, Day 240 and Day 360

Population: mITT population: All randomized and treated participants with at least 3 post-randomization height measurements during the double-blind treatment period, excluding those from GCP noncompliant sites.

Global efficacy was assessed by the participant (with the help of a parent/guardian/caregiver) using the following scale: * 0 = no relief (symptoms unchanged or worse than before) * 1 = slight relief (symptoms were present and only minimally improved) * 2 = moderate relief (symptoms were present and could have been troublesome but were noticeably improved) * 3 = marked relief (symptoms were greatly improved and although present were scarcely troublesome) * 4 = complete relief (virtually no symptom present)

Outcome measures

Outcome measures
Measure	Placebo n=133 Participants 3 to 9 year old participants with PAR administered * Placebo (once to demonstrate IP administration in the baseline/screening period) * Placebo in the double-blind treatment period All participants were provided Children's Claritin® Syrup as a rescue medication.	TAA-AQ n=134 Participants 3 to 9 year old participants with PAR administered * Placebo (once to demonstrate IP administration in the baseline/screening period) * TAA-AQ in the double-blind treatment period All participants were provided Children's Claritin® Syrup as a rescue medication.
Global Efficacy as Assessed by the Participant (With the Help of a Parent/Guardian/Caregiver) During and at the End of the Double-blind Treatment Period Day 120 (N=127, N=131)	1.87 score on a scale Standard Deviation 1.10	2.09 score on a scale Standard Deviation 1.00
Global Efficacy as Assessed by the Participant (With the Help of a Parent/Guardian/Caregiver) During and at the End of the Double-blind Treatment Period Day 240 (N=115, N=116)	1.97 score on a scale Standard Deviation 1.04	2.16 score on a scale Standard Deviation 1.03
Global Efficacy as Assessed by the Participant (With the Help of a Parent/Guardian/Caregiver) During and at the End of the Double-blind Treatment Period Day 360 (N=125, N=125)	1.86 score on a scale Standard Deviation 1.08	2.18 score on a scale Standard Deviation 1.19

SECONDARY outcome

Timeframe: Day 120, Day 240 and Day 360

Global efficacy was assessed by the investigator using the following scale: * 0 = no relief (symptoms unchanged or worse than before) * 1 = slight relief (symptoms were present and only minimally improved) * 2 = moderate relief (symptoms were present and could have been troublesome but were noticeably improved) * 3 = marked relief (symptoms were greatly improved and although present were scarcely troublesome) * 4 = complete relief (virtually no symptom present)

Outcome measures

Outcome measures
Measure	Placebo n=133 Participants 3 to 9 year old participants with PAR administered * Placebo (once to demonstrate IP administration in the baseline/screening period) * Placebo in the double-blind treatment period All participants were provided Children's Claritin® Syrup as a rescue medication.	TAA-AQ n=134 Participants 3 to 9 year old participants with PAR administered * Placebo (once to demonstrate IP administration in the baseline/screening period) * TAA-AQ in the double-blind treatment period All participants were provided Children's Claritin® Syrup as a rescue medication.
Global Efficacy as Assessed by the Investigator During and at the End of the Double-blind Treatment Period Day 120 (N=128, N=130)	1.89 score on a scale Standard Deviation 1.11	2.04 score on a scale Standard Deviation 1.04
Global Efficacy as Assessed by the Investigator During and at the End of the Double-blind Treatment Period Day 240 (N=115, N=136)	2.11 score on a scale Standard Deviation 1.07	2.21 score on a scale Standard Deviation 1.08
Global Efficacy as Assessed by the Investigator During and at the End of the Double-blind Treatment Period Day 360 (N=125, N=125)	1.80 score on a scale Standard Deviation 0.98	2.14 score on a scale Standard Deviation 1.16

SECONDARY outcome

Timeframe: Baseline (4-6 months before Day 1), double-blind treatment period (Day 1 to Day 360) and follow-up (Day 361 to Day 420)

Children's Claritin® syrup was provided as a rescue medication to control allergic rhinitis (AR) symptoms and could be used throughout the study on an as needed basis. Use of rescue medication was to be documented in the participant's diary. The percentage of participants who used the rescue medication during each of the study periods is reported.

Outcome measures

Outcome measures
Measure	Placebo n=133 Participants 3 to 9 year old participants with PAR administered * Placebo (once to demonstrate IP administration in the baseline/screening period) * Placebo in the double-blind treatment period All participants were provided Children's Claritin® Syrup as a rescue medication.	TAA-AQ n=134 Participants 3 to 9 year old participants with PAR administered * Placebo (once to demonstrate IP administration in the baseline/screening period) * TAA-AQ in the double-blind treatment period All participants were provided Children's Claritin® Syrup as a rescue medication.
Percentage of Participants Who Used the Rescue Medication During the Double-blind Phase of the Study	81.2 percentage of participants	90.3 percentage of participants

SECONDARY outcome

Timeframe: double-blind treatment period (Day 1 to Day 360)

Children's Claritin® syrup was provided as a rescue medication to control allergic rhinitis (AR) symptoms and could be used throughout the study on an as needed basis. Use of rescue medication was to be documented in the participant's diary. The percentage of days that participants used the rescue medication during the double-blind treatment phase of the study.

Outcome measures

Outcome measures
Measure	Placebo n=133 Participants 3 to 9 year old participants with PAR administered * Placebo (once to demonstrate IP administration in the baseline/screening period) * Placebo in the double-blind treatment period All participants were provided Children's Claritin® Syrup as a rescue medication.	TAA-AQ n=134 Participants 3 to 9 year old participants with PAR administered * Placebo (once to demonstrate IP administration in the baseline/screening period) * TAA-AQ in the double-blind treatment period All participants were provided Children's Claritin® Syrup as a rescue medication.
Percentage of Days Participants Used the Rescue Medication During the Double-blind Treatment Phase of the Study	20.39 percentage of days Standard Deviation 28.02	15.69 percentage of days Standard Deviation 21.53

SECONDARY outcome

Timeframe: Baseline (2 to 6 weeks before Day 1), end of treatment (Day 360), and at follow-up (Day 420)

Population: All randomized and treated participants, excluding those from GCP noncompliant sites.

Urine cortisol levels was determined at screening, at the end of treatment, and at follow-up visit using routine laboratory testing. The normal range for urinary free cortisol for 3- to 9-year-olds was considered to be \[1.4 - 21 μg/24 hours\].

Outcome measures

Outcome measures
Measure	Placebo n=147 Participants 3 to 9 year old participants with PAR administered * Placebo (once to demonstrate IP administration in the baseline/screening period) * Placebo in the double-blind treatment period All participants were provided Children's Claritin® Syrup as a rescue medication.	TAA-AQ n=146 Participants 3 to 9 year old participants with PAR administered * Placebo (once to demonstrate IP administration in the baseline/screening period) * TAA-AQ in the double-blind treatment period All participants were provided Children's Claritin® Syrup as a rescue medication.
24 Hour Urinary Free Cortisol Levels at baseline (N=146, N=141)	7.44 μg/24 hours Standard Deviation 4.23	7.44 μg/24 hours Standard Deviation 4.04
24 Hour Urinary Free Cortisol Levels at end of treatment (EOT) (N=114, N=118)	7.05 μg/24 hours Standard Deviation 5.33	7.42 μg/24 hours Standard Deviation 5.93
24 Hour Urinary Free Cortisol Levels at follow-up (N=96, N=97)	7.85 μg/24 hours Standard Deviation 5.65	7.00 μg/24 hours Standard Deviation 5.28

SECONDARY outcome

Timeframe: Baseline (2 to 6 weeks before Day 1), end of treatment (Day 360), and at follow-up (Day 420)

Population: All randomized and treated participants, excluding those from GCP noncompliant sites.

Urine cortisol and creatinine levels were determined at screening, at the end of treatment, and at follow-up visit using routine laboratory testing. The normal range for urinary free cortisol for 3- to 9-year-olds was considered to be \[1.4 - 21 μg/24 hours\]. No normal range is available for cortisol/creatinine ratio.

Outcome measures

Outcome measures
Measure	Placebo n=147 Participants 3 to 9 year old participants with PAR administered * Placebo (once to demonstrate IP administration in the baseline/screening period) * Placebo in the double-blind treatment period All participants were provided Children's Claritin® Syrup as a rescue medication.	TAA-AQ n=146 Participants 3 to 9 year old participants with PAR administered * Placebo (once to demonstrate IP administration in the baseline/screening period) * TAA-AQ in the double-blind treatment period All participants were provided Children's Claritin® Syrup as a rescue medication.
24 Hour Cortisol/Creatinine Ratio at baseline (N=145, N=141)	18.94 μg/g Creatinine Standard Deviation 9.64	19.44 μg/g Creatinine Standard Deviation 10.62
24 Hour Cortisol/Creatinine Ratio at end of treatment (N=114, N=118)	15.47 μg/g Creatinine Standard Deviation 12.60	15.86 μg/g Creatinine Standard Deviation 10.77
24 Hour Cortisol/Creatinine Ratio at follow-up (N=96, N=97)	17.01 μg/g Creatinine Standard Deviation 12.63	15.10 μg/g Creatinine Standard Deviation 9.54

SECONDARY outcome

Timeframe: From Day 1 to 7 days following end of treatment (Day 360)

Population: All randomized and treated participants, excluding those from GCP noncompliant sites.

Adverse events that developed, worsened, or became serious during the double-blind treatment period or within 7 days after the last dose of double-blind investigational product (IP) are defined as TEAEs. A serious adverse event (SAE) was defined as any untoward medical occurrence that at any dose: * Resulted in death * Was life-threatening * Required inpatient hospitalization or prolongation of existing hospitalization * Resulted in persistent or significant disability/incapacity * Was a congenital anomaly/birth defect * Was a medically important event

Outcome measures

Outcome measures
Measure	Placebo n=147 Participants 3 to 9 year old participants with PAR administered * Placebo (once to demonstrate IP administration in the baseline/screening period) * Placebo in the double-blind treatment period All participants were provided Children's Claritin® Syrup as a rescue medication.	TAA-AQ n=146 Participants 3 to 9 year old participants with PAR administered * Placebo (once to demonstrate IP administration in the baseline/screening period) * TAA-AQ in the double-blind treatment period All participants were provided Children's Claritin® Syrup as a rescue medication.
Number of Participants With Treatment-emergent Adverse Events (TEAE) with any TEAE	113 participants	117 participants
Number of Participants With Treatment-emergent Adverse Events (TEAE) with any treatment emergent SAE	0 participants	2 participants
Number of Participants With Treatment-emergent Adverse Events (TEAE) with any TEAE leading to permanent discontinuation	3 participants	1 participants
Number of Participants With Treatment-emergent Adverse Events (TEAE) with any TEAE leading to death	0 participants	0 participants
Number of Participants With Treatment-emergent Adverse Events (TEAE) with investigational product (IP) overdose TEAE	0 participants	0 participants

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 98 other events

Deaths: 0 deaths

TAA-AQ

Serious events: 2 serious events

Other events: 109 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=147 participants at risk 3 to 9 year old participants with PAR administered * Placebo (once to demonstrate IP administration in the baseline/screening period) * Placebo in the double-blind treatment period All participants were provided Children's Claritin® Syrup as a rescue medication	TAA-AQ n=146 participants at risk 3 to 9 year old participants with PAR administered * Placebo (once to demonstrate IP administration in the baseline/screening period) * TAA-AQ in the double-blind treatment period All participants were provided Children's Claritin® Syrup as a rescue medication
Gastrointestinal disorders Colitis ulcerative	0.00% 0/147 • From treatment initiation to 7 days after the last dose of double-blind treatment (double blind treatment period) Adverse events that developed, worsened, or became serious during the double-blind treatment period or within 7 days after the last dose of double-blind period, i.e. Treatment-emergent adverse events.	0.68% 1/146 • From treatment initiation to 7 days after the last dose of double-blind treatment (double blind treatment period) Adverse events that developed, worsened, or became serious during the double-blind treatment period or within 7 days after the last dose of double-blind period, i.e. Treatment-emergent adverse events.
Injury, poisoning and procedural complications Animal bite	0.00% 0/147 • From treatment initiation to 7 days after the last dose of double-blind treatment (double blind treatment period) Adverse events that developed, worsened, or became serious during the double-blind treatment period or within 7 days after the last dose of double-blind period, i.e. Treatment-emergent adverse events.	0.68% 1/146 • From treatment initiation to 7 days after the last dose of double-blind treatment (double blind treatment period) Adverse events that developed, worsened, or became serious during the double-blind treatment period or within 7 days after the last dose of double-blind period, i.e. Treatment-emergent adverse events.

Other adverse events

Additional Information

Trial Transparency Team

sanofi-aventis

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The investigator can independently publish study results from his site after the primary publication by the steering committee, or 12 months after the completion of the study by all sites. He must provide the sponsor a copy of any such publication derived from the study for review and comment at least 45 days (20 days for abstracts) in advance of any submission, and delay publication till the approval of the publication is given in writing by the Sponsor (not to exceed ninety days).
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo n=147 participants at risk 3 to 9 year old participants with PAR administered * Placebo (once to demonstrate IP administration in the baseline/screening period) * Placebo in the double-blind treatment period All participants were provided Children's Claritin® Syrup as a rescue medication	TAA-AQ n=146 participants at risk 3 to 9 year old participants with PAR administered * Placebo (once to demonstrate IP administration in the baseline/screening period) * TAA-AQ in the double-blind treatment period All participants were provided Children's Claritin® Syrup as a rescue medication
Infections and infestations Nasopharyngitis	12.2% 18/147 • From treatment initiation to 7 days after the last dose of double-blind treatment (double blind treatment period) Adverse events that developed, worsened, or became serious during the double-blind treatment period or within 7 days after the last dose of double-blind period, i.e. Treatment-emergent adverse events.	19.2% 28/146 • From treatment initiation to 7 days after the last dose of double-blind treatment (double blind treatment period) Adverse events that developed, worsened, or became serious during the double-blind treatment period or within 7 days after the last dose of double-blind period, i.e. Treatment-emergent adverse events.
Infections and infestations Upper respiratory tract infection	12.9% 19/147 • From treatment initiation to 7 days after the last dose of double-blind treatment (double blind treatment period) Adverse events that developed, worsened, or became serious during the double-blind treatment period or within 7 days after the last dose of double-blind period, i.e. Treatment-emergent adverse events.	17.1% 25/146 • From treatment initiation to 7 days after the last dose of double-blind treatment (double blind treatment period) Adverse events that developed, worsened, or became serious during the double-blind treatment period or within 7 days after the last dose of double-blind period, i.e. Treatment-emergent adverse events.
Infections and infestations Pharyngitis streptococcal	6.8% 10/147 • From treatment initiation to 7 days after the last dose of double-blind treatment (double blind treatment period) Adverse events that developed, worsened, or became serious during the double-blind treatment period or within 7 days after the last dose of double-blind period, i.e. Treatment-emergent adverse events.	8.2% 12/146 • From treatment initiation to 7 days after the last dose of double-blind treatment (double blind treatment period) Adverse events that developed, worsened, or became serious during the double-blind treatment period or within 7 days after the last dose of double-blind period, i.e. Treatment-emergent adverse events.
Infections and infestations Sinusitis	7.5% 11/147 • From treatment initiation to 7 days after the last dose of double-blind treatment (double blind treatment period) Adverse events that developed, worsened, or became serious during the double-blind treatment period or within 7 days after the last dose of double-blind period, i.e. Treatment-emergent adverse events.	8.2% 12/146 • From treatment initiation to 7 days after the last dose of double-blind treatment (double blind treatment period) Adverse events that developed, worsened, or became serious during the double-blind treatment period or within 7 days after the last dose of double-blind period, i.e. Treatment-emergent adverse events.
Infections and infestations Influenza	2.0% 3/147 • From treatment initiation to 7 days after the last dose of double-blind treatment (double blind treatment period) Adverse events that developed, worsened, or became serious during the double-blind treatment period or within 7 days after the last dose of double-blind period, i.e. Treatment-emergent adverse events.	6.8% 10/146 • From treatment initiation to 7 days after the last dose of double-blind treatment (double blind treatment period) Adverse events that developed, worsened, or became serious during the double-blind treatment period or within 7 days after the last dose of double-blind period, i.e. Treatment-emergent adverse events.
Infections and infestations Viral infection	2.0% 3/147 • From treatment initiation to 7 days after the last dose of double-blind treatment (double blind treatment period) Adverse events that developed, worsened, or became serious during the double-blind treatment period or within 7 days after the last dose of double-blind period, i.e. Treatment-emergent adverse events.	6.2% 9/146 • From treatment initiation to 7 days after the last dose of double-blind treatment (double blind treatment period) Adverse events that developed, worsened, or became serious during the double-blind treatment period or within 7 days after the last dose of double-blind period, i.e. Treatment-emergent adverse events.
Infections and infestations Viral upper respiratory tract infection	6.1% 9/147 • From treatment initiation to 7 days after the last dose of double-blind treatment (double blind treatment period) Adverse events that developed, worsened, or became serious during the double-blind treatment period or within 7 days after the last dose of double-blind period, i.e. Treatment-emergent adverse events.	6.2% 9/146 • From treatment initiation to 7 days after the last dose of double-blind treatment (double blind treatment period) Adverse events that developed, worsened, or became serious during the double-blind treatment period or within 7 days after the last dose of double-blind period, i.e. Treatment-emergent adverse events.
Infections and infestations Gastroenteritis viral	4.1% 6/147 • From treatment initiation to 7 days after the last dose of double-blind treatment (double blind treatment period) Adverse events that developed, worsened, or became serious during the double-blind treatment period or within 7 days after the last dose of double-blind period, i.e. Treatment-emergent adverse events.	5.5% 8/146 • From treatment initiation to 7 days after the last dose of double-blind treatment (double blind treatment period) Adverse events that developed, worsened, or became serious during the double-blind treatment period or within 7 days after the last dose of double-blind period, i.e. Treatment-emergent adverse events.
Infections and infestations Otitis media	5.4% 8/147 • From treatment initiation to 7 days after the last dose of double-blind treatment (double blind treatment period) Adverse events that developed, worsened, or became serious during the double-blind treatment period or within 7 days after the last dose of double-blind period, i.e. Treatment-emergent adverse events.	2.7% 4/146 • From treatment initiation to 7 days after the last dose of double-blind treatment (double blind treatment period) Adverse events that developed, worsened, or became serious during the double-blind treatment period or within 7 days after the last dose of double-blind period, i.e. Treatment-emergent adverse events.
Nervous system disorders Headache	21.1% 31/147 • From treatment initiation to 7 days after the last dose of double-blind treatment (double blind treatment period) Adverse events that developed, worsened, or became serious during the double-blind treatment period or within 7 days after the last dose of double-blind period, i.e. Treatment-emergent adverse events.	23.3% 34/146 • From treatment initiation to 7 days after the last dose of double-blind treatment (double blind treatment period) Adverse events that developed, worsened, or became serious during the double-blind treatment period or within 7 days after the last dose of double-blind period, i.e. Treatment-emergent adverse events.
Ear and labyrinth disorders Ear pain	9.5% 14/147 • From treatment initiation to 7 days after the last dose of double-blind treatment (double blind treatment period) Adverse events that developed, worsened, or became serious during the double-blind treatment period or within 7 days after the last dose of double-blind period, i.e. Treatment-emergent adverse events.	4.8% 7/146 • From treatment initiation to 7 days after the last dose of double-blind treatment (double blind treatment period) Adverse events that developed, worsened, or became serious during the double-blind treatment period or within 7 days after the last dose of double-blind period, i.e. Treatment-emergent adverse events.
Respiratory, thoracic and mediastinal disorders Cough	20.4% 30/147 • From treatment initiation to 7 days after the last dose of double-blind treatment (double blind treatment period) Adverse events that developed, worsened, or became serious during the double-blind treatment period or within 7 days after the last dose of double-blind period, i.e. Treatment-emergent adverse events.	19.9% 29/146 • From treatment initiation to 7 days after the last dose of double-blind treatment (double blind treatment period) Adverse events that developed, worsened, or became serious during the double-blind treatment period or within 7 days after the last dose of double-blind period, i.e. Treatment-emergent adverse events.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	12.2% 18/147 • From treatment initiation to 7 days after the last dose of double-blind treatment (double blind treatment period) Adverse events that developed, worsened, or became serious during the double-blind treatment period or within 7 days after the last dose of double-blind period, i.e. Treatment-emergent adverse events.	11.6% 17/146 • From treatment initiation to 7 days after the last dose of double-blind treatment (double blind treatment period) Adverse events that developed, worsened, or became serious during the double-blind treatment period or within 7 days after the last dose of double-blind period, i.e. Treatment-emergent adverse events.
Respiratory, thoracic and mediastinal disorders Epistaxis	4.8% 7/147 • From treatment initiation to 7 days after the last dose of double-blind treatment (double blind treatment period) Adverse events that developed, worsened, or became serious during the double-blind treatment period or within 7 days after the last dose of double-blind period, i.e. Treatment-emergent adverse events.	11.0% 16/146 • From treatment initiation to 7 days after the last dose of double-blind treatment (double blind treatment period) Adverse events that developed, worsened, or became serious during the double-blind treatment period or within 7 days after the last dose of double-blind period, i.e. Treatment-emergent adverse events.
Respiratory, thoracic and mediastinal disorders Asthma	6.8% 10/147 • From treatment initiation to 7 days after the last dose of double-blind treatment (double blind treatment period) Adverse events that developed, worsened, or became serious during the double-blind treatment period or within 7 days after the last dose of double-blind period, i.e. Treatment-emergent adverse events.	6.8% 10/146 • From treatment initiation to 7 days after the last dose of double-blind treatment (double blind treatment period) Adverse events that developed, worsened, or became serious during the double-blind treatment period or within 7 days after the last dose of double-blind period, i.e. Treatment-emergent adverse events.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	6.1% 9/147 • From treatment initiation to 7 days after the last dose of double-blind treatment (double blind treatment period) Adverse events that developed, worsened, or became serious during the double-blind treatment period or within 7 days after the last dose of double-blind period, i.e. Treatment-emergent adverse events.	5.5% 8/146 • From treatment initiation to 7 days after the last dose of double-blind treatment (double blind treatment period) Adverse events that developed, worsened, or became serious during the double-blind treatment period or within 7 days after the last dose of double-blind period, i.e. Treatment-emergent adverse events.
Respiratory, thoracic and mediastinal disorders Nasal congestion	7.5% 11/147 • From treatment initiation to 7 days after the last dose of double-blind treatment (double blind treatment period) Adverse events that developed, worsened, or became serious during the double-blind treatment period or within 7 days after the last dose of double-blind period, i.e. Treatment-emergent adverse events.	4.1% 6/146 • From treatment initiation to 7 days after the last dose of double-blind treatment (double blind treatment period) Adverse events that developed, worsened, or became serious during the double-blind treatment period or within 7 days after the last dose of double-blind period, i.e. Treatment-emergent adverse events.
Gastrointestinal disorders Vomiting	5.4% 8/147 • From treatment initiation to 7 days after the last dose of double-blind treatment (double blind treatment period) Adverse events that developed, worsened, or became serious during the double-blind treatment period or within 7 days after the last dose of double-blind period, i.e. Treatment-emergent adverse events.	13.0% 19/146 • From treatment initiation to 7 days after the last dose of double-blind treatment (double blind treatment period) Adverse events that developed, worsened, or became serious during the double-blind treatment period or within 7 days after the last dose of double-blind period, i.e. Treatment-emergent adverse events.
Gastrointestinal disorders Abdominal pain upper	10.2% 15/147 • From treatment initiation to 7 days after the last dose of double-blind treatment (double blind treatment period) Adverse events that developed, worsened, or became serious during the double-blind treatment period or within 7 days after the last dose of double-blind period, i.e. Treatment-emergent adverse events.	11.0% 16/146 • From treatment initiation to 7 days after the last dose of double-blind treatment (double blind treatment period) Adverse events that developed, worsened, or became serious during the double-blind treatment period or within 7 days after the last dose of double-blind period, i.e. Treatment-emergent adverse events.
Skin and subcutaneous tissue disorders Rash	2.7% 4/147 • From treatment initiation to 7 days after the last dose of double-blind treatment (double blind treatment period) Adverse events that developed, worsened, or became serious during the double-blind treatment period or within 7 days after the last dose of double-blind period, i.e. Treatment-emergent adverse events.	6.8% 10/146 • From treatment initiation to 7 days after the last dose of double-blind treatment (double blind treatment period) Adverse events that developed, worsened, or became serious during the double-blind treatment period or within 7 days after the last dose of double-blind period, i.e. Treatment-emergent adverse events.
General disorders Pyrexia	25.2% 37/147 • From treatment initiation to 7 days after the last dose of double-blind treatment (double blind treatment period) Adverse events that developed, worsened, or became serious during the double-blind treatment period or within 7 days after the last dose of double-blind period, i.e. Treatment-emergent adverse events.	21.2% 31/146 • From treatment initiation to 7 days after the last dose of double-blind treatment (double blind treatment period) Adverse events that developed, worsened, or became serious during the double-blind treatment period or within 7 days after the last dose of double-blind period, i.e. Treatment-emergent adverse events.