Trial Outcomes & Findings for Efficacy and Long-Term Safety of Ragweed (Ambrosia Artemisiifolia) Sublingual Tablet (SCH 39641) in Adults With a History of Ragweed-Induced Rhinoconjunctivitis With or Without Asthma (Study P05234) (NCT NCT00770315)

Last Updated: 2017-03-03

Results Overview

The total combined score is a composite endpoint that combines the rhinoconjuntivitis DSS and the rhinoconjunctivitis DMS. The rhinoconjunctivitis DSS consisted of a total of 6 symptoms (runny nose, blocked nose, sneezing, itchy nose, gritty feeling/red/itchy eyes and watery eyes) that were measured on a scale of 0 to 3 (0=no symptoms, 3=severe symptoms; score range: 0-18), with a lower score indicating less rhinoconjunctivitis symptoms. Rhinoconjunctivitis DMS was based on use of specific study-provided rescue medication, with different rescue medications being assigned different scores/dose unit (score range: 0-36), with a lower score indicating less rhinconjunctivitis medication use. The sum of the rhinoconjunctivitis DSS+DMS could range from 0 to 54, with a lower score indicating less rhinoconjuntivitis symptoms and medication use. Raw means were converted to adjusted means using an ANOVA model with baseline asthmatic condition, pollen region and treatment group as fixed effects.

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

784 participants

Primary outcome timeframe

The 15-day period during the ragweed season with the highest moving pollen average

Results posted on

2017-03-03

Participant Flow

Participant milestones

Participant milestones
Measure	SCH 39641 1.5 Amb a 1-U Participants receive Ambrosia artemisiifolia allergan extract (SCH 39641 1.5 Amb a 1-U) rapidly dissolving sublingual tablets, administered once daily for approximately 52 weeks	SCH 39641 6 Amb a 1-U Participants receive Ambrosia artemisiifolia allergan extract (SCH 39641 6 Amb a 1-U) rapidly dissolving sublingual tablets, administered once daily for approximately 52 weeks	SCH 39641 12 Amb a 1-U Participants receive Ambrosia artemisiifolia allergan extract (SCH 39641 12 Amb a 1-U) rapidly dissolving sublingual tablets, administered once daily for approximately 52 weeks	Placebo Participants receive placebo matching Ambrosia artemisiifolia allergan extract rapidly dissolving sublingual tablets, administered once daily for approximately 52 weeks
Overall Study STARTED	197	195	194	198
Overall Study COMPLETED	157	152	137	160
Overall Study NOT COMPLETED	40	43	57	38

Reasons for withdrawal

Reasons for withdrawal
Measure	SCH 39641 1.5 Amb a 1-U Participants receive Ambrosia artemisiifolia allergan extract (SCH 39641 1.5 Amb a 1-U) rapidly dissolving sublingual tablets, administered once daily for approximately 52 weeks	SCH 39641 6 Amb a 1-U Participants receive Ambrosia artemisiifolia allergan extract (SCH 39641 6 Amb a 1-U) rapidly dissolving sublingual tablets, administered once daily for approximately 52 weeks	SCH 39641 12 Amb a 1-U Participants receive Ambrosia artemisiifolia allergan extract (SCH 39641 12 Amb a 1-U) rapidly dissolving sublingual tablets, administered once daily for approximately 52 weeks	Placebo Participants receive placebo matching Ambrosia artemisiifolia allergan extract rapidly dissolving sublingual tablets, administered once daily for approximately 52 weeks
Overall Study Adverse Event	11	17	16	6
Overall Study Lost to Follow-up	9	5	10	3
Overall Study Withdrawal by Subject	13	17	24	20
Overall Study Noncompliance with Protocol	7	4	7	9

Baseline Characteristics

Efficacy and Long-Term Safety of Ragweed (Ambrosia Artemisiifolia) Sublingual Tablet (SCH 39641) in Adults With a History of Ragweed-Induced Rhinoconjunctivitis With or Without Asthma (Study P05234)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	SCH 39641 1.5 Amb a 1-U n=197 Participants Participants receive Ambrosia artemisiifolia allergan extract (SCH 39641 1.5 Amb a 1-U) rapidly dissolving sublingual tablets, administered once daily for approximately 52 weeks	SCH 39641 6 Amb a 1-U n=195 Participants Participants receive Ambrosia artemisiifolia allergan extract (SCH 39641 6 Amb a 1-U) rapidly dissolving sublingual tablets, administered once daily for approximately 52 weeks	SCH 39641 12 Amb a 1-U n=194 Participants Participants receive Ambrosia artemisiifolia allergan extract (SCH 39641 12 Amb a 1-U) rapidly dissolving sublingual tablets, administered once daily for approximately 52 weeks	Placebo n=198 Participants Participants receive placebo matching Ambrosia artemisiifolia allergan extract rapidly dissolving sublingual tablets, administered once daily for approximately 52 weeks	Total n=784 Participants Total of all reporting groups
Age, Continuous	36.2 years STANDARD_DEVIATION 8.83 • n=5 Participants	36.9 years STANDARD_DEVIATION 8.80 • n=7 Participants	35.6 years STANDARD_DEVIATION 8.75 • n=5 Participants	36.7 years STANDARD_DEVIATION 8.54 • n=4 Participants	36.4 years STANDARD_DEVIATION 8.73 • n=21 Participants
Gender Female	110 Participants n=5 Participants	103 Participants n=7 Participants	91 Participants n=5 Participants	96 Participants n=4 Participants	400 Participants n=21 Participants
Gender Male	87 Participants n=5 Participants	92 Participants n=7 Participants	103 Participants n=5 Participants	102 Participants n=4 Participants	384 Participants n=21 Participants

PRIMARY outcome

Timeframe: The 15-day period during the ragweed season with the highest moving pollen average

Population: The Full Analysis Set (FAS) population consisted of all randomized participants who took at least one dose of study medication and had at least one post-randomization efficacy measurement.

Outcome measures

Outcome measures
Measure	SCH 39641 1.5 Amb a 1-U n=169 Participants Participants receive Ambrosia artemisiifolia allergan extract (SCH 39641 1.5 Amb a 1-U) rapidly dissolving sublingual tablets, administered once daily for approximately 52 weeks	SCH 39641 6 Amb a 1-U n=167 Participants Participants receive Ambrosia artemisiifolia allergan extract (SCH 39641 6 Amb a 1-U) rapidly dissolving sublingual tablets, administered once daily for approximately 52 weeks	SCH 39641 12 Amb a 1-U n=152 Participants Participants receive Ambrosia artemisiifolia allergan extract (SCH 39641 12 Amb a 1-U) rapidly dissolving sublingual tablets, administered once daily for approximately 52 weeks	Placebo n=169 Participants Participants receive matching placebo rapidly dissolving sublingual tablets, administered once daily for approximately 52 weeks
Combined (Sum of) Rhinoconjunctivitis Daily Symptom Score (DSS) and Daily Medication Score (DMS) Averaged Over the Peak Ragweed Season (RS)	7.70 score on a scale Standard Error 0.517 • Interval -1.98 to 0.45	6.88 score on a scale Standard Error 0.526 • Interval -2.8 to -0.36	6.41 score on a scale Standard Error 0.534 • Interval -3.3 to -0.79	8.46 score on a scale Standard Error 0.535

SECONDARY outcome

Timeframe: Approximately 5 weeks

Population: The FAS population consisted of all randomized participants who took at least one dose of study medication and had at least one post-randomization efficacy measurement.

Outcome measures

Outcome measures
Measure	SCH 39641 1.5 Amb a 1-U n=171 Participants Participants receive Ambrosia artemisiifolia allergan extract (SCH 39641 1.5 Amb a 1-U) rapidly dissolving sublingual tablets, administered once daily for approximately 52 weeks	SCH 39641 6 Amb a 1-U n=172 Participants Participants receive Ambrosia artemisiifolia allergan extract (SCH 39641 6 Amb a 1-U) rapidly dissolving sublingual tablets, administered once daily for approximately 52 weeks	SCH 39641 12 Amb a 1-U n=158 Participants Participants receive Ambrosia artemisiifolia allergan extract (SCH 39641 12 Amb a 1-U) rapidly dissolving sublingual tablets, administered once daily for approximately 52 weeks	Placebo n=174 Participants Participants receive matching placebo rapidly dissolving sublingual tablets, administered once daily for approximately 52 weeks
Average Combined Rhinoconjunctivitis DSS and DMS Over the Entire RS	6.22 score on a scale Standard Error 0.432 • Interval -1.88 to 0.13	5.81 score on a scale Standard Error 0.433 • Interval -2.29 to -0.28	5.18 score on a scale Standard Error 0.439 • Interval -2.95 to -0.88	7.09 score on a scale Standard Error 0.441

SECONDARY outcome

Timeframe: The 15-day period during the ragweed season with the highest moving pollen average

Population: The FAS population consisted of all randomized participants who took at least one dose of study medication and had at least one post-randomization efficacy measurement.

The rhinoconjunctivitis DSS consisted of a total of 6 symptoms (runny nose, blocked nose, sneezing, itchy nose, gritty feeling/red/itchy eyes and watery eyes) that were measured on a scale of 0 to 3 (0=no symptoms, 3=severe symptoms; score range: 0-18), with a lower score indicating less rhinoconjunctivitis symptoms. Raw means were converted to adjusted means using an ANOVA model with baseline asthmatic condition, pollen region and treatment group as fixed effects.

Outcome measures

Outcome measures
Measure	SCH 39641 1.5 Amb a 1-U n=169 Participants Participants receive Ambrosia artemisiifolia allergan extract (SCH 39641 1.5 Amb a 1-U) rapidly dissolving sublingual tablets, administered once daily for approximately 52 weeks	SCH 39641 6 Amb a 1-U n=167 Participants Participants receive Ambrosia artemisiifolia allergan extract (SCH 39641 6 Amb a 1-U) rapidly dissolving sublingual tablets, administered once daily for approximately 52 weeks	SCH 39641 12 Amb a 1-U n=152 Participants Participants receive Ambrosia artemisiifolia allergan extract (SCH 39641 12 Amb a 1-U) rapidly dissolving sublingual tablets, administered once daily for approximately 52 weeks	Placebo n=169 Participants Participants receive matching placebo rapidly dissolving sublingual tablets, administered once daily for approximately 52 weeks
Average Rhinoconjunctivitis DSS for the Peak RS	5.11 score on a scale Standard Error 0.301 • Interval -0.96 to 0.45	4.87 score on a scale Standard Error 0.306 • Interval -1.21 to 0.21	4.43 score on a scale Standard Error 0.311 • Interval -1.67 to -0.21	5.37 score on a scale Standard Error 0.311

SECONDARY outcome

Timeframe: Approximately 5 weeks

Population: The FAS population consisted of all randomized participants who took at least one dose of study medication and had at least one post-randomization efficacy measurement.

Outcome measures

Outcome measures
Measure	SCH 39641 1.5 Amb a 1-U n=171 Participants Participants receive Ambrosia artemisiifolia allergan extract (SCH 39641 1.5 Amb a 1-U) rapidly dissolving sublingual tablets, administered once daily for approximately 52 weeks	SCH 39641 6 Amb a 1-U n=172 Participants Participants receive Ambrosia artemisiifolia allergan extract (SCH 39641 6 Amb a 1-U) rapidly dissolving sublingual tablets, administered once daily for approximately 52 weeks	SCH 39641 12 Amb a 1-U n=158 Participants Participants receive Ambrosia artemisiifolia allergan extract (SCH 39641 12 Amb a 1-U) rapidly dissolving sublingual tablets, administered once daily for approximately 52 weeks	Placebo n=174 Participants Participants receive matching placebo rapidly dissolving sublingual tablets, administered once daily for approximately 52 weeks
Average Rhinoconjunctivitis DSS for the Entire RS	4.24 score on a scale Standard Error 0.255 • Interval -0.93 to 0.25	4.19 score on a scale Standard Error 0.256 • Interval -0.99 to 0.2	3.62 score on a scale Standard Error 0.259 • Interval -1.57 to -0.35	4.58 score on a scale Standard Error 0.261

SECONDARY outcome

Timeframe: The 15-day period during the ragweed season with the highest moving pollen average

Population: The FAS population consisted of all randomized participants who took at least one dose of study medication and had at least one post-randomization efficacy measurement.

Rhinoconjunctivitis DMS was based on participant use of specific study-provided rescue medication, with different rescue medications being assigned different scores/dose unit (score range: 0-36), with a lower score indicating less rhinconjunctivitis medication use. Raw means were converted to adjusted means using an ANOVA model with baseline asthmatic condition, pollen region and treatment group as fixed effects.

Outcome measures

Outcome measures
Measure	SCH 39641 1.5 Amb a 1-U n=169 Participants Participants receive Ambrosia artemisiifolia allergan extract (SCH 39641 1.5 Amb a 1-U) rapidly dissolving sublingual tablets, administered once daily for approximately 52 weeks	SCH 39641 6 Amb a 1-U n=167 Participants Participants receive Ambrosia artemisiifolia allergan extract (SCH 39641 6 Amb a 1-U) rapidly dissolving sublingual tablets, administered once daily for approximately 52 weeks	SCH 39641 12 Amb a 1-U n=152 Participants Participants receive Ambrosia artemisiifolia allergan extract (SCH 39641 12 Amb a 1-U) rapidly dissolving sublingual tablets, administered once daily for approximately 52 weeks	Placebo n=169 Participants Participants receive matching placebo rapidly dissolving sublingual tablets, administered once daily for approximately 52 weeks
Average Rhinoconjunctivitis DMS for the Peak RS	2.58 score on a scale Standard Error 0.322 • Interval -1.26 to 0.25	2.01 score on a scale Standard Error 0.328 • Interval -1.84 to -0.32	1.99 score on a scale Standard Error 0.333 • Interval -1.89 to -0.32	3.09 score on a scale Standard Error 0.333

Adverse Events

SCH 39641 1.5 Amb a 1-U

Serious events: 5 serious events

Other events: 105 other events

Deaths: 0 deaths

SCH 39641 6 Amb a 1-U

Serious events: 4 serious events

Other events: 108 other events

Deaths: 0 deaths

SCH 39641 12 Amb a 1-U

Serious events: 4 serious events

Other events: 125 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 78 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	SCH 39641 1.5 Amb a 1-U n=196 participants at risk Participants receive Ambrosia artemisiifolia allergan extract (SCH 39641 1.5 Amb a 1-U) rapidly dissolving sublingual tablets, administered once daily for approximately 52 weeks	SCH 39641 6 Amb a 1-U n=195 participants at risk Participants receive Ambrosia artemisiifolia allergan extract (SCH 39641 6 Amb a 1-U) rapidly dissolving sublingual tablets, administered once daily for approximately 52 weeks	SCH 39641 12 Amb a 1-U n=194 participants at risk Participants receive Ambrosia artemisiifolia allergan extract (SCH 39641 12 Amb a 1-U) rapidly dissolving sublingual tablets, administered once daily for approximately 52 weeks	Placebo n=198 participants at risk Participants receive placebo matching Ambrosia artemisiifolia allergan extract rapidly dissolving sublingual tablets, administered once daily for approximately 52 weeks
Congenital, familial and genetic disorders Hydrocele	0.00% 0/196 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	0.00% 0/195 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	0.52% 1/194 • Number of events 1 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	0.00% 0/198 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.
Gastrointestinal disorders Abdominal hernia obstructive	0.00% 0/196 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	0.51% 1/195 • Number of events 1 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	0.00% 0/194 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	0.00% 0/198 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.
Gastrointestinal disorders Pancreatitis acute	0.51% 1/196 • Number of events 2 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	0.00% 0/195 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	0.00% 0/194 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	0.00% 0/198 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.
Hepatobiliary disorders Cholelithiasis	0.51% 1/196 • Number of events 1 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	0.00% 0/195 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	0.00% 0/194 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	0.00% 0/198 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.
Immune system disorders Hypersensitivity	0.00% 0/196 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	0.00% 0/195 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	0.52% 1/194 • Number of events 1 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	0.00% 0/198 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.
Infections and infestations Bronchitis	0.00% 0/196 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	0.51% 1/195 • Number of events 1 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	0.00% 0/194 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	0.00% 0/198 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.
Infections and infestations Pneumonia chlamydial	0.00% 0/196 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	0.00% 0/195 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	0.00% 0/194 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	0.51% 1/198 • Number of events 1 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.
Infections and infestations Postoperative abscess	0.00% 0/196 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	0.51% 1/195 • Number of events 1 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	0.00% 0/194 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	0.00% 0/198 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.
Injury, poisoning and procedural complications Ligament rupture	0.51% 1/196 • Number of events 1 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	0.00% 0/195 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	0.00% 0/194 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	0.00% 0/198 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.
Metabolism and nutrition disorders Diabetes mellitus inadequate control	0.00% 0/196 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	0.00% 0/195 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	0.52% 1/194 • Number of events 1 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	0.00% 0/198 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.51% 1/196 • Number of events 1 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	0.51% 1/195 • Number of events 1 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	0.00% 0/194 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	0.00% 0/198 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.
Pregnancy, puerperium and perinatal conditions Abortion spontaneous	0.51% 1/196 • Number of events 1 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	0.51% 1/195 • Number of events 1 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	0.00% 0/194 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	0.00% 0/198 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.
Reproductive system and breast disorders Ovarian cyst	0.00% 0/196 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	0.00% 0/195 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	0.52% 1/194 • Number of events 1 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	0.00% 0/198 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.
Surgical and medical procedures Abortion induced	0.51% 1/196 • Number of events 1 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	0.00% 0/195 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	0.00% 0/194 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	0.00% 0/198 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.

Other adverse events

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The investigator agrees to provide to the sponsor 45 days prior to submission for publication or presentation, review copies of abstracts or manuscripts for publication that report any results of the study.
Publication restrictions are in place

Restriction type: OTHER

Measure	SCH 39641 1.5 Amb a 1-U n=196 participants at risk Participants receive Ambrosia artemisiifolia allergan extract (SCH 39641 1.5 Amb a 1-U) rapidly dissolving sublingual tablets, administered once daily for approximately 52 weeks	SCH 39641 6 Amb a 1-U n=195 participants at risk Participants receive Ambrosia artemisiifolia allergan extract (SCH 39641 6 Amb a 1-U) rapidly dissolving sublingual tablets, administered once daily for approximately 52 weeks	SCH 39641 12 Amb a 1-U n=194 participants at risk Participants receive Ambrosia artemisiifolia allergan extract (SCH 39641 12 Amb a 1-U) rapidly dissolving sublingual tablets, administered once daily for approximately 52 weeks	Placebo n=198 participants at risk Participants receive placebo matching Ambrosia artemisiifolia allergan extract rapidly dissolving sublingual tablets, administered once daily for approximately 52 weeks
Infections and infestations Bronchitis	2.6% 5/196 • Number of events 7 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	3.1% 6/195 • Number of events 6 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	4.1% 8/194 • Number of events 8 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	6.1% 12/198 • Number of events 14 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.
Infections and infestations Nasopharyngitis	15.8% 31/196 • Number of events 40 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	14.4% 28/195 • Number of events 35 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	17.0% 33/194 • Number of events 42 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	17.7% 35/198 • Number of events 45 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.
Infections and infestations Sinusitis	6.1% 12/196 • Number of events 13 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	4.6% 9/195 • Number of events 10 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	4.1% 8/194 • Number of events 9 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	3.5% 7/198 • Number of events 10 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.
Infections and infestations Upper respiratory tract infection	4.6% 9/196 • Number of events 9 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	9.2% 18/195 • Number of events 22 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	4.6% 9/194 • Number of events 12 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	4.5% 9/198 • Number of events 11 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.
Nervous system disorders Headache	7.7% 15/196 • Number of events 33 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	6.2% 12/195 • Number of events 17 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	9.3% 18/194 • Number of events 49 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	10.1% 20/198 • Number of events 34 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders Cough	5.6% 11/196 • Number of events 13 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	5.1% 10/195 • Number of events 10 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	6.2% 12/194 • Number of events 14 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	3.0% 6/198 • Number of events 8 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	7.1% 14/196 • Number of events 17 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	2.6% 5/195 • Number of events 5 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	4.6% 9/194 • Number of events 10 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	2.0% 4/198 • Number of events 4 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders Sneezing	5.1% 10/196 • Number of events 11 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	3.1% 6/195 • Number of events 7 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	4.1% 8/194 • Number of events 10 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	2.0% 4/198 • Number of events 8 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders Throat irritation	14.3% 28/196 • Number of events 29 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	21.5% 42/195 • Number of events 46 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	21.1% 41/194 • Number of events 45 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	5.6% 11/198 • Number of events 11 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.
Ear and labyrinth disorders Ear pruritus	7.1% 14/196 • Number of events 15 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	13.8% 27/195 • Number of events 30 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	12.9% 25/194 • Number of events 26 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	1.0% 2/198 • Number of events 2 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.
Gastrointestinal disorders Oral pruritus	5.6% 11/196 • Number of events 12 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	14.9% 29/195 • Number of events 37 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	8.2% 16/194 • Number of events 17 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	1.0% 2/198 • Number of events 2 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.
Gastrointestinal disorders Paraesthesia oral	5.1% 10/196 • Number of events 11 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	7.7% 15/195 • Number of events 18 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	4.6% 9/194 • Number of events 14 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	2.5% 5/198 • Number of events 9 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.
Gastrointestinal disorders Swollen tongue	5.6% 11/196 • Number of events 11 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	6.2% 12/195 • Number of events 14 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	7.7% 15/194 • Number of events 16 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	0.51% 1/198 • Number of events 1 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.
Gastrointestinal disorders Tongue oedema	4.1% 8/196 • Number of events 8 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	7.7% 15/195 • Number of events 16 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	6.2% 12/194 • Number of events 14 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	0.00% 0/198 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.
Gastrointestinal disorders Tongue pruritus	6.6% 13/196 • Number of events 14 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	9.7% 19/195 • Number of events 26 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	9.3% 18/194 • Number of events 21 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.	1.5% 3/198 • Number of events 3 • Up to 53 weeks The population consisted of all randomized participants who took at least one dose of study medication.