Trial Outcomes & Findings for Efficacy and Long-Term Safety of Ragweed (Ambrosia Artemisiifolia) Sublingual Tablet in Adults With a History of Ragweed-Induced Rhinoconjunctivitis With or Without Asthma (Study P05233)(COMPLETED) (NCT NCT00783198)

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). Rhinoconjunctivitis DMS was based on participant use of specific study-provided rescue medicationwith different rescue medications being assigned different scores/dose unit. The maximum rhinoconjunctivitis DMS score was 36. The sum of the rhinoconjunctivitis DSS and DMS could range from 0 to 54, with a lower score indicating less rhinoconjuntivitis symptoms and medication use. Raw means for DSS+DMS were converted to adjusted means based on an analysis of variance (ANOVA) model with baseline asthmatic condition, pollen region and treatment group as fixed effects.

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

565 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 6 Amb a 1-U Participants receive Ambrosia artemisiifolia allergen extract (SCH 39641 6 Amb a 1-U) rapidly dissolving tablets, administered once daily sublingually for approximately 52 weeks	SCH 39641 12 Amb a 1-U Participants receive Ambrosia artemisiifolia allergen extract (SCH 39641 12 Amb a 1-U) rapidly dissolving tablets, administered once daily sublingually for approximately 52 weeks	Placebo Participants receive placebo matching ambrosia artemisiifolia allergen extract, rapidly dissolving tablets, administered once daily sublingually for approximately 52 weeks
Overall Study STARTED	190	187	188
Overall Study COMPLETED	133	144	146
Overall Study NOT COMPLETED	57	43	42

Reasons for withdrawal

Reasons for withdrawal
Measure	SCH 39641 6 Amb a 1-U Participants receive Ambrosia artemisiifolia allergen extract (SCH 39641 6 Amb a 1-U) rapidly dissolving tablets, administered once daily sublingually for approximately 52 weeks	SCH 39641 12 Amb a 1-U Participants receive Ambrosia artemisiifolia allergen extract (SCH 39641 12 Amb a 1-U) rapidly dissolving tablets, administered once daily sublingually for approximately 52 weeks	Placebo Participants receive placebo matching ambrosia artemisiifolia allergen extract, rapidly dissolving tablets, administered once daily sublingually for approximately 52 weeks
Overall Study Adverse Event	15	19	3
Overall Study Lost to Follow-up	11	1	7
Overall Study Withdrawal by Subject	22	14	20
Overall Study Noncompliance with protocol	7	7	10
Overall Study Did not meet protocol eligibility	0	1	0
Overall Study Administrative	2	1	2

Baseline Characteristics

Efficacy and Long-Term Safety of Ragweed (Ambrosia Artemisiifolia) Sublingual Tablet in Adults With a History of Ragweed-Induced Rhinoconjunctivitis With or Without Asthma (Study P05233)(COMPLETED)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	SCH 39641 6 Amb a 1-U n=190 Participants Participants receive Ambrosia artemisiifolia allergen extract (SCH 39641 6 Amb a 1-U) rapidly dissolving tablets, administered once daily sublingually for approximately 52 weeks	SCH 39641 12 Amb a 1-U n=187 Participants Participants receive Ambrosia artemisiifolia allergen extract (SCH 39641 12 Amb a 1-U) rapidly dissolving tablets, administered once daily sublingually for approximately 52 weeks	Placebo n=188 Participants Participants receive placebo matching ambrosia artemisiifolia allergen extract, rapidly dissolving tablets, administered once daily sublingually for approximately 52 weeks	Total n=565 Participants Total of all reporting groups
Age, Continuous	35.3 years STANDARD_DEVIATION 9.00 • n=5 Participants	34.9 years STANDARD_DEVIATION 9.41 • n=7 Participants	35.9 years STANDARD_DEVIATION 9.13 • n=5 Participants	35.4 years STANDARD_DEVIATION 9.17 • n=4 Participants
Gender Female	84 Participants n=5 Participants	109 Participants n=7 Participants	93 Participants n=5 Participants	286 Participants n=4 Participants
Gender Male	106 Participants n=5 Participants	78 Participants n=7 Participants	95 Participants n=5 Participants	279 Participants n=4 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. A total of 5 participants at one site were excluded from all efficacy analyses due to Good Clinical Practice (GCP) issues.

Outcome measures

Outcome measures
Measure	SCH 39641 6 Amb a 1-U n=150 Participants Participants receive Ambrosia artemisiifolia allergen extract (SCH 39641 6 Amb a 1-U) rapidly dissolving tablets, administered once daily sublingually for approximately 52 weeks	SCH 39641 12 Amb a 1-U n=159 Participants Participants receive Ambrosia artemisiifolia allergen extract (SCH 39641 12 Amb a 1-U) rapidly dissolving tablets, administered once daily sublingually for approximately 52 weeks	Placebo n=164 Participants Participants receive placebo matching ambrosia artemisiifolia allergen extract, rapidly dissolving tablets, administered once daily sublingually for approximately 52 weeks
Combined (Sum of) Rhinoconjunctivitis Daily Symptom Score (DSS) and Daily Medication Score (DMS) Averaged Over the Peak Ragweed Season (RS)	6.70 score on a scale Standard Error 0.563 • Interval -2.95 to -0.57	6.22 score on a scale Standard Error 0.543 • Interval -3.41 to -1.07	8.46 score on a scale Standard Error 0.521

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. A total of 5 participants at one site were excluded from all efficacy analyses due to GCP issues.

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). Rhinoconjunctivitis DMS was based on participant use of specific study-provided rescue medicationwith different rescue medications being assigned different scores/dose unit. The maximum rhinoconjunctivitis DMS score was 36. The sum of the rhinoconjunctivitis DSS and DMS could range from 0 to 54, with a lower score indicating less rhinoconjuntivitis symptoms and medication use. Raw means for DSS+DMS were converted to adjusted means based on an ANOVA model with baseline asthmatic condition, pollen region and treatment group as fixed effects.

Outcome measures

Outcome measures
Measure	SCH 39641 6 Amb a 1-U n=152 Participants Participants receive Ambrosia artemisiifolia allergen extract (SCH 39641 6 Amb a 1-U) rapidly dissolving tablets, administered once daily sublingually for approximately 52 weeks	SCH 39641 12 Amb a 1-U n=160 Participants Participants receive Ambrosia artemisiifolia allergen extract (SCH 39641 12 Amb a 1-U) rapidly dissolving tablets, administered once daily sublingually for approximately 52 weeks	Placebo n=166 Participants Participants receive placebo matching ambrosia artemisiifolia allergen extract, rapidly dissolving tablets, administered once daily sublingually for approximately 52 weeks
Average Combined Rhinoconjunctivitis DSS and DMS Over the Entire RS	5.92 score on a scale Standard Error 0.467 • Interval -2.08 to -0.09	5.21 score on a scale Standard Error 0.450 • Interval -2.78 to -0.82	7.01 score on a scale Standard Error 0.434

SECONDARY outcome

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

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 rhinoconjuntivitis symptoms. Raw means for DSS were converted to adjusted means based on an ANOVA model with baseline asthmatic condition, pollen region and treatment group as fixed effects.

Outcome measures

Outcome measures
Measure	SCH 39641 6 Amb a 1-U n=150 Participants Participants receive Ambrosia artemisiifolia allergen extract (SCH 39641 6 Amb a 1-U) rapidly dissolving tablets, administered once daily sublingually for approximately 52 weeks	SCH 39641 12 Amb a 1-U n=159 Participants Participants receive Ambrosia artemisiifolia allergen extract (SCH 39641 12 Amb a 1-U) rapidly dissolving tablets, administered once daily sublingually for approximately 52 weeks	Placebo n=164 Participants Participants receive placebo matching ambrosia artemisiifolia allergen extract, rapidly dissolving tablets, administered once daily sublingually for approximately 52 weeks
Average Rhinoconjunctivitis DSS for the Peak RS	4.81 score on a scale Standard Error 0.362 • Interval -1.54 to -0.01	4.65 score on a scale Standard Error 0.349 • Interval -1.7 to -0.19	5.59 score on a scale Standard Error 0.335

SECONDARY outcome

Timeframe: Approximately 5 weeks

Outcome measures

Outcome measures
Measure	SCH 39641 6 Amb a 1-U n=152 Participants Participants receive Ambrosia artemisiifolia allergen extract (SCH 39641 6 Amb a 1-U) rapidly dissolving tablets, administered once daily sublingually for approximately 52 weeks	SCH 39641 12 Amb a 1-U n=160 Participants Participants receive Ambrosia artemisiifolia allergen extract (SCH 39641 12 Amb a 1-U) rapidly dissolving tablets, administered once daily sublingually for approximately 52 weeks	Placebo n=166 Participants Participants receive placebo matching ambrosia artemisiifolia allergen extract, rapidly dissolving tablets, administered once daily sublingually for approximately 52 weeks
Average Rhinoconjunctivitis DSS for the Entire RS	4.41 score on a scale Standard Error 0.306 • Interval -1.11 to 0.19	4.05 score on a scale Standard Error 0.295 • Interval -1.46 to -0.18	4.87 score on a scale Standard Error 0.285

SECONDARY outcome

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

Rhinoconjunctivitis DMS was based on participant use of specific study-provided rescue medicationwith different rescue medications being assigned different scores/dose unit. The maximum rhinoconjunctivitis DMS score was 36, with a lower score indicating less rhinoconjuntivitis medication use. Raw means for DMS were converted to adjusted means based on an ANOVA model with baseline asthmatic condition, pollen region and treatment group as fixed effects.

Outcome measures

Outcome measures
Measure	SCH 39641 6 Amb a 1-U n=150 Participants Participants receive Ambrosia artemisiifolia allergen extract (SCH 39641 6 Amb a 1-U) rapidly dissolving tablets, administered once daily sublingually for approximately 52 weeks	SCH 39641 12 Amb a 1-U n=159 Participants Participants receive Ambrosia artemisiifolia allergen extract (SCH 39641 12 Amb a 1-U) rapidly dissolving tablets, administered once daily sublingually for approximately 52 weeks	Placebo n=164 Participants Participants receive placebo matching ambrosia artemisiifolia allergen extract, rapidly dissolving tablets, administered once daily sublingually for approximately 52 weeks
Average Rhinoconjunctivitis DMS for the Peak RS	1.89 score on a scale Standard Error 0.314 • Interval -1.65 to -0.32	1.57 score on a scale Standard Error 0.303 • Interval -1.95 to -0.64	2.87 score on a scale Standard Error 0.291

Adverse Events

SCH 39641 6 Amb a 1-U

Serious events: 2 serious events

Other events: 124 other events

Deaths: 0 deaths

SCH 39641 12 Amb a 1-U

Serious events: 3 serious events

Other events: 136 other events

Deaths: 0 deaths

Placebo

Serious events: 4 serious events

Other events: 93 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	SCH 39641 6 Amb a 1-U n=188 participants at risk Participants receive Ambrosia artemisiifolia allergen extract (SCH 39641 6 Amb a 1-U) rapidly dissolving tablets, administered once daily sublingually for approximately 52 weeks	SCH 39641 12 Amb a 1-U n=186 participants at risk Participants receive Ambrosia artemisiifolia allergen extract (SCH 39641 12 Amb a 1-U) rapidly dissolving tablets, administered once daily sublingually for approximately 52 weeks	Placebo n=186 participants at risk Participants receive placebo matching ambrosia artemisiifolia allergen extract, rapidly dissolving tablets, administered once daily sublingually for approximately 52 weeks
General disorders Pelvic mass	0.53% 1/188 • Number of events 1 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.	0.00% 0/186 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.	0.00% 0/186 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.
Hepatobiliary disorders Cholelithiasis	0.00% 0/188 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.	0.00% 0/186 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.	0.54% 1/186 • Number of events 1 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.
Infections and infestations Appendicitis	0.00% 0/188 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.	0.54% 1/186 • Number of events 1 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.	0.54% 1/186 • Number of events 1 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.
Infections and infestations Lobar pneumonia	0.00% 0/188 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.	0.54% 1/186 • Number of events 1 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.	0.00% 0/186 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.
Injury, poisoning and procedural complications Soft tissue injury	0.00% 0/188 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.	0.00% 0/186 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.	0.54% 1/186 • Number of events 1 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.
Injury, poisoning and procedural complications Stab wound	0.00% 0/188 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.	0.00% 0/186 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.	0.54% 1/186 • Number of events 1 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.
Renal and urinary disorders Tubulointerstitial nephritis	0.00% 0/188 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.	0.54% 1/186 • Number of events 1 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.	0.00% 0/186 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.
Reproductive system and breast disorders Ovarian cyst	0.53% 1/188 • Number of events 1 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.	0.00% 0/186 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.	0.00% 0/186 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.
Reproductive system and breast disorders Pelvic pain	0.53% 1/188 • Number of events 1 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.	0.00% 0/186 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.	0.00% 0/186 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.
Reproductive system and breast disorders Uterine enlargement	0.53% 1/188 • Number of events 1 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.	0.00% 0/186 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.	0.00% 0/186 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.
Reproductive system and breast disorders Uterine haemorrhage	0.53% 1/188 • Number of events 1 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.	0.00% 0/186 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.	0.00% 0/186 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.
Reproductive system and breast disorders Uterine prolapse	0.53% 1/188 • Number of events 1 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.	0.00% 0/186 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.	0.00% 0/186 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/188 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.	0.54% 1/186 • Number of events 1 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.	0.00% 0/186 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.
Respiratory, thoracic and mediastinal disorders Tonsillar hypertrophy	0.53% 1/188 • Number of events 1 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.	0.00% 0/186 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.	0.00% 0/186 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.

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 6 Amb a 1-U n=188 participants at risk Participants receive Ambrosia artemisiifolia allergen extract (SCH 39641 6 Amb a 1-U) rapidly dissolving tablets, administered once daily sublingually for approximately 52 weeks	SCH 39641 12 Amb a 1-U n=186 participants at risk Participants receive Ambrosia artemisiifolia allergen extract (SCH 39641 12 Amb a 1-U) rapidly dissolving tablets, administered once daily sublingually for approximately 52 weeks	Placebo n=186 participants at risk Participants receive placebo matching ambrosia artemisiifolia allergen extract, rapidly dissolving tablets, administered once daily sublingually for approximately 52 weeks
Ear and labyrinth disorders Ear pruritus	16.0% 30/188 • Number of events 39 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.	16.1% 30/186 • Number of events 33 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.	2.2% 4/186 • Number of events 5 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.
Gastrointestinal disorders Lip swelling	3.2% 6/188 • Number of events 10 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.	7.5% 14/186 • Number of events 16 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.	1.6% 3/186 • Number of events 4 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.
Gastrointestinal disorders Nausea	3.2% 6/188 • Number of events 11 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.	7.0% 13/186 • Number of events 16 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.	1.1% 2/186 • Number of events 2 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.
Gastrointestinal disorders Oral pruritus	19.1% 36/188 • Number of events 41 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.	19.4% 36/186 • Number of events 44 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.	3.2% 6/186 • Number of events 7 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.
Gastrointestinal disorders Paraesthesia oral	7.4% 14/188 • Number of events 18 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.	10.8% 20/186 • Number of events 28 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.	2.2% 4/186 • Number of events 5 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.
Gastrointestinal disorders Swollen tongue	11.7% 22/188 • Number of events 24 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.	19.4% 36/186 • Number of events 51 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.	3.2% 6/186 • Number of events 7 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.
Gastrointestinal disorders Tongue pruritus	17.0% 32/188 • Number of events 41 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.	14.5% 27/186 • Number of events 36 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.	1.6% 3/186 • Number of events 3 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.
Infections and infestations Nasopharyngitis	16.5% 31/188 • Number of events 41 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.	14.5% 27/186 • Number of events 45 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.	17.7% 33/186 • Number of events 42 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.
Infections and infestations Sinusitis	4.8% 9/188 • Number of events 13 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.	6.5% 12/186 • Number of events 14 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.	5.9% 11/186 • Number of events 11 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.
Infections and infestations Upper respiratory tract infection	11.7% 22/188 • Number of events 33 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.	10.2% 19/186 • Number of events 26 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.	15.1% 28/186 • Number of events 38 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.
Nervous system disorders Headache	7.4% 14/188 • Number of events 19 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.	10.8% 20/186 • Number of events 29 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.	8.6% 16/186 • Number of events 23 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.
Respiratory, thoracic and mediastinal disorders Cough	7.4% 14/188 • Number of events 18 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.	8.1% 15/186 • Number of events 16 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.	2.7% 5/186 • Number of events 6 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.
Respiratory, thoracic and mediastinal disorders Dry throat	5.3% 10/188 • Number of events 10 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.	2.2% 4/186 • Number of events 6 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.	0.54% 1/186 • Number of events 1 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	5.3% 10/188 • Number of events 10 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.	7.0% 13/186 • Number of events 15 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.	4.8% 9/186 • Number of events 10 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.
Respiratory, thoracic and mediastinal disorders Throat irritation	25.5% 48/188 • Number of events 73 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.	29.6% 55/186 • Number of events 73 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.	5.4% 10/186 • Number of events 13 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.
Skin and subcutaneous tissue disorders Pruritus	6.9% 13/188 • Number of events 17 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.	5.4% 10/186 • Number of events 12 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.	1.1% 2/186 • Number of events 2 • Up to 53 weeks A total of 5 participants (2 in the SCH 39641 6 Amb a 1-U group, 1 in the SCH 39641 12 Amb a 1-U group and 2 in the Placebo group) at one site were excluded from all safety analyses due to GCP issues. Adverse events are reported for the remaining participants.