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)

• Sponsor: ALK-Abelló A/S (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00770315
• Collaborator: (none)
• Enrollment: 784
• Arms: 4
• Duration (Months): 19.9

Study Details

Study Description

Brief Summary

This study will evaluate the efficacy and safety of ragweed sublingual tablet (SCH 39641/MK-3641/Amb a 1-U) compared with placebo in participants with ragweed-induced rhinoconjunctivitis over a one-year period. It is expected that ragweed allergic participants on one of the active arms of the trial will have decreased allergic rhinoconjunctivitis symptoms and require less allergy rescue medications during ragweed pollen season.

Condition or Disease	Intervention/Treatment	Phase
Rhinitis, Allergic; Conjunctivitis	Biological: Ambrosia artemisiifolia allergen extract (Amb a 1-U); Biological: Placebo	Phase 2/Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 784 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Double-Blind, Randomized, Placebo-Controlled, Parallel-Group Study Evaluating the Efficacy and Long-Term Safety of Ragweed (Ambrosia Artemisiifolia) Sublingual Tablet (SCH 39641) in Adult Subjects With a History of Ragweed-Induced Rhinoconjunctivitis With or Without Asthma
• Study Start Date: Sep 1, 2009
• Actual Primary Completion Date: May 1, 2011
• Actual Study Completion Date: May 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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	Biological: Ambrosia artemisiifolia allergen extract (Amb a 1-U); Rapidly dissolving tablet administered sublingually once daily, at a dose of 1.5, 6 or 12 units.; Other Names: SCH 39641 MK-3641
Experimental: 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	Biological: Ambrosia artemisiifolia allergen extract (Amb a 1-U); Rapidly dissolving tablet administered sublingually once daily, at a dose of 1.5, 6 or 12 units.; Other Names: SCH 39641 MK-3641
Experimental: 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	Biological: Ambrosia artemisiifolia allergen extract (Amb a 1-U); Rapidly dissolving tablet administered sublingually once daily, at a dose of 1.5, 6 or 12 units.; Other Names: SCH 39641 MK-3641
Placebo Comparator: Placebo Participants receive matching placebo rapidly dissolving sublingual tablets, administered once daily for approximately 52 weeks	Biological: Placebo; Placebo matching Ambrosia artemisiifolia allergen extract rapidly dissolving tablet, administered sublingually once daily

Outcome Measures

Primary Outcome Measures

1. Combined (Sum of) Rhinoconjunctivitis Daily Symptom Score (DSS) and Daily Medication Score (DMS) Averaged Over the Peak Ragweed Season (RS) [The 15-day period during the ragweed season with the highest moving pollen average]

   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.

Secondary Outcome Measures

1. Average Combined Rhinoconjunctivitis DSS and DMS Over the Entire RS [Approximately 5 weeks]

   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.

2. Average Rhinoconjunctivitis DSS for the Peak RS [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 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.

3. Average Rhinoconjunctivitis DSS for the Entire RS [Approximately 5 weeks]

   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.

4. Average Rhinoconjunctivitis DMS for the Peak RS [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 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 50 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Must have a clinical history of significant ragweed-induced allergic rhinoconjunctivitis of at least 2 years duration, with or without asthma and have received treatment during the previous ragweed season (RS).

• Must have a positive skin prick test response to Ambrosia artemisiifolia at Screening Visit.

• Must be positive for specific immunoglobulin E (IgE) against Ambrosia artemisiifolia at Screening Visit.

• Must have an forced expiratory volume in one second (FEV1) of at least 70% of predicted at Screening Visit.

• Safety laboratory tests and vital signs conducted at the Screening Visit must be within normal limits or clinically acceptable to the investigator/sponsor.

• Must be willing to give written informed consent and be able to adhere to dose and visit schedules.

• Female participants of childbearing potential must be using a medically acceptable and adequate form of birth control. These include: hormonal contraceptives as prescribed by a physician (oral, hormonal vaginal ring, hormonal implant or depot injectable); medically prescribed intra-uterine device; medically prescribed topically-applied transdermal contraceptive patch; double-barrier method (eg, condom in combination with a spermicide).

• Female participants of childbearing potential should be counseled in the appropriate use of birth control while in the study. Female participants who are not currently sexually active must and consent to use one of the above-mentioned methods if she becomes sexually active during the study.

• Female participants of childbearing potential must have a negative urine pregnancy test at Screening Visit. Women who have been surgically sterilized or at least 1 year postmenopausal are not considered to be of childbearing potential.

Exclusion Criteria:

• Clinical history of symptomatic seasonal allergic rhinitis and/or asthma having received regular medication, due to another during or potentially overlapping the RS.

• Clinical history of significant symptomatic perennial allergic rhinitis and/or asthma due to an allergen to which the participant is regularly exposed.

• Receipt of an immunosuppressive treatment within 3 months prior to the Screening Visit (except steroids for allergic and asthma symptoms).

• Clinical history of severe asthma.

• Asthma requiring medium or high dose inhaled corticosteroids (ICS).

• History of anaphylaxis with cardiorespiratory symptoms.

• History of chronic urticaria and angioedema.

• Clinical history of chronic sinusitis 2 years prior to the Screening Visit.

• Current severe atopic dermatitis.

• Breast-feeding, pregnancy, or intending to become pregnant.

• Had previous treatment by immunotherapy with ragweed allergen or any other allergen 5 years prior to Screening Visit.

• History of allergy, hypersensitivity or intolerance to the ingredients of the investigational medicinal products (except for Ambrosia artemisiifolia), rescue medications, or self-injectable epinephrine.

• Any clinically significant condition or situation, other than the condition being studied that, in the opinion of the investigator, would interfere with the study evaluations or optimal participation in the study.

• Use of any investigational drugs within 30 days of Screening Visit.

• Participation in any other clinical study.

• Being a family member of the study staff.

• Inability to meet medication washout requirements.

• Unlikely to be able to complete the trial, or likely to travel for an extended time during the RS.

• Clinically significant abnormal vital sign or lab value.

• Participation in this same study at another site.

• Randomized into this study more than once.

• Inability to or will not comply with the use of self-injectable epinephrine.

• Greater risk of developing adverse reactions after epinephrine administration.

• History of self-injectable epinephrine use

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• ALK-Abelló A/S

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: ALK-Abelló A/S
• ClinicalTrials.gov Identifier: NCT00770315
• Other Study ID Numbers: P05234; 3810249; 2008-003864-20; MK-3641-002
• First Posted: Oct 10, 2008
• Last Update Posted: Mar 3, 2017
• Last Verified: Jan 1, 2017

• Additional relevant MeSH terms: Rhinitis; Rhinitis, Allergic; Conjunctivitis

Study Results

Participant Flow

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

Baseline Characteristics

Arm/Group Title	SCH 39641 1.5 Amb a 1-U	SCH 39641 6 Amb a 1-U	SCH 39641 12 Amb a 1-U	Placebo	Total
Arm/Group Description	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	Participants receive Ambrosia artemisiifolia allergan extract (SCH 39641 6 Amb a 1-U) rapidly dissolving sublingual tablets, administered once daily for approximately 52 weeks	Participants receive Ambrosia artemisiifolia allergan extract (SCH 39641 12 Amb a 1-U) rapidly dissolving sublingual tablets, administered once daily for approximately 52 weeks	Participants receive placebo matching Ambrosia artemisiifolia allergan extract rapidly dissolving sublingual tablets, administered once daily for approximately 52 weeks	Total of all reporting groups
Overall Participants	197	195	194	198	784
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	36.2 (8.83)	36.9 (8.80)	35.6 (8.75)	36.7 (8.54)	36.4 (8.73)
Gender (Count of Participants)
Female	110 55.8%	103 52.8%	91 46.9%	96 48.5%	400 51%
Male	87 44.2%	92 47.2%	103 53.1%	102 51.5%	384 49%

Outcome Measures

1. Primary Outcome

Title	Combined (Sum of) Rhinoconjunctivitis Daily Symptom Score (DSS) and Daily Medication Score (DMS) Averaged Over the Peak Ragweed Season (RS)
Description	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.
Time Frame	The 15-day period during the ragweed season with the highest moving pollen average

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	SCH 39641 1.5 Amb a 1-U	SCH 39641 6 Amb a 1-U	SCH 39641 12 Amb a 1-U	Placebo
Arm/Group Description	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	Participants receive Ambrosia artemisiifolia allergan extract (SCH 39641 6 Amb a 1-U) rapidly dissolving sublingual tablets, administered once daily for approximately 52 weeks	Participants receive Ambrosia artemisiifolia allergan extract (SCH 39641 12 Amb a 1-U) rapidly dissolving sublingual tablets, administered once daily for approximately 52 weeks	Participants receive matching placebo rapidly dissolving sublingual tablets, administered once daily for approximately 52 weeks
Measure Participants	169	167	152	169
Mean (Standard Error) [score on a scale]	7.70 (0.517)	6.88 (0.526)	6.41 (0.534)	8.46 (0.535)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SCH 39641 1.5 Amb a 1-U, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2192
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.76
	Confidence Interval	(2-Sided) 95%; -1.98 to 0.45
	Parameter Dispersion	Type: Value:
	Estimation Comments	ANOVA model with baseline asthmatic condition, pollen region and treatment group as fixed effects

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	SCH 39641 6 Amb a 1-U, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0113
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.58
	Confidence Interval	(2-Sided) 95%; -2.80 to -0.36
	Parameter Dispersion	Type: Value:
	Estimation Comments	ANOVA model with baseline asthmatic condition, pollen region and treatment group as fixed effects

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	SCH 39641 12 Amb a 1-U, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0015
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.04
	Confidence Interval	(2-Sided) 95%; -3.30 to -0.79
	Parameter Dispersion	Type: Value:
	Estimation Comments	ANOVA model with baseline asthmatic condition, pollen region and treatment group as fixed effects

2. Secondary Outcome

Title	Average Combined Rhinoconjunctivitis DSS and DMS Over the Entire RS
Description	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.
Time Frame	Approximately 5 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	SCH 39641 1.5 Amb a 1-U	SCH 39641 6 Amb a 1-U	SCH 39641 12 Amb a 1-U	Placebo
Arm/Group Description	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	Participants receive Ambrosia artemisiifolia allergan extract (SCH 39641 6 Amb a 1-U) rapidly dissolving sublingual tablets, administered once daily for approximately 52 weeks	Participants receive Ambrosia artemisiifolia allergan extract (SCH 39641 12 Amb a 1-U) rapidly dissolving sublingual tablets, administered once daily for approximately 52 weeks	Participants receive matching placebo rapidly dissolving sublingual tablets, administered once daily for approximately 52 weeks
Measure Participants	171	172	158	174
Mean (Standard Error) [score on a scale]	6.22 (0.432)	5.81 (0.433)	5.18 (0.439)	7.09 (0.441)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SCH 39641 1.5 Amb a 1-U, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0878
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.88
	Confidence Interval	(2-Sided) 95%; -1.88 to 0.13
	Parameter Dispersion	Type: Value:
	Estimation Comments	ANOVA model with baseline asthmatic condition, pollen region and treatment group as fixed effects

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	SCH 39641 6 Amb a 1-U, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0125
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.28
	Confidence Interval	(2-Sided) 95%; -2.29 to -0.28
	Parameter Dispersion	Type: Value:
	Estimation Comments	ANOVA model with baseline asthmatic condition, pollen region and treatment group as fixed effects

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	SCH 39641 12 Amb a 1-U, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0003
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.92
	Confidence Interval	(2-Sided) 95%; -2.95 to -0.88
	Parameter Dispersion	Type: Value:
	Estimation Comments	ANOVA model with baseline asthmatic condition, pollen region and treatment group as fixed effects

3. Secondary Outcome

Title	Average Rhinoconjunctivitis DSS for the Peak RS
Description	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.
Time Frame	The 15-day period during the ragweed season with the highest moving pollen average

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	SCH 39641 1.5 Amb a 1-U	SCH 39641 6 Amb a 1-U	SCH 39641 12 Amb a 1-U	Placebo
Arm/Group Description	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	Participants receive Ambrosia artemisiifolia allergan extract (SCH 39641 6 Amb a 1-U) rapidly dissolving sublingual tablets, administered once daily for approximately 52 weeks	Participants receive Ambrosia artemisiifolia allergan extract (SCH 39641 12 Amb a 1-U) rapidly dissolving sublingual tablets, administered once daily for approximately 52 weeks	Participants receive matching placebo rapidly dissolving sublingual tablets, administered once daily for approximately 52 weeks
Measure Participants	169	167	152	169
Mean (Standard Error) [score on a scale]	5.11 (0.301)	4.87 (0.306)	4.43 (0.311)	5.37 (0.311)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SCH 39641 1.5 Amb a 1-U, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4781
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.26
	Confidence Interval	(2-Sided) 95%; -0.96 to 0.45
	Parameter Dispersion	Type: Value:
	Estimation Comments	ANOVA model with baseline asthmatic condition, pollen region and treatment group as fixed effects

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	SCH 39641 6 Amb a 1-U, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1695
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.50
	Confidence Interval	(2-Sided) 95%; -1.21 to 0.21
	Parameter Dispersion	Type: Value:
	Estimation Comments	ANOVA model with baseline asthmatic condition, pollen region and treatment group as fixed effects

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	SCH 39641 12 Amb a 1-U, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0118
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.94
	Confidence Interval	(2-Sided) 95%; -1.67 to -0.21
	Parameter Dispersion	Type: Value:
	Estimation Comments	ANOVA model with baseline asthmatic condition, pollen region and treatment group as fixed effects

4. Secondary Outcome

Title	Average Rhinoconjunctivitis DSS for the Entire RS
Description	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.
Time Frame	Approximately 5 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	SCH 39641 1.5 Amb a 1-U	SCH 39641 6 Amb a 1-U	SCH 39641 12 Amb a 1-U	Placebo
Arm/Group Description	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	Participants receive Ambrosia artemisiifolia allergan extract (SCH 39641 6 Amb a 1-U) rapidly dissolving sublingual tablets, administered once daily for approximately 52 weeks	Participants receive Ambrosia artemisiifolia allergan extract (SCH 39641 12 Amb a 1-U) rapidly dissolving sublingual tablets, administered once daily for approximately 52 weeks	Participants receive matching placebo rapidly dissolving sublingual tablets, administered once daily for approximately 52 weeks
Measure Participants	171	172	158	174
Mean (Standard Error) [score on a scale]	4.24 (0.255)	4.19 (0.256)	3.62 (0.259)	4.58 (0.261)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SCH 39641 1.5 Amb a 1-U, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2622
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.34
	Confidence Interval	(2-Sided) 95%; -0.93 to 0.25
	Parameter Dispersion	Type: Value:
	Estimation Comments	ANOVA model with baseline asthmatic condition, pollen region and treatment group as fixed effects

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	SCH 39641 6 Amb a 1-U, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1914
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.40
	Confidence Interval	(2-Sided) 95%; -0.99 to 0.20
	Parameter Dispersion	Type: Value:
	Estimation Comments	ANOVA model with baseline asthmatic condition, pollen region and treatment group as fixed effects

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	SCH 39641 12 Amb a 1-U, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0021
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.96
	Confidence Interval	(2-Sided) 95%; -1.57 to -0.35
	Parameter Dispersion	Type: Value:
	Estimation Comments	ANOVA model with baseline asthmatic condition, pollen region and treatment group as fixed effects

5. Secondary Outcome

Title	Average Rhinoconjunctivitis DMS for the Peak RS
Description	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.
Time Frame	The 15-day period during the ragweed season with the highest moving pollen average

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	SCH 39641 1.5 Amb a 1-U	SCH 39641 6 Amb a 1-U	SCH 39641 12 Amb a 1-U	Placebo
Arm/Group Description	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	Participants receive Ambrosia artemisiifolia allergan extract (SCH 39641 6 Amb a 1-U) rapidly dissolving sublingual tablets, administered once daily for approximately 52 weeks	Participants receive Ambrosia artemisiifolia allergan extract (SCH 39641 12 Amb a 1-U) rapidly dissolving sublingual tablets, administered once daily for approximately 52 weeks	Participants receive matching placebo rapidly dissolving sublingual tablets, administered once daily for approximately 52 weeks
Measure Participants	169	167	152	169
Mean (Standard Error) [score on a scale]	2.58 (0.322)	2.01 (0.328)	1.99 (0.333)	3.09 (0.333)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SCH 39641 1.5 Amb a 1-U, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1900
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.51
	Confidence Interval	(2-Sided) 95%; -1.26 to 0.25
	Parameter Dispersion	Type: Value:
	Estimation Comments	ANOVA model with baseline asthmatic condition, pollen region and treatment group as fixed effects

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	SCH 39641 6 Amb a 1-U, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0053
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.08
	Confidence Interval	(2-Sided) 95%; -1.84 to -0.32
	Parameter Dispersion	Type: Value:
	Estimation Comments	ANOVA model with baseline asthmatic condition, pollen region and treatment group as fixed effects

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	SCH 39641 12 Amb a 1-U, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0058
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.10
	Confidence Interval	(2-Sided) 95%; -1.89 to -0.32
	Parameter Dispersion	Type: Value:
	Estimation Comments	ANOVA model with baseline asthmatic condition, pollen region and treatment group as fixed effects

Adverse Events

Time Frame	Up to 53 weeks
Adverse Event Reporting Description	The population consisted of all randomized participants who took at least one dose of study medication.
Arm/Group Title	SCH 39641 1.5 Amb a 1-U		SCH 39641 6 Amb a 1-U		SCH 39641 12 Amb a 1-U		Placebo
Arm/Group Description	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		Participants receive Ambrosia artemisiifolia allergan extract (SCH 39641 6 Amb a 1-U) rapidly dissolving sublingual tablets, administered once daily for approximately 52 weeks		Participants receive Ambrosia artemisiifolia allergan extract (SCH 39641 12 Amb a 1-U) rapidly dissolving sublingual tablets, administered once daily for approximately 52 weeks		Participants receive placebo matching Ambrosia artemisiifolia allergan extract rapidly dissolving sublingual tablets, administered once daily for approximately 52 weeks
All Cause Mortality
	SCH 39641 1.5 Amb a 1-U		SCH 39641 6 Amb a 1-U		SCH 39641 12 Amb a 1-U		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	SCH 39641 1.5 Amb a 1-U		SCH 39641 6 Amb a 1-U		SCH 39641 12 Amb a 1-U		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/196 (2.6%)		4/195 (2.1%)		4/194 (2.1%)		1/198 (0.5%)
Congenital, familial and genetic disorders
Hydrocele	0/196 (0%)	0	0/195 (0%)	0	1/194 (0.5%)	1	0/198 (0%)	0
Gastrointestinal disorders
Abdominal hernia obstructive	0/196 (0%)	0	1/195 (0.5%)	1	0/194 (0%)	0	0/198 (0%)	0
Pancreatitis acute	1/196 (0.5%)	2	0/195 (0%)	0	0/194 (0%)	0	0/198 (0%)	0
Hepatobiliary disorders
Cholelithiasis	1/196 (0.5%)	1	0/195 (0%)	0	0/194 (0%)	0	0/198 (0%)	0
Immune system disorders
Hypersensitivity	0/196 (0%)	0	0/195 (0%)	0	1/194 (0.5%)	1	0/198 (0%)	0
Infections and infestations
Bronchitis	0/196 (0%)	0	1/195 (0.5%)	1	0/194 (0%)	0	0/198 (0%)	0
Pneumonia chlamydial	0/196 (0%)	0	0/195 (0%)	0	0/194 (0%)	0	1/198 (0.5%)	1
Postoperative abscess	0/196 (0%)	0	1/195 (0.5%)	1	0/194 (0%)	0	0/198 (0%)	0
Injury, poisoning and procedural complications
Ligament rupture	1/196 (0.5%)	1	0/195 (0%)	0	0/194 (0%)	0	0/198 (0%)	0
Metabolism and nutrition disorders
Diabetes mellitus inadequate control	0/196 (0%)	0	0/195 (0%)	0	1/194 (0.5%)	1	0/198 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer	1/196 (0.5%)	1	1/195 (0.5%)	1	0/194 (0%)	0	0/198 (0%)	0
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous	1/196 (0.5%)	1	1/195 (0.5%)	1	0/194 (0%)	0	0/198 (0%)	0
Reproductive system and breast disorders
Ovarian cyst	0/196 (0%)	0	0/195 (0%)	0	1/194 (0.5%)	1	0/198 (0%)	0
Surgical and medical procedures
Abortion induced	1/196 (0.5%)	1	0/195 (0%)	0	0/194 (0%)	0	0/198 (0%)	0
Other (Not Including Serious) Adverse Events
	SCH 39641 1.5 Amb a 1-U		SCH 39641 6 Amb a 1-U		SCH 39641 12 Amb a 1-U		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	105/196 (53.6%)		108/195 (55.4%)		125/194 (64.4%)		78/198 (39.4%)
Ear and labyrinth disorders
Ear pruritus	14/196 (7.1%)	15	27/195 (13.8%)	30	25/194 (12.9%)	26	2/198 (1%)	2
Gastrointestinal disorders
Oral pruritus	11/196 (5.6%)	12	29/195 (14.9%)	37	16/194 (8.2%)	17	2/198 (1%)	2
Paraesthesia oral	10/196 (5.1%)	11	15/195 (7.7%)	18	9/194 (4.6%)	14	5/198 (2.5%)	9
Swollen tongue	11/196 (5.6%)	11	12/195 (6.2%)	14	15/194 (7.7%)	16	1/198 (0.5%)	1
Tongue oedema	8/196 (4.1%)	8	15/195 (7.7%)	16	12/194 (6.2%)	14	0/198 (0%)	0
Tongue pruritus	13/196 (6.6%)	14	19/195 (9.7%)	26	18/194 (9.3%)	21	3/198 (1.5%)	3
Infections and infestations
Bronchitis	5/196 (2.6%)	7	6/195 (3.1%)	6	8/194 (4.1%)	8	12/198 (6.1%)	14
Nasopharyngitis	31/196 (15.8%)	40	28/195 (14.4%)	35	33/194 (17%)	42	35/198 (17.7%)	45
Sinusitis	12/196 (6.1%)	13	9/195 (4.6%)	10	8/194 (4.1%)	9	7/198 (3.5%)	10
Upper respiratory tract infection	9/196 (4.6%)	9	18/195 (9.2%)	22	9/194 (4.6%)	12	9/198 (4.5%)	11
Nervous system disorders
Headache	15/196 (7.7%)	33	12/195 (6.2%)	17	18/194 (9.3%)	49	20/198 (10.1%)	34
Respiratory, thoracic and mediastinal disorders
Cough	11/196 (5.6%)	13	10/195 (5.1%)	10	12/194 (6.2%)	14	6/198 (3%)	8
Oropharyngeal pain	14/196 (7.1%)	17	5/195 (2.6%)	5	9/194 (4.6%)	10	4/198 (2%)	4
Sneezing	10/196 (5.1%)	11	6/195 (3.1%)	7	8/194 (4.1%)	10	4/198 (2%)	8
Throat irritation	28/196 (14.3%)	29	42/195 (21.5%)	46	41/194 (21.1%)	45	11/198 (5.6%)	11

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.