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)
Study Details
Study Description
Brief Summary
This study will evaluate the efficacy and safety of ragweed sublingual tablet (SCH 39641/MK-3641) 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 |
|---|---|---|
|
Phase 2/Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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 |
Biological: SCH 39641 6 Amb a 1-U
SCH 39641 6 Amb a 1-U sublingual tablets administered once daily
Other Names:
|
| Experimental: 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 |
Biological: SCH 39641 12 Amb a 1-U
SCH 39641 12 Amb a 1-U sublingual tablets administered once daily
Other Names:
|
| Placebo Comparator: Placebo Participants receive placebo matching ambrosia artemisiifolia allergen extract, rapidly dissolving tablets, administered once daily sublingually for approximately 52 weeks |
Biological: Placebo
matching placebo sublingual tablets administered once daily
|
Outcome Measures
Primary Outcome Measures
- 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). 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.
Secondary Outcome Measures
- 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). 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.
- 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 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.
- 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 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.
- 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 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.
Eligibility Criteria
Criteria
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 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 1 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
Exclusion Criteria:
-
Clinical history of symptomatic seasonal allergic rhinitis and/or asthma having received regular medication, due to another allergen 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.
-
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, pregnant, 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.
-
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.- P05233
- 2008-003863-38
- MK-3641-002
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | SCH 39641 6 Amb a 1-U | SCH 39641 12 Amb a 1-U | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants receive Ambrosia artemisiifolia allergen extract (SCH 39641 6 Amb a 1-U) rapidly dissolving tablets, administered once daily sublingually for approximately 52 weeks | Participants receive Ambrosia artemisiifolia allergen extract (SCH 39641 12 Amb a 1-U) rapidly dissolving tablets, administered once daily sublingually for approximately 52 weeks | Participants receive placebo matching ambrosia artemisiifolia allergen extract, rapidly dissolving tablets, administered once daily sublingually for approximately 52 weeks |
| Period Title: Overall Study | |||
| STARTED | 190 | 187 | 188 |
| COMPLETED | 133 | 144 | 146 |
| NOT COMPLETED | 57 | 43 | 42 |
Baseline Characteristics
| Arm/Group Title | SCH 39641 6 Amb a 1-U | SCH 39641 12 Amb a 1-U | Placebo | Total |
|---|---|---|---|---|
| Arm/Group Description | Participants receive Ambrosia artemisiifolia allergen extract (SCH 39641 6 Amb a 1-U) rapidly dissolving tablets, administered once daily sublingually for approximately 52 weeks | Participants receive Ambrosia artemisiifolia allergen extract (SCH 39641 12 Amb a 1-U) rapidly dissolving tablets, administered once daily sublingually for approximately 52 weeks | Participants receive placebo matching ambrosia artemisiifolia allergen extract, rapidly dissolving tablets, administered once daily sublingually for approximately 52 weeks | Total of all reporting groups |
| Overall Participants | 190 | 187 | 188 | 565 |
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
35.3
(9.00)
|
34.9
(9.41)
|
35.9
(9.13)
|
35.4
(9.17)
|
| Gender (Count of Participants) | ||||
| Female |
84
44.2%
|
109
58.3%
|
93
49.5%
|
286
50.6%
|
| Male |
106
55.8%
|
78
41.7%
|
95
50.5%
|
279
49.4%
|
Outcome Measures
| 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). 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. |
| 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. A total of 5 participants at one site were excluded from all efficacy analyses due to Good Clinical Practice (GCP) issues. |
| Arm/Group Title | SCH 39641 6 Amb a 1-U | SCH 39641 12 Amb a 1-U | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants receive Ambrosia artemisiifolia allergen extract (SCH 39641 6 Amb a 1-U) rapidly dissolving tablets, administered once daily sublingually for approximately 52 weeks | Participants receive Ambrosia artemisiifolia allergen extract (SCH 39641 12 Amb a 1-U) rapidly dissolving tablets, administered once daily sublingually for approximately 52 weeks | Participants receive placebo matching ambrosia artemisiifolia allergen extract, rapidly dissolving tablets, administered once daily sublingually for approximately 52 weeks |
| Measure Participants | 150 | 159 | 164 |
| Mean (Standard Error) [score on a scale] |
6.70
(0.563)
|
6.22
(0.543)
|
8.46
(0.521)
|
Statistical Analysis 1
| 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 | 0.0039 |
| Comments | ||
| Method | ANOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -1.76 | |
| Confidence Interval |
(2-Sided) 95% -2.95 to -0.57 |
|
| 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 12 Amb a 1-U, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0002 |
| Comments | ||
| Method | ANOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -2.24 | |
| Confidence Interval |
(2-Sided) 95% -3.41 to -1.07 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ANOVA model with baseline asthmatic condition, pollen region and treatment group as fixed effects | |
| 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). 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. |
| 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. A total of 5 participants at one site were excluded from all efficacy analyses due to GCP issues. |
| Arm/Group Title | SCH 39641 6 Amb a 1-U | SCH 39641 12 Amb a 1-U | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants receive Ambrosia artemisiifolia allergen extract (SCH 39641 6 Amb a 1-U) rapidly dissolving tablets, administered once daily sublingually for approximately 52 weeks | Participants receive Ambrosia artemisiifolia allergen extract (SCH 39641 12 Amb a 1-U) rapidly dissolving tablets, administered once daily sublingually for approximately 52 weeks | Participants receive placebo matching ambrosia artemisiifolia allergen extract, rapidly dissolving tablets, administered once daily sublingually for approximately 52 weeks |
| Measure Participants | 152 | 160 | 166 |
| Mean (Standard Error) [score on a scale] |
5.92
(0.467)
|
5.21
(0.450)
|
7.01
(0.434)
|
Statistical Analysis 1
| 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 | 0.0320 |
| Comments | ||
| Method | ANOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -1.09 | |
| Confidence Interval |
(2-Sided) 95% -2.08 to -0.09 |
|
| 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 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 | -1.80 | |
| Confidence Interval |
(2-Sided) 95% -2.78 to -0.82 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ANOVA model with baseline asthmatic condition, pollen region and treatment group as fixed effects | |
| 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 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. |
| 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. A total of 5 participants at one site were excluded from all efficacy analyses due to GCP issues. |
| Arm/Group Title | SCH 39641 6 Amb a 1-U | SCH 39641 12 Amb a 1-U | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants receive Ambrosia artemisiifolia allergen extract (SCH 39641 6 Amb a 1-U) rapidly dissolving tablets, administered once daily sublingually for approximately 52 weeks | Participants receive Ambrosia artemisiifolia allergen extract (SCH 39641 12 Amb a 1-U) rapidly dissolving tablets, administered once daily sublingually for approximately 52 weeks | Participants receive placebo matching ambrosia artemisiifolia allergen extract, rapidly dissolving tablets, administered once daily sublingually for approximately 52 weeks |
| Measure Participants | 150 | 159 | 164 |
| Mean (Standard Error) [score on a scale] |
4.81
(0.362)
|
4.65
(0.349)
|
5.59
(0.335)
|
Statistical Analysis 1
| 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 | 0.0472 |
| Comments | ||
| Method | ANOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.78 | |
| Confidence Interval |
(2-Sided) 95% -1.54 to -0.01 |
|
| 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 12 Amb a 1-U, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0144 |
| Comments | ||
| Method | ANOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.94 | |
| Confidence Interval |
(2-Sided) 95% -1.70 to -0.19 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ANOVA model with baseline asthmatic condition, pollen region and treatment group as fixed effects | |
| 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 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. |
| 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. A total of 5 participants at one site were excluded from all efficacy analyses due to GCP issues. |
| Arm/Group Title | SCH 39641 6 Amb a 1-U | SCH 39641 12 Amb a 1-U | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants receive Ambrosia artemisiifolia allergen extract (SCH 39641 6 Amb a 1-U) rapidly dissolving tablets, administered once daily sublingually for approximately 52 weeks | Participants receive Ambrosia artemisiifolia allergen extract (SCH 39641 12 Amb a 1-U) rapidly dissolving tablets, administered once daily sublingually for approximately 52 weeks | Participants receive placebo matching ambrosia artemisiifolia allergen extract, rapidly dissolving tablets, administered once daily sublingually for approximately 52 weeks |
| Measure Participants | 152 | 160 | 166 |
| Mean (Standard Error) [score on a scale] |
4.41
(0.306)
|
4.05
(0.295)
|
4.87
(0.285)
|
Statistical Analysis 1
| 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 | 0.1686 |
| Comments | ||
| Method | ANOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.46 | |
| Confidence Interval |
(2-Sided) 95% -1.11 to 0.19 |
|
| 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 12 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 | -0.82 | |
| Confidence Interval |
(2-Sided) 95% -1.46 to -0.18 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ANOVA model with baseline asthmatic condition, pollen region and treatment group as fixed effects | |
| Title | Average Rhinoconjunctivitis DMS for the Peak RS |
|---|---|
| Description | 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. |
| 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. A total of 5 participants at one site were excluded from all efficacy analyses due to GCP issues. |
| Arm/Group Title | SCH 39641 6 Amb a 1-U | SCH 39641 12 Amb a 1-U | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants receive Ambrosia artemisiifolia allergen extract (SCH 39641 6 Amb a 1-U) rapidly dissolving tablets, administered once daily sublingually for approximately 52 weeks | Participants receive Ambrosia artemisiifolia allergen extract (SCH 39641 12 Amb a 1-U) rapidly dissolving tablets, administered once daily sublingually for approximately 52 weeks | Participants receive placebo matching ambrosia artemisiifolia allergen extract, rapidly dissolving tablets, administered once daily sublingually for approximately 52 weeks |
| Measure Participants | 150 | 159 | 164 |
| Mean (Standard Error) [score on a scale] |
1.89
(0.314)
|
1.57
(0.303)
|
2.87
(0.291)
|
Statistical Analysis 1
| 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 | 0.0039 |
| Comments | ||
| Method | ANOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.98 | |
| Confidence Interval |
(2-Sided) 95% -1.65 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 2
| 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 | 0.0001 |
| Comments | ||
| Method | ANOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -1.30 | |
| Confidence Interval |
(2-Sided) 95% -1.95 to -0.64 |
|
| 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 | 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. | |||||
| Arm/Group Title | SCH 39641 6 Amb a 1-U | SCH 39641 12 Amb a 1-U | Placebo | |||
| Arm/Group Description | Participants receive Ambrosia artemisiifolia allergen extract (SCH 39641 6 Amb a 1-U) rapidly dissolving tablets, administered once daily sublingually for approximately 52 weeks | Participants receive Ambrosia artemisiifolia allergen extract (SCH 39641 12 Amb a 1-U) rapidly dissolving tablets, administered once daily sublingually for approximately 52 weeks | Participants receive placebo matching ambrosia artemisiifolia allergen extract, rapidly dissolving tablets, administered once daily sublingually for approximately 52 weeks | |||
All Cause Mortality |
||||||
| 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 | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| 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 | |
| Total | 2/188 (1.1%) | 3/186 (1.6%) | 4/186 (2.2%) | |||
| General disorders | ||||||
| Pelvic mass | 1/188 (0.5%) | 1 | 0/186 (0%) | 0 | 0/186 (0%) | 0 |
| Hepatobiliary disorders | ||||||
| Cholelithiasis | 0/188 (0%) | 0 | 0/186 (0%) | 0 | 1/186 (0.5%) | 1 |
| Infections and infestations | ||||||
| Appendicitis | 0/188 (0%) | 0 | 1/186 (0.5%) | 1 | 1/186 (0.5%) | 1 |
| Lobar pneumonia | 0/188 (0%) | 0 | 1/186 (0.5%) | 1 | 0/186 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||
| Soft tissue injury | 0/188 (0%) | 0 | 0/186 (0%) | 0 | 1/186 (0.5%) | 1 |
| Stab wound | 0/188 (0%) | 0 | 0/186 (0%) | 0 | 1/186 (0.5%) | 1 |
| Renal and urinary disorders | ||||||
| Tubulointerstitial nephritis | 0/188 (0%) | 0 | 1/186 (0.5%) | 1 | 0/186 (0%) | 0 |
| Reproductive system and breast disorders | ||||||
| Ovarian cyst | 1/188 (0.5%) | 1 | 0/186 (0%) | 0 | 0/186 (0%) | 0 |
| Pelvic pain | 1/188 (0.5%) | 1 | 0/186 (0%) | 0 | 0/186 (0%) | 0 |
| Uterine enlargement | 1/188 (0.5%) | 1 | 0/186 (0%) | 0 | 0/186 (0%) | 0 |
| Uterine haemorrhage | 1/188 (0.5%) | 1 | 0/186 (0%) | 0 | 0/186 (0%) | 0 |
| Uterine prolapse | 1/188 (0.5%) | 1 | 0/186 (0%) | 0 | 0/186 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| Hypoxia | 0/188 (0%) | 0 | 1/186 (0.5%) | 1 | 0/186 (0%) | 0 |
| Tonsillar hypertrophy | 1/188 (0.5%) | 1 | 0/186 (0%) | 0 | 0/186 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||
| 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 | |
| Total | 124/188 (66%) | 136/186 (73.1%) | 93/186 (50%) | |||
| Ear and labyrinth disorders | ||||||
| Ear pruritus | 30/188 (16%) | 39 | 30/186 (16.1%) | 33 | 4/186 (2.2%) | 5 |
| Gastrointestinal disorders | ||||||
| Lip swelling | 6/188 (3.2%) | 10 | 14/186 (7.5%) | 16 | 3/186 (1.6%) | 4 |
| Nausea | 6/188 (3.2%) | 11 | 13/186 (7%) | 16 | 2/186 (1.1%) | 2 |
| Oral pruritus | 36/188 (19.1%) | 41 | 36/186 (19.4%) | 44 | 6/186 (3.2%) | 7 |
| Paraesthesia oral | 14/188 (7.4%) | 18 | 20/186 (10.8%) | 28 | 4/186 (2.2%) | 5 |
| Swollen tongue | 22/188 (11.7%) | 24 | 36/186 (19.4%) | 51 | 6/186 (3.2%) | 7 |
| Tongue pruritus | 32/188 (17%) | 41 | 27/186 (14.5%) | 36 | 3/186 (1.6%) | 3 |
| Infections and infestations | ||||||
| Nasopharyngitis | 31/188 (16.5%) | 41 | 27/186 (14.5%) | 45 | 33/186 (17.7%) | 42 |
| Sinusitis | 9/188 (4.8%) | 13 | 12/186 (6.5%) | 14 | 11/186 (5.9%) | 11 |
| Upper respiratory tract infection | 22/188 (11.7%) | 33 | 19/186 (10.2%) | 26 | 28/186 (15.1%) | 38 |
| Nervous system disorders | ||||||
| Headache | 14/188 (7.4%) | 19 | 20/186 (10.8%) | 29 | 16/186 (8.6%) | 23 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| Cough | 14/188 (7.4%) | 18 | 15/186 (8.1%) | 16 | 5/186 (2.7%) | 6 |
| Dry throat | 10/188 (5.3%) | 10 | 4/186 (2.2%) | 6 | 1/186 (0.5%) | 1 |
| Oropharyngeal pain | 10/188 (5.3%) | 10 | 13/186 (7%) | 15 | 9/186 (4.8%) | 10 |
| Throat irritation | 48/188 (25.5%) | 73 | 55/186 (29.6%) | 73 | 10/186 (5.4%) | 13 |
| Skin and subcutaneous tissue disorders | ||||||
| Pruritus | 13/188 (6.9%) | 17 | 10/186 (5.4%) | 12 | 2/186 (1.1%) | 2 |
Limitations/Caveats
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.
Results Point of Contact
| Name/Title | Senior Vice President, Global Clinical Development |
|---|---|
| Organization | Merck Sharp & Dohme Corp. |
| Phone | |
| ClinicalTrialsDisclosure@merck.com |
- P05233
- 2008-003863-38
- MK-3641-002