Safety Study of Ragweed Allergy Immunotherapy Tablet in Subjects 50 Years of Age and Older (Study P06081)

Sponsor
ALK-Abelló A/S (Industry)
Overall Status
Completed
CT.gov ID
NCT00978029
Collaborator
(none)
203
3
3

Study Details

Study Description

Brief Summary

The purpose of this study was to assess the safety and tolerability of a ragweed allergy immunotherapy tablet (AIT) administered sublingually (under-the tongue) in subjects 50 years of age and older with ragweed-induced rhinoconjunctivitis, with or without asthma.

Condition or Disease Intervention/Treatment Phase
  • Drug: Placebo
  • Biological: SCH 39641
  • Biological: SCH 39641
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
203 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A 28-Day Study Evaluating the Safety of Ragweed (Ambrosia Artemisiifolia) Sublingual Tablet (SCH 39641) in Adult Subjects 50 Years of Age and Older With Ragweed-Induced Rhinoconjunctivitis (Protocol No. P06081)
Study Start Date :
Nov 1, 2009
Actual Primary Completion Date :
Feb 1, 2010
Actual Study Completion Date :
Feb 1, 2010

Arms and Interventions

Arm Intervention/Treatment
Placebo Comparator: Placebo

Matching placebo tablet sublingual, once daily

Drug: Placebo
Placebo sublingual tablet, once daily

Experimental: SCH 39641 6 Amb a 1-U

6 Units Short Ragweed (Ambrosia artemisiifolia) Major Allergen 1 (Amb a 1-U) in an AIT, sublingual, once daily

Biological: SCH 39641
Allergy immunotherapy tablet (sublingual)
Other Names:
  • MK-3641
  • Experimental: SCH 39641 12 Amb a 1-U

    12 Amb a 1-U in an AIT, sublingual, once daily

    Biological: SCH 39641
    Allergy immunotherapy tablet (sublingual)
    Other Names:
  • MK-3641
  • Outcome Measures

    Primary Outcome Measures

    1. The Proportion of Participants Reporting Treatment-emergent Adverse Events (AEs) [Up to Day 42]

      Participants were treated for 28 days with either 6 or 12 Units of SCH 39641 or placebo, and the proportion with treatment-emergent AEs were recorded. An AE is any unfavorable and unintended sign, symptom or disease temporarily associated with the use of a medicinal product, whether or not considered related to the medicinal product. Treatment-emergent AEs are new AEs that occur after participants have been randomized into the trial, or existing AEs that occurred during Screening that increase in severity after randomization.

    Secondary Outcome Measures

    1. Proportion of Participants Reporting Oral Pruritus [Up to Day 42]

      Participants were treated for 28 days with either 6 or 12 Units of SCH 39641 or placebo, and the proportion with oral pruritus were reported.

    2. Proportion of Participants Reporting Ear Pruritus [Up to Day 42]

      Participants were treated for 28 days with either 6 or 12 Units of SCH 39641 or placebo, and the proportion with ear pruritus were reported.

    3. Proportion of Participants Reporting Throat Irritation [Up to Day 42]

      Participants were treated for 28 days with either 6 or 12 Units of SCH 39641 or placebo, and the proportion with throat irritation were reported.

    4. Proportion of Participants Reporting Mouth Oedema [Up to Day 42]

      Participants were treated for 28 days with either 6 or 12 Units of SCH 39641 or placebo, and the proportion with mouth oedema were reported.

    5. Proportion of Participants Who Discontinued Due to Adverse Events. [Up to Day 28]

      Participants were treated for 28 days with either 6 or 12 Units of SCH 39641 or placebo, and the proportion with AEs leading to study discontinuation were reported. An AE is any unfavorable and unintended sign, symptom or disease temporarily associated with the use of a medicinal product, whether or not considered related to the medicinal product.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    50 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Subject must be 50 years of age or older, of either sex, and of any race/ethnicity.

    • Subject must have a clinical history of ragweed-induced allergic rhinoconjunctivitis with or without asthma.

    • Subject must have a positive skin prick test response to Ambrosia artemisiifolia at the Screening Visit

    • Subject must have a forced expiratory volume in 1 second (FEV1) of at least 70% of predicted value at the Screening Visit and at Randomization.

    • A subject's clinical laboratory tests, electrocardiogram (ECG) and vital signs conducted at the Screening Visit must be within normal limits or clinically acceptable to the investigator.

    Exclusion Criteria:
    • Subject with asthma who requires inhaled corticosteroids for the treatment of their asthma during the study period.

    • Subject requiring anti-allergy medications during the time period from randomization to study completion.

    • Subject who has received an immunosuppressive treatment within 3 months prior to the Screening Visit (except steroids for allergic and asthma symptoms).

    • Subject with a history of anaphylaxis with cardiorespiratory symptoms.

    • Subject with a history of chronic urticaria or angioedema.

    • Subject with current severe atopic dermatitis.

    • Female subject who is breastfeeding, pregnant, or intending to become pregnant.

    • Subject with a history of allergy, hypersensitivity or intolerance to the ingredients of the investigational medicinal products (IMPs) (except for Ambrosia artemisiifolia), or self-injectable epinephrine.

    • Subject with a 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:
    NCT00978029
    Other Study ID Numbers:
    • P06081
    • MK-3641-004
    First Posted:
    Sep 16, 2009
    Last Update Posted:
    Mar 3, 2017
    Last Verified:
    Jan 1, 2017
    Keywords provided by ALK-Abelló A/S
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail Due to non-compliance with Good Clinical Practice (GCP) 7 randomized participants who completed treatment were excluded from all subsequent analysis.
    Arm/Group Title Placebo SCH 39641 6 Amb a 1-U SCH 39641 12 Amb a 1-U
    Arm/Group Description Matching placebo tablet sublingual, once daily 6 Units Short Ragweed (Ambrosia artemisiifolia) Major Allergen 1 (Amb a 1-U) in an Allergy Immunotherapy Tablet (AIT) sublingual, once daily 12 Amb a 1-U in an AIT, sublingual, once daily
    Period Title: Overall Study
    STARTED 65 66 65
    COMPLETED 64 63 59
    NOT COMPLETED 1 3 6

    Baseline Characteristics

    Arm/Group Title Placebo SCH 39641 6 Amb a 1-U SCH 39641 12 Amb a 1-U Total
    Arm/Group Description Matching placebo tablet sublingual, once daily 6 Amb a 1-U in an AIT, sublingual, once daily 12 Amb a 1-U in an AIT, sublingual, once daily Total of all reporting groups
    Overall Participants 65 66 65 196
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    56.4
    (4.7)
    56.4
    (5.4)
    56.2
    (5.7)
    56.3
    (5.3)
    Gender (Count of Participants)
    Female
    38
    58.5%
    43
    65.2%
    40
    61.5%
    121
    61.7%
    Male
    27
    41.5%
    23
    34.8%
    25
    38.5%
    75
    38.3%

    Outcome Measures

    1. Primary Outcome
    Title The Proportion of Participants Reporting Treatment-emergent Adverse Events (AEs)
    Description Participants were treated for 28 days with either 6 or 12 Units of SCH 39641 or placebo, and the proportion with treatment-emergent AEs were recorded. An AE is any unfavorable and unintended sign, symptom or disease temporarily associated with the use of a medicinal product, whether or not considered related to the medicinal product. Treatment-emergent AEs are new AEs that occur after participants have been randomized into the trial, or existing AEs that occurred during Screening that increase in severity after randomization.
    Time Frame Up to Day 42

    Outcome Measure Data

    Analysis Population Description
    All subjects as treated (ASAT) consisting of all randomized participants who received at least one dose of study treatment. Due to non-compliance with GCP 7 participants were excluded from this analysis.
    Arm/Group Title Placebo SCH 39641 6 Amb a 1-U SCH 39641 12 Amb a 1-U
    Arm/Group Description Matching placebo tablet sublingual, once daily 6 Amb a 1-U in an AIT, sublingual, once daily 12 Amb a 1-U in an AIT, sublingual, once daily
    Measure Participants 65 66 65
    Number [Proportion of Participants]
    0.446
    0.7%
    0.515
    0.8%
    0.615
    0.9%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, SCH 39641 6 Amb a 1-U
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.486
    Comments
    Method Fisher Exact
    Comments
    Method of Estimation Estimation Parameter Percent Difference
    Estimated Value 6.9
    Confidence Interval (2-Sided) 95%
    -10.17 to 23.97
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, SCH 39641 12 Amb a 1-U
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.078
    Comments
    Method Fisher Exact
    Comments
    Method of Estimation Estimation Parameter Percent Difference
    Estimated Value 16.9
    Confidence Interval (2-Sided) 95%
    0.01 to 33.83
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    Title Proportion of Participants Reporting Oral Pruritus
    Description Participants were treated for 28 days with either 6 or 12 Units of SCH 39641 or placebo, and the proportion with oral pruritus were reported.
    Time Frame Up to Day 42

    Outcome Measure Data

    Analysis Population Description
    ASAT consisting of all randomized participants who received at least one dose of study treatment. Due to non-compliance with GCP 7 participants were excluded from this analysis.
    Arm/Group Title Placebo SCH 39641 6 Amb a 1-U SCH 39641 12 Amb a 1-U
    Arm/Group Description Matching placebo tablet sublingual, once daily 6 Amb a 1-U in an AIT, sublingual, once daily 12 Amb a 1-U in an AIT, sublingual, once daily
    Measure Participants 65 66 65
    Number [Proportion of Participants]
    0.015
    0%
    0.167
    0.3%
    0.169
    0.3%
    3. Secondary Outcome
    Title Proportion of Participants Reporting Ear Pruritus
    Description Participants were treated for 28 days with either 6 or 12 Units of SCH 39641 or placebo, and the proportion with ear pruritus were reported.
    Time Frame Up to Day 42

    Outcome Measure Data

    Analysis Population Description
    ASAT consisting of all randomized participants who received at least one dose of study treatment. Due to non-compliance with GCP 7 participants were excluded from this analysis.
    Arm/Group Title Placebo SCH 39641 6 Amb a 1-U SCH 39641 12 Amb a 1-U
    Arm/Group Description Matching placebo tablet sublingual, once daily 6 Amb a 1-U in an AIT, sublingual, once daily 12 Amb a 1-U in an AIT, sublingual, once daily
    Measure Participants 65 66 65
    Number [Proportion of Participants]
    0
    0%
    0.061
    0.1%
    0.077
    0.1%
    4. Secondary Outcome
    Title Proportion of Participants Reporting Throat Irritation
    Description Participants were treated for 28 days with either 6 or 12 Units of SCH 39641 or placebo, and the proportion with throat irritation were reported.
    Time Frame Up to Day 42

    Outcome Measure Data

    Analysis Population Description
    ASAT consisting of all randomized participants who received at least one dose of study treatment. Due to non-compliance with GCP 7 participants were excluded from this analysis.
    Arm/Group Title Placebo SCH 39641 6 Amb a 1-U SCH 39641 12 Amb a 1-U
    Arm/Group Description Matching placebo tablet sublingual, once daily 6 Amb a 1-U in an AIT, sublingual, once daily 12 Amb a 1-U in an AIT, sublingual, once daily
    Measure Participants 65 66 65
    Number [Proportion of Participants]
    0.015
    0%
    0.121
    0.2%
    0.077
    0.1%
    5. Secondary Outcome
    Title Proportion of Participants Reporting Mouth Oedema
    Description Participants were treated for 28 days with either 6 or 12 Units of SCH 39641 or placebo, and the proportion with mouth oedema were reported.
    Time Frame Up to Day 42

    Outcome Measure Data

    Analysis Population Description
    ASAT consisting of all randomized participants who received at least one dose of study treatment. Due to non-compliance with GCP 7 participants were excluded from this analysis.
    Arm/Group Title Placebo SCH 39641 6 Amb a 1-U SCH 39641 12 Amb a 1-U
    Arm/Group Description Matching placebo tablet sublingual, once daily 6 Amb a 1-U in an AIT, sublingual, once daily 12 Amb a 1-U in an AIT, sublingual, once daily
    Measure Participants 65 66 65
    Number [Proportion of Participants]
    0
    0%
    0.015
    0%
    0
    0%
    6. Secondary Outcome
    Title Proportion of Participants Who Discontinued Due to Adverse Events.
    Description Participants were treated for 28 days with either 6 or 12 Units of SCH 39641 or placebo, and the proportion with AEs leading to study discontinuation were reported. An AE is any unfavorable and unintended sign, symptom or disease temporarily associated with the use of a medicinal product, whether or not considered related to the medicinal product.
    Time Frame Up to Day 28

    Outcome Measure Data

    Analysis Population Description
    ASAT consisting of all randomized participants who received at least one dose of study treatment. Due to non-compliance with GCP 7 participants were excluded from this analysis.
    Arm/Group Title Placebo SCH 39641 6 Amb a 1-U SCH 39641 12 Amb a 1-U
    Arm/Group Description Matching placebo tablet sublingual, once daily 6 Amb a 1-U in an AIT, sublingual, once daily 12 Amb a 1-U in an AIT, sublingual, once daily
    Measure Participants 65 66 65
    Number [Proportion of Participants]
    0.015
    0%
    0.03
    0%
    0.077
    0.1%

    Adverse Events

    Time Frame Up to Day 42
    Adverse Event Reporting Description ASAT consisting of all randomized participants who received at least one dose of study treatment. Due to non-compliance with GCP 7 participants were excluded from this analysis.
    Arm/Group Title Placebo SCH 39641 6 Amb a 1-U SCH 39641 12 Amb a 1-U
    Arm/Group Description Matching placebo tablet sublingual, once daily 6 Amb a 1-U in an AIT, sublingual, once daily 12 Amb a 1-U in an AIT, sublingual, once daily
    All Cause Mortality
    Placebo SCH 39641 6 Amb a 1-U SCH 39641 12 Amb a 1-U
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Placebo SCH 39641 6 Amb a 1-U SCH 39641 12 Amb a 1-U
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/65 (0%) 0/66 (0%) 1/65 (1.5%)
    Hepatobiliary disorders
    Cholecystitis acute 0/65 (0%) 0 0/66 (0%) 0 1/65 (1.5%) 1
    Injury, poisoning and procedural complications
    Post procedural bile leak 0/65 (0%) 0 0/66 (0%) 0 1/65 (1.5%) 1
    Other (Not Including Serious) Adverse Events
    Placebo SCH 39641 6 Amb a 1-U SCH 39641 12 Amb a 1-U
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 11/65 (16.9%) 23/66 (34.8%) 23/65 (35.4%)
    Ear and labyrinth disorders
    Ear pruritus 0/65 (0%) 0 4/66 (6.1%) 5 5/65 (7.7%) 5
    Eye disorders
    Eye pruritus 4/65 (6.2%) 4 2/66 (3%) 2 4/65 (6.2%) 4
    Gastrointestinal disorders
    Dry mouth 2/65 (3.1%) 2 1/66 (1.5%) 1 4/65 (6.2%) 6
    Hypoaesthesia oral 0/65 (0%) 0 1/66 (1.5%) 1 4/65 (6.2%) 5
    Oral pruritus 1/65 (1.5%) 1 11/66 (16.7%) 15 11/65 (16.9%) 21
    Paraesthesia oral 3/65 (4.6%) 3 3/66 (4.5%) 3 4/65 (6.2%) 4
    Respiratory, thoracic and mediastinal disorders
    Nasal congestion 1/65 (1.5%) 1 4/66 (6.1%) 5 2/65 (3.1%) 2
    Throat irritation 2/65 (3.1%) 2 8/66 (12.1%) 11 6/65 (9.2%) 7

    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 for review 45 days prior to submission for publication or presentation, copies of abstracts or manuscripts for publication that report any results of the trial. If the parties disagree concerning the sponsor's confidential information, the investigator agrees to meet with the sponsor's representative, prior to submission for publication, in order to make good faith efforts to discuss and resolve any issues or disagreements.

    Results Point of Contact

    Name/Title Senior Vice President, Global Clinical Development
    Organization Merck Sharp & Dohme Corp.
    Phone
    Email ClinicalTrialsDisclosure@merck.com
    Responsible Party:
    ALK-Abelló A/S
    ClinicalTrials.gov Identifier:
    NCT00978029
    Other Study ID Numbers:
    • P06081
    • MK-3641-004
    First Posted:
    Sep 16, 2009
    Last Update Posted:
    Mar 3, 2017
    Last Verified:
    Jan 1, 2017