Clinical Trial Results:
A Phase IIb, Randomized, Placebo-Controlled, Dose-Finding Clinical Trial to Study the Safety and Efficacy of MK-8237 Using an Environmental Exposure Chamber in Subjects with House Dust Induced Allergic Rhinitis/Rhinoconjunctivitis
Summary
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EudraCT number |
2012-001855-38 |
Trial protocol |
AT |
Global end of trial date |
27 Aug 2013
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Results information
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Results version number |
v2(current) |
This version publication date |
05 Jan 2017
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First version publication date |
28 Jan 2015
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Other versions |
v1 |
Version creation reason |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
P07627
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01644617 | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
P07627: SCH 900237, MK-8237-003: Merck Registration | ||
Sponsors
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Sponsor organisation name |
Merck Sharp & Dohme Corp.
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Sponsor organisation address |
2000 Galloping Hill Road, Kenilworth, NJ, United States, 07033
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Public contact |
Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com
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Scientific contact |
Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
27 Aug 2013
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
16 Aug 2013
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Global end of trial reached? |
Yes
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Global end of trial date |
27 Aug 2013
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To evaluate the dose-related efficacy of MK-8237 sublingual house dust mite (HDM) tablet versus placebo in the treatment of HDM-induced rhinitis based on the average total nasal symptom score (TNSS) determined during the chamber challenge session at Week 24.
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Protection of trial subjects |
The study was conducted in conformance with Good Clinical Practice standards and applicable country and/or local statutes and regulations regarding ethical committee review, informed consent, and the protection of human subjects participating in biomedical research.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 Oct 2012
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Austria: 124
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Worldwide total number of subjects |
124
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EEA total number of subjects |
124
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
124
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Participants were recruited from one study site in Austria. | ||||||||||||||||||||||||||||
Pre-assignment
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Screening details |
This study enrolled male and female participants, 18 years of age and older, with a history of allergic rhinitis/rhinoconjunctivitis to house dust of 1-year duration or more (with or without asthma). | ||||||||||||||||||||||||||||
Period 1
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Period 1 title |
Treatment (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||||||||||||
Roles blinded |
Investigator, Monitor, Subject | ||||||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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MK-8237 6 DU | ||||||||||||||||||||||||||||
Arm description |
Participants receive MK-8237 6 Development Units (DU) sublingual tablets once daily (QD), preferably at the same time each day, for 24 weeks. | ||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||
Investigational medicinal product name |
MK-8237 6 DU sublingual tablets
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Investigational medicinal product code |
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Other name |
SCH 900237
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Pharmaceutical forms |
Sublingual tablet
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Routes of administration |
Sublingual use
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Dosage and administration details |
One MK-8237 6 DU sublingual tablet once daily for 24 weeks
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Arm title
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MK-8237 12 DU | ||||||||||||||||||||||||||||
Arm description |
Participants receive MK-8237 12 DU sublingual tablets, QD, preferably at the same time each day, for 24 weeks. | ||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||
Investigational medicinal product name |
MK-8237 12 DU sublingual tablets
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Investigational medicinal product code |
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Other name |
SCH 900237
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Pharmaceutical forms |
Sublingual tablet
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Routes of administration |
Sublingual use
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Dosage and administration details |
One MK-8237 12 DU sublingual tablet once daily for 24 weeks
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Arm title
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Placebo | ||||||||||||||||||||||||||||
Arm description |
Participants receive Placebo sublingual tablets, QD, preferably at the same time each day, for 24 weeks. | ||||||||||||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo sublingual tablets
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Sublingual tablet
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Routes of administration |
Sublingual use
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Dosage and administration details |
Placebo sublingual tablets once daily for 24 weeks
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Baseline characteristics reporting groups
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Reporting group title |
MK-8237 6 DU
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Reporting group description |
Participants receive MK-8237 6 Development Units (DU) sublingual tablets once daily (QD), preferably at the same time each day, for 24 weeks. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
MK-8237 12 DU
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Reporting group description |
Participants receive MK-8237 12 DU sublingual tablets, QD, preferably at the same time each day, for 24 weeks. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Participants receive Placebo sublingual tablets, QD, preferably at the same time each day, for 24 weeks. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
MK-8237 6 DU
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Reporting group description |
Participants receive MK-8237 6 Development Units (DU) sublingual tablets once daily (QD), preferably at the same time each day, for 24 weeks. | ||
Reporting group title |
MK-8237 12 DU
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Reporting group description |
Participants receive MK-8237 12 DU sublingual tablets, QD, preferably at the same time each day, for 24 weeks. | ||
Reporting group title |
Placebo
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Reporting group description |
Participants receive Placebo sublingual tablets, QD, preferably at the same time each day, for 24 weeks. |
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End point title |
Average Total Nasal Symptom Score (TNSS) During Environmental Exposure Chamber (EEC) Challenge Session at Week 24 | ||||||||||||||||
End point description |
TNSS was the total score for 4 nasal symptoms (itchy nose, blocked nose, runny nose and sneezing), each scored on a 4-point scale (0=No symptoms to 3=Severe symptoms). Total TNSS ranged from 0 to 12 points, with a higher score indicating more severe nasal symptoms. The end point was calculated based on participant diary entries over the last 4 hours of the EEC challenge session at Week 24.
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End point type |
Primary
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End point timeframe |
Week 24
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Notes [1] - Full Analysis Set (FAS): Took ≥1 study drug dose and had ≥1 post-randomization efficacy measurement. [2] - FAS: Took ≥1 study drug dose and had ≥1 post-randomization efficacy measurement. [3] - FAS: Took ≥1 study drug dose and had ≥1 post-randomization efficacy measurement. |
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Statistical analysis title |
Difference in Least Squares (LS) Means at Week 24 | ||||||||||||||||
Statistical analysis description |
Difference in TNSS LS means at Week 24: MK-8237 6 DU vs. Placebo - Analysis via analysis of covariance (ANCOVA) with treatment and Baseline end point score as fixed effects, and adjusted for different error variation for each treatment group. Treatment difference relative to Placebo was calculated by (MK-8237-Placebo)/Placebo * 100%. Confidence intervals were calculated by the bootstrap method.
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Comparison groups |
MK-8237 6 DU v Placebo
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Number of subjects included in analysis |
70
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.003 | ||||||||||||||||
Method |
ANCOVA | ||||||||||||||||
Parameter type |
Difference in LS Means | ||||||||||||||||
Point estimate |
-1.98
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Confidence interval |
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level |
95% | ||||||||||||||||
sides |
2-sided
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lower limit |
-3.24 | ||||||||||||||||
upper limit |
-0.72 | ||||||||||||||||
Statistical analysis title |
Difference in LS Means at Week 24 | ||||||||||||||||
Statistical analysis description |
Difference in TNSS LS means at Week 24: MK-8237 12 DU vs. Placebo - Analysis via ANCOVA with treatment and Baseline endpoint score as fixed effects, and adjusted for different error variation for each treatment group. Treatment difference relative to Placebo was calculated by (MK-8237-Placebo)/Placebo * 100%. Confidence intervals were calculated by the bootstrap method.
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Comparison groups |
MK-8237 12 DU v Placebo
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Number of subjects included in analysis |
70
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||
Method |
ANCOVA | ||||||||||||||||
Parameter type |
Difference in LS Means | ||||||||||||||||
Point estimate |
-3.62
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Confidence interval |
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level |
95% | ||||||||||||||||
sides |
2-sided
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lower limit |
-4.85 | ||||||||||||||||
upper limit |
-2.39 |
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End point title |
Average Total Symptom Score (TSS [TNSS + TOSS]) During EEC Challenge Sessions at Weeks 8, 16 and 24 | ||||||||||||||||||||||||||||
End point description |
TSS was the sum of the TNSS and Total Ocular Symptom Score (TOSS). TOSS was the total of scores for 2 ocular symptom scores (gritty feeling/red/itchy eyes and watery eyes), each scored on a 4-point scale (0=No symptoms to 3=Severe symptoms; TOSS range: 0 to 6 points). Total TSS ranged from 0 to 18 points, with a higher score indicating more severe nasal and ocular symptoms. The end point was calculated based on participant diary entries over the last 4 hours of the EEC challenge sessions at Weeks 8, 16 and 24.
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End point type |
Secondary
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End point timeframe |
Week 8, Week 16, Week 24
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Notes [4] - FAS: Took ≥1 study drug dose and had ≥1 post-randomization efficacy measurement. [5] - FAS: Took ≥1 study drug dose and had ≥1 post-randomization efficacy measurement. [6] - FAS: Took ≥1 study drug dose and had ≥1 post-randomization efficacy measurement. |
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Statistical analysis title |
Difference in LS Means at Week 24 | ||||||||||||||||||||||||||||
Statistical analysis description |
Difference in TSS LS means at Week 24: MK-8237 6 DU vs. Placebo - Analysis via ANCOVA with treatment and Baseline end point score as fixed effects, and adjusted for different error variation for each treatment group. Treatment difference relative to Placebo was calculated by (MK-8237-Placebo)/Placebo * 100%. Confidence intervals were calculated by the bootstrap method. Number of participants included in analysis=70.
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Comparison groups |
MK-8237 6 DU v Placebo
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Number of subjects included in analysis |
79
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||||||||||||||
P-value |
= 0.003 | ||||||||||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||||||||||
Parameter type |
Difference in LS Means | ||||||||||||||||||||||||||||
Point estimate |
-2.65
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Confidence interval |
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level |
95% | ||||||||||||||||||||||||||||
sides |
2-sided
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lower limit |
-4.35 | ||||||||||||||||||||||||||||
upper limit |
-0.95 | ||||||||||||||||||||||||||||
Statistical analysis title |
Difference in LS Means at Week 24 | ||||||||||||||||||||||||||||
Statistical analysis description |
Difference in TSS LS means at Week 24: MK-8237 12 DU vs. Placebo - Analysis via ANCOVA with treatment and Baseline end point score as fixed effects, and adjusted for different error variation for each treatment group. Treatment difference relative to Placebo was calculated by (MK-8237-Placebo)/Placebo * 100%. Confidence intervals were calculated by the bootstrap method. Number of participants included in analysis=70.
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Comparison groups |
MK-8237 12 DU v Placebo
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Number of subjects included in analysis |
80
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||||||||||
Parameter type |
Difference in LS Means | ||||||||||||||||||||||||||||
Point estimate |
-4.84
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Confidence interval |
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level |
95% | ||||||||||||||||||||||||||||
sides |
2-sided
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lower limit |
-6.59 | ||||||||||||||||||||||||||||
upper limit |
-3.09 | ||||||||||||||||||||||||||||
Statistical analysis title |
Difference in LS Means at Week 8 | ||||||||||||||||||||||||||||
Statistical analysis description |
Difference in TSS LS means at Week 8: MK-8237 6 DU vs. Placebo - Analysis via ANCOVA with treatment and Baseline end point score as fixed effects, and adjusted for different error variation for each treatment group. Treatment difference relative to Placebo was calculated by (MK-8237-Placebo)/Placebo * 100%. Confidence intervals were calculated by the bootstrap method. Number of participants included in analysis=78.
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Comparison groups |
MK-8237 6 DU v Placebo
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Number of subjects included in analysis |
79
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||||||||||||||
P-value |
= 0.181 | ||||||||||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||||||||||
Parameter type |
Difference in LS Means | ||||||||||||||||||||||||||||
Point estimate |
-0.83
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Confidence interval |
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level |
95% | ||||||||||||||||||||||||||||
sides |
2-sided
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lower limit |
-2.06 | ||||||||||||||||||||||||||||
upper limit |
0.4 | ||||||||||||||||||||||||||||
Statistical analysis title |
Difference in LS Means at Week 8 | ||||||||||||||||||||||||||||
Statistical analysis description |
Difference in TSS LS means at Week 8: MK-8237 12 DU vs. Placebo - Analysis via ANCOVA with treatment and Baseline end point score as fixed effects, and adjusted for different error variation for each treatment group. Treatment difference relative to Placebo was calculated by (MK-8237-Placebo)/Placebo * 100%. Confidence intervals were calculated by the bootstrap method. Number of participants included in analysis=79.
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Comparison groups |
MK-8237 12 DU v Placebo
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Number of subjects included in analysis |
80
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||||||||||||||
P-value |
= 0.004 | ||||||||||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||||||||||
Parameter type |
Difference in LS Means | ||||||||||||||||||||||||||||
Point estimate |
-1.97
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Confidence interval |
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level |
95% | ||||||||||||||||||||||||||||
sides |
2-sided
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lower limit |
-3.3 | ||||||||||||||||||||||||||||
upper limit |
-0.64 | ||||||||||||||||||||||||||||
Statistical analysis title |
Difference in LS Means at Week 16 | ||||||||||||||||||||||||||||
Statistical analysis description |
Difference in TSS LS means at Week 16: MK-8237 6 DU vs. Placebo - Analysis via ANCOVA with treatment and Baseline end point score as fixed effects, and adjusted for different error variation for each treatment group. Treatment difference relative to Placebo was calculated by (MK-8237-Placebo)/Placebo * 100%. Confidence intervals were calculated by the bootstrap method. Number of participants included in analysis=74.
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Comparison groups |
MK-8237 6 DU v Placebo
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Number of subjects included in analysis |
79
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||||||||||||||
P-value |
= 0.091 | ||||||||||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||||||||||
Parameter type |
Difference in LS Means | ||||||||||||||||||||||||||||
Point estimate |
-1.37
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Confidence interval |
|||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||
sides |
2-sided
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lower limit |
-2.96 | ||||||||||||||||||||||||||||
upper limit |
0.22 | ||||||||||||||||||||||||||||
Statistical analysis title |
Difference in LS Means at Week 16 | ||||||||||||||||||||||||||||
Statistical analysis description |
Difference in TSS LS means at Week 16: MK-8237 12 DU vs. Placebo - Analysis via ANCOVA with treatment and Baseline end point score as fixed effects, and adjusted for different error variation for each treatment group. Treatment difference relative to Placebo was calculated by (MK-8237-Placebo)/Placebo * 100%. Confidence intervals were calculated by the bootstrap method. Number of participants included in analysis=77.
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Comparison groups |
MK-8237 12 DU v Placebo
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Number of subjects included in analysis |
80
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||||||||||
Parameter type |
Difference in LS Means | ||||||||||||||||||||||||||||
Point estimate |
-2.62
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Confidence interval |
|||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||
sides |
2-sided
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lower limit |
-4.12 | ||||||||||||||||||||||||||||
upper limit |
-1.13 |
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End point title |
Average Total Ocular Symptom Score (TOSS) During EEC Challenge Sessions at Weeks 8, 16 and 24 | ||||||||||||||||||||||||||||
End point description |
TOSS was the total of scores for 2 ocular symptom scores (gritty feeling/red/itchy eyes and watery eyes), each scored on a 4-point scale (0=No symptoms to 3=Severe symptoms). Total TOSS ranged from 0 to 6 points, with a higher score indicating more severe ocular symptoms. The end point was calculated based on participant diary entries over the last 4 hours of the EEC challenge sessions at Weeks 8, 16 and 24.
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End point type |
Secondary
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End point timeframe |
Week 8, Week 16, Week 24
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Notes [7] - FAS: Took ≥1 study drug dose and had ≥1 post-randomization efficacy measurement. [8] - FAS: Took ≥1 study drug dose and had ≥1 post-randomization efficacy measurement. [9] - FAS: Took ≥1 study drug dose and had ≥1 post-randomization efficacy measurement. |
|||||||||||||||||||||||||||||
Statistical analysis title |
Difference in LS Means at Week 24 | ||||||||||||||||||||||||||||
Statistical analysis description |
Difference in TOSS LS means at Week 24: MK-8237 6 DU vs. Placebo - Analysis via ANCOVA with treatment and Baseline end point score as fixed effects, and adjusted for different error variation for each treatment group. Treatment difference relative to Placebo was calculated by (MK-8237-Placebo)/Placebo * 100%. Confidence intervals were calculated by the bootstrap method. Number of participants included in analysis=70.
|
||||||||||||||||||||||||||||
Comparison groups |
MK-8237 6 DU v Placebo
|
||||||||||||||||||||||||||||
Number of subjects included in analysis |
79
|
||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||||||
P-value |
= 0.023 | ||||||||||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||||||||||
Parameter type |
Difference in LS Means | ||||||||||||||||||||||||||||
Point estimate |
-0.77
|
||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||
lower limit |
-1.43 | ||||||||||||||||||||||||||||
upper limit |
-0.11 | ||||||||||||||||||||||||||||
Statistical analysis title |
Difference in LS Means at Week 24 | ||||||||||||||||||||||||||||
Statistical analysis description |
Difference in TOSS LS means at Week 24: MK-8237 12 DU vs. Placebo - Analysis via ANCOVA with treatment and Baseline end point score as fixed effects, and adjusted for different error variation for each treatment group. Treatment difference relative to Placebo was calculated by (MK-8237-Placebo)/Placebo * 100%. Confidence intervals were calculated by the bootstrap method. Number of participants included in analysis=70.
|
||||||||||||||||||||||||||||
Comparison groups |
MK-8237 12 DU v Placebo
|
||||||||||||||||||||||||||||
Number of subjects included in analysis |
80
|
||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||||||||||
Parameter type |
Difference in LS Means | ||||||||||||||||||||||||||||
Point estimate |
-1.27
|
||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||
lower limit |
-1.92 | ||||||||||||||||||||||||||||
upper limit |
-0.62 | ||||||||||||||||||||||||||||
Statistical analysis title |
Difference in LS Means at Week 8 | ||||||||||||||||||||||||||||
Statistical analysis description |
Difference in TOSS LS means at Week 8: MK-8237 6 DU vs. Placebo - Analysis via ANCOVA with treatment and Baseline end point score as fixed effects, and adjusted for different error variation for each treatment group. Treatment difference relative to Placebo was calculated by (MK-8237-Placebo)/Placebo * 100%. Confidence intervals were calculated by the bootstrap method. Number of participants included in analysis=78.
|
||||||||||||||||||||||||||||
Comparison groups |
MK-8237 6 DU v Placebo
|
||||||||||||||||||||||||||||
Number of subjects included in analysis |
79
|
||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||||||
P-value |
= 0.235 | ||||||||||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||||||||||
Parameter type |
Difference in LS Means | ||||||||||||||||||||||||||||
Point estimate |
-0.34
|
||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||
lower limit |
-0.9 | ||||||||||||||||||||||||||||
upper limit |
0.22 | ||||||||||||||||||||||||||||
Statistical analysis title |
Difference in LS Means at Week 8 | ||||||||||||||||||||||||||||
Statistical analysis description |
Difference in TOSS LS means at Week 8: MK-8237 12 DU vs. Placebo - Analysis via ANCOVA with treatment and Baseline end point score as fixed effects, and adjusted for different error variation for each treatment group. Treatment difference relative to Placebo was calculated by (MK-8237-Placebo)/Placebo * 100%. Confidence intervals were calculated by the bootstrap method. Number of participants included in analysis=79.
|
||||||||||||||||||||||||||||
Comparison groups |
MK-8237 12 DU v Placebo
|
||||||||||||||||||||||||||||
Number of subjects included in analysis |
80
|
||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||||||
P-value |
= 0.023 | ||||||||||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||||||||||
Parameter type |
Difference in LS Means | ||||||||||||||||||||||||||||
Point estimate |
-0.61
|
||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||
lower limit |
-1.14 | ||||||||||||||||||||||||||||
upper limit |
-0.09 | ||||||||||||||||||||||||||||
Statistical analysis title |
Difference in LS Means at Week 16 | ||||||||||||||||||||||||||||
Statistical analysis description |
Difference in TOSS LS means at Week 16: MK-8237 6 DU vs. Placebo - Analysis via ANCOVA with treatment and Baseline end point score as fixed effects, and adjusted for different error variation for each treatment group. Treatment difference relative to Placebo was calculated by (MK-8237-Placebo)/Placebo * 100%. Confidence intervals were calculated by the bootstrap method. Number of participants included in analysis=74.
|
||||||||||||||||||||||||||||
Comparison groups |
MK-8237 6 DU v Placebo
|
||||||||||||||||||||||||||||
Number of subjects included in analysis |
79
|
||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||||||
P-value |
= 0.691 | ||||||||||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||||||||||
Parameter type |
Difference in LS Means | ||||||||||||||||||||||||||||
Point estimate |
-0.13
|
||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||
lower limit |
-0.79 | ||||||||||||||||||||||||||||
upper limit |
0.52 | ||||||||||||||||||||||||||||
Statistical analysis title |
Difference in LS Means at Week 16 | ||||||||||||||||||||||||||||
Statistical analysis description |
Difference in TOSS LS means at Week 16: MK-8237 12 DU vs. Placebo - Analysis via ANCOVA with treatment and Baseline end point score as fixed effects, and adjusted for different error variation for each treatment group. Treatment difference relative to Placebo was calculated by (MK-8237-Placebo)/Placebo * 100%. Confidence intervals were calculated by the bootstrap method. Number of participants included in analysis=77.
|
||||||||||||||||||||||||||||
Comparison groups |
MK-8237 12 DU v Placebo
|
||||||||||||||||||||||||||||
Number of subjects included in analysis |
80
|
||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||||||
P-value |
= 0.082 | ||||||||||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||||||||||
Parameter type |
Difference in LS Means | ||||||||||||||||||||||||||||
Point estimate |
-0.53
|
||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||
lower limit |
-1.13 | ||||||||||||||||||||||||||||
upper limit |
0.07 |
|
|||||||||||||||||||||||||
End point title |
Change From Baseline in House Dust Mite (HDM)-specific Immunoglobulin E (IgE) Levels at Week 8 | ||||||||||||||||||||||||
End point description |
Participant IgE levels against Dermatophagoides pteronyssinus (D. pteronyssinus) and Dermatophagoides farinae (D. farinae) were measured using the Immunocap® assay at baseline and Week 8. IgE levels were expressed in Log 10 scale kilo units/Liter (kU/L). Mean Week 8 IgE levels were compared to the mean IgE levels at baseline. Analysis was based on the analysis of variance parametric (ANOVA) model with treatment as the fixed effect and reported as a least squares mean with 95% confidence interval.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Baseline and Week 8
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
Notes [10] - FAS: Took ≥1 study drug dose and had ≥1 post-randomization efficacy measurement. [11] - FAS: Took ≥1 study drug dose and had ≥1 post-randomization efficacy measurement. [12] - FAS: Took ≥1 study drug dose and had ≥1 post-randomization efficacy measurement. |
|||||||||||||||||||||||||
Statistical analysis title |
Difference in LS Means - D. farinae | ||||||||||||||||||||||||
Statistical analysis description |
Difference in LS means for D. farinae IgE levels: MK-8237 6 DU vs. Placebo - Analysis via ANOVA with treatment as fixed effect and adjusted for different error variation for each treatment group.
|
||||||||||||||||||||||||
Comparison groups |
MK-8237 6 DU v Placebo
|
||||||||||||||||||||||||
Number of subjects included in analysis |
79
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||||||
Parameter type |
Difference in LS Means | ||||||||||||||||||||||||
Point estimate |
0.39
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
0.3 | ||||||||||||||||||||||||
upper limit |
0.48 | ||||||||||||||||||||||||
Statistical analysis title |
Difference in LS Means - D. farinae | ||||||||||||||||||||||||
Statistical analysis description |
Difference in LS means for D. farinae IgE levels: MK-8237 12 DU vs. Placebo - Analysis via ANOVA with treatment as fixed effect and adjusted for different error variation for each treatment group.
|
||||||||||||||||||||||||
Comparison groups |
MK-8237 12 DU v Placebo
|
||||||||||||||||||||||||
Number of subjects included in analysis |
80
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||||||
Parameter type |
Difference in LS Means | ||||||||||||||||||||||||
Point estimate |
0.52
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
0.41 | ||||||||||||||||||||||||
upper limit |
0.64 | ||||||||||||||||||||||||
Statistical analysis title |
Difference in LS Means - D. pteronyssinus | ||||||||||||||||||||||||
Statistical analysis description |
Difference in LS means for D. pteronyssinus IgE levels: MK-8237 6 DU vs. Placebo - Analysis via ANOVA with treatment as fixed effect and adjusted for different error variation for each treatment group.
|
||||||||||||||||||||||||
Comparison groups |
MK-8237 6 DU v Placebo
|
||||||||||||||||||||||||
Number of subjects included in analysis |
79
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||||||
Parameter type |
Difference in LS Means | ||||||||||||||||||||||||
Point estimate |
0.42
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
0.33 | ||||||||||||||||||||||||
upper limit |
0.52 | ||||||||||||||||||||||||
Statistical analysis title |
Difference in LS Means - D. pteronyssinus | ||||||||||||||||||||||||
Statistical analysis description |
Difference in LS means for D. pteronyssinus IgE levels: MK-8237 12 DU vs Placebo - Analysis via ANOVA with treatment as fixed effect and adjusted for different error variation for each treatment group.
|
||||||||||||||||||||||||
Comparison groups |
MK-8237 12 DU v Placebo
|
||||||||||||||||||||||||
Number of subjects included in analysis |
80
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||||||
Parameter type |
Difference in LS Means | ||||||||||||||||||||||||
Point estimate |
0.55
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
0.43 | ||||||||||||||||||||||||
upper limit |
0.68 |
|
|||||||||||||||||||||||||
End point title |
Change From Baseline in HDM-specific Immunoglobulin G4 (IgG4) Levels at Week 8 | ||||||||||||||||||||||||
End point description |
D. pteronyssinus and D. farinae serum IgG4 levels were measured using the Immunocap® assay at baseline and Week 8. IgG4 levels were expressed in Log 10 scale miligrams/Liter (mg/L). Mean Week 8 IgG4 levels were compared to the mean IgG4 levels at baseline. Analysis was based on the ANOVA model with treatment as the fixed effect and reported as a least squares mean with 95% confidence interval.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Baseline and Week 8
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
Notes [13] - FAS: Took ≥1 study drug dose and had ≥1 post-randomization efficacy measurement. [14] - FAS: Took ≥1 study drug dose and had ≥1 post-randomization efficacy measurement. [15] - FAS: Took ≥1 study drug dose and had ≥1 post-randomization efficacy measurement. |
|||||||||||||||||||||||||
Statistical analysis title |
Difference in LS Means - D. pteronyssinus | ||||||||||||||||||||||||
Statistical analysis description |
Difference in LS means in D. pteronyssinus IgG4 levels: MK-8237 6 DU vs. Placebo - Analysis via ANOVA with treatment as fixed effect and adjusted for different error variation for each treatment group.
|
||||||||||||||||||||||||
Comparison groups |
MK-8237 6 DU v Placebo
|
||||||||||||||||||||||||
Number of subjects included in analysis |
79
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||||||
Parameter type |
Difference in LS Means | ||||||||||||||||||||||||
Point estimate |
0.19
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
0.12 | ||||||||||||||||||||||||
upper limit |
0.25 | ||||||||||||||||||||||||
Statistical analysis title |
Difference in LS Means - D. pteronyssinus | ||||||||||||||||||||||||
Statistical analysis description |
Difference in LS means in D. pteronyssinus IgG4 levels: MK-8237 12 DU vs. Placebo - Analysis via ANOVA with treatment as fixed effect and adjusted for different error variation for each treatment group.
|
||||||||||||||||||||||||
Comparison groups |
MK-8237 12 DU v Placebo
|
||||||||||||||||||||||||
Number of subjects included in analysis |
80
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||||||
Parameter type |
Difference in LS Means | ||||||||||||||||||||||||
Point estimate |
0.23
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
0.13 | ||||||||||||||||||||||||
upper limit |
0.33 | ||||||||||||||||||||||||
Statistical analysis title |
Difference in LS Means - D. farinae | ||||||||||||||||||||||||
Statistical analysis description |
Difference in LS means in D. farinae IgG4 levels: MK-8237 6 DU vs. Placebo - Analysis via ANOVA with treatment as fixed effect and adjusted for different error variation for each treatment group.
|
||||||||||||||||||||||||
Comparison groups |
MK-8237 6 DU v Placebo
|
||||||||||||||||||||||||
Number of subjects included in analysis |
79
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||||||
Parameter type |
Difference in LS Means | ||||||||||||||||||||||||
Point estimate |
0.25
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
0.16 | ||||||||||||||||||||||||
upper limit |
0.33 | ||||||||||||||||||||||||
Statistical analysis title |
Difference in LS Means - D. farinae | ||||||||||||||||||||||||
Statistical analysis description |
Difference in LS means in D. farinae IgG4 levels: MK-8237 12 DU vs. Placebo - Analysis via ANOVA with treatment as fixed effect and adjusted for different error variation for each treatment group.
|
||||||||||||||||||||||||
Comparison groups |
MK-8237 12 DU v Placebo
|
||||||||||||||||||||||||
Number of subjects included in analysis |
80
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||||||
Parameter type |
Difference in LS Means | ||||||||||||||||||||||||
Point estimate |
0.32
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
0.23 | ||||||||||||||||||||||||
upper limit |
0.42 |
|
|||||||||||||||||||||||||
End point title |
Average TNSS During EEC Challenge Sessions at Weeks 8 and 16 | ||||||||||||||||||||||||
End point description |
TNSS was the total score for 4 nasal symptoms (itchy nose, blocked nose, runny nose and sneezing), each scored on a 4-point scale (0=No symptoms to 3=Severe symptoms). Total TNSS ranged from 0 to 12 points, with a higher score indicating more severe nasal symptoms. The end point was calculated based on participant diary entries over the last 4 hours of the EEC challenge sessions at Weeks 8 and 16.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Week 8, Week 16
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
Notes [16] - FAS: Took ≥1 study drug dose and had ≥1 post-randomization efficacy measurement. [17] - FAS: Took ≥1 study drug dose and had ≥1 post-randomization efficacy measurement. [18] - FAS: Took ≥1 study drug dose and had ≥1 post-randomization efficacy measurement. |
|||||||||||||||||||||||||
Statistical analysis title |
Difference in LS Means at Week 8 | ||||||||||||||||||||||||
Statistical analysis description |
Difference in TNSS LS means at Week 8: MK-8237 6 DU vs. Placebo - Analysis via ANCOVA with treatment and Baseline end point score as fixed effects, and adjusted for different error variation for each treatment group. Treatment difference relative to Placebo was calculated by (MK-8237-Placebo)/Placebo * 100%. Confidence intervals were calculated by the bootstrap method. Number of participants included in analysis=78.
|
||||||||||||||||||||||||
Comparison groups |
MK-8237 6 DU v Placebo
|
||||||||||||||||||||||||
Number of subjects included in analysis |
79
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||
P-value |
= 0.198 | ||||||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||||||
Parameter type |
Difference in LS Means | ||||||||||||||||||||||||
Point estimate |
-0.54
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
-1.38 | ||||||||||||||||||||||||
upper limit |
0.29 | ||||||||||||||||||||||||
Statistical analysis title |
Difference in LS Means at Week 16 | ||||||||||||||||||||||||
Statistical analysis description |
Difference in TNSS LS means at Week 16: MK-8237 6 DU vs. Placebo - Analysis via ANCOVA with treatment and Baseline end point score as fixed effects, and adjusted for different error variation for each treatment group. Treatment difference relative to Placebo was calculated by (MK-8237-Placebo)/Placebo * 100%. Confidence intervals were calculated by the bootstrap method. Number of participants included in analysis=74.
|
||||||||||||||||||||||||
Comparison groups |
MK-8237 6 DU v Placebo
|
||||||||||||||||||||||||
Number of subjects included in analysis |
79
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||
P-value |
= 0.032 | ||||||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||||||
Parameter type |
Difference in LS Means | ||||||||||||||||||||||||
Point estimate |
-1.23
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
-2.36 | ||||||||||||||||||||||||
upper limit |
-0.11 | ||||||||||||||||||||||||
Statistical analysis title |
Difference in LS Means at Week 8 | ||||||||||||||||||||||||
Statistical analysis description |
Difference in TNSS LS means at Week 8: MK-8237 12 DU vs. Placebo - Analysis via ANCOVA with treatment and Baseline end point score as fixed effects, and adjusted for different error variation for each treatment group. Treatment difference relative to Placebo was calculated by (MK-8237-Placebo)/Placebo * 100%. Confidence intervals were calculated by the bootstrap method. Number of participants included in analysis=79.
|
||||||||||||||||||||||||
Comparison groups |
MK-8237 12 DU v Placebo
|
||||||||||||||||||||||||
Number of subjects included in analysis |
80
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||
P-value |
= 0.007 | ||||||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||||||
Parameter type |
Difference in LS Means | ||||||||||||||||||||||||
Point estimate |
-1.37
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
-2.34 | ||||||||||||||||||||||||
upper limit |
-0.39 | ||||||||||||||||||||||||
Statistical analysis title |
Difference in LS Means at Week 16 | ||||||||||||||||||||||||
Statistical analysis description |
Difference in TNSS LS means at Week 16: MK-8237 12 DU vs. Placebo - Analysis via ANCOVA with treatment and Baseline end point score as fixed effects, and adjusted for different error variation for each treatment group. Treatment difference relative to Placebo was calculated by (MK-8237-Placebo)/Placebo * 100%. Confidence intervals were calculated by the bootstrap method. Number of participants included in analysis=77.
|
||||||||||||||||||||||||
Comparison groups |
MK-8237 12 DU v Placebo
|
||||||||||||||||||||||||
Number of subjects included in analysis |
80
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||||||
Parameter type |
Difference in LS Means | ||||||||||||||||||||||||
Point estimate |
-2.08
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
-3.14 | ||||||||||||||||||||||||
upper limit |
-1.03 |
|
|||||||||||||
End point title |
Number of Participants Who Experienced At Least One Adverse Event (AE) | ||||||||||||
End point description |
An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to this study drug.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to 26 weeks (Up to 2 weeks after last dose of study drug)
|
||||||||||||
|
|||||||||||||
Notes [19] - All Participants as Treated (APaT): All randomized participants who took ≥1 study drug dose. [20] - APaT: All randomized participants who took ≥1 study drug dose. [21] - APaT: All randomized participants who took ≥1 study drug dose. |
|||||||||||||
Statistical analysis title |
Difference in Percentage vs. Placebo | ||||||||||||
Statistical analysis description |
Difference in percentage of participants who experienced at least one AE vs. Placebo: MK-8237 12 DU vs. Placebo - Analysis based on Miettinen & Nurminen method.
|
||||||||||||
Comparison groups |
MK-8237 12 DU v Placebo
|
||||||||||||
Number of subjects included in analysis |
83
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
Method |
Miettinen & Nurminen Method | ||||||||||||
Parameter type |
Difference in Percentages | ||||||||||||
Point estimate |
12.4
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-3.6 | ||||||||||||
upper limit |
28.9 | ||||||||||||
Statistical analysis title |
Difference in Percentage vs. Placebo | ||||||||||||
Statistical analysis description |
Difference in percentage of participants who experienced at least one AE vs. Placebo: MK-8237 6 DU vs. Placebo - Analysis based on Miettinen & Nurminen method.
|
||||||||||||
Comparison groups |
MK-8237 6 DU v Placebo
|
||||||||||||
Number of subjects included in analysis |
82
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
Method |
Miettinen & Nurminen Method | ||||||||||||
Parameter type |
Difference in Percentages | ||||||||||||
Point estimate |
9.8
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-7 | ||||||||||||
upper limit |
26.6 |
|
|||||||||||||
End point title |
Number of Participants Who Discontinued Study Drug Due to an AE | ||||||||||||
End point description |
An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to this study drug.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to 24 weeks
|
||||||||||||
|
|||||||||||||
Notes [22] - APaT: All randomized participants who took ≥1 study drug dose. [23] - APaT: All randomized participants who took ≥1 study drug dose. [24] - APaT: All randomized participants who took ≥1 study drug dose. |
|||||||||||||
Statistical analysis title |
Difference in Percentage vs. Placebo | ||||||||||||
Statistical analysis description |
Difference in percentage of participants who discontinued study drug due to an AE vs. Placebo: MK-8237 6 DU vs. Placebo - Analysis based on Miettinen & Nurminen method.
|
||||||||||||
Comparison groups |
MK-8237 6 DU v Placebo
|
||||||||||||
Number of subjects included in analysis |
82
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
Method |
|||||||||||||
Parameter type |
Difference in Percentages | ||||||||||||
Point estimate |
-14.6
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-28.5 | ||||||||||||
upper limit |
-5.4 | ||||||||||||
Statistical analysis title |
Difference in Percentage vs. Placebo | ||||||||||||
Statistical analysis description |
Difference in percentage of participants who discontinued study drug due to an AE vs. Placebo: MK-8237 12 DU vs. Placebo - Analysis based on Miettinen & Nurminen method.
|
||||||||||||
Comparison groups |
MK-8237 12 DU v Placebo
|
||||||||||||
Number of subjects included in analysis |
83
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
Method |
|||||||||||||
Parameter type |
Difference in Percentages | ||||||||||||
Point estimate |
-7.5
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-22.6 | ||||||||||||
upper limit |
6.7 |
|
|||||||||||||||||||||||||
End point title |
HDM-specific IgE Levels at Week 8 | ||||||||||||||||||||||||
End point description |
D. pteronyssinus and D. farinae serum IgE levels were measured using the Immunocap® assay at Week 8. IgE levels were expressed in Log 10 scale kU/L. Analysis was based on the ANOVA model with treatment as the fixed effect and reported as mean IgE with a standard deviation.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Week 8
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
HDM-specific IgG4 Levels at Week 8 | ||||||||||||||||||||||||
End point description |
D. pteronyssinus and D. farinae serum IgG4 levels were measured using the Immunocap® assay at Week 8. IgG4 levels were expressed in Log 10 scale mg/L. Analysis was based on the ANOVA model with treatment as the fixed effect and reported as mean IgG4 with a standard deviation.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Week 8
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Up to 26 weeks (Up to 2 weeks after last dose of study drug)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
APaT: All randomized participants who took ≥1 study drug dose.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
16.0
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
MK-8237 6 DU
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants receive MK-8237 6 Development Units (DU) sublingual tablets once daily (QD), preferably at the same time each day, for 24 weeks | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
MK-8237 12 DU
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants receive MK-8237 12 DU sublingual tablets, QD, preferably at the same time each day, for 24 weeks | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants receive Placebo sublingual tablets, QD, preferably at the same time each day, for 24 weeks | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
|||
Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |