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Clinical Trial Results:
A Double-Blind, Randomized, Placebo-Controlled, Multicenter, Parallel-Group, Adaptive-Design, Dose-Ranging Study of MK-1029 in Adult Subjects with Persistent Asthma.

Summary
EudraCT number	2012-000643-27
Trial protocol	DE IT GB
Global end of trial date	08 Jul 2014

Results information
Results version number	v1(current)
This version publication date	08 Mar 2016
First version publication date	24 Jun 2015
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

1029-012

ISRCTN number

US NCT number

NCT01656395

WHO universal trial number (UTN)

Other trial identifiers

MK-1029-012: Merck protocol number

Sponsor organisation name

Merck Sharp & Dohme Corp.

Sponsor organisation address

2000 Galloping Hill Road, Kenilworth, NJ, United States, 07033

Public contact

Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com

Scientific contact

Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

08 Jul 2014

Is this the analysis of the primary completion data?

Yes

Primary completion date

08 Jul 2014

Global end of trial reached?

Yes

Global end of trial date

08 Jul 2014

Was the trial ended prematurely?

Yes

Main objective of the trial

This adaptive design, dose-ranging study of MK-1029 will assess the dose-related efficacy and safety of MK-1029 compared with placebo using measures of lung function (forced expiratory volume in 1 second [FEV1]). The primary objectives are (1) To demonstrate that MK-1029, compared with placebo, results in dose-related improvements in FEV1 over the last 6 weeks of the 12-week active-treatment period; and (2) To determine the dose-related safety and tolerability of MK-1029 as monotherapy and as concomitant dosing with montelukast over 12 weeks. The primary hypothesis is: MK-1029 is superior to placebo in a dose-related fashion in the average change from baseline in FEV1 over the last 6 weeks of the 12-week active-treatment period.

Protection of trial subjects

This 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. The following additional measure defined for this individual study was in place for the protection of trial subjects: Participants were provided with a short-acting ß-agonist (SABA, albuterol/salbutamol) to use as rescue medication throughout the study.

Background therapy

Evidence for comparator

Actual start date of recruitment

23 Aug 2012

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

United Kingdom: 10

Country: Number of subjects enrolled

France: 10

Country: Number of subjects enrolled

Germany: 132

Country: Number of subjects enrolled

Italy: 31

Country: Number of subjects enrolled

Canada: 22

Country: Number of subjects enrolled

Chile: 5

Country: Number of subjects enrolled

Colombia: 20

Country: Number of subjects enrolled

Guatemala: 50

Country: Number of subjects enrolled

Japan: 74

Country: Number of subjects enrolled

Peru: 60

Country: Number of subjects enrolled

Puerto Rico: 5

Country: Number of subjects enrolled

South Africa: 26

Country: Number of subjects enrolled

United States: 131

Worldwide total number of subjects

576

EEA total number of subjects

183

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

563

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

Participants aged 18 to 65 (changed from "aged 18 to 75" in Protocol Amendment 02) with a consistent clinical history, for at least one year, of symptoms of persistent asthma that may include, but are not limited to, dyspnea, wheezing, chest tightness, cough, and/or sputum production were screened for this study.

Period 1 title

Treatment Period - 12 weeks (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Data analyst, Assessor

Blinding implementation details

Study drug was administered in a double-blind, double-dummy fashion.

Are arms mutually exclusive

Yes

MK-1029 10 mg

Arm description

Parts I-II: Participants receive MK-1029 10 mg tablets once daily (QD) for 12 weeks

Arm type

Experimental

Investigational medicinal product name

MK-1029

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

MK-1029 10 mg, 30 mg or 150 mg oral tablets taken QD at bedtime

MK-1029 30 mg

Arm description

Parts I-II: Participants receive MK-1029 30 mg tablets QD for 12 weeks

Arm type

Experimental

Investigational medicinal product name

MK-1029

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

MK-1029 10 mg, 30 mg or 150 mg oral tablets taken QD at bedtime

MK-1029 60 mg

Arm description

Parts I-II: Participants receive MK-1029 30 mg tablets QD for 12 weeks

Arm type

Experimental

Investigational medicinal product name

MK-1029

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

MK-1029 10 mg, 30 mg or 150 mg oral tablets taken QD at bedtime

MK-1029 150 mg

Arm description

Parts I-II: Participants receive MK-1029 150 mg tablets QD for 12 weeks

Arm type

Experimental

Investigational medicinal product name

MK-1029

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

MK-1029 10 mg, 30 mg or 150 mg oral tablets taken QD at bedtime

Montelukast

Arm description

Parts I-II: Participants receive montelukast 10 mg tablets QD for 12 weeks

Arm type

Active comparator

Investigational medicinal product name

Montelukast

Investigational medicinal product code

Other name

SINGULAIR®

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Montelukast 10 mg oral tablet taken QD at bedtime

Placebo

Arm description

Parts I-II: Participants receive placebo tablets QD for 12 weeks

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Placebo oral tablets taken QD at bedtime

Number of subjects in period 1	MK-1029 10 mg	MK-1029 30 mg	MK-1029 60 mg	MK-1029 150 mg	Montelukast	Placebo
Started	60	127	142	53	60	134
Completed	43	93	106	41	46	94
Not completed	17	34	36	12	14	40
Consent withdrawn by subject	3	1	4	2	-	3
Physician decision	2	3	3	2	3	3
Adverse event, non-fatal	1	14	5	4	5	7
Other, unspecified	-	-	1	-	-	1
Pregnancy	-	-	1	-	-	-
Non-compliance with study drug	1	1	-	-	1	1
Screen failure	2	1	7	1	-	8
Lost to follow-up	1	-	-	-	-	-
Progressive disease	-	-	-	-	-	1
Lack of efficacy	1	8	6	1	1	6
Protocol deviation	6	6	9	2	4	10

Baseline characteristics

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Reporting group title

MK-1029 10 mg

Reporting group description

Parts I-II: Participants receive MK-1029 10 mg tablets once daily (QD) for 12 weeks

Reporting group title

MK-1029 30 mg

Reporting group description

Parts I-II: Participants receive MK-1029 30 mg tablets QD for 12 weeks

Reporting group title

MK-1029 60 mg

Reporting group description

Parts I-II: Participants receive MK-1029 30 mg tablets QD for 12 weeks

Reporting group title

MK-1029 150 mg

Reporting group description

Parts I-II: Participants receive MK-1029 150 mg tablets QD for 12 weeks

Reporting group title

Montelukast

Reporting group description

Parts I-II: Participants receive montelukast 10 mg tablets QD for 12 weeks

Reporting group title

Placebo

Reporting group description

Parts I-II: Participants receive placebo tablets QD for 12 weeks

Reporting group values	MK-1029 10 mg	MK-1029 30 mg	MK-1029 60 mg	MK-1029 150 mg	Montelukast	Placebo	Total
Number of subjects	60	127	142	53	60	134	576
Age categorical
Units: Subjects
Adults (18-64 years)	60	123	138	52	58	132	563
From 65-84 years	0	4	4	1	2	2	13
Gender categorical
Units: Subjects
Female	33	78	77	31	32	87	338
Male	27	49	65	22	28	47	238

End points

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Reporting group title

MK-1029 10 mg

Reporting group description

Parts I-II: Participants receive MK-1029 10 mg tablets once daily (QD) for 12 weeks

Reporting group title

MK-1029 30 mg

Reporting group description

Parts I-II: Participants receive MK-1029 30 mg tablets QD for 12 weeks

Reporting group title

MK-1029 60 mg

Reporting group description

Parts I-II: Participants receive MK-1029 30 mg tablets QD for 12 weeks

Reporting group title

MK-1029 150 mg

Reporting group description

Parts I-II: Participants receive MK-1029 150 mg tablets QD for 12 weeks

Reporting group title

Montelukast

Reporting group description

Parts I-II: Participants receive montelukast 10 mg tablets QD for 12 weeks

Reporting group title

Placebo

Reporting group description

Parts I-II: Participants receive placebo tablets QD for 12 weeks

Primary: Average Change from Baseline in Forced Expiratory Volume in 1 Second (FEV1)

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End point title

Average Change from Baseline in Forced Expiratory Volume in 1 Second (FEV1)

End point description

FEV1 is the amount of air (in liters) forcibly exhaled in one second. The Full Analysis Set included participants who were considered T helper cell type 2 (TH2)-High participants. TH2-High participants had EITHER a peripheral blood absolute eosinophil count ≥0.30 X 10^9/L OR a peripheral blood absolute eosinophil count ≥0.14 X 10^9/L and serum total Immunoglobulin E (IgE) ≥100 IU/mL at Visit 1. TH2-Low asthmatics were operationally defined as meeting neither of these criteria. Baseline was the average FEV1 during the placebo run-in period. The ending value was the average FEV1 over the last 6 weeks of a 12-week treatment period.

End point type

Primary

End point timeframe

Baseline and last 6 weeks of treatment

End point values	MK-1029 10 mg	MK-1029 30 mg	MK-1029 60 mg	MK-1029 150 mg	Montelukast	Placebo
Number of subjects analysed	57 ^[1]	50 ^[2]	47 ^[3]	52 ^[4]	60 ^[5]	58 ^[6]
Units: Liters
least squares mean (confidence interval 95%)	0.065 (-0.009 to 0.139)	0.004 (-0.075 to 0.083)	0.063 (-0.019 to 0.144)	0.036 (-0.04 to 0.112)	0.039 (-0.033 to 0.111)	0.043 (-0.032 to 0.119)

Notes
[1] - TH2-High participants who received ≥1 study drug dose & were evaluable for this end point.
[2] - TH2-High participants who received ≥1 study drug dose & were evaluable for this end point.
[3] - TH2-High participants who received ≥1 study drug dose & were evaluable for this end point.
[4] - TH2-High participants who received ≥1 study drug dose & were evaluable for this end point.
[5] - TH2-High participants who received ≥1 study drug dose & were evaluable for this end point.
[6] - TH2-High participants who received ≥1 study drug dose & were evaluable for this end point.

Change in FEV1: MK-1029 10 mg vs. Placebo

Statistical analysis description

Difference in least squares (LS) means for average change from Baseline over Week 6 to Week 12 in FEV1: MK-1029 10 mg vs. Placebo. Constrained longitudinal data analysis (cLDA) model includes terms for visit as categorical variable, prior inhaled corticosteroid (ICS) use (Yes/No) and treatment by visit. Positive differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).

Comparison groups

MK-1029 10 mg v Placebo

Number of subjects included in analysis

115

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.685

Method

cLDA model

Parameter type

Mean difference (final values)

Point estimate

0.022

Confidence interval

level

95%

sides

2-sided

lower limit

-0.084

upper limit

0.127

Change in FEV1: MK-1029 30 mg vs. Placebo

Statistical analysis description

Difference in LS means for average change from Baseline over Week 6 to Week 12 in FEV1: MK-1029 30 mg vs. Placebo. cLDA model includes terms for visit as categorical variable, prior ICS use (Yes/No) and treatment by visit. Positive differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).

Comparison groups

MK-1029 30 mg v Placebo

Number of subjects included in analysis

108

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.477

Method

cLDA model

Parameter type

Mean difference (final values)

Point estimate

-0.04

Confidence interval

level

95%

sides

2-sided

lower limit

-0.149

upper limit

0.07

Change in FEV1: MK-1029 60 mg vs. Placebo

Statistical analysis description

Difference in LS means for average change from Baseline over Week 6 to Week 12 in FEV1: MK-1029 60 mg vs. Placebo. cLDA model includes terms for visit as categorical variable, prior ICS use (Yes/No) and treatment by visit. Positive differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).

Comparison groups

MK-1029 60 mg v Placebo

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.733

Method

cLDA model

Parameter type

Mean difference (final values)

Point estimate

0.019

Confidence interval

level

95%

sides

2-sided

lower limit

-0.092

upper limit

0.13

Change in FEV1: MK-1029 150 mg vs. Placebo

Statistical analysis description

Difference in LS means for average change from Baseline over Week 6 to Week 12 in FEV1: MK-1029 150 mg vs. Placebo. cLDA model includes terms for visit as categorical variable, prior ICS use (Yes/No) and treatment by visit. Positive differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).

Comparison groups

MK-1029 150 mg v Placebo

Number of subjects included in analysis

110

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.89

Method

cLDA model

Parameter type

Mean difference (final values)

Point estimate

-0.008

Confidence interval

level

95%

sides

2-sided

lower limit

-0.115

upper limit

0.1

Change in FEV1: Montelukast vs. Placebo

Statistical analysis description

Difference in LS means for average change from Baseline over Week 6 to Week 12 in FEV1: Montelukast vs. Placebo. cLDA model includes terms for visit as categorical variable, prior ICS use (Yes/No) and treatment by visit. Positive differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).

Comparison groups

Montelukast v Placebo

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.935

Method

cLDA model

Parameter type

Mean difference (final values)

Point estimate

-0.004

Confidence interval

level

95%

sides

2-sided

lower limit

-0.109

upper limit

0.1

Primary: Percentage of Participants Who Experience Adverse Events (AEs)

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End point title

Percentage of Participants Who Experience Adverse Events (AEs) ^[7]

End point description

An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the study drug. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition which is temporally associated with the use of the study drug, is also an AE.

End point type

Primary

End point timeframe

Up to 14 weeks

Notes
[7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses were planned for this end point.

End point values	MK-1029 10 mg	MK-1029 30 mg	MK-1029 60 mg	MK-1029 150 mg	Montelukast	Placebo
Number of subjects analysed	58 ^[8]	126 ^[9]	135 ^[10]	52 ^[11]	60 ^[12]	126 ^[13]
Units: Percentage of participants
number (not applicable)	44.8	48.4	47.4	53.8	56.7	57.9

Notes
[8] - All randomized participants who received ≥1 dose of study drug.
[9] - All randomized participants who received ≥1 dose of study drug.
[10] - All randomized participants who received ≥1 dose of study drug.
[11] - All randomized participants who received ≥1 dose of study drug.
[12] - All randomized participants who received ≥1 dose of study drug.
[13] - All randomized participants who received ≥1 dose of study drug.

No statistical analyses for this end point

Primary: Percentage of Participants Who Discontinue Study Drug Due to AEs

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End point title

Percentage of Participants Who Discontinue Study Drug Due to AEs ^[14]

End point description

End point type

Primary

End point timeframe

Up to 12 weeks

Notes
[14] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses were planned for this end point.

End point values	MK-1029 10 mg	MK-1029 30 mg	MK-1029 60 mg	MK-1029 150 mg	Montelukast	Placebo
Number of subjects analysed	58 ^[15]	126 ^[16]	135 ^[17]	52 ^[18]	60 ^[19]	126 ^[20]
Units: Percentage of participants
number (not applicable)	1.7	10.3	3.7	7.7	8.3	5.6

Notes
[15] - All randomized participants who received ≥1 dose of study drug.
[16] - All randomized participants who received ≥1 dose of study drug.
[17] - All randomized participants who received ≥1 dose of study drug.
[18] - All randomized participants who received ≥1 dose of study drug.
[19] - All randomized participants who received ≥1 dose of study drug.
[20] - All randomized participants who received ≥1 dose of study drug.

No statistical analyses for this end point

Secondary: Percentage of Days with Asthma Exacerbations

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End point title

Percentage of Days with Asthma Exacerbations

End point description

An asthma exacerbation day was defined as a day with ANY of the following: a decrease from Baseline in morning (AM) Peak Expiratory Flow (PEF) of more than 20%, an AM PEF of less than 180 L/min, an increase in SABA use of more than 70% (and a minimum increase of at least 2 puffs), an increase from Baseline in Daytime Asthma Symptom Score of more than 50%, an overnight asthma symptom of: Awake "all night", or an asthma attack. The percentage of asthma exacerbation days was calculated. The ending value was calculated as the percentage of days with asthma exacerbations over the last 6 weeks of a 12-week treatment period.

End point type

Secondary

End point timeframe

Last 6 weeks of treatment

End point values	MK-1029 10 mg	MK-1029 30 mg	MK-1029 60 mg	MK-1029 150 mg	Montelukast	Placebo
Number of subjects analysed	44 ^[21]	39 ^[22]	37 ^[23]	46 ^[24]	47 ^[25]	39 ^[26]
Units: Percent of asthma exacerbation days
least squares mean (confidence interval 95%)	17.704 (10.657 to 24.75)	15.812 (8.334 to 23.29)	15.435 (7.752 to 23.118)	20.238 (13.353 to 27.124)	19.657 (12.845 to 26.47)	24.904 (17.424 to 32.384)

Notes
[21] - TH2-High participants who received ≥1 study drug dose & were evaluable for this end point.
[22] - TH2-High participants who received ≥1 study drug dose & were evaluable for this end point.
[23] - TH2-High participants who received ≥1 study drug dose & were evaluable for this end point.
[24] - TH2-High participants who received ≥1 study drug dose & were evaluable for this end point.
[25] - TH2-High participants who received ≥1 study drug dose & were evaluable for this end point.
[26] - TH2-High participants who received ≥1 study drug dose & were evaluable for this end point.

Asthma Exacerbation Days: MK-1029 10 mg

Statistical analysis description

Difference in LS means for percent of asthma exacerbation day over Week 6 through Week 12: MK-1029 10 mg vs. Placebo. Analysis of covariance (ANCOVA) model with the covariate for treatment groups and prior ICS use (Yes/No). Negative differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).

Comparison groups

MK-1029 10 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.169

Method

ANOVA

Parameter type

Mean difference (final values)

Point estimate

-7.2

Confidence interval

level

95%

sides

2-sided

lower limit

-17.48

upper limit

3.08

Asthma Exacerbation Days: MK-1029 30 mg

Statistical analysis description

Difference in LS means for percent of asthma exacerbation days over Week 6 through Week 12: MK-1029 30 mg vs. Placebo. ANOVA model includes terms for prior ICS use (Yes/No) and treatment. Negative differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).

Comparison groups

MK-1029 30 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.092

Method

ANOVA

Parameter type

Mean difference (final values)

Point estimate

-9.092

Confidence interval

level

95%

sides

2-sided

lower limit

-19.67

upper limit

1.485

Asthma Exacerbation Days: MK-1029 60 mg

Statistical analysis description

Difference in LS means for percent of asthma exacerbation days over Week 6 through Week 12: MK-1029 60 mg vs. Placebo. ANOVA model included terms for prior ICS use (Yes/No) and treatment. Negative differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).

Comparison groups

MK-1029 60 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.083

Method

ANOVA

Parameter type

Mean difference (final values)

Point estimate

-9.469

Confidence interval

level

95%

sides

2-sided

lower limit

-20.19

upper limit

1.25

Asthma Exacerbation Days: MK-1029 150 mg

Statistical analysis description

Difference in LS means for percent of asthma exacerbation day over Week 6 through Week 12: MK-1029 150 mg vs. Placebo. ANOVA model includes terms for prior ICS use (Yes/No) and treatment. Negative differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).

Comparison groups

MK-1029 150 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.367

Method

ANOVA

Parameter type

Mean difference (final values)

Point estimate

-4.666

Confidence interval

level

95%

sides

2-sided

lower limit

-14.83

upper limit

5.501

Asthma Exacerbation Days: Montelukast

Statistical analysis description

Difference in LS means for percent of asthma exacerbation days over Week 6 through Week 12: Montelukast vs. Placebo. ANOVA model includes terms for prior ICS use (Yes/No) and treatment. Negative differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).

Comparison groups

Montelukast v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.308

Method

ANOVA

Parameter type

Mean difference (final values)

Point estimate

-5.247

Confidence interval

level

95%

sides

2-sided

lower limit

-15.36

upper limit

4.871

Secondary: Average Change from Baseline in Daytime Symptom Score (DSS)

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End point title

Average Change from Baseline in Daytime Symptom Score (DSS)

End point description

In the evening just before going to bed, participants scored their asthma symptoms for the period since arising by answering the following 4 questions in eDiaries: 1) How often did you experience asthma symptoms today?, 2) How much did your asthma symptoms bother you?, 3) How much activity could you do today? and 4) How often did your asthma affect your activities today? The 4 questions were scored on a 7-point scale (0=best to 6=worst). Baseline was the average DSS score during the placebo run-in period. The ending value was the average DSS Score over the last 6 weeks of a 12-week treatment period.

End point type

Secondary

End point timeframe

Baseline and last 6 weeks of treatment

End point values	MK-1029 10 mg	MK-1029 30 mg	MK-1029 60 mg	MK-1029 150 mg	Montelukast	Placebo
Number of subjects analysed	45 ^[27]	41 ^[28]	40 ^[29]	49 ^[30]	49 ^[31]	43 ^[32]
Units: Score on a scale
least squares mean (confidence interval 95%)	-0.398 (-0.612 to -0.184)	-0.134 (-0.358 to 0.091)	-0.364 (-0.591 to -0.137)	-0.12 (-0.325 to 0.086)	-0.411 (-0.617 to -0.206)	-0.276 (-0.495 to -0.056)

Notes
[27] - TH2-High participants who received ≥1 study drug dose & were evaluable for this end point.
[28] - TH2-High participants who received ≥1 study drug dose & were evaluable for this end point.
[29] - TH2-High participants who received ≥1 study drug dose & were evaluable for this end point.
[30] - TH2-High participants who received ≥1 study drug dose & were evaluable for this end point.
[31] - TH2-High participants who received ≥1 study drug dose & were evaluable for this end point.
[32] - TH2-High participants who received ≥1 study drug dose & were evaluable for this end point.

Change in DSS: MK-1029 10 mg vs. Placebo

Statistical analysis description

Difference in LS means for average change from Baseline to Week 12 in DSS: MK-1029 10 mg vs. Placebo. cLDA model includes terms for visit as categorical variable, prior ICS use (Yes/No) and treatment by visit. Negative differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).

Comparison groups

MK-1029 10 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.429

Method

cLDA model

Parameter type

Mean difference (final values)

Point estimate

-0.122

Confidence interval

level

95%

sides

2-sided

lower limit

-0.427

upper limit

0.182

Change in DSS: MK-1029 30 mg vs. Placebo

Statistical analysis description

Difference in LS means for average change from Baseline to Week 12 in DSS: MK-1029 30 mg vs. Placebo. cLDA model includes terms for visit as categorical variable, prior ICS use (Yes/No) and treatment by visit. Negative differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).

Comparison groups

MK-1029 30 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.37

Method

cLDA model

Parameter type

Mean difference (final values)

Point estimate

0.142

Confidence interval

level

95%

sides

2-sided

lower limit

-0.169

upper limit

0.454

Change in DSS: MK-1029 60 mg vs. Placebo

Statistical analysis description

Difference in LS means for average change from Baseline to Week 12 in DSS: MK-1029 60 mg vs. Placebo. cLDA model includes terms for visit as categorical variable, prior ICS use (Yes/No) and treatment by visit. Negative differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).

Comparison groups

MK-1029 60 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.579

Method

cLDA model

Parameter type

Mean difference (final values)

Point estimate

-0.089

Confidence interval

level

95%

sides

2-sided

lower limit

-0.402

upper limit

0.225

Change in DSS: MK-1029 150 mg vs. Placebo

Statistical analysis description

Difference in LS means for average change from Baseline to Week 12 in DSS: MK-1029 150 mg vs. Placebo. cLDA model includes terms for visit as categorical variable, prior ICS use (Yes/No) and treatment by visit. Negative differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).

Comparison groups

MK-1029 150 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.305

Method

cLDA model

Parameter type

Mean difference (final values)

Point estimate

0.156

Confidence interval

level

95%

sides

2-sided

lower limit

-0.142

upper limit

0.454

Change in DSS: Montelukast vs. Placebo

Statistical analysis description

Difference in LS means for average change from Baseline to Week 12 in DSS: Montelukast vs. Placebo. cLDA model includes terms for visit as categorical variable, prior ICS use (Yes/No) and treatment by visit. Negative differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).

Comparison groups

Montelukast v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.372

Method

cLDA model

Parameter type

Mean difference (final values)

Point estimate

-0.136

Confidence interval

level

95%

sides

2-sided

lower limit

-0.434

upper limit

0.163

Secondary: Average Change from Baseline in Use of SABA

Top of page

End point title

Average Change from Baseline in Use of SABA

End point description

Twice daily (upon arising and before going to sleep), participants recorded the total number of puff (actuations) of SABA used for asthma symptoms in their eDiaries. This end point was defined as the number of SABA puffs used in one day and was calculated based on eDiary entries as the sum of daytime and nighttime number of puffs of SABA. Baseline was the average number of SABA puffs used in one day during the placebo run-in period. The ending value was calculated as the average number of SABA puffs used in one day over the last 6 weeks of a 12-week treatment period.

End point type

Secondary

End point timeframe

Baseline and last 6 weeks of treatment

End point values	MK-1029 10 mg	MK-1029 30 mg	MK-1029 60 mg	MK-1029 150 mg	Montelukast	Placebo
Number of subjects analysed	46 ^[33]	41 ^[34]	40 ^[35]	49 ^[36]	49 ^[37]	43 ^[38]
Units: Puffs
least squares mean (confidence interval 95%)	-1.373 (-1.847 to -0.899)	-0.902 (-1.42 to -0.421)	-0.955 (-1.461 to -0.45)	-0.571 (-1.031 to -0.111)	-1.234 (-1.694 to -0.774)	-0.845 (-1.334 to -0.356)

Notes
[33] - TH2-High participants who received ≥1 study drug dose & were evaluable for this end point.
[34] - TH2-High participants who received ≥1 study drug dose & were evaluable for this end point.
[35] - TH2-High participants who received ≥1 study drug dose & were evaluable for this end point.
[36] - TH2-High participants who received ≥1 study drug dose & were evaluable for this end point.
[37] - TH2-High participants who received ≥1 study drug dose & were evaluable for this end point.
[38] - TH2-High participants who received ≥1 study drug dose & were evaluable for this end point.

Change in SABA Use: MK-1029 10 mg vs. Placebo

Statistical analysis description

Difference in LS means for average change from Baseline over Week 6 to Week 12 in SABA use: MK-1029 10 mg vs. Placebo. cLDA model includes terms for visit as categorical variable, prior ICS use (Yes/No) and treatment by visit. Negative differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).

Comparison groups

MK-1029 10 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.114

Method

cLDA model

Parameter type

Mean difference (final values)

Point estimate

-0.528

Confidence interval

level

95%

sides

2-sided

lower limit

-1.184

upper limit

0.128

Change in SABA Use: MK-1029 30 mg vs. Placebo

Statistical analysis description

Difference in LS means for average change from Baseline over Week 6 to Week 12 in SABA use: MK-1029 30 mg vs. Placebo. cLDA model includes terms for visit as categorical variable, prior ICS use (Yes/No) and treatment by visit. Negative differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).

Comparison groups

Placebo v MK-1029 30 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.827

Method

cLDA model

Parameter type

Mean difference (final values)

Point estimate

-0.075

Confidence interval

level

95%

sides

2-sided

lower limit

-0.75

upper limit

0.6

Change in SABA Use: MK-1029 60 mg vs. Placebo

Statistical analysis description

Difference in LS means for average change from Baseline over Week 6 to Week 12 in SABA use: MK-1029 60 mg vs. Placebo. cLDA model includes terms for visit as categorical variable, prior ICS use (Yes/No) and treatment by visit. Negative differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).

Comparison groups

MK-1029 60 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.75

Method

cLDA model

Parameter type

Mean difference (final values)

Point estimate

-0.11

Confidence interval

level

95%

sides

2-sided

lower limit

-0.789

upper limit

0.569

Change in SABA Use: MK-1029 150 mg vs. Placebo

Statistical analysis description

Difference in LS means for average change from Baseline over Week 6 to Week 12 in SABA use: MK-1029 150 mg vs. Placebo. cLDA model includes terms for visit as categorical variable, prior ICS use (Yes/No) and treatment by visit. Negative differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).

Comparison groups

Placebo v MK-1029 150 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.403

Method

cLDA model

Parameter type

Mean difference (final values)

Point estimate

0.275

Confidence interval

level

95%

sides

2-sided

lower limit

-0.371

upper limit

0.921

Change in SABA Use: Montelukast vs. Placebo

Statistical analysis description

Difference in LS means for average change from Baseline over Week 6 to Week 12 in SABA use: Montelukast vs. Placebo. cLDA model includes terms for visit as categorical variable, prior ICS use (Yes/No) and treatment by visit. Negative differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).

Comparison groups

Montelukast v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.237

Method

cLDA model

Parameter type

Mean difference (final values)

Point estimate

-0.389

Confidence interval

level

95%

sides

2-sided

lower limit

-1.035

upper limit

0.257

Secondary: Average Change from Baseline in Number of Nocturnal Awakenings

Top of page

End point title

Average Change from Baseline in Number of Nocturnal Awakenings

End point description

This end point was defined as the number of nights per week (between consecutive visits) that a participant awakened with asthma. The end point was based on eDiariy entries and was calculated by dividing the number of nights a participant awakened with asthma (positive responses of once, more than once, awake "all night") by the total number of nights (all responses) and then multiplying by 7 (standardized to a 7-day period). Baseline was the average number of nocturnal awakenings during the placebo run-in period. The ending value was calculated as the average number of nocturnal awakenings over the last 6 weeks of a 12-week treatment period.

End point type

Secondary

End point timeframe

Baseline and last 6 weeks of treatment

End point values	MK-1029 10 mg	MK-1029 30 mg	MK-1029 60 mg	MK-1029 150 mg	Montelukast	Placebo
Number of subjects analysed	46 ^[39]	41 ^[40]	40 ^[41]	49 ^[42]	49 ^[43]	43 ^[44]
Units: Numer of awakenings
least squares mean (confidence interval 95%)	-1.277 (-1.861 to -0.692)	-0.9 (-1.518 to -0.282)	-1.286 (-1.912 to -0.661)	-1.277 (-1.844 to -0.71)	-1.107 (-1.674 to -0.54)	-1.036 (-1.639 to -0.432)

Notes
[39] - TH2-High participants who received ≥1 study drug dose & were evaluable for this end point.
[40] - TH2-High participants who received ≥1 study drug dose & were evaluable for this end point.
[41] - TH2-High participants who received ≥1 study drug dose & were evaluable for this end point.
[42] - TH2-High participants who received ≥1 study drug dose & were evaluable for this end point.
[43] - TH2-High participants who received ≥1 study drug dose & were evaluable for this end point.
[44] - TH2-High participants who received ≥1 study drug dose & were evaluable for this end point.

Change in Nocturnal Awakenings: MK-1029 10 mg

Statistical analysis description

Difference in LS means for average change from Baseline over Week 6 to Week 12 in nocturnal awakenings: MK-1029 10 mg vs. Placebo. cLDA model includes terms for visit as categorical variable, prior ICS use (Yes/No) and treatment by visit. Negative differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).

Comparison groups

MK-1029 10 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.565

Method

cLDA model

Parameter type

Mean difference (final values)

Point estimate

-0.241

Confidence interval

level

95%

sides

2-sided

lower limit

-1.066

upper limit

0.583

Change in Nocturnal Awakenings: MK-1029 30 mg

Statistical analysis description

Difference in LS means for average change from Baseline over Week 6 to Week 12 in nocturnal awakenings: MK-1029 30 mg vs. Placebo. cLDA model includes terms for visit as categorical variable, prior ICS use (Yes/No) and treatment by visit. Negative differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).

Comparison groups

MK-1029 30 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.754

Method

cLDA model

Parameter type

Mean difference (final values)

Point estimate

0.135

Confidence interval

level

95%

sides

2-sided

lower limit

-0.713

upper limit

0.983

Change in Nocturnal Awakenings: MK-1029 60 mg

Statistical analysis description

Difference in LS means for average change from Baseline over Week 6 to Week 12 in nocturnal awakenings: MK-1029 60 mg vs. Placebo. cLDA model includes terms for visit as categorical variable, prior ICS use (Yes/No) and treatment by visit. Negative differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).

Comparison groups

MK-1029 60 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.563

Method

cLDA model

Parameter type

Mean difference (final values)

Point estimate

-0.251

Confidence interval

level

95%

sides

2-sided

lower limit

-1.104

upper limit

0.603

Change in Nocturnal Awakenings: MK-1029 150 mg

Statistical analysis description

Difference in LS means for average change from Baseline over Week 6 to Week 12 in nocturnal awakenings: MK-1029 150 mg vs. Placebo. cLDA model includes terms for visit as categorical variable, prior ICS use (Yes/No) and treatment by visit. Negative differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).

Comparison groups

MK-1029 150 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.559

Method

cLDA model

Parameter type

Mean difference (final values)

Point estimate

-0.241

Confidence interval

level

95%

sides

2-sided

lower limit

-1.053

upper limit

0.571

Change in Nocturnal Awakenings: Montelukast

Statistical analysis description

Difference in LS means for average change from Baseline over Week 6 to Week 12 in nocturnal awakenings: Montelukast vs. Placebo. cLDA model includes terms for visit as categorical variable, prior ICS use (Yes/No) and treatment by visit. Negative differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).

Comparison groups

Montelukast v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.863

Method

cLDA model

Parameter type

Mean difference (final values)

Point estimate

-0.071

Confidence interval

level

95%

sides

2-sided

lower limit

-0.883

upper limit

0.741

Secondary: Average Change from Baseline in Morning (AM) and Evening (PM) Peak Expiratory Flow (PEF)

Top of page

End point title

Average Change from Baseline in Morning (AM) and Evening (PM) Peak Expiratory Flow (PEF)

End point description

PEF is a measure in liters, of the maximum flow during an exhalation. The average change from Baseline in AM/PM PEF over the last 6 weeks of a 12-week treatment period was calculated. Baseline was the average AM/PM PEF value during the placebo run-in period.

End point type

Secondary

End point timeframe

Baseline and last 6 weeks of treatment

End point values	MK-1029 10 mg	MK-1029 30 mg	MK-1029 60 mg	MK-1029 150 mg	Montelukast	Placebo
Number of subjects analysed	46 ^[45]	41 ^[46]	40 ^[47]	49 ^[48]	49 ^[49]	43 ^[50]
Units: Liters
least squares mean (confidence interval 95%)	-1.857 (-16.13 to 12.413)	3.85 (-11.26 to 18.96)	7.174 (-8.124 to 22.472)	2.713 (-11.12 to 16.543)	-4.005 (-17.83 to 9.825)	-2.401 (-17.16 to 12.357)

Notes
[45] - TH2-High participants who received ≥1 study drug dose & were evaluable for this end point.
[46] - TH2-High participants who received ≥1 study drug dose & were evaluable for this end point.
[47] - TH2-High participants who received ≥1 study drug dose & were evaluable for this end point.
[48] - TH2-High participants who received ≥1 study drug dose & were evaluable for this end point.
[49] - TH2-High participants who received ≥1 study drug dose & were evaluable for this end point.
[50] - TH2-High participants who received ≥1 study drug dose & were evaluable for this end point.

Change in AM/PM PEF: MK-1029 10 mg vs. Placebo

Statistical analysis description

Difference in LS means for average change from Baseline over Week 6 to Week 12 in AM/PM PEF: MK-1029 10 mg vs. Placebo. cLDA model includes terms for visit as categorical variable, prior ICS use (Yes/No) and treatment by visit. Negative differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).

Comparison groups

MK-1029 10 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.958

Method

cLDA model

Parameter type

Mean difference (final values)

Point estimate

0.544

Confidence interval

level

95%

sides

2-sided

lower limit

-19.92

upper limit

21.007

Change in AM/PM PEF: MK-1029 30 mg vs. Placebo

Statistical analysis description

Difference in LS means for average change from Baseline over Week 6 to Week 12 in AM/PM PEF: MK-1029 30 mg vs. Placebo. cLDA model includes terms for visit as categorical variable, prior ICS use (Yes/No) and treatment by visit. Negative differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).

Comparison groups

MK-1029 30 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.559

Method

cLDA model

Parameter type

Mean difference (final values)

Point estimate

6.251

Confidence interval

level

95%

sides

2-sided

lower limit

-14.81

upper limit

27.307

Change in AM/PM PEF: MK-1029 60 mg vs. Placebo

Statistical analysis description

Difference in LS means for average change from Baseline over Week 6 to Week 12 in AM/PM PEF: MK-1029 60 mg vs. Placebo. cLDA model includes terms for visit as categorical variable, prior ICS use (Yes/No) and treatment by visit. Negative differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).

Comparison groups

MK-1029 60 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.374

Method

cLDA model

Parameter type

Mean difference (final values)

Point estimate

9.575

Confidence interval

level

95%

sides

2-sided

lower limit

-11.62

upper limit

30.766

Change in AM/PM PEF: MK-1029 150 mg vs. Placebo

Statistical analysis description

Difference in LS means for average change from Baseline over Week 6 to Week 12 in AM/PM PEF: MK-1029 150 mg vs. Placebo. cLDA model includes terms for visit as categorical variable, prior ICS use (Yes/No) and treatment by visit. Negative differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).

Comparison groups

MK-1029 150 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.618

Method

cLDA model

Parameter type

Mean difference (final values)

Point estimate

5.114

Confidence interval

level

95%

sides

2-sided

lower limit

-15.04

upper limit

25.272

Change in AM/PM PEF: Montelukast vs. Placebo

Statistical analysis description

Difference in LS means for average change from Baseline over Week 6 to Week 12 in AM/PM PEF: Montelukast vs. Placebo. cLDA model includes terms for visit as categorical variable, prior ICS use (Yes/No) and treatment by visit. Negative differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).

Comparison groups

Montelukast v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.876

Method

cLDA model

Parameter type

Mean difference (final values)

Point estimate

-1.604

Confidence interval

level

95%

sides

2-sided

lower limit

-21.76

upper limit

18.554

Secondary: Change from Baseline in Asthma Quality of Life Questionnaire with Standardised Activities [AQLQ(S)] Overall and Domain Scores

Top of page

End point title

Change from Baseline in Asthma Quality of Life Questionnaire with Standardised Activities [AQLQ(S)] Overall and Domain Scores

End point description

The AQLQ(S) is a 32-item questionnaire with questions on 4 domains (asthma symptoms, activity limitation, emotional function and environmental stimuli) over the previous 2 weeks. Responses were scored on a 7-point scale (1=worst to 7=best). Each domain score is defined as the average score of all answered questions in that domain. The AQLQ(S) Overall Score is defined as the average of all available item scores. The changes from baseline are presented for the overall scores and the individual domain scores. Baseline was the last measurement taken prior to the first double-blind study drug. The ending values were calculated as the average AQLQ(S) Overall Score and domain scores at Week 12 of a 12-week treatment period. Statistical analyses are provided for the AQLQ(S) Overall Scores only.

End point type

Secondary

End point timeframe

Baseline and Week 12

End point values	MK-1029 10 mg	MK-1029 30 mg	MK-1029 60 mg	MK-1029 150 mg	Montelukast	Placebo
Number of subjects analysed	53 ^[51]	47 ^[52]	42 ^[53]	47 ^[54]	53 ^[55]	54 ^[56]
Units: Score on a scale
arithmetic mean (standard deviation)
Overall Score	0.53 ( 1.01 )	0.26 ( 1 )	0.7 ( 1.04 )	1 ( 1.25 )	0.74 ( 1.03 )	0.46 ( 1.18 )
Activity Domain	0.46 ( 1.05 )	0.27 ( 0.98 )	0.62 ( 1.08 )	0.96 ( 1.32 )	0.66 ( 1.03 )	0.44 ( 1.18 )
Symptoms Domain	0.59 ( 1.2 )	0.34 ( 1.24 )	0.8 ( 1.12 )	1.02 ( 1.25 )	0.83 ( 1.11 )	0.47 ( 1.29 )
Emotional Function Domain	0.55 ( 1.35 )	0.06 ( 1.17 )	0.75 ( 1.26 )	1.12 ( 1.62 )	0.7 ( 1.2 )	0.45 ( 1.37 )
Environmental Stimuli Domain	0.53 ( 1.19 )	0.21 ( 0.9 )	0.54 ( 1.2 )	0.89 ( 1.47 )	0.7 ( 1.18 )	0.49 ( 1.43 )

Notes
[51] - TH2-High participants who received ≥1 study drug dose & were evaluable for this end point.
[52] - TH2-High participants who received ≥1 study drug dose & were evaluable for this end point.
[53] - TH2-High participants who received ≥1 study drug dose & were evaluable for this end point.
[54] - TH2-High participants who received ≥1 study drug dose & were evaluable for this end point.
[55] - TH2-High participants who received ≥1 study drug dose & were evaluable for this end point.
[56] - TH2-High participants who received ≥1 study drug dose & were evaluable for this end point.

Change in AQLQ(S) Overall Score: MK-1029 10 mg

Statistical analysis description

Difference in LS means for change from Baseline to Week 12 in AQLQ(S) Overall Score: MK-1029 10 mg vs. Placebo. cLDA model includes terms for visit as categorical variable, prior ICS use (Yes/No) and treatment by visit. Positive differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).

Comparison groups

MK-1029 10 mg v Placebo

Number of subjects included in analysis

107

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.682

Method

cLDA model

Parameter type

Mean difference (final values)

Point estimate

0.076

Confidence interval

level

95%

sides

2-sided

lower limit

-0.288

upper limit

0.44

Change in AQLQ(S) Overall Score: MK-1029 30 mg

Statistical analysis description

Difference in LS means for change from Baseline to Week 12 in AQLQ(S) Overall Score: MK-1029 30 mg vs. Placebo. cLDA model includes terms for visit as categorical variable, prior ICS use (Yes/No) and treatment by visit. Positive differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).

Comparison groups

MK-1029 30 mg v Placebo

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.807

Method

cLDA model

Parameter type

Mean difference (final values)

Point estimate

-0.047

Confidence interval

level

95%

sides

2-sided

lower limit

-0.422

upper limit

0.329

Change in AQLQ(S) Overall Score: MK-1029 60 mg

Statistical analysis description

Difference in LS means for change from Baseline to Week 12 in AQLQ(S) Overall Score: MK-1029 60 mg vs. Placebo. cLDA model includes terms for visit as categorical variable, prior ICS use (Yes/No) and treatment by visit. Positive differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).

Comparison groups

MK-1029 60 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.403

Method

cLDA model

Parameter type

Mean difference (final values)

Point estimate

0.165

Confidence interval

level

95%

sides

2-sided

lower limit

-0.222

upper limit

0.552

Change in AQLQ(S) Overall Score: MK-1029 150 mg

Statistical analysis description

Difference in LS means for change from Baseline to Week 12 in AQLQ(S) Overall Score: MK-1029 150 mg vs. Placebo. cLDA model includes terms for visit as categorical variable, prior ICS use (Yes/No) and treatment by visit. Positive differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).

Comparison groups

MK-1029 150 mg v Placebo

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.051

Method

cLDA model

Parameter type

Mean difference (final values)

Point estimate

0.375

Confidence interval

level

95%

sides

2-sided

lower limit

-0.001

upper limit

0.751

Change in AQLQ(S) Overall Score: Montelukast

Statistical analysis description

Difference in LS means for change from Baseline to Week 12 in AQLQ(S) Overall Score: Montelukast vs. Placebo. cLDA model includes terms for visit as categorical variable, prior ICS use (Yes/No) and treatment by visit. Positive differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).

Comparison groups

Montelukast v Placebo

Number of subjects included in analysis

107

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.086

Method

cLDA model

Parameter type

Mean difference (final values)

Point estimate

0.319

Confidence interval

level

95%

sides

2-sided

lower limit

-0.045

upper limit

0.683

Secondary: Percentage of Participants with a ≥0.5 Increase in AQLQ(S) Overall and Domain Scores from Baseline

Top of page

End point title

Percentage of Participants with a ≥0.5 Increase in AQLQ(S) Overall and Domain Scores from Baseline

End point description

The percentage of participants who experienced a ≥0.5 increase in AQLQ(S) Overall and Domain Scores at Week 12 compared to Baseline was calculated. Statistical analyses are provide for the AQLQ(S) Overall Score response rate only.

End point type

Secondary

End point timeframe

Week 12

End point values	MK-1029 10 mg	MK-1029 30 mg	MK-1029 60 mg	MK-1029 150 mg	Montelukast	Placebo
Number of subjects analysed	53 ^[57]	47 ^[58]	42 ^[59]	45 ^[60]	52 ^[61]	53 ^[62]
Units: Percentage of participants
number (not applicable)
Overall Score	48.99	40.49	57.22	64.48	64.08	46.14
Activity Domain	47.19	40.46	50	60.07	52.36	42.61
Symptoms Domain	52.59	42.63	59.66	57.76	64.08	48.13
Emotional Function Domain	56.19	31.95	62.1	57.76	53.91	49.9
Environmental Stimuli Domain	41.79	42.6	59.66	59.97	53.16	48.13

Notes
[57] - TH2-High participants who received ≥1 study drug dose & were evaluable for this end point.
[58] - TH2-High participants who received ≥1 study drug dose & were evaluable for this end point.
[59] - TH2-High participants who received ≥1 study drug dose & were evaluable for this end point.
[60] - TH2-High participants who received ≥1 study drug dose & were evaluable for this end point.
[61] - TH2-High participants who received ≥1 study drug dose & were evaluable for this end point.
[62] - TH2-High participants who received ≥1 study drug dose & were evaluable for this end point.

AQLQ(S) Response: MK-1029 10 mg vs. Placebo

Statistical analysis description

Difference in LS means for AQLQ(S) Response Rate: MK-1029 10 mg vs. Placebo. P-values, estimates and 95% confidence intervals (CIs) are based on the Miettinen and Nurminen (MN) method stratified by prior ICS use (Yes/No).

Comparison groups

MK-1029 10 mg v Placebo

Number of subjects included in analysis

106

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7687

Method

MN method

Parameter type

Mean difference (final values)

Point estimate

2.8

Confidence interval

level

95%

sides

2-sided

lower limit

-16

upper limit

21.3

AQLQ(S) Response: MK-1029 30 mg vs. Placebo

Statistical analysis description

Difference in LS means for AQLQ(S) Response Rate: MK-1029 30 mg vs. Placebo. P-values, estimates and 95% CIs are based on the MN method stratified by prior ICS use (Yes/No).

Comparison groups

MK-1029 30 mg v Placebo

Number of subjects included in analysis

100

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4943

Method

MN method

Parameter type

Mean difference (final values)

Point estimate

-6.6

Confidence interval

level

95%

sides

2-sided

lower limit

-24.9

upper limit

12.2

AQLQ(S) Response: MK-1029 60 mg vs. Placebo

Statistical analysis description

Difference in LS means for AQLQ(S) Response Rate: MK-1029 60 mg vs. Placebo. P-values, estimates and 95% CIs are based on the MN method stratified by prior ICS use (Yes/No).

Comparison groups

MK-1029 60 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3003

Method

MN method

Parameter type

Mean difference (final values)

Point estimate

10.5

Confidence interval

level

95%

sides

2-sided

lower limit

-9.4

upper limit

29.6

AQLQ(S) Response: MK-1029 150 mg vs. Placebo

Statistical analysis description

Difference in LS means for AQLQ(S) Response Rate: MK-1029 150 mg vs. Placebo. P-values, estimates and 95% CIs are based on the MN method stratified by prior ICS use (Yes/No).

Comparison groups

MK-1029 150 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0774

Method

MN method

Parameter type

Mean difference (final values)

Point estimate

17.5

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

35.7

AQLQ(S) Response: Montelukast vs. Placebo

Statistical analysis description

Difference in LS means for AQLQ(S) Response Rate: Montelukast vs. Placebo. P-values, estimates and 95% CIs are based on the MN method stratified by prior ICS use (Yes/No).

Comparison groups

Montelukast v Placebo

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0555

Method

MN method

Parameter type

Mean difference (final values)

Point estimate

18.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.4

upper limit

35.5

Secondary: Change from Baseline in Asthma Control Questionnaire (ACQ) Score

Top of page

End point title

Change from Baseline in Asthma Control Questionnaire (ACQ) Score

End point description

Participants were asked to evaluate their asthma over the previous week by answering these 6 questions: How often were you woken by your asthma during the night? How bad were your asthma symptoms when you woke up in the morning? How limited were you in your activities because of your asthma? How much shortness of breath did you experience because of your asthma? How much of the time did you wheeze? How many puffs/inhalations of short-acting bronchodilator (e.g. Ventolin/Bricanyl) have you used each day? Each response to a question was scored on a 7-point scale (0=best to 6=worst). The ACQ score is the average of the 6-items scores. The Baseline value was the last measurement taken prior to the first double-blind study drug. The ending value was calculated as the average ACQ Score at Week 12 of a 12-week treatment period.

End point type

Secondary

End point timeframe

Baseline and Week 12

End point values	MK-1029 10 mg	MK-1029 30 mg	MK-1029 60 mg	MK-1029 150 mg	Montelukast	Placebo
Number of subjects analysed	53 ^[63]	47 ^[64]	42 ^[65]	47 ^[66]	52 ^[67]	54 ^[68]
Units: Score on a scale
least squares mean (confidence interval 95%)	-0.807 (-1.088 to -0.527)	-0.736 (-1.033 to -0.438)	-0.855 (-1.17 to -0.541)	-1.066 (-1.364 to -0.768)	-0.931 (-1.215 to -0.648)	-0.704 (-0.982 to -0.426)

Notes
[63] - TH2-High participants who received ≥1 study drug dose & were evaluable for this end point.
[64] - TH2-High participants who received ≥1 study drug dose & were evaluable for this end point.
[65] - TH2-High participants who received ≥1 study drug dose & were evaluable for this end point.
[66] - TH2-High participants who received ≥1 study drug dose & were evaluable for this end point.
[67] - TH2-High participants who received ≥1 study drug dose & were evaluable for this end point.
[68] - TH2-High participants who received ≥1 study drug dose & were evaluable for this end point.

Change in ACQ Score: MK-1029 10 mg vs. Placebo

Statistical analysis description

Difference in LS means for change from Baseline to Week 12 in ACQ Score: MK-1029 10 mg vs. Placebo. cLDA model includes terms for visit as categorical variable, prior ICS use (Yes/No) and treatment by visit. Negative differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).

Comparison groups

MK-1029 10 mg v Placebo

Number of subjects included in analysis

107

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.603

Method

cLDA model

Parameter type

Mean difference (final values)

Point estimate

-0.104

Confidence interval

level

95%

sides

2-sided

lower limit

-0.495

upper limit

0.288

Change in ACQ Score: MK-1029 30 mg vs. Placebo

Statistical analysis description

Difference in LS means for change from Baseline to Week 12 in ACQ Score: MK-1029 30 mg vs. Placebo. cLDA model includes terms for visit as categorical variable, prior ICS use (Yes/No) and treatment by visit. Negative differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).

Comparison groups

MK-1029 30 mg v Placebo

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.875

Method

cLDA model

Parameter type

Mean difference (final values)

Point estimate

-0.032

Confidence interval

level

95%

sides

2-sided

lower limit

-0.436

upper limit

0.372

Change in ACQ Score: MK-1029 60 mg vs. Placebo

Statistical analysis description

Difference in LS means for change from Baseline to Week 12 in ACQ Score: MK-1029 60 mg vs. Placebo. cLDA model includes terms for visit as categorical variable, prior ICS use (Yes/No) and treatment by visit. Negative differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).

Comparison groups

MK-1029 60 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.476

Method

cLDA model

Parameter type

Mean difference (final values)

Point estimate

-0.151

Confidence interval

level

95%

sides

2-sided

lower limit

-0.568

upper limit

0.265

Change in ACQ Score: MK-1029 150 mg vs. Placebo

Statistical analysis description

Difference in LS means for change from Baseline to Week 12 in ACQ Score: MK-1029 150 mg vs. Placebo. cLDA model includes terms for visit as categorical variable, prior ICS use (Yes/No) and treatment by visit. Negative differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).

Comparison groups

MK-1029 150 mg v Placebo

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.079

Method

cLDA model

Parameter type

Mean difference (final values)

Point estimate

-0.362

Confidence interval

level

95%

sides

2-sided

lower limit

-0.767

upper limit

0.042

Change in ACQ Score: Montelukast vs. Placebo

Statistical analysis description

Difference in LS means for change from Baseline to Week 12 in ACQ Score: Montelukast vs. Placebo. cLDA model includes terms for visit as categorical variable, prior ICS use (Yes/No) and treatment by visit. Negative differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).

Comparison groups

Montelukast v Placebo

Number of subjects included in analysis

106

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.257

Method

cLDA model

Parameter type

Mean difference (final values)

Point estimate

-0.227

Confidence interval

level

95%

sides

2-sided

lower limit

-0.621

upper limit

0.166

Secondary: Percentage of Participants with a ≥0.5 Decrease in ACQ Score from Baseline

Top of page

End point title

Percentage of Participants with a ≥0.5 Decrease in ACQ Score from Baseline

End point description

The percentage of participants who experienced a ≥0.5 decrease in ACQ Score at Week 12 compared to Baseline was calculated.

End point type

Secondary

End point timeframe

Week 12

End point values	MK-1029 10 mg	MK-1029 30 mg	MK-1029 60 mg	MK-1029 150 mg	Montelukast	Placebo
Number of subjects analysed	53 ^[69]	47 ^[70]	42 ^[71]	45 ^[72]	51 ^[73]	54 ^[74]
Units: Percentage of participants
number (not applicable)	65.51	59.57	66.6	71.11	64.72	62.43

Notes
[69] - TH2-High participants who received ≥1 study drug dose & were evaluable for this end point.
[70] - TH2-High participants who received ≥1 study drug dose & were evaluable for this end point.
[71] - TH2-High participants who received ≥1 study drug dose & were evaluable for this end point.
[72] - TH2-High participants who received ≥1 study drug dose & were evaluable for this end point.
[73] - TH2-High participants who received ≥1 study drug dose & were evaluable for this end point.
[74] - TH2-High participants who received ≥1 study drug dose & were evaluable for this end point.

ACQ Response: MK-1029 10 mg vs. Placebo

Statistical analysis description

Difference in LS means for change from Baseline to Week 12 in ACQ response rate: MK-1029 10 mg vs. Placebo. P-values, estimates and 95% CIs are based on the MN method stratified by prior ICS use (Yes/No).

Comparison groups

MK-1029 10 mg v Placebo

Number of subjects included in analysis

107

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.742

Method

MN method

Parameter type

Mean difference (final values)

Point estimate

3.1

Confidence interval

level

95%

sides

2-sided

lower limit

-15.1

upper limit

21.1

ACQ Response: MK-1029 30 mg vs. Placebo

Statistical analysis description

Difference in LS means for change from Baseline to Week 12 in ACQ response rate: MK-1029 30 mg vs. Placebo. P-values, estimates and 95% CIs are based on the MN method stratified by prior ICS use (Yes/No).

Comparison groups

MK-1029 30 mg v Placebo

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7248

Method

MN method

Parameter type

Mean difference (final values)

Point estimate

-3.4

Confidence interval

level

95%

sides

2-sided

lower limit

-22.1

upper limit

15.4

ACQ Response: MK-1029 60 mg vs. Placebo

Statistical analysis description

Difference in LS means for change from Baseline to Week 12 in ACQ response rate: MK-1029 60 mg vs. Placebo. P-values, estimates and 95% CIs are based on the MN method stratified by prior ICS use (Yes/No).

Comparison groups

MK-1029 60 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.6991

Method

MN method

Parameter type

Mean difference (final values)

Point estimate

3.8

Confidence interval

level

95%

sides

2-sided

lower limit

-15.6

upper limit

22.6

ACQ Response: MK-1029 150 mg vs. Placebo

Statistical analysis description

Difference in LS means for change from Baseline to Week 12 in ACQ response rate: MK-1029 150 mg vs. Placebo. P-values, estimates and 95% CIs are based on the MN method stratified by prior ICS use (Yes/No).

Comparison groups

Placebo v MK-1029 150 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3934

Method

MN method

Parameter type

Mean difference (final values)

Point estimate

8.1

Confidence interval

level

95%

sides

2-sided

lower limit

-10.6

upper limit

26.2

ACQ Response: Montelukast vs. Placebo

Statistical analysis description

Difference in LS means for change from Baseline to Week 12 in ACQ response rate: Montelukast vs. Placebo. P-values, estimates and 95% CIs are based on the MN method stratified by prior ICS use (Yes/No).

Comparison groups

Montelukast v Placebo

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.8032

Method

MN method

Parameter type

Mean difference (final values)

Point estimate

2.3

Confidence interval

level

95%

sides

2-sided

lower limit

-16

upper limit

20.5

Secondary: Percentage of Participants with Asthma Attacks

Top of page

End point title

Percentage of Participants with Asthma Attacks

End point description

An asthma attack was defined as asthma symptoms during the previous 24 hours requiring one or more of the following: Corticosteroid use (systemic), Unscheduled visit to the doctor or urgent care clinic, Unscheduled visit to the emergency department or Hospitalization. The ending value was calculated as the average percentage of participants who experienced asthma attacks over Week 6 to Week 12 of a 12-week treatment period.

End point type

Secondary

End point timeframe

Over Week 6 to Week 12

End point values	MK-1029 10 mg	MK-1029 30 mg	MK-1029 60 mg	MK-1029 150 mg	Montelukast	Placebo
Number of subjects analysed	43 ^[75]	39 ^[76]	37 ^[77]	45 ^[78]	47 ^[79]	39 ^[80]
Units: Percentage of participants
least squares mean (confidence interval 95%)	0.482 (-0.159 to 1.122)	0.182 (-0.49 to 0.854)	0.017 (-0.673 to 0.708)	0.637 (0.011 to 1.262)	0.248 (-0.364 to 0.86)	0.557 (-0.115 to 1.23)

Notes
[75] - TH2-High participants who received ≥1 study drug dose & were evaluable for this end point.
[76] - TH2-High participants who received ≥1 study drug dose & were evaluable for this end point.
[77] - TH2-High participants who received ≥1 study drug dose & were evaluable for this end point.
[78] - TH2-High participants who received ≥1 study drug dose & were evaluable for this end point.
[79] - TH2-High participants who received ≥1 study drug dose & were evaluable for this end point.
[80] - TH2-High participants who received ≥1 study drug dose & were evaluable for this end point.

Asthma Attack Days: MK-1029 10 mg vs. Placebo

Statistical analysis description

Difference in LS means for percent of asthma attack days over Week 6 to Week 12 of a 12-week treatment period: MK-1209 10 mg vs. Placebo. ANOVA model includes terms for prior ICS use (Yes/No) and treatment. Negative differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).

Comparison groups

MK-1029 10 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.873

Method

ANOVA

Parameter type

Mean difference (final values)

Point estimate

-0.075

Confidence interval

level

95%

sides

2-sided

lower limit

-1.004

upper limit

0.853

Asthma Attack Days: MK-1029 30 mg vs. Placebo

Statistical analysis description

Difference in LS means for percent of asthma attack days over Week 6 to Week 12 of a 12-week treatment period: MK-1209 30 mg vs. Placebo. ANOVA model includes terms for prior ICS use (Yes/No) and treatment. Negative differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).

Comparison groups

MK-1029 30 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.437

Method

ANOVA

Parameter type

Mean difference (final values)

Point estimate

-0.376

Confidence interval

level

95%

sides

2-sided

lower limit

-1.326

upper limit

0.575

Asthma Attack Days: MK-1029 60 mg vs. Placebo

Statistical analysis description

Difference in LS means for percent of asthma attack days over Week 6 to Week 12 of a 12-week treatment period: MK-1209 60 mg vs. Placebo. ANOVA model includes terms for prior ICS use (Yes/No) and treatment. Negative differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).

Comparison groups

MK-1029 60 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.27

Method

ANOVA

Parameter type

Mean difference (final values)

Point estimate

-0.54

Confidence interval

level

95%

sides

2-sided

lower limit

-1.504

upper limit

0.423

Asthma Attack Days: MK-1029 150 mg vs. Placebo

Statistical analysis description

Difference in LS means for percent of asthma attack days over Week 6 to Week 12 of a 12-week treatment period: MK-1209 150 mg vs. Placebo. ANOVA model includes terms for prior ICS use (Yes/No) and treatment. Negative differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).

Comparison groups

MK-1029 150 mg v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.865

Method

ANOVA

Parameter type

Mean difference (final values)

Point estimate

0.079

Confidence interval

level

95%

sides

2-sided

lower limit

-0.839

upper limit

0.997

Asthma Attack Days: Montelukast vs. Placebo

Statistical analysis description

Difference in LS means for percent of asthma attack days over Week 6 to Week 12 of a 12-week treatment period: Montelukast vs. Placebo. ANOVA model includes terms for prior ICS use (Yes/No) and treatment. Negative differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).

Comparison groups

Montelukast v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.503

Method

ANOVA

Parameter type

Mean difference (final values)

Point estimate

-0.309

Confidence interval

level

95%

sides

2-sided

lower limit

-1.219

upper limit

0.6

Adverse events

Top of page

Timeframe for reporting adverse events

Up to 14 weeks (Up to 2 weeks after last dose of study drug)

Adverse event reporting additional description

The safety population consisted of all randomized participants who received ≥1 dose of study drug.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

17.0

Reporting group title

MK-1029 10 mg

Reporting group description

Parts I-II: Participants receive MK-1029 10 mg tablets QD for 12 weeks

Reporting group title

MK-1029 30 mg

Reporting group description

Parts I-II: Participants receive MK-1029 30 mg tablets QD for 12 weeks

Reporting group title

MK-1029 60 mg

Reporting group description

Parts I-II: Participants receive MK-1029 30 mg tablets QD for 12 weeks

Reporting group title

MK-1029 150 mg

Reporting group description

Parts I-II: Participants receive MK-1029 150 mg tablets QD for 12 weeks

Reporting group title

Montelukast

Reporting group description

Parts I-II: Participants receive montelukast 10 mg tablets QD for 12 weeks

Reporting group title

Placebo

Reporting group description

Parts I-II: Participants receive placebo tablets QD for 12 weeks

Serious adverse events	MK-1029 10 mg	MK-1029 30 mg	MK-1029 60 mg	MK-1029 150 mg	Montelukast	Placebo
Total subjects affected by serious adverse events
subjects affected / exposed	0 / 58 (0.00%)	2 / 126 (1.59%)	2 / 135 (1.48%)	1 / 52 (1.92%)	0 / 60 (0.00%)	1 / 126 (0.79%)
number of deaths (all causes)	0	0	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine leiomyoma
subjects affected / exposed	0 / 58 (0.00%)	1 / 126 (0.79%)	0 / 135 (0.00%)	0 / 52 (0.00%)	0 / 60 (0.00%)	0 / 126 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Cardiac failure congestive
subjects affected / exposed	0 / 58 (0.00%)	0 / 126 (0.00%)	1 / 135 (0.74%)	0 / 52 (0.00%)	0 / 60 (0.00%)	0 / 126 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Tension headache
subjects affected / exposed	0 / 58 (0.00%)	0 / 126 (0.00%)	0 / 135 (0.00%)	0 / 52 (0.00%)	0 / 60 (0.00%)	1 / 126 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Asthma
subjects affected / exposed	0 / 58 (0.00%)	1 / 126 (0.79%)	0 / 135 (0.00%)	0 / 52 (0.00%)	0 / 60 (0.00%)	0 / 126 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory failure
subjects affected / exposed	0 / 58 (0.00%)	0 / 126 (0.00%)	1 / 135 (0.74%)	0 / 52 (0.00%)	0 / 60 (0.00%)	0 / 126 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Kaposi's varicelliform eruption
subjects affected / exposed	0 / 58 (0.00%)	1 / 126 (0.79%)	0 / 135 (0.00%)	0 / 52 (0.00%)	0 / 60 (0.00%)	0 / 126 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	0 / 58 (0.00%)	0 / 126 (0.00%)	1 / 135 (0.74%)	0 / 52 (0.00%)	0 / 60 (0.00%)	0 / 126 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Hyperglycaemia
subjects affected / exposed	0 / 58 (0.00%)	0 / 126 (0.00%)	0 / 135 (0.00%)	1 / 52 (1.92%)	0 / 60 (0.00%)	0 / 126 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	MK-1029 10 mg	MK-1029 30 mg	MK-1029 60 mg	MK-1029 150 mg	Montelukast	Placebo
Total subjects affected by non serious adverse events
subjects affected / exposed	15 / 58 (25.86%)	24 / 126 (19.05%)	27 / 135 (20.00%)	19 / 52 (36.54%)	19 / 60 (31.67%)	42 / 126 (33.33%)
Injury, poisoning and procedural complications
Accidental overdose
subjects affected / exposed	4 / 58 (6.90%)	2 / 126 (1.59%)	7 / 135 (5.19%)	1 / 52 (1.92%)	2 / 60 (3.33%)	6 / 126 (4.76%)
occurrences all number	4	2	10	1	3	6
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	0 / 58 (0.00%)	4 / 126 (3.17%)	2 / 135 (1.48%)	3 / 52 (5.77%)	0 / 60 (0.00%)	3 / 126 (2.38%)
occurrences all number	0	4	2	3	0	3
Respiratory, thoracic and mediastinal disorders
Asthma
subjects affected / exposed	4 / 58 (6.90%)	15 / 126 (11.90%)	5 / 135 (3.70%)	8 / 52 (15.38%)	11 / 60 (18.33%)	17 / 126 (13.49%)
occurrences all number	5	19	5	8	12	19
Infections and infestations
Bronchitis
subjects affected / exposed	1 / 58 (1.72%)	2 / 126 (1.59%)	2 / 135 (1.48%)	3 / 52 (5.77%)	1 / 60 (1.67%)	3 / 126 (2.38%)
occurrences all number	1	2	2	3	1	3
Cystitis
subjects affected / exposed	0 / 58 (0.00%)	1 / 126 (0.79%)	2 / 135 (1.48%)	3 / 52 (5.77%)	0 / 60 (0.00%)	2 / 126 (1.59%)
occurrences all number	0	1	2	3	0	2
Gastroenteritis
subjects affected / exposed	3 / 58 (5.17%)	0 / 126 (0.00%)	1 / 135 (0.74%)	2 / 52 (3.85%)	0 / 60 (0.00%)	2 / 126 (1.59%)
occurrences all number	3	0	1	2	0	2
Nasopharyngitis
subjects affected / exposed	4 / 58 (6.90%)	6 / 126 (4.76%)	10 / 135 (7.41%)	7 / 52 (13.46%)	5 / 60 (8.33%)	12 / 126 (9.52%)
occurrences all number	4	6	10	7	5	14

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Were there any global substantial amendments to the protocol? Yes

22 Jun 2012

Amendment 01: The major reasons for this amendment are to: 1) Specify that the list of excluded medications includes strong inhibitors, or substrates, of organic anion transporting polypeptide 1B1 (OATP1B1) and OATP1B3, to modify the list, and to indicate that the list provided is not exclusive; 2) Insert flexible language allowing investigators to administer between 2 and 4 puffs of albuterol/salbutamol for reversibility testing; and 3) Add additional exploratory analyses for the relationship between efficacy of MK-1029 and peripheral-blood eosinophil counts and/or serum total IgE concentrations in the Statistical Analysis Plan.

03 Jan 2013

Amendment 02: The primary reasons for this amendment are to 1) Conform with requests by regulatory authorities (e.g., clarify which visits apply to pharmacokinetic measurements in Japan and better define “abstinence” in Subject Inclusion Criterion 3; 2) Indicate changes to the inclusion criteria related to age range, FEV1 predicted values for participants on controllers, and participant treatment categories; and 3) Revise the definition of TH2-High participants on controllers.

Were there any global interruptions to the trial? Yes

Date	Interruption	Restart date
08 Jul 2014	This study was terminated due to futility based on Interim Analysis #2.	-

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: A Double-Blind, Randomized, Placebo-Controlled, Multicenter, Parallel-Group, Adaptive-Design, Dose-Ranging Study of MK-1029 in Adult Subjects with Persistent Asthma.

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Average Change from Baseline in Forced Expiratory Volume in 1 Second (FEV1)

Primary: Average Change from Baseline in Forced Expiratory Volume in 1 Second (FEV1)

Primary: Percentage of Participants Who Experience Adverse Events (AEs)

Primary: Percentage of Participants Who Experience Adverse Events (AEs)

Primary: Percentage of Participants Who Discontinue Study Drug Due to AEs

Primary: Percentage of Participants Who Discontinue Study Drug Due to AEs

Secondary: Percentage of Days with Asthma Exacerbations

Secondary: Percentage of Days with Asthma Exacerbations

Secondary: Average Change from Baseline in Daytime Symptom Score (DSS)

Secondary: Average Change from Baseline in Daytime Symptom Score (DSS)

Secondary: Average Change from Baseline in Use of SABA

Secondary: Average Change from Baseline in Use of SABA

Secondary: Average Change from Baseline in Number of Nocturnal Awakenings

Secondary: Average Change from Baseline in Number of Nocturnal Awakenings

Secondary: Average Change from Baseline in Morning (AM) and Evening (PM) Peak Expiratory Flow (PEF)

Secondary: Average Change from Baseline in Morning (AM) and Evening (PM) Peak Expiratory Flow (PEF)

Secondary: Change from Baseline in Asthma Quality of Life Questionnaire with Standardised Activities [AQLQ(S)] Overall and Domain Scores

Secondary: Change from Baseline in Asthma Quality of Life Questionnaire with Standardised Activities [AQLQ(S)] Overall and Domain Scores

Secondary: Percentage of Participants with a ≥0.5 Increase in AQLQ(S) Overall and Domain Scores from Baseline

Secondary: Percentage of Participants with a ≥0.5 Increase in AQLQ(S) Overall and Domain Scores from Baseline

Secondary: Change from Baseline in Asthma Control Questionnaire (ACQ) Score

Secondary: Change from Baseline in Asthma Control Questionnaire (ACQ) Score

Secondary: Percentage of Participants with a ≥0.5 Decrease in ACQ Score from Baseline

Secondary: Percentage of Participants with a ≥0.5 Decrease in ACQ Score from Baseline

Secondary: Percentage of Participants with Asthma Attacks

Secondary: Percentage of Participants with Asthma Attacks

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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Clinical Trial Results:
A Double-Blind, Randomized, Placebo-Controlled, Multicenter, Parallel-Group, Adaptive-Design, Dose-Ranging Study of MK-1029 in Adult Subjects with Persistent Asthma.