Download PDF

Clinical Trial Results:
A Double-Blind, Randomized, Placebo-Controlled, Multicenter, Crossover Study of MK-1029 in Adult Subjects with Persistent Asthma Who Remain Uncontrolled While Being Maintained on Montelukast

Summary
EudraCT number	2012-000642-35
Trial protocol	DE
Global end of trial date	05 May 2014

Results information
Results version number	v1(current)
This version publication date	13 Apr 2016
First version publication date	02 May 2015
Other versions

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

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

MK-1029-011

ISRCTN number

US NCT number

NCT01624974

WHO universal trial number (UTN)

Other trial identifiers

MK-1029-011: 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

05 May 2014

Is this the analysis of the primary completion data?

Yes

Primary completion date

05 May 2014

Global end of trial reached?

Yes

Global end of trial date

05 May 2014

Was the trial ended prematurely?

Main objective of the trial

The purpose of this study is to assess the efficacy and safety of MK-1029+montelukast, compared with placebo+montelukast, in participants aged 18 to 75 years (changed to 65 years with protocol amendment 02) with evidence of asthma uncontrolled on montelukast, using measures of lung function (forced expiratory volume in 1 second [FEV1], peak expiratory flow [PEF]) and participant-reported end points, including symptoms, short-acting β-agonist (SABA) use and Asthma Control Questionnaire responses (percentage of days with asthma exacerbations). The primary objective is to demonstrate that MK-1029+montelukast, compared with placebo+montelukast, results in improvement in FEV1 after 4 weeks of treatment with MK-1029+montelukast.

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: subjects were permitted to use investigator-supplied inhaled SABA (albuterol or salbutamol) throughout the study on an “as-needed” basis for relief of asthma symptoms.

Background therapy

Subjects were permitted to use investigator-supplied inhaled SABA (albuterol or salbutamol) throughout the study on an “as-needed” basis for relief of asthma symptoms.

Evidence for comparator

Actual start date of recruitment

09 Aug 2012

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Germany: 21

Country: Number of subjects enrolled

Canada: 6

Country: Number of subjects enrolled

Colombia: 11

Country: Number of subjects enrolled

Guatemala: 26

Country: Number of subjects enrolled

Peru: 27

Country: Number of subjects enrolled

United States: 24

Worldwide total number of subjects

115

EEA total number of subjects

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)

112

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

Screening details

Participants were aged 18 to 65 years, had persistent asthma that remained uncontrolled while being maintained on montelukast, demonstrated reversibility of airway obstruction defined as an increase in FEV1 of ≥12% after SABA administration and ≥200 mL, and had an FEV1 of ≥55% and ≤85% of the predicted value.

Period 1 title

Treatment Period 1

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Data analyst

Are arms mutually exclusive

Yes

MK-1029 150 mg+Montelukast then Placebo+Montelukast

Arm description

Treatment Period 1: Participants received MK-1029 150 mg administered orally (PO) once daily (QD) in the evening plus montelukast 10 mg PO QD in the evening for 4 weeks. Treatment Period 2: Participants received placebo to MK-1029 PO QD in the evening plus montelukast 10 mg PO QD in the evening for 4 weeks. Treatment Periods 1 and 2 were separated by a 4-week washout period during which participants received placebo to MK-1029 plus montelukast 10 mg.

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 150 mg tablet administered PO QD in the evening for 4 weeks

Investigational medicinal product name

Montelukast

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Montelukast 10 mg tablet administered PO QD in the evening for 4 weeks

Placebo+Montelukast then MK-1029 150 mg+Montelukast

Arm description

Treatment Period 1: Participants received placebo to MK-1029 PO QD in the evening plus montelukast 10 mg PO QD in the evening for 4 weeks. Treatment Period 2: Participants received MK-1029 150 mg administered PO QD in the evening plus montelukast 10 mg PO QD in the evening for 4 weeks. Treatment Periods 1 and 2 were separated by a 4-week washout period during which participants received placebo to MK-1029 plus montelukast 10 mg.

Arm type

Active comparator

Investigational medicinal product name

Placebo to MK-1029

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Placebo tablet administered PO QD in the evening for 4 weeks

Investigational medicinal product name

Montelukast

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Montelukast 10 mg tablet administered PO QD in the evening for 4 weeks

Number of subjects in period 1	MK-1029 150 mg+Montelukast then Placebo+Montelukast	Placebo+Montelukast then MK-1029 150 mg+Montelukast
Started	59	56
Treated	54	53
Completed	47	45
Not completed	12	11
Physician decision	5	3
Randomization error, not treated	5	3
Adverse event, non-fatal	-	1
Noncompliance with protocol	1	2
Protocol deviation	1	-
Lack of efficacy	-	2

Period 2 title

Washout Period

Is this the baseline period?

Allocation method

Non-randomised - controlled

Blinding used

Single blind

Roles blinded

Subject

Are arms mutually exclusive

Yes

MK-1029 150 mg+Montelukast then Placebo+Montelukast

Arm description

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 150 mg tablet administered PO QD in the evening for 4 weeks

Investigational medicinal product name

Montelukast

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Montelukast 10 mg tablet administered PO QD in the evening for 4 weeks

Placebo+Montelukast then MK-1029 150 mg+Montelukast

Arm description

Arm type

Active comparator

Investigational medicinal product name

Placebo to MK-1029

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Placebo tablet administered PO QD in the evening for 4 weeks

Investigational medicinal product name

Montelukast

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Montelukast 10 mg tablet administered PO QD in the evening for 4 weeks

Number of subjects in period 2	MK-1029 150 mg+Montelukast then Placebo+Montelukast	Placebo+Montelukast then MK-1029 150 mg+Montelukast
Started	47	45
Completed	44	42
Not completed	3	3
Consent withdrawn by subject	-	1
Adverse event, non-fatal	2	-
Noncompliance with protocol	-	1
Lack of efficacy	1	1

Period 3 title

Treatment Period 2

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Data analyst

Are arms mutually exclusive

Yes

MK-1029 150 mg+Montelukast then Placebo+Montelukast

Arm description

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 150 mg tablet administered PO QD in the evening for 4 weeks

Investigational medicinal product name

Montelukast

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Montelukast 10 mg tablet administered PO QD in the evening for 4 weeks

Placebo+Montelukast then MK-1029 150 mg+Montelukast

Arm description

Arm type

Active comparator

Investigational medicinal product name

Placebo to MK-1029

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Placebo tablet administered PO QD in the evening for 4 weeks

Investigational medicinal product name

Montelukast

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Montelukast 10 mg tablet administered PO QD in the evening for 4 weeks

Number of subjects in period 3	MK-1029 150 mg+Montelukast then Placebo+Montelukast	Placebo+Montelukast then MK-1029 150 mg+Montelukast
Started	44	42
Completed	39	42
Not completed	5	0
Physician decision	3	-
Adverse event, non-fatal	1	-
Lack of efficacy	1	-

Baseline characteristics

Top of page

Reporting group title

MK-1029 150 mg+Montelukast then Placebo+Montelukast

Reporting group description

Reporting group title

Placebo+Montelukast then MK-1029 150 mg+Montelukast

Reporting group description

Reporting group values	MK-1029 150 mg+Montelukast then Placebo+Montelukast	Placebo+Montelukast then MK-1029 150 mg+Montelukast	Total
Number of subjects	59	56	115
Age categorical
Units: Subjects
In utero	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0
Newborns (0-27 days)	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0
Children (2-11 years)	0	0	0
Adolescents (12-17 years)	0	0	0
Adults (18-64 years)	58	54	112
From 65-84 years	1	2	3
85 years and over	0	0	0
Gender categorical
Units: Subjects
Male	19	16	35
Female	40	40	80

End points

Top of page

Reporting group title

MK-1029 150 mg+Montelukast then Placebo+Montelukast

Reporting group description

Reporting group title

Placebo+Montelukast then MK-1029 150 mg+Montelukast

Reporting group description

Reporting group title

MK-1029 150 mg+Montelukast then Placebo+Montelukast

Reporting group description

Reporting group title

Placebo+Montelukast then MK-1029 150 mg+Montelukast

Reporting group description

Reporting group title

MK-1029 150 mg+Montelukast then Placebo+Montelukast

Reporting group description

Reporting group title

Placebo+Montelukast then MK-1029 150 mg+Montelukast

Reporting group description

Subject analysis set title

MK-1029 150 mg+Montelukast

Subject analysis set type

Full analysis

Subject analysis set description

The analysis set consists of all participants who received at least one dose of study drug in any of the crossover periods and had at least one measurement for the analysis end point (pre-dose baseline or post-randomization observation).

Subject analysis set title

Placebo+Montelukast

Subject analysis set type

Full analysis

Subject analysis set description

Primary: Change from Baseline in FEV1

Top of page

End point title

Change from Baseline in FEV1

End point description

FEV1 is the measurement, in liters, of the amount of air exhaled in the first second of forced exhalation. At each study visit, participant FEV1 was measured in triplicate, with the largest FEV1 being recorded. The end point was based on spirometry performed at each site visit. Two baseline values were established for the analysis of this crossover study. The baseline value for the first treatment period was obtained at Week 0. The baseline value for the second treatment period was obtained at Week 8. The ending value for each treatment period was obtained at the end of the fourth week of each 4-week treatment period.

End point type

Primary

End point timeframe

Baseline and Week 4 of each Treatment Period

End point values	MK-1029 150 mg+Montelukast	Placebo+Montelukast
Number of subjects analysed	93 ^[1]	97 ^[2]
Units: liters
least squares mean (confidence interval 95%)	0.065 (0.003 to 0.126)	0.017 (-0.044 to 0.078)

Notes
[1] - Participants who took ≥1 dose of study drug in any treatment period and had ≥1 end point measurement
[2] - Participants who took ≥1 dose of study drug in any treatment period and had ≥1 end point measurement

Difference in Changes from Baseline in FEV1

Statistical analysis description

The difference in least squares (LS) means of change from baseline in FEV1 (MK-1029 150 mg+Montelukast compared to Placebo+Montelukast) was estimated using a longitudinal data analysis (LDA) model with FEV1 obtained at baseline, Week 2 and Week 4 as response. Model included treatment, visit, period and treatment-by-visit interactions as fixed effects and participant as random effect. The unstructured covariance matrix was used to model the correlation among repeated measurements.

Comparison groups

MK-1029 150 mg+Montelukast v Placebo+Montelukast

Number of subjects included in analysis

190

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.282

Method

LDA model

Parameter type

Difference in LS means

Point estimate

0.047

Confidence interval

level

95%

sides

2-sided

lower limit

-0.039

upper limit

0.134

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

Top of page

End point title

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 evaluated on a 7-point scale (0=best to 6=worst). The endpoint was calculated based on the eDiary entries as the average of the 4 questions about asthma symptoms (end point range: 0=best to 6=worst). Two baseline values were established for the analysis of this crossover study. The baseline value for the first treatment period was based on the 7-day period prior to Week 0. The baseline value for the second treatment period was based on the 7-day period prior to Week 8. The ending value in a treatment period was calculated as the average DSS over the last week of a 4-week treatment period.

End point type

Secondary

End point timeframe

Baseline and Week 4 of each Treatment Period

End point values	MK-1029 150 mg+Montelukast	Placebo+Montelukast
Number of subjects analysed	91 ^[3]	96 ^[4]
Units: score on a scale
least squares mean (confidence interval 95%)	-0.18 (-0.34 to -0.03)	-0.09 (-0.24 to 0.06)

Notes
[3] - Participants who took ≥1 dose of study drug in any treatment period and had ≥1 end point measurement
[4] - Participants who took ≥1 dose of study drug in any treatment period and had ≥1 end point measurement

Difference in Changes from Baseline in DSS

Statistical analysis description

The difference in LS means of change from baseline in DSS (MK-1029 150 mg+Montelukast compared to Placebo+Montelukast) was estimated using a LDA model with DSS obtained at Baseline, Week 2 and Week 4 as response. The model included treatment, visit, period and treatment-by-visit interaction as fixed effects and participant as random effect. The unstructured covariance matrix was used to model the correlation among repeated measurements.

Comparison groups

MK-1029 150 mg+Montelukast v Placebo+Montelukast

Number of subjects included in analysis

187

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.381

Method

LDA model

Parameter type

Difference in LS means

Point estimate

-0.09

Confidence interval

level

95%

sides

2-sided

lower limit

-0.31

upper limit

0.12

Secondary: Change from Baseline in Use of Short-acting ß-agonist (SABA)

Top of page

End point title

Change from Baseline in Use of Short-acting ß-agonist (SABA)

End point description

Twice daily (upon arising and before going to sleep), participants recorded the total number of puffs (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. Two baseline values were established for the analysis of this crossover study. The baseline value for the first treatment period was based on the 7-day period prior to Week 0. The baseline value for the second treatment period was based on the 7-day period prior to Week 8. The ending value in a treatment period was calculated as the average number of SABA puffs used in one day over the last week of a 4-week treatment period.

End point type

Secondary

End point timeframe

Baseline and Week 4 of each Treatment Period

End point values	MK-1029 150 mg+Montelukast	Placebo+Montelukast
Number of subjects analysed	94 ^[5]	98 ^[6]
Units: puffs
least squares mean (confidence interval 95%)	-0.648 (-1.059 to -0.236)	-0.538 (-0.933 to -0.143)

Notes
[5] - Participants who took ≥1 dose of study drug in any treatment period and had ≥1 end point measurement
[6] - Participants who took ≥1 dose of study drug in any treatment period and had ≥1 end point measurement

Difference in Changes from Baseline in SABA Use

Statistical analysis description

The difference in LS means of change from baseline in SABA use (MK-1029 150 mg+Montelukast compared to Placebo+Montelukast) was estimated using a LDA model with SABA use (puffs) obtained at Baseline, Week 2 and Week 4 as response. The model included treatment, visit, period and treatment-by-visit interaction as fixed effects and participant as random effect. The unstructured covariance matrix was used to model the correlation among repeated measurements.

Comparison groups

MK-1029 150 mg+Montelukast v Placebo+Montelukast

Number of subjects included in analysis

192

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.704

Method

LDA model

Parameter type

Difference in LS means

Point estimate

-0.11

Confidence interval

level

95%

sides

2-sided

lower limit

-0.679

upper limit

0.46

Secondary: Change from Baseline in Number of Nocturnal Awakenings

Top of page

End point title

Change from Baseline in Number of Nocturnal Awakenings

End point description

This end point was defined as the total number of nights a participant awakened with asthma. The end point was calculated based on eDiary entries 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). Two baseline values were established for the analysis of this crossover study. The baseline value for the first treatment period was based on the 7-day period prior to Week 0. The baseline value for the second treatment period was based on the 7-day period prior to Week 8. The ending value in a treatment period was calculated as the average number of nights awake over the last week of a 4-week treatment period.

End point type

Secondary

End point timeframe

Baseline and Week 4 of each Treatment Period

End point values	MK-1029 150 mg+Montelukast	Placebo+Montelukast
Number of subjects analysed	69 ^[7]	74 ^[8]
Units: number of nights awake
least squares mean (confidence interval 95%)	-0.98 (-1.64 to -0.33)	-0.91 (-1.53 to -0.28)

Notes
[7] - Participants who took ≥1 dose of study drug in any treatment period and had ≥1 end point measurement
[8] - Participants who took ≥1 dose of study drug in any treatment period and had ≥1 end point measurement

Difference in Changes in Nocturnal Awakenings

Statistical analysis description

The difference in LS means of change from baseline in number of nights awake (MK-1029 150 mg+Montelukast compared to Placebo+Montelukast) was estimated using a LDA model with number of nights awake obtained at Baseline, Week 2 and Week 4 as response. The model included treatment, visit, period and treatment-by-visit interaction as fixed effects and participant as random effect. The unstructured covariance matrix was used to model the correlation among repeated measurements.

Comparison groups

MK-1029 150 mg+Montelukast v Placebo+Montelukast

Number of subjects included in analysis

143

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.866

Method

LDA model

Parameter type

Difference in LS means

Point estimate

-0.08

Confidence interval

level

95%

sides

2-sided

lower limit

-0.98

upper limit

0.82

Secondary: Change from Baseline in Morning Peak Expiratory Flow (PEF)

Top of page

End point title

Change from Baseline in Morning Peak Expiratory Flow (PEF)

End point description

A peak flow meter was provided to all participants for the measurement of PEF in liters/minute at home. Participants performed triplicate PEF measurements in the morning upon arising. All 3 values were to be recorded in the eDiaries; the best value was determined through the eDiaries. The end point was calculated based on eDiary entries. Two baseline values were established for the analysis of this crossover study. The baseline value for the first treatment period was based on the 7-day period prior to Week 0. The baseline value for the second treatment period was based on the 7-day period prior to Week 8. The ending value in a treatment period was calculated as the average morning PEF over the last week of a 4-week treatment period.

End point type

Secondary

End point timeframe

Baseline and Week 4 of each Treatment Period

End point values	MK-1029 150 mg+Montelukast	Placebo+Montelukast
Number of subjects analysed	93 ^[9]	98 ^[10]
Units: liters/minute
least squares mean (confidence interval 95%)	6.55 (-1.66 to 14.75)	-3.42 (-11.54 to 4.71)

Notes
[9] - Participants who took ≥1 dose of study drug in any treatment period and had ≥1 end point measurement
[10] - Participants who took ≥1 dose of study drug in any treatment period and had ≥1 end point measurement

Difference in Changes from Baseline in Morning PEF

Statistical analysis description

The difference in LS means of change from baseline in morning PEF (MK-1029 150 mg+Montelukast compared to Placebo+Montelukast) was estimated using a LDA model with morning PEF (L/min) obtained at Baseline, Week 2 and Week 4 as response. The model included treatment, visit, period and treatment-by-visit interaction as fixed effects and participant as random effect. The unstructured covariance matrix was used to model the correlation among repeated measurements.

Comparison groups

MK-1029 150 mg+Montelukast v Placebo+Montelukast

Number of subjects included in analysis

191

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.09

Method

LDA model

Parameter type

Difference in LS means

Point estimate

9.96

Confidence interval

level

95%

sides

2-sided

lower limit

-1.58

upper limit

21.5

Secondary: Change from Baseline in Nighttime PEF

Top of page

End point title

Change from Baseline in Nighttime PEF

End point description

A peak flow meter was provided to all participants for the measurement of PEF in liters/minute at home. Participants performed triplicate PEF measurements at night, immediately before study drug adminstration, at bedtime. All 3 values were to be recorded in the eDiaries; the best value was determined through the eDiaries. The end point was calculated based on eDiary entries. Two baseline values were established for the analysis of this crossover study. The baseline value for the first treatment period was based on the 7-day period prior to Week 0. The baseline value for the second treatment period was based on the 7-day period prior to Week 8. The ending value in a treatment period was calculated as the average nighttime PEF over the last week of a 4-week treatment period.

End point type

Secondary

End point timeframe

Baseline and Week 4 of each Treatment Period

End point values	MK-1029 150 mg+Montelukast	Placebo+Montelukast
Number of subjects analysed	91 ^[11]	96 ^[12]
Units: liters/minute
least squares mean (confidence interval 95%)	7.51 (-0.81 to 15.83)	-4.31 (-12.49 to 3.87)

Notes
[11] - Participants who took ≥1 dose of study drug in any treatment period and had ≥1 end point measurement
[12] - Participants who took ≥1 dose of study drug in any treatment period and had ≥1 end point measurement

Difference in Changes in Nighttime PEF

Statistical analysis description

The difference in LS means of change from baseline in nighttime PEF (MK-1029 150 mg+Montelukast compared to Placebo+Montelukast) was estimated using a LDA model with nighttime PEF (L/min) obtained at Baseline, Week 2 and Week 4 as response. The model included treatment, visit, period and treatment-by-visit interaction as fixed effects and participant as random effect. The unstructured covariance matrix was used to model the correlation among repeated measurements.

Comparison groups

MK-1029 150 mg+Montelukast v Placebo+Montelukast

Number of subjects included in analysis

187

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.047

Method

LDA model

Parameter type

Difference in LS means

Point estimate

11.81

Confidence interval

level

95%

sides

2-sided

lower limit

0.15

upper limit

23.48

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 answer 6 questions about their asthma control over the previous week: 1) How often were you woken by your asthma during the night? 2) How bad were your asthma symptoms when you woke up in the morning? 3) How limited were you in your activities because of your asthma? 4) How much shortness of breath did you experience because of your asthma? 5) How much of the time did you wheeze? and 6) How many puffs/inhalations of SABA bronchodilator have you used each day? The AQC is scored as the mean of the responses to the 6 questions (score range: 0=totally controlled to 6=extremely poorly controlled). Two baseline values were established for this analysis. The baseline value for the first treatment period was obtained at Week 0. The baseline value for the second treatment period was obtained at Week 8. The ending value in a 4-week treatment period was participant responses at Week 4 of each treatment period.

End point type

Secondary

End point timeframe

Baseline and Week 4 of each Treatment Period

End point values	MK-1029 150 mg+Montelukast	Placebo+Montelukast
Number of subjects analysed	97 ^[13]	99 ^[14]
Units: score on a scale
least squares mean (confidence interval 95%)	-0.54 (-0.74 to -0.35)	-0.5 (-0.69 to -0.3)

Notes
[13] - Participants who took ≥1 dose of study drug in any treatment period and had ≥1 end point measurement
[14] - Participants who took ≥1 dose of study drug in any treatment period and had ≥1 end point measurement

Difference in Changes from Baseline in ACQ Score

Statistical analysis description

The difference in LS means of change from baseline in ACQ score (MK-1029 150 mg+Montelukast compared to Placebo+Montelukast) was estimated using a LDA model with ACQ score obtained at Baseline and Week 4 as response. The model included treatment, visit, period and treatment-by-visit interaction as fixed effects and participant as random effect. The unstructured covariance matrix was used to model the correlation among repeated measurements.

Comparison groups

MK-1029 150 mg+Montelukast v Placebo+Montelukast

Number of subjects included in analysis

196

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.746

Method

LDA model

Parameter type

Difference in LS means

Point estimate

-0.05

Confidence interval

level

95%

sides

2-sided

lower limit

-0.32

upper limit

0.23

Adverse events

Top of page

Timeframe for reporting adverse events

Up to 2 weeks after last dose of study drug in a treatment period (Up to 14 weeks)

Adverse event reporting additional description

Population includes all randomized participants who received ≥1 dose of study drug. Participants are included in the treatment corresponding to the study drug they actually received. A given participant can be counted under both treatment arms if the participant experienced adverse events in both treatment periods.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

17.0

Reporting group title

Placebo + Montelukast

Reporting group description

The reporting group consists of participants who received at least one dose of placebo plus montelukast in at least one of the two treatment periods. Participants were to receive placebo administered PO QD in the evening plus montelukast 10 mg PO QD in the evening for 4 weeks.

Reporting group title

MK-1029 150 mg + Montelukast

Reporting group description

The reporting group consists of participants who received at least one dose of MK-1029 150 mg plus montelukast in at least one of the two treatment periods. Participants were to receive MK-1029 150 mg administered PO QD in the evening plus montelukast 10 mg PO QD in the evening for 4 weeks.

Serious adverse events	Placebo + Montelukast	MK-1029 150 mg + Montelukast
Total subjects affected by serious adverse events
subjects affected / exposed	0 / 97 (0.00%)	0 / 96 (0.00%)
number of deaths (all causes)	0	0
number of deaths resulting from adverse events	0	0

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

Non-serious adverse events	Placebo + Montelukast	MK-1029 150 mg + Montelukast
Total subjects affected by non serious adverse events
subjects affected / exposed	14 / 97 (14.43%)	14 / 96 (14.58%)
Respiratory, thoracic and mediastinal disorders
Asthma
subjects affected / exposed	9 / 97 (9.28%)	7 / 96 (7.29%)
occurrences all number	10	7
Infections and infestations
Nasopharyngitis
subjects affected / exposed	8 / 97 (8.25%)	8 / 96 (8.33%)
occurrences all number	8	9

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

21 Sep 2012

Amendment 01: The major reasons for this amendment were (1) to note changes in the inclusion criteria to allow for participants on oral controllers to participate in the trial; (2) to specify that the list of excluded medications included strong inhibitors, or substrates, of organic anion-transporting polypeptide (OATP) 1B1 and OATP1B3, to modify the list, and to indicate that the list provided was not exclusive; and (3) to insert flexible language allowing investigators to administer between 2 and 4 puffs of albuterol/salbutamol for reversibility testing and to maintain flexible language throughout the protocol.

01 Mar 2013

Amendment 02: The primary reason for this amendment was to conform with requests by regulatory authorities, to note changes to the inclusion criteria related to age range (changed to 18 to 65 years of age), FEV1 predicted values for participants on controllers, and participant treatment categories. In addition, the definition of the T helper cell type 2 (Th2)-high participant on controllers was revised.

Were there any global interruptions to the trial? No

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

None reported

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Clinical trials

Clinical Trial Results:
A Double-Blind, Randomized, Placebo-Controlled, Multicenter, Crossover Study of MK-1029 in Adult Subjects with Persistent Asthma Who Remain Uncontrolled While Being Maintained on Montelukast

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Change from Baseline in FEV1

Primary: Change from Baseline in FEV1

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

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

Secondary: Change from Baseline in Use of Short-acting ß-agonist (SABA)

Secondary: Change from Baseline in Use of Short-acting ß-agonist (SABA)

Secondary: Change from Baseline in Number of Nocturnal Awakenings

Secondary: Change from Baseline in Number of Nocturnal Awakenings

Secondary: Change from Baseline in Morning Peak Expiratory Flow (PEF)

Secondary: Change from Baseline in Morning Peak Expiratory Flow (PEF)

Secondary: Change from Baseline in Nighttime PEF

Secondary: Change from Baseline in Nighttime PEF

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

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

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials

Clinical Trial Results: A Double-Blind, Randomized, Placebo-Controlled, Multicenter, Crossover Study of MK-1029 in Adult Subjects with Persistent Asthma Who Remain Uncontrolled While Being Maintained on Montelukast

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Change from Baseline in FEV1

Primary: Change from Baseline in FEV1

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

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

Secondary: Change from Baseline in Use of Short-acting ß-agonist (SABA)

Secondary: Change from Baseline in Use of Short-acting ß-agonist (SABA)

Secondary: Change from Baseline in Number of Nocturnal Awakenings

Secondary: Change from Baseline in Number of Nocturnal Awakenings

Secondary: Change from Baseline in Morning Peak Expiratory Flow (PEF)

Secondary: Change from Baseline in Morning Peak Expiratory Flow (PEF)

Secondary: Change from Baseline in Nighttime PEF

Secondary: Change from Baseline in Nighttime PEF

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

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

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Double-Blind, Randomized, Placebo-Controlled, Multicenter, Crossover Study of MK-1029 in Adult Subjects with Persistent Asthma Who Remain Uncontrolled While Being Maintained on Montelukast