Clinical Trial Results:
A Six-week Evaluator-Blind, Randomized, Active-Controlled Evaluation of the Effects of Three Doses of Mometasone Furoate/Formoterol Fumarate (MF/F) Metered Dose Inhaler (MDI), Montelukast, and Beclomethasone Dipropionate (BDP HFA) on the HPA Axis in Asthmatic Children 5 to 11 Years of Age (Protocol No. P05574/PN158)

Trial information Top of page
Trial identification
Sponsor protocol code	P05574
Additional study identifiers
ISRCTN number	-
US NCT number	NCT01615874
WHO universal trial number (UTN)	-
Sponsors
Sponsor organisation name	Merck Sharp & Dohme Corp.
Sponsor organisation address	2000 Galloping Hill Road, Kenilworth, NJ, United States,
Public contact	Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com
Scientific contact	Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com
Paediatric regulatory details
Is trial part of an agreed paediatric investigation plan (PIP)	Yes
EMA paediatric investigation plan number(s)	EMEA-999999-PIP99-99
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?	No
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?	Yes
Results analysis stage
Analysis stage	Final
Date of interim/final analysis	13 Sep 2013
Is this the analysis of the primary completion data?	No
Global end of trial reached?	Yes
Global end of trial date	13 Sep 2013
Was the trial ended prematurely?	Yes
General information about the trial
Main objective of the trial	The purpose of this study is to assess the effect of one of five possible study medications used in the treatment of asthma on blood plasma cortisol levels in children aged 5-11 years with persistent asthma.
Protection of trial subjects	N/A
Background therapy	-
Evidence for comparator	-
Actual start date of recruitment	10 Jan 2013
Long term follow-up planned	No
Independent data monitoring committee (IDMC) involvement?	No
Population of trial subjects
Number of subjects enrolled per country
Country: Number of subjects enrolled	Argentina: 99999
Country: Number of subjects enrolled	Brazil: 99999
Country: Number of subjects enrolled	Bulgaria: 99999
Country: Number of subjects enrolled	Canada: 99999
Country: Number of subjects enrolled	Chile: 99999
Worldwide total number of subjects	499995
EEA total number of subjects	99999
Number of subjects enrolled per age group
In utero	0
Preterm newborn - gestational age < 37 wk	0
Newborns (0-27 days)	0
Infants and toddlers (28 days-23 months)	0
Children (2-11 years)	499995
Adolescents (12-17 years)	0
Adults (18-64 years)	0
From 65 to 84 years	0
85 years and over	0

Trial information Top of page

Subject disposition Top of page
Recruitment
Recruitment details	Note: This trial was withdrawn. No participants were ever enrolled in it.
Pre-assignment
Screening details	N/A
Period 1
Period 1 title	Overall study (overall period)
Is this the baseline period?	Yes
Allocation method	Randomised - controlled
Blinding used	Single blind
Roles blinded	Investigator [1]
Arms
Are arms mutually exclusive	Yes
Arm title	MF/F MDI 50/10 mcg BID
Arm description	-
Arm type	Experimental
Investigational medicinal product name	MF/F Metered Dose Inhaler (MDI) 25/5 mcg
Investigational medicinal product code
Other name	SCH 418131 MK-0887A DULERA®
Pharmaceutical forms	Inhalation vapour
Routes of administration	Inhalation use
Dosage and administration details	MF/F MDI 25/5 mcg, 2 inhalations twice a day (BID)
Investigational medicinal product name	Rescue medication: short-acting beta-2 agonist (SABA) MDI
Investigational medicinal product code
Other name
Pharmaceutical forms	Inhalation vapour
Routes of administration	Inhalation use
Dosage and administration details	albuterol MDI 90 mcg OR or salbutamol HFA MDI 100 mcg for rescue medication, taken as directed
Investigational medicinal product name	Rescue medication: Prednisone/Prednisolone
Investigational medicinal product code
Other name
Pharmaceutical forms	Tablet, Oral solution, Oral drops, emulsion, Syrup
Routes of administration	Oral use
Dosage and administration details	Prednisone/Prednisolone for rescue medication, taken as directed
Arm title	MF/F MDI 100/10 mcg BID
Arm description	-
Arm type	Experimental
Investigational medicinal product name	MF/F MDI 50/5 mcg
Investigational medicinal product code
Other name	SCH 418131 MK-0887A DULERA®
Pharmaceutical forms	Inhalation vapour
Routes of administration	Inhalation use
Dosage and administration details	MF/F MDI 50/5 mcg, 2 inhalations BID
Investigational medicinal product name	Rescue medication: short-acting beta-2 agonist (SABA) MDI
Investigational medicinal product code
Other name
Pharmaceutical forms	Inhalation vapour
Routes of administration	Inhalation use
Dosage and administration details	albuterol MDI 90 mcg OR or salbutamol HFA MDI 100 mcg for rescue medication, taken as directed
Investigational medicinal product name	Rescue medication: Prednisone/Prednisolone
Investigational medicinal product code
Other name
Pharmaceutical forms	Tablet, Oral solution, Oral drops, emulsion, Syrup
Routes of administration	Oral use
Dosage and administration details	Prednisone/Prednisolone for rescue medication, taken as directed
Arm title	MF/F MDI 200/10 mcg BID
Arm description	-
Arm type	Experimental
Investigational medicinal product name	MF/F MDI 100/5 mcg
Investigational medicinal product code
Other name	SCH 418131 MK-0887A DULERA®
Pharmaceutical forms	Inhalation vapour
Routes of administration	Inhalation use
Dosage and administration details	MF/F MDI 100/5 mcg, 2 inhalations BID
Investigational medicinal product name	Rescue medication: Prednisone/Prednisolone
Investigational medicinal product code
Other name
Pharmaceutical forms	Tablet, Oral solution, Oral drops, emulsion, Syrup
Routes of administration	Oral use
Dosage and administration details	Prednisone/Prednisolone for rescue medication, taken as directed
Investigational medicinal product name	Rescue medication: short-acting beta-2 agonist (SABA) MDI
Investigational medicinal product code
Other name
Pharmaceutical forms	Inhalation vapour
Routes of administration	Inhalation use
Dosage and administration details	albuterol MDI 90 mcg OR or salbutamol HFA MDI 100 mcg for rescue medication, taken as directed
Arm title	BDP HFA 160 mcg BID
Arm description	-
Arm type	Active comparator
Investigational medicinal product name	BDP hydrofluoroalkane (HFA) 80 mcg
Investigational medicinal product code
Other name	BECONASE AQ® QVAR®
Pharmaceutical forms	Inhalation vapour
Routes of administration	Inhalation use
Dosage and administration details	BDP HFA 80 mcg, 2 inhalations BID
Investigational medicinal product name	Rescue medication: Prednisone/Prednisolone
Investigational medicinal product code
Other name
Pharmaceutical forms	Tablet, Oral solution, Oral drops, emulsion, Syrup
Routes of administration	Oral use
Dosage and administration details	Prednisone/Prednisolone for rescue medication, taken as directed
Investigational medicinal product name	Rescue medication: short-acting beta-2 agonist (SABA) MDI
Investigational medicinal product code
Other name
Pharmaceutical forms	Inhalation vapour
Routes of administration	Inhalation use
Dosage and administration details	albuterol MDI 90 mcg OR or salbutamol HFA MDI 100 mcg for rescue medication, taken as directed
Arm title	Montelukast 5 mg QD (4 mg QD for 5-year-olds)
Arm description	-
Arm type	Active comparator
Investigational medicinal product name	Montelukast tablets 5 mg (4 mg for children 5 years of age)
Investigational medicinal product code
Other name	MK-0476 SINGULAIR®
Pharmaceutical forms	Chewable tablet
Routes of administration	Oral use
Dosage and administration details	Montelukast chewable tablets 5 mg once daily (QD) for children 6-11 years of age OR Montelukast chewable tablets 4 mg QD for children 5 years of age
Investigational medicinal product name	Rescue medication: short-acting beta-2 agonist (SABA) MDI
Investigational medicinal product code
Other name
Pharmaceutical forms	Inhalation vapour
Routes of administration	Inhalation use
Dosage and administration details	albuterol MDI 90 mcg OR or salbutamol HFA MDI 100 mcg for rescue medication, taken as directed
Investigational medicinal product name	Rescue medication: Prednisone/Prednisolone
Investigational medicinal product code
Other name
Pharmaceutical forms	Tablet, Oral solution, Oral drops, emulsion, Syrup
Routes of administration	Oral use
Dosage and administration details	Prednisone/Prednisolone for rescue medication, taken as directed
Notes [1] - The roles blinded appear inconsistent with a simple blinded trial. Justification: Note: This was to be an investigator-blinded study. But this trial was withdrawn. No participants were ever enrolled in it.
Number of subjects in period 1 MF/F MDI 50/10 mcg BID MF/F MDI 100/10 mcg BID MF/F MDI 200/10 mcg BID BDP HFA 160 mcg BID Montelukast 5 mg QD (4 mg QD for 5-year-olds) Started 99999 99999 99999 99999 99999 Completed 99999 99999 99999 99999 99999

Subject disposition Top of page

Baseline characteristics Top of page
Baseline characteristics reporting groups
Reporting group title	MF/F MDI 50/10 mcg BID
Reporting group description	-
Reporting group title	MF/F MDI 100/10 mcg BID
Reporting group description	-
Reporting group title	MF/F MDI 200/10 mcg BID
Reporting group description	-
Reporting group title	BDP HFA 160 mcg BID
Reporting group description	-
Reporting group title	Montelukast 5 mg QD (4 mg QD for 5-year-olds)
Reporting group description	-
Reporting group values MF/F MDI 50/10 mcg BID MF/F MDI 100/10 mcg BID MF/F MDI 200/10 mcg BID BDP HFA 160 mcg BID Montelukast 5 mg QD (4 mg QD for 5-year-olds) Total Number of subjects 99999 99999 99999 99999 99999 499995 Age Categorical Units: Subjects     In utero 0 0 0 0 0 0     Preterm newborn infants (gestational age < 37 wks) 0 0 0 0 0 0     Newborns (0-27 days) 0 0 0 0 0 0     Infants and toddlers (28 days-23 months) 0 0 0 0 0 0     Children (2-11 years) 99999 99999 99999 99999 99999 499995     Adolescents (12-17 years) 0 0 0 0 0 0     Adults (18-64 years) 0 0 0 0 0 0     From 65-84 years 0 0 0 0 0 0     85 years and over 0 0 0 0 0 0 Age Continuous Units: years     arithmetic mean (standard deviation) 0 ± 0 0 ± 0 0 ± 0 0 ± 0 0 ± 0 - Gender Categorical Units: Subjects     Female 99999 99999 99999 99999 99999 499995     Male 0 0 0 0 0 0

Baseline characteristics Top of page

End points Top of page
End points reporting groups
Reporting group title	MF/F MDI 50/10 mcg BID
Reporting group description	-
Reporting group title	MF/F MDI 100/10 mcg BID
Reporting group description	-
Reporting group title	MF/F MDI 200/10 mcg BID
Reporting group description	-
Reporting group title	BDP HFA 160 mcg BID
Reporting group description	-
Reporting group title	Montelukast 5 mg QD (4 mg QD for 5-year-olds)
Reporting group description	-

End points Top of page

Primary: Change from Baseline in Plasma Cortisol Area Under the Curve (AUC) 0-24 hrs Top of page
End point title	Change from Baseline in Plasma Cortisol Area Under the Curve (AUC) 0-24 hrs [1]
End point description
End point type	Primary
End point timeframe	Baseline (Day 1) and Day 42
Notes [1] - 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: Note: This trial was withdrawn. No participants were ever enrolled in it.
End point values MF/F MDI 50/10 mcg BID MF/F MDI 100/10 mcg BID MF/F MDI 200/10 mcg BID BDP HFA 160 mcg BID Montelukast 5 mg QD (4 mg QD for 5-year-olds) Number of subjects analysed 0 [2] 0 [3] 0 [4] 0 [5] 0 [6] Units: nM*hr     geometric mean (geometric coefficient of variation) ± ± ± ± ±
Notes [2] - Note: This trial was withdrawn. No participants were ever enrolled in it. [3] - Note: This trial was withdrawn. No participants were ever enrolled in it. [4] - Note: This trial was withdrawn. No participants were ever enrolled in it. [5] - Note: This trial was withdrawn. No participants were ever enrolled in it. [6] - Note: This trial was withdrawn. No participants were ever enrolled in it.
No statistical analyses for this end point

Primary: Change from Baseline in Plasma Cortisol Area Under the Curve (AUC) 0-24 hrs Top of page

Secondary: Change from Baseline in Plasma Cortisol Trough Concentration (Ctrough) Top of page
End point title	Change from Baseline in Plasma Cortisol Trough Concentration (Ctrough)
End point description
End point type	Secondary
End point timeframe	Baseline (Day 1) and Day 42
End point values MF/F MDI 50/10 mcg BID MF/F MDI 100/10 mcg BID MF/F MDI 200/10 mcg BID BDP HFA 160 mcg BID Montelukast 5 mg QD (4 mg QD for 5-year-olds) Number of subjects analysed 0 [7] 0 [8] 0 [9] 0 [10] 0 [11] Units: ug/mL     geometric mean (geometric coefficient of variation) ± ± ± ± ±
Notes [7] - Note: This trial was withdrawn. No participants were ever enrolled in it. [8] - Note: This trial was withdrawn. No participants were ever enrolled in it. [9] - Note: This trial was withdrawn. No participants were ever enrolled in it. [10] - Note: This trial was withdrawn. No participants were ever enrolled in it. [11] - Note: This trial was withdrawn. No participants were ever enrolled in it.
No statistical analyses for this end point

Secondary: Change from Baseline in Plasma Cortisol Trough Concentration (Ctrough) Top of page

Adverse events Top of page
Adverse events information [1]
Timeframe for reporting adverse events	N/A
Assessment type	Systematic
Dictionary used for adverse event reporting
Dictionary name	MedDRA
Dictionary version	N/A
Reporting groups
Reporting group title	MF/F MDI 50/10 mcg BID
Reporting group description	-
Reporting group title	MF/F MDI 100/10 mcg BID
Reporting group description	-
Reporting group title	MF/F MDI 200/10 mcg BID
Reporting group description	-
Reporting group title	BDP HFA 160 mcg BID
Reporting group description	-
Reporting group title	Montelukast 5 mg QD (4 mg QD for 5-year-olds)
Reporting group description	-
Serious adverse events MF/F MDI 50/10 mcg BID MF/F MDI 100/10 mcg BID MF/F MDI 200/10 mcg BID BDP HFA 160 mcg BID Montelukast 5 mg QD (4 mg QD for 5-year-olds) Total subjects affected by serious adverse events      subjects affected / exposed 0 / 99999 (0.00%) 0 / 99999 (0.00%) 0 / 99999 (0.00%) 0 / 99999 (0.00%) 0 / 99999 (0.00%)      number of deaths (all causes) 0 0 0 0 0      number of deaths resulting from adverse events 0 0 0 0 0
Frequency threshold for reporting non-serious adverse events: 0%
Non-serious adverse events MF/F MDI 50/10 mcg BID MF/F MDI 100/10 mcg BID MF/F MDI 200/10 mcg BID BDP HFA 160 mcg BID Montelukast 5 mg QD (4 mg QD for 5-year-olds) Total subjects affected by non serious adverse events      subjects affected / exposed 0 / 99999 (0.00%) 0 / 99999 (0.00%) 0 / 99999 (0.00%) 0 / 99999 (0.00%) 0 / 99999 (0.00%)
Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: Note: This trial was withdrawn. No participants were ever enrolled in it.

Adverse events Top of page

More information Top of page
Substantial protocol amendments (globally)
Were there any global substantial amendments to the protocol? No
Interruptions (globally)
Were there any global interruptions to the trial? No
Limitations and caveats
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
Note: This trial was withdrawn. No participants were ever enrolled in it.

More information Top of page