Clinical Trials Register

Summary
EudraCT Number:	2012-000642-35
Sponsor's Protocol Code Number:	MK-1029-011-00
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-07-26
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Germany - BfArM

A.2

EudraCT number

2012-000642-35

A.3

Full title of the trial

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

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A study in adults who have ongoing asthma, using a new product combined with Montelukast.

A.3.2

Name or abbreviated title of the trial where available

Crossover Study of MK-1029 in Adults with Persistent Asthma Receiving Montelukast

A.4.1

Sponsor's protocol code number

MK-1029-011-00

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
B.5.2	Functional name of contact point	Ami Cappizano
B.5.3	Address:
B.5.3.1	Street Address	One Merck Drive
B.5.3.2	Town/ city	Whitehouse Station
B.5.3.3	Post code	08889
B.5.3.4	Country	United States
B.5.4	Telephone number	019087406544
B.5.5	Fax number	019082593958
B.5.6	E-mail	ami.capizzano@merck.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	MK-1029
D.3.2	Product code	MK-1029
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	NA
D.3.9.1	CAS number	NA
D.3.9.2	Current sponsor code	MK-1029
D.3.9.3	Other descriptive name	MK-1029
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	150
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Singulair
D.2.1.1.2	Name of the Marketing Authorisation holder	MSD SHARP & DOHME GMBH
D.2.1.2	Country which granted the Marketing Authorisation	Germany
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Montelukast sodium
D.3.2	Product code	MK-0476
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	MONTELUKAST
D.3.9.1	CAS number	158966-92-8
D.3.9.2	Current sponsor code	MK-0476
D.3.9.4	EV Substance Code	SUB09054MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Adult subjects, 18 to 75 years of age, with persistent asthma

E.1.1.1

Medical condition in easily understood language

Adults with chronic asthma

E.1.1.2

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	16.1
E.1.2	Level	LLT
E.1.2	Classification code	10001705
E.1.2	Term	Allergic asthma
E.1.2	System Organ Class	100000004855

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

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

E.2.2

Secondary objectives of the trial

The secondary objectives are to demonstrate that MK-1029, compared with placebo, results in improvements in peak expiratory flow and subject reported endpoints of daytime asthma symptom score, “as needed” short-acting β-agonist use, nocturnal awakenings, and Asthma Control Questionnaire (ACQ) score after 4 weeks of treatment with MK-1029.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Subject is a female or male subject between 18 and 75 years of age
• Subject has 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 and and has an elevated blood eosinophil count and/or serum IgE.
• While withholding SABAs for at least 6 hours and LABAs for at least 14 hours (withholding LABAs for 12-14 hours is acceptable, but not preferred), subject has a FEV1 ≥60% and ≤85% of the predicted value (≥65% and ≤90% of the predicted value if subject is receiving controllers)
• While withholding SABAs for at least 6 hours and LABAs for at least 12 hours, subject has evidence of reversibility of airway obstruction defined as an increase of FEV1 of 12% or greater, and at least 200 mL, 10 to 30 minutes after β-agonist administration.
• Subject’s asthma treatment must fall into one of two categories:
- The subject must have been using only “as-needed” inhaled short acting β agonists (albuterol/salbutamol) and not using inhaled corticosteroids (ICS) or combination ICS and long-acting β-agonists (ICS/LABA); OR
- The subject must have been on a stable dose of ICS or combination ICS/LABA (any dose) for at least 4 weeks prior to Visit 1 and must be able to tolerate tapering of ICS or combination ICS/LABA to montelukast 10 mg QD
• Subject has never smoked or is a non-smoker for at least 1 year, with a smoking history of no more than 10 pack-years (i.e., 1 pack [20 cigarettes] per day for 10 years)

E.4

Principal exclusion criteria

• Subject has a recent history (≤3 months) of myocardial infarction, congestive heart failure, or uncontrolled cardiac arrhythmia prior to Visit 1
• Subject is hospitalized or has been hospitalized in the 4 weeks prior to Visit 1
• Subject has undergone any major surgical procedure within 4 weeks prior to Visit 1
• Subject has evidence of another clinically significant, active pulmonary disorder such as bronchiectasis or COPD documented by history, physical examination, or chest x-ray
• Subject has been treated in an emergency room for asthma within 4 weeks of Visit 1 or has been hospitalized for asthma within 2 months prior to Visit 1
• Subject has evidence of uncontrolled hypertension, defined as systolic >160 mmHg and/or diastolic >100 mmHg, during at least 2 of the first 3 study visits (Visit 1, Visit 2, and Visit 3)
• Screening electrocardiogram (ECG) demonstrates clinically significant or unexplained abnormality, that may include but is not limited to: a clinically significant conduction disturbance (e.g., second or third degree AV block), clinically significant tachycardia, active cardiac ischemia, or a QTc > 460 msec
• Subject has used any medication with a narrow therapeutic index (e.g., warfarin, coumadin, dicoumarol, digoxin, digitoxin) within 2 weeks prior to Visit 1 or plans to take such medications during the study.

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy endpoint for this study is the change from baseline in FEV1 at the end of the 4-week treatment period

E.5.1.1

Timepoint(s) of evaluation of this end point

This will be measured at end of each 4-week treatment period

E.5.2

Secondary end point(s)

Change from baseline in the following endpoints at the last week (the 4th week) of the 4-week treatment period:
• Daytime Symptom Score (DSS);
• "as needed" short-acting β-agonist use ;
• Nocturnal Awakenings;
• AM and PM Peak Expiratory Flow (PEF);
• Asthma Control Questionnaire (ACQ).

E.5.2.1

Timepoint(s) of evaluation of this end point

This will be measured at the last week ( the 4th week) of each 4-week treatment period (i.e., the 4th week of Period III and the 4th week of Period V in this crossover study).

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

E.8.1.6

Cross over

Yes

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Canada

Colombia

Peru

United States

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial months

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

100

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Once a subject has ended his/her participation in the trial, the investigational product(s) will no longer be available to the subject, and any future care will be provided to the subject by the subject's personal physician/healthcare provider.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2012-09-21

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-10-25

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2014-05-05

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