Clinical Trials Register

Summary
EudraCT Number:	2009-014551-80
Sponsor's Protocol Code Number:	1268.16
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2010-03-17
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

UK - MHRA

A.2

EudraCT number

2009-014551-80

A.3

Full title of the trial

Randomised, double-blind, double-dummy, placebo-controlled,
parallel group study to assess the efficacy and safety of 6 weeks
of oral BI 671800 ED 400 mg b.i.d., Montelukast 10 mg q.d., or
placebo in symptomatic asthma patients on fluticasone
propionate MDI

A.4.1

Sponsor's protocol code number

1268.16

A.7

Trial is part of a Paediatric Investigation Plan

Information not present in EudraCT

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Boehringer Ingelheim Limited
B.1.3.4	Country	United Kingdom
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
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

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	BI 671800 ED 100 mg
D.3.2	Product code	BI 671800 ED 100 mg
D.3.4	Pharmaceutical form	Capsule*
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.2	Current sponsor code	BI 671800 ED
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	100 mg
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
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 tablets, 10 mg film-coated tablets
D.2.1.1.2	Name of the Marketing Authorisation holder	Merck & Co. Inc
D.2.1.2	Country which granted the Marketing Authorisation	United States
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
D.3.4	Pharmaceutical form	Capsule*
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
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 SODIUM
D.3.9.1	CAS number	151767-02-1
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
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	Capsule*
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule*
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

Symptomatic asthmatic patients on inhaled corticosteroids

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	12.1
E.1.2	Level	LLT
E.1.2	Classification code	10003553
E.1.2	Term	Asthma

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To investigate the efficacy, safety and tolerability of BI 671800 ED 400 mg b.i.d. compared to placebo or montelukast 10 mg q.d., given for 6 weeks as add-on therapy to fluticasone propionate MDI (50 μg 2 puffs b.i.d.) in symptomatic asthmatic
patients.

E.2.2

Secondary objectives of the trial

- Efficacy: Morning trough forced expiratory volume in one second (FEV1) % predicted, FEV1, forced vital capacity, Forced expiratory flow (FEF) 25-75%, Peak FEV1, Peak FVC, FEV1 area under the curve (AUC)0-3h, FVC AUC0-3h, asthma control
questionnaire (ACQ) and sub-scores, standardised asthma quality of life questionnaire (AQLQ(S)), daily symptom scores (a.m. and p.m.), weekly means of daily puffs of rescue medication usage, peak expiratory flow (PEF) and FEV1, asthma symptom-free days, asthma controlled weeks, asthma exacerbations, fractional exhaled Nitric Oxide (FeNO), total IgE and eosinophilic cationic protein (ECP).
- PK: Population PK from plasma concentrations of BI 671800 sampled
during the treatment period (total of 2 samples)
- Pharmacogenomics: Unspecified pharmacogenomic (PGx) testing
- Safety: AEs, routine laboratory,

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Signed informed consent prior to any study procedures, which includes medication washout and restrictions.
2. Diagnosis of asthma by a physician at least 3 months prior to Visit 2. The diagnosis must be according to the 2008 GINA Guidelines and must meet the following spirometric criteria:
a) Pre-bronchodilator clinic measured FEV1 ≥ 60% and ≤ 85% of predicted normal
(calculated according to modified NHANES [R04-1001] measured ≥ 6 hours after the
last use of salbutamol/albuterol rescue medication on the day of randomisation.
b) FEV1 reversibility: Improvement in FEV1 ≥ 12% above baseline and an absolute
change of at least 200 ml within 15-30 minutes after 400 μg salbutamol HFA MDI. Reversibility testing must be performed during the run-in at Visit 2 and may be repeated once at Visit 3. It must not occur on the day of randomisation.
3. Patient must be on at least iCS for at least 3 months and at a stable dose for at least 6 weeks prior to screening Visit 2.
4. Diagnosis of asthma made before the age of 40 years.
5. Patient must be symptomatic with an ACQ ≥ 1.5 on the day of randomisation.
6. Male or female patients 18 to 65 years of age inclusive.
7. BMI between 18 ≥ and ≤ 35
8. Non-smokers or ex-smokers with cigarette smoking history of ≤ 10 pack-years (and smoking cessation for at least one year prior to enrolment). Patients must have a negative urinary cotinine at visit 2.
9. Able to perform technically acceptable pulmonary function tests and
electronic PEF measurements, and must be able to maintain records (AM2+®)

E.4

Principal exclusion criteria

1. Significant pulmonary disease other than asthma or other medical conditions that may put the patient at risk, influence the results of the study, cause concern regarding the patient’s ability to participate in the study. Patients with malignancy for which the patient has undergone resection, radiation or chemotherapy within past 5yrs. Patients with treated basal cell carcinoma or fully cured squamous cell carcinoma are allowed. 2. Clinically relevant abnormal baseline haematology, blood chemistry, or urinalysis at screening, if the abnormality defines a significant disease. Patients with AST, ALT, γGT, TBIL or INR>1.5 ULN at Visit2. 3. Hospitalisation for asthma exacerb. within 3mths or intubation for asthma within 3yrs of Visit2. 4. Partially controlled (ACQ6>1.5) on iCS plus any other asthma controller at Visit2. 5. Respiratory tract infection or asthma exacerb. in the 4wks prior to Visit2 or during the run-in. In case of URTI (without asthma exacerb.) during run-in, patients can be pre-screened again 4wks after resolution. 6. Thoracotomy with pulmonary resection. Thoracotomy for other reasons should be assessed (excl.1). 7. Any safety net criteria are met during the run-in period a)In clinic FEV1 %predicted pre-bronchodilator<40%, b)>12puffs rescue salbutamol HFA MDI per day for >2 consec. days, c)Exacerbation of asthma. If AM2+ indicates a drop in absolute PEF of 30% from average absolute PEF of the last pre-screening week or last week prior to Visit4, for >2 consec. days, an alert is generated, the patient should contact the study site for immediate assessment. 8. Previous participation in this study or participation in a current interventional study. 9. Significant alcohol or drug abuse within past 2yrs of Visit2. 10. Pregnant or nursing women. 11. Women of childbearing potential not using two effective methods of birth control (one barrier and one non-barrier). Female patients will be considered to be of childbearing potential unless surgically sterilised by hysterectomy or bilateral tubal ligation, or post-menopausal for at least 2yrs. Effective methods of birth control include established use of oral, injected or implanted hormonal methods of contraception, placement of an IUD or IUS, barrier method of contraception: condom or occlusive cap with spermicidal foam/gel/film/cream/suppository or male sterilization (with appropriate post-vasectomy documentation of the absence of sperm in the ejaculate). 12. Known hypersensitivity to any component of the investigat. treatment, salbutamol, fluticasone MDI or montelukast components. 13. Patients who have been treated with any of the following medications in the given interval prior to Visit2: a)An investigational drug within 1mth or 6 1/2 lives (whichever is greater). b)Started on immunotherapy <1yr prior to Visit2. Patient should on the same course of immunotherapy for at least 1yr to be admitted into the study. Adjustment in dose within 1yr is allowed, as long as it involves the same course of immunotherapy and they have been on that dose for at least 6mths prior to Visit2. c)A biological based antagonist therapy including Omalizumab or immune modulator within 6 mths. d)A systemic (iv, im or oral) corticosteroid within 3mths. e)A long acting anticholinergic bronchodilator within 2wks. f) Any of the following bronchodilators within 24hrs: inhaled anticholinergic agents, including fixed dose anticholinergic/ ß2 adrenergics, LABA including combination iCS/LABA, methylxanthines, and oral β2 agonists. g)Leukotriene modifiers, orally inhaled or oral nedocromil sodium/sodium cromoglycate, mucolytics from morning of Visit2 h)The following anti-allergy medications within 2wks: topical nasal steroid (ocular steroids allowed) or cromolyn (nasal and oral cromones allowed), oral antihistamines, oral decongestants. Topical antihistamines and topical decongestants are permitted on an as needed basis for symptoms of allergic rhino-conjunctivitis. i)Non-steroidal anti-inflammatory medication including COX-2 inhibitors and aspirin (except ocular formulations) within 1wk. j)Non-cardio-selective β-blocker medications (e.g., propranolol) within 2wks. Topical β-blocker eye medications are allowed. 14) Patients taking specific CYP2C8 and CYP2C9 substrates and potent or moderate CYP3A4 inhibitors at screening Visit2 or within 5 1/2 lives of Visit4, whichever is longer. A list of the specifically prohibited drugs is provided in the ISF at each site and updated as necessary by the sponsor. Any specific query should be directed to the sponsor prior to enrolment. 15) Patients with a risk for prolonged QT interval effects including: a)A marked baseline prolongation of QTc interval (demonstration of a QTc interval > 450 ms with confirmation on a repeat ECG) b)A history of additional risk factors for Torsade de Pointes (TdP) (e.g., heart failure, hypokalemia, family, history of Long QT Syndrome, etc); c)Patients on concomitant medications known to prolong the QT/QTc interval.

E.5 End points

E.5.1

Primary end point(s)

FEV1 % predicted trough change from baseline after 6 weeks of treatment.

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

Yes

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

Yes

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Double - dummy

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

Yes

E.8.2.3

Other

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

Yes

E.8.5.1

Number of sites anticipated in the EEA

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

Information not present in EudraCT

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

E.8.7

Trial has a data monitoring committee

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

Last patient out (last visit of the last subject entering the trial)

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 years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

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.1.3

Elderly (>=65 years)

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

400

F.4.2.2

In the whole clinical trial

700

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)

Patients will go back on their usual medication (as per prior to entering the study).

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

2010-01-25

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2010-04-21

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2011-08-09

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