Clinical Trials Register

Summary
EudraCT Number:	2012-003966-42
Sponsor's Protocol Code Number:	ADC3680-07
National Competent Authority:	Czechia - SUKL
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2013-02-27
Trial 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

Czechia - SUKL

A.2

EudraCT number

2012-003966-42

A.3

Full title of the trial

A Randomised, Double Blind, Placebo-Controlled, Multi-Centre, Parallel Group Study to Evaluate the Efficacy and Safety of ADC3680 Administered Once Daily as an Add-On Therapy to Inhaled Corticosteroids and when Co-Administered with Montelukast in Subjects with Inadequately-Controlled Asthma.

Randomizovaná, dvojitě zaslepená, placebem kontrolovaná, multicentrická studie s paralelními skupinami ke zhodnocení účinnosti a bezpečnosti přípravku ADC3680 podávaného jednou denně jako přídatná terapie k inhalačním kortikosteroidům a při souběžném podávání s montelukastem u subjektů s neadekvátně kontrolovaným astmatem.

A.3.1

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

A.4.1

Sponsor's protocol code number

ADC3680-07

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT01730027

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	Pulmagen Therapeutics LLP
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	Pulmagen Therapeutics (Asthma) Ltd
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Pulmagen Therapeutics LLP
B.5.2	Functional name of contact point	Clinical Trials Information
B.5.3	Address:
B.5.3.1	Street Address	The Coach House, Grenville Court, Britwell Road
B.5.3.2	Town/ city	Burnham
B.5.3.3	Post code	SL1 8DF
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	441753251345
B.5.5	Fax number	4408082801180
B.5.6	E-mail	clinical@pulmagen.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	ADC3680
D.3.2	Product code	ADC3680
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	not available
D.3.9.2	Current sponsor code	ADC3680
D.3.9.3	Other descriptive name	ADC3680B
D.3.9.4	EV Substance Code	SUB32366
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	20
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 Polska Sp. z o.o
D.2.1.2	Country which granted the Marketing Authorisation	Poland
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	Singulair
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 sodium
D.3.9.1	CAS number	151767-02-01
D.3.9.3	Other descriptive name	MONTELUKAST SODIUM
D.3.9.4	EV Substance Code	SUB03324MIG
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	Film-coated 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

asthma

E.1.1.1

Medical condition in easily understood language

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	17.0
E.1.2	Level	PT
E.1.2	Classification code	10003553
E.1.2	Term	Asthma
E.1.2	System Organ Class	10038738 - Respiratory, thoracic and mediastinal disorders

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 evaluate the efficacy of 20 mg ADC3680 OD compared with placebo in improving lung function (FEV1) in subjects with inadequately-controlled asthma despite treatment with ICS controller therapy, in the 10 week treatment period (Visit 3 to Visit 6).
 To evaluate the effect of adding 10 mg montelukast OD to 20 mg ADC3680 OD on lung function (FEV1) in the 2 week extension period (Visit 6 to Visit 7).

E.2.2

Secondary objectives of the trial

 To evaluate the efficacy of 20 mg ADC3680 OD compared with placebo on asthma symptoms (ACQ), other measures of lung function, frequency of severe exacerbations, and reliever therapy use in the 10 week treatment period (Visit 3 to Visit 6).
 To evaluate the effects of 20 mg ADC3680 OD compared with placebo on blood eosinophil counts and serum IgE levels in the 10 week treatment period (Visit 3 to Visit 6).
 To evaluate the effect of adding 10 mg montelukast OD to 20 mg ADC3680 OD on asthma symptoms (ACQ), other measures of lung function and reliever therapy use in the 2 week extension period (Visit 6 to Visit 7).
 To evaluate the effect of adding 10 mg montelukast OD to 20 mg ADC3680 OD on blood eosinophil counts in the 2 week extension period (Visit 6 to Visit 7).
 To assess the safety and tolerability of ADC3680 in subjects with inadequately-controlled asthma, both alone and in combination with montelukast.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

 Male or female subjects aged 18 to 50 years inclusive.
 A diagnosis of asthma according to the GINA guidelines, including a demonstration of reversible airway obstruction at screening (Visit 2) or randomisation (Visit 3).
 Reversible airway obstruction is defined as either a post-bronchodilator increase in FEV1 of ≥ 12% and ≥ 200 ml over the subject’s pre-bronchodilator value in litres; or an increase of ≥ 10% in FEV1 % predicted when compared with the subject’s pre-bronchodilator value.
 Subjects with a pre-bronchodilator FEV1 value ≥ 40% and ≤ 85% of the predicted normal value at screening (Visit 2) and baseline (Visit 3).
 A score of 1.5 or greater on the Asthma Control Questionnaire at screening (Visit 2) and at baseline (Visit 3).
 Receiving a low to moderate dose of an inhaled corticosteroid (equivalent to budesonide ≤ 800 μg per day) at a stable dose for at least 4 weeks before Visit 1.
 Prescribed a short-acting inhaled bronchodilator as reliever therapy for relief of symptoms.
 A peripheral blood eosinophil count ≥ 0.17 x 109/L at Visit 1.
 Non-smoker or former smoker with a smoking history of ≤ 10 pack years who has not smoked for at least 6 months before screening (Visit 2) and has a negative urine cotinine at Visit 2.
 Body mass index (BMI) ≥ 17 and ≤ 35 kg/m2.
 Able to understand the nature of the study and comply with the protocol requirements, instructions and restrictions.
 Able to provide signed and dated written informed consent to participate in the study.

E.4

Principal exclusion criteria

Subjects who are pregnant or breast-feeding. Female subjects of childbearing potential who do not agree to use an adequate method of contraception and female subjects who do not provide a negative pregnancy test prior to receiving study drug.
 Severe asthma exacerbation (defined as requiring treatment with oral or injectable corticosteroids, an emergency room visit or hospitalisation in the 4 weeks before Visit 1 or during the pre-treatment period).
 Respiratory tract infection requiring treatment with antibiotics or a change in asthma therapy in the 4 weeks before Visit 1 or during the pre-treatment period.
 A decrease in FEV1 and pre-bronchodilator PEF of at least 20% at baseline (Visit 3) when compared with the screening (Visit 2) values.
 An increase in ACQ total score of 2.0 or more at baseline (Visit 3) when compared with the ACQ total score at screening (Visit 2).
 Known cause of eosinophilia other than allergic airways disease.
 Seasonal allergies that will necessitate introduction of intra-nasal corticosteroids during the study.
 Oral β2 agonists, long-acting inhaled anticholinergics, LABAs, methylxanthines or cromones taken in the 4 weeks before randomisation (Visit 3) or leukotriene receptor antagonists or monoclonal antibody therapy 12 weeks before randomisation (Visit 3). Subjects who have received allergen immunotherapy within the previous 12 months are not eligible to participate in the study. Subjects who are taking oral beta blockers are not eligible to participate in the study.
 Diagnosed with COPD or other relevant lung diseases (e.g., tuberculosis, bronchiolitis, α1-antitrypsin deficiency, interstitial lung disease, fibrosis, sarcoidosis, cystic fibrosis, bronchiectasis).
 Abnormal and clinically significant safety laboratory values indicating an underlying unknown concomitant disease that requires further evaluation.
 Subjects who, in the judgment of the investigator, have a clinically significant condition such as (but not limited to) cardiovascular, gastrointestinal, hepatic, renal, haematological, endocrine, metabolic, psychiatric or neurological disease that might compromise subject safety or compliance, interfere with evaluation, or preclude completion of the study.Subjects with malignant disease are excluded, unless they have had a primary cancer treated at least 10 years previously with no subsequent evidence of recurrence, or have a basal cell skin cancer only.
 History of intolerance to leukotriene receptor antagonists.
 History of lactose intolerance.
 History of alcohol or substance abuse.
 Has participated in a study with an investigational inhaled corticosteroid or a long acting bronchodilator (anti-cholinergic or beta 2 agonist) alone or in combination in the previous 4 weeks, has participated in a study with any other new molecular entity in the previous 12 weeks, has already been randomised into this study, or has an affiliation with either the Sponsor or the study centre.

E.5 End points

E.5.1

Primary end point(s)

Primary Endpoint for the Treatment Period
 Change in trough (AM pre-dose and pre-reliever bronchodilator) FEV1 from
baseline (Visit 3) to Week 10 (Visit 6) for ADC3680 compared to placebo.
Nested Primary Endpoint for the Extension Period
 Change in trough (AM pre-dose and pre-reliever bronchodilator) FEV1 from
Week 10 (Visit 6) to Week 12 (Visit 7) for montelukast added to ADC3680.
This endpoint will be considered only if the analysis of the primary endpoint
for the treatment period (above) is found to be significant.

E.5.1.1

Timepoint(s) of evaluation of this end point

see E.5.1

E.5.2

Secondary end point(s)

Secondary endpoints for the Treatment period
Change in Asthma Control Questionnaire (ACQ) from baseline (Visit 3) to
Week 10 (Visit 6) for ADC3680 compared to placebo.
 Change in trough pre-bronchodilator FEV1 from baseline (Visit 3) to Week 2
(Visit 4) for ADC3680 compared to placebo.
 Change in trough pre-bronchodilator FEV1 from baseline (Visit 3) to Week 6
(Visit 5) for ADC3680 compared to placebo.
 Change in trough pre-bronchodilator FEV1 % predicted from baseline (Visit 3)
to Week 2 (Visit 4) for ADC3680 compared to placebo.
 Change in trough pre-bronchodilator FEV1 % predicted from baseline (Visit 3)
to Week 6 (Visit 5) for ADC3680 compared to placebo.
 Change in trough pre-bronchodilator FEV1 % predicted from baseline (Visit 3)
to Week 10 (Visit 6) for ADC3680 compared to placebo.
 Change in post-bronchodilator FEV1 from baseline (Visit 3) to Week 10 (Visit
6) for ADC3680 compared to placebo.
 Change in pre-bronchodilator PEF (in-clinic) from baseline (Visit 3) to Week
2 (Visit 4) for ADC3680 compared to placebo.
 Change in pre-bronchodilator PEF (in-clinic) from baseline (Visit 3) to Week
6 (Visit 5) for ADC3680 compared to placebo.
 Change in pre-bronchodilator PEF (in-clinic) from baseline (Visit 3) to Week
10 (Visit 6) for ADC3680 compared to placebo.
 Frequency of exacerbations during the treatment period for ADC3680
compared to placebo.
 Change in blood eosinophils from baseline (Visit 3) to Week 10 (Visit 6) for
ADC3680 compared to placebo.
 Change in serum IgE from baseline (Visit 3) to Week 10 (Visit 6) for
ADC3680 compared to placebo.
2.2.4 Secondary Endpoints for the Extension Period
 Change in trough pre-bronchodilator FEV1 % predicted from extension
baseline (Week 10) to Week 12 (Visit 7) for ADC3680 plus montelukast.
 Change in pre-bronchodilator PEF (in-clinic) from extension baseline (Week
10) to Week 12 (Visit 7) for ADC3680 plus montelukast.
 Change in ACQ from extension baseline (Week 10) to Week 12 (Visit 7) for
ADC3680 plus montelukast.
 Change in blood eosinophils from extension baseline (Week 10) to Week 12
(Visit 7) for ADC3680 plus montelukast.

E.5.2.1

Timepoint(s) of evaluation of this end point

see E.5.2

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

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

Yes

E.8.1.6

Cross over

E.8.1.7

Other

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.8.2.4

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

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

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

Croatia

Czech Republic

Germany

Hungary

Poland

United States

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

LVLS (or last assessment for last subject in case of premature tearmination)

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

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:

248

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

180

F.4.2.2

In the whole clinical trial

248

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)

Pulmagen Therapeutics LLP does not intend to provide ADC3680 or other study
interventions to subjects after the subject’s completion of protocol-specific treatment
or any earlier withdrawal from the treatment period. Subjects should continue to be
treated for their condition at the discretion of their doctor/treating physician.

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

2013-05-27

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-05-09

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2014-12-06

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