Clinical Trials Register

Summary
EudraCT Number:	2017-001593-42
Sponsor's Protocol Code Number:	CIDD001D2402
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Temporarily Halted
Date on which this record was first entered in the EudraCT database:	2018-04-30
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

Netherlands - Competent Authority

A.2

EudraCT number

2017-001593-42

A.3

Full title of the trial

A 24-week randomized, multicenter, single blinded, international
study to evaluate the effect of reminder notifications and
motivational/adaptive messaging on treatment adherence of COPD
subjects receiving Ultibro® Breezhaler® treatment using the
Concept2 inhaler for dose tracking

A.3.1

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

A 24-week randomized, single blinded study in subjects with
Chronic Obstructive Pulmonary Disease (COPD) to evaluate the
effect of reminders and motivational/adaptive messages on treatment
adherence tracked by the Concept2 inhaler

A.4.1

Sponsor's protocol code number

CIDD001D2402

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	Novartis Pharma AG
B.1.3.4	Country	Switzerland
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	Novartis Pharma AG
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Novartis Pharma Services AG
B.5.2	Functional name of contact point	Clinical Trial Information Desk
B.5.3	Address:
B.5.3.1	Street Address	Lichtstrasse 35
B.5.3.2	Town/ city	Bazel
B.5.3.3	Post code	4056
B.5.3.4	Country	Switzerland
B.5.4	Telephone number	+44 61 324 1111
B.5.5	Fax number	+44 61 324 8001
B.5.6	E-mail	clinicaltrial.enquiries@novartis.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	Yes
D.2.1.1.1	Trade name	Ultibro Breezhaler
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Europharm Limited
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	indacaterol maleate/glycopyrronium
D.3.2	Product code	QVA149
D.3.4	Pharmaceutical form	Inhalation powder, hard capsule
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Inhalation use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	indacaterol maleate
D.3.9.1	CAS number	753498-25-8
D.3.9.3	Other descriptive name	INDACATEROL MALEATE
D.3.9.4	EV Substance Code	SUB30300
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	110
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	GLYCOPYRRONIUM BROMIDE
D.3.9.1	CAS number	596-51-0
D.3.9.3	Other descriptive name	GLYCOPYRRONIUM BROMIDE
D.3.9.4	EV Substance Code	SUB07951MIG
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
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	Yes
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Chronic Obstructive Pulmonary Disease (COPD)

E.1.1.1

Medical condition in easily understood language

COPD is a chronic condition of the lungs which causes people to suffer
symptoms such as shortness of breath and coughing.

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	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10010952
E.1.2	Term	COPD
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

To evaluate the effect of dose tracking in conjunction with reminder notifications and motivational/adaptive messages sent by the patient application over 24 weeks on the subject’s on-time treatment adherence
and therefore treatment behavior

(1) the effect of the intervention on the on-time treatment adherence of the subjects
(2) the effect of the intervention on the total treatment adherence of the subjects

E.2.2

Secondary objectives of the trial

To evaluate the effect of dose tracking in conjunction with reminder notifications and
motivational/adaptive messages sent by the patient application over 24 weeks on the subject’s
 On-time adherence over the last four weeks of the Interventional period
 Total adherence over the last four weeks of the Interventional period

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Written informed consent must be obtained before any assessment is performed.
2. Male and female adults aged ≥ 18 years.
3. Current or ex-smokers who have a smoking history of at least 10 pack years. (Ten
pack- years are defined as 20 cigarettes a day for 10 years, or 10 cigarettes a day for 20
years).
4. A diagnosis of COPD confirmed by a post-bronchodilator FEV1 ≥ 30% and < 80% of
the predicted normal value, and post-bronchodilator FEV1/FVC < 0.70 at some point
in the past year.
5. Have been taking Ultibro® Breezhaler® for at least 3 months prior to Visit 1 (in
accordance with the local product label).
6. Have a total adherence of more than 10% but less than or equal to 70% during
Screening period. Total adherence is defined as percentage of days on which the
subject inhaled a dose of Ultibro® Breezhaler®.
7. Have been in the Screening period ≥ 35 days.

E.4

Principal exclusion criteria

1. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female
after conception and until the termination of gestation, confirmed by a positive hCG
(human Chorionic Gonadotropin) laboratory test.
2. Women of child-bearing potential, defined as all women physiologically capable of
becoming pregnant, unless they are using effective methods of contraception during the
study. Effective contraception methods include:
• Total abstinence (when this is in line with the preferred and usual lifestyle of the
subject). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation
methods) and withdrawal are not acceptable methods of contraception.
• Female sterilization defined as surgical hysterectomy, bilateral oophorectomy, or tubal
ligation at least six weeks before entering the study (Single oophorectomy does not meet
the definition of female sterilization).
• Male sterilization (at least 6 m prior to screening). For female subjects on the study, the
vasectomized male partner should be the sole partner for that subject.
• Barrier methods of contraception: Condom or Occlusive cap (diaphragm or
cervical/vault caps). For UK: with spermicidal foam/gel/film/cream/ vaginal suppository.
• Use of oral, injected or implanted hormonal methods of contraception or other forms of
hormonal contraception that have comparable efficacy (failure rate < 1%), for example
hormone vaginal ring or transdermal hormone contraception. In case of use of oral
contraception, women should have been stable on the same pill for a minimum of 3
months before entering the study.
• Placement of an intrauterine device (IUD) or intrauterine system (IUS).
• Women are considered post-menopausal and not of child bearing potential if they have
had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile
(e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral
oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago. In
the case of oophorectomy alone, only when the reproductive status of the woman has
been confirmed by follow up hormone level assessment is she considered not of child
bearing potential.
3. Subjects contraindicated for treatment with, or having a history of reactions/
hypersensitivity to any of the following inhaled drugs, drugs of a similar class or any
component thereof:
• anticholinergic agents
• long and short acting beta-2 agonists
• sympathomimetic amines
4. Subjects contraindicated for having a history of reactions/ hypersensitivity to lactose or any
of the other excipients of trial medication.
5. Subjects with a history of malignancy of any organ system, treated or untreated, within the
past 5 years whether or not there is evidence of local recurrence or metastases, with the
exception of localized basal cell carcinoma of the skin.
6. Subjects with narrow-angle glaucoma, symptomatic benign prostatic hyperplasia or
bladder-neck obstruction or moderate to severe renal impairment or urinary retention.
Benign Prostatic Hyperplasia (BPH) subjects who are stable on treatment can be
considered.
7. Subjects who have had a COPD exacerbation that required treatment with antibiotics and/or
systemic corticosteroids and/or hospitalization in 6 weeks prior to Visit 1.
8. Subjects who develop a COPD exacerbation between screening (Visit 1) and prior to
intervention (Visit 110) will not be eligible but will be permitted to be re-screened after a
minimum of 6 weeks after the resolution of the COPD exacerbation.
9. Subjects who have had a respiratory tract infection within 3 weeks prior to Visit 1.
10. Subjects who develop a respiratory tract infection between screening (Visit 1) and prior to
intervention (Visit 110) will not be eligible, but will be permitted to be re-screened 3 weeks
after the resolution of the respiratory tract infection.
For full list please see protocol

E.5 End points

E.5.1

Primary end point(s)

Co-primary endpoint 1: on- time adherence defined as percentage of days on which the subject inhaled a t least one
dose within (±) 2 hours of the agreed preferred daily inhalation time (PIT).
Co-primary objective 2: total adherence defined as percentage of days on which the subject inhaled at least one
dose and represents the sum of on-time adherence and off-time adherence.
Off-time adherence is defined as percentage of days on which the subject inhaled a dose of
medication, but did not do so within the target window (±) 2 hours of the agreed PIT.

E.5.1.1

Timepoint(s) of evaluation of this end point

24 weeks

E.5.2

Secondary end point(s)

· On-time adherence over the last four weeks of the Interventional period
· Total adherence over the last four weeks of the Interventional period

E.5.2.1

Timepoint(s) of evaluation of this end point

The secondary endpoint is evaluated at week 24 of the interventional phase

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

E.6.4

Safety

E.6.5

Efficacy

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

Yes

E.6.13.1

Other scope of the trial description

study to evaluate the effect of reminder notifications and motivational/adaptive messaging on treatment adherence of COPD subjects receiving Ultibro®
Breezhaler® treatment using the Concept2 inhaler for dose tracking

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)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

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

Yes

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

treat. arm with investigational software application-med dev compared to control arm no software app

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

treatment arm with investigational software application compared to control arm with no software app

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

E.8.6.2

Trial being conducted completely outside of the EEA

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 last visit

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:

116

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

146

F.4.2.2

In the whole clinical trial

146

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)

The investigator must provide follow-up medical care for all subjects completing the study or who are prematurely withdrawn from the study, or must refer them for appropriate ongoing care.

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

2018-06-11

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-02-01

P. End of Trial
P.	End of Trial Status	Temporarily Halted

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